I. Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials
Skin cancer affects more than 50% of post-transplant patients. There is a higher rate of squamous cell carcinoma to basal cell carcinoma in comparison to general population with an incidence of 65 to 250 times higher than general population.
Once skin cancer developed, management options are limited.
There is greater burden of skin cancer and cancer related mortality. The risk of death from invasive and metastatic skin cancer is three to nine times higher than general population.
Current recommendations for prevention as frequent skin self examination and annual to biannual total body skin examination ,sun protective measures ( use of sunscreens, protective clothing and limiting sun exposure during peak hours of high ultraviolet index days) and alteration of immunosuppression
May not be applicable to solid organ transplant patients.
Aim of study: Determine the effectiveness of interventions that promote behavioral changes and skin cancer prevention in solid organ transplant.
Method
Study design: systematic review
Inclusion criteria: All randomized controlled trials or quasi RCTs of interventions for skin cancer prevention in solid organ transplant patients.
Exclusion criteria: Titles and abstracts were reviewed and those who didn’t meet the Inclusion criteria were discarded.
Data extraction and synthesis: Risks of bias and evidence of certainty were assessed using Cochrane and the Grading of recommendations Assessment Development and Evaluation framework.
Results : 20 trials including 2295 participants. It is uncertain whether behavioral interventions improve sun protection behavior and knowledge as the quality of evidence is very low.
It is uncertain of the effect of mTOR inhibitors on the incidence of non melanocytic skin cancer as the quality of evidence is very low.
Conclusion
Behavioral and pharmaceutical preventive interventions may improve sun protective behavior and knowledge and reduce the incidence of non melanocytic skin cancer, but the overall quality of the evidence is very low to guide decision-making and clinical practice.
What is the difference between errors and bias?
Bias produces systematically prejudiced results. Biases are identified manually or through available software programs.
Errors produce inaccurate results. Errors are identified through calculations and metrics such as false positive rates.
Introduction
Skin cancer is a very common post-renal transplant affecting around 50% of transplant recipients.
Squamous cell carcinoma increased by 65 to 250 folds greater than aged match general populations. This affects patient survival. Immune therapy may not be suitable as it may induce rejection, limiting treatment options for this group of patients. Preventive measures recommended for the general population have not been tested and validated in transplant recipients, such as sunscreen, protective cloths and avoidance of sun exposure during peak UV light. Methods
This is a systematic review and meta-analysis. Inclusion criteria All randomized controlled trials (RCTs) or quasi-RCTs of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were included. Outcome measures The prespecified outcome measures were incidence of precancerous and cancerous lesions, sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance), knowledge and attitude, skin self-examination, sun exposure (including skin irritation, sunburn) and biologic measures (including measurement of melanin index and sun damage assessment). Result:
They identified 1280 articles, 1201 were excluded after abstract and title review. After further assessment of 79 studies, 22 reports were found eligible articles for inclusion. Twenty of them were RCT (n=2295 participants) were included.
It is uncertain whether behavioural interventions improve sun protection behaviour as the quality of evidence is very low.
We are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of non melanocytic skin cancer (n=5, n=1080, relative risk 0.46, 95%CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low
Conclusion
Preventative measures including behavioural, switch to mTORis and other pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients. However with low quality level.
What is the level of evidence provided by this article?
Level 1
What is the difference between bias and errors?
An error is a term used to refer to anything that is incorrect and inaccurate. In machine learning, errors give insight into how accurate predictions are. Alternatively, errors can also refer to the difference between the predictions and the ground truth value. Bias produces systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates and RMSE. Biases are identified manually or through available software programs.
Skin cancer, including melanoma and nonmelanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post-transplantation recipients.Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC).Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population.Sun protective behaviours including use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days are potential measures for skin cancer prevention.Further, alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
Methods
This systematic review followed a prespecified protocol registered in PROSPERO and is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist.
Inclusion criteria –
All randomised controlled trials (RCTs) or quasi RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were included. Behavioural interventions defined as any strategy used to promote sun protective behaviour including passive (eg, pamphlets), active (eg, group workshops, counselling, dermatology clinic) and provision of sun protective equipment; and pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoid.
RESULTS-
Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour (n=3, n=414, standardised mean difference (SMD) 0.89, 95%CI −0.84 to 2.62, I2 =98%) and knowledge (n=4, n=489, SMD 0.50, 95%CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low. We are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of nonmelanocytic skin cancer (n=5, n=1080, relative risk 0.46, 95%CI 0.28).
Conclusions
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
What is the level of evidence provided by this article?
Level 1
What is the difference between bias and errors?
Bias produces systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates and RMSE. Biases are identified manually or through available software programs.
Solid organ transplantation (SOT) is known to be the definitive treatment for almost end organ failure, yet among the most irritating disadvantage is the relation between heavy immunosuppression and increased incidence of malignancies. Up to our knowledge Skin cancer, including melanoma and non-melanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among SOT recipients more than 50%. The cumulative incidence of NMSC is elevating with time after transplantation from 5%–10% at 2 years to 40%–80% at 20 years. There is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender-matched general population.
The development of malignant conditions affects markedly the immunosuppressive regimen for such patients, being less than the proper doses needed leads to more exposure to rejection episodes. Recently registry data show progress in survival rates of transplant recipients as a result of improved transplantation techniques as well as better management of immunosuppression reduction, yet there is still a great burden of skin cancer and cancer-related mortality.
We still face the excess risk of death after invasive and metastatic skin cancer, such as SCC and melanoma are encountered by three to nine times higher than the general population, with 5-year overall survival of <30%. One known factor can be identified which is sun exposure behaviour being the most significant modifiable factor in the prevention of skin cancers in the general population. So preventative strategies are being suggested as frequent skin self-examination and annual to biannual total body skin examination. Other strategies include using proper sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days. Tailoring of maintenance immunosuppression by switching to mammalian target of rapamaycin inhibitors (mTORis) and administration of retinoid acitretin are crucial for management of skin cancers in high-risk transplant recipients.
The study aims to assess the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
Methods
It is a systematic review, including all randomised controlled trials (RCTs) till November 2019 concerned by interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients.
Outcome measures the incidence of precancerous, cancerous lesions and sun protection behaviour.
Results
There were 22 eligible articles only for the study to be included with total 20 RCTs of 2295 participants. The median number of participants was 44 (range 17–830) and the median follow-up duration was 10 months (range 1 day to 60 months). Finally a total of 15 (76%) of 21 studies supplied sufficient data for the meta-analyses.
Limitations
Main obstacles were the poor overall quality of the evidence for all outcomes, limitations in study design, heterogeneity in the intervention, outcome measures, the very small sample size of individual studies and the small number of studies for each specific outcome.
Moreover, the assessment of reporting of sun protection behaviour and sun protection knowledge was not possible as outcomes were inconsistent owing to the large diversity of interventions used.
Interventions
Three classified groups according to the intervention applied ether behavioural or shifting to mTORi or other including photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide categories.
Effect of behavioural interventions on sun protection outcomes
Sun protection behaviour
It is best described by as total hours spent outdoors per week, use of sunscreen, wearing protective clothing and seeking shade. Sun protection is assessed in three trials. Fortunately, those patients who adopted behavioural interventions reported improved sun protection behaviour scores (3 studies, 414 participants, SMD 0.89, 95% CI −0.84 to 2.62, I2 98%).
Only a single trial was concerned by self-skin examination reported improvement after 1 month (75 participants, RR 4.14, 95% CI 2.22 to 7.72).
Also one trial was minded by the reduction of total number of hours spent outdoors which was also improved (170 participants, MD −6.12, 95% CI −711 to −5.13).
Sun protection knowledge
Six trials were concerned by the improvement of the sun protection knowledge whereas the knowledge scores were raised (4 studies, 489 participants, SMD 0.50, 95% CI 0.12 to 0.87, I2 76%).
Sun protection attitude
The study expressed an overall improvement in scores of concern about developing cancer (3 studies, 348 participants, SMD 1.85, 95% CI 1.59 to 2.11, I2 96%).
Two studies included 273 participants estimated improvement in scores of understanding the personal risk of skin cancer by (SMD 0.61, 95% CI −0.60 to 1.82, I2 96%), adherence to sun protection (SMD 0.77, 95% CI −0.14 to 1.68, I2 92%) as well as the intention to change behaviour (SMD 1.70, 95% CI −1.68 to 5.07, I2 99%).
To our knowledge one study included 75 participants reported an improvement in scores of ability to recognise a potential skin cancer (MD 1.80, 95% CI 1.35 to 2.25), importance of skin self-examination (MD 1.05, 95% CI 0.61 to 1.49) and having a partner help for skin self-examination (MD 1.59, 95% CI1.10 to 2.08).
Also one single study reported better improvement in the necessity of engaging in sun protection (measured using 5-point Likert scale, 101 participants, MD 7.00, 95% CI 2.94 to 11.06).
Skin complications and biologic measures
A total of 271 renal transplant recipients were encountered in two trials concerned by the behavioural interventions. The intervention group exhibited reduction of the incidence of skin irritation by (RR 1.00, 95% CI 0.89 to 1.13, I2 95%) as well as sunburn by (RR 3.19, 95% CI 2.47 to 4.10, I2 99%).
Fortunately a significant decrease in melanin index (right forearm, SMD −0.42, 95% CI −0.66 to −0.18; cheek SMD −0.25, 95% CI −0.64 to −0.15) besides reduced severity of sun damage (SMD −0.13, 95% CI −0.40 to 0.13) on sun exposed areas.
Effect of pharmaceutical interventions on skin cancer prevention
Topical/local interventions
A trial of 14 participants assessed an immune response modifier revealed a reduction in the incidence of skin dysplasia (RR 2.14, 95% CI 0.31 to 14.65), skin atypia (RR 3.00, 95% CI 0.47 to 19.35), and viral warts (RR 7.00, 95% CI 0.46 to 106.10).
A famous Danish study consisted of 26 renal transplant recipients concerned by the use of photodynamic therapy documented a relative reduction by nearly 40% in the incidence of NMSC on the treated area (RR 0.59, 95% CI 0.34 to 21.03, p 0.06).
A significant lower incidence of SCC was reported in one trial after using an immune response modifier (14 participants, RR 0.09, 95% CI 0.0.01 to 1.70). Furthermore, Two trials studied both photodynamic therapy as well as immune response modifiers in recipients with diagnosed keratoses revealed a complete response rate of 60% compared with 24% in the control group (50 participants, RR 5.03, 95% CI 0.14 to 176.17, I2 85%).
However the effects of photodynamic therapy on the incidence of precancerous lesions couldn’t be assessed owing to the very low quality of evidence.
It is wise to mention that a trial which was not included in the meta-analysis, reported a higher cumulative incidence of actinic keratosis lesions in untreated skin (63%) compared with skin treated by photodynamic therapy (28%).
Systemic interventions
A number of 5 trials studied the role of mTORis therapy in reduction of the incidence of NMSC in comparison to CNIs maintenance therapy (5 trials, 1082 participants, RR 0.46, 95% CI 0.28 to 0.75, I2 72%). Unfortunately, there was lack of evidence because of short follow-up periods, variability in dosing of mTORis and significant rates of loss to follow-up.
A single trial considered switching from CNI to mTORi therapy reported marked improvement in skin dysplasia (32 participants, RR 24.35, 95% CI 1.55 to 381.99).
Two trials assessing the use of an oral retinoid, acitretin reported an improved lower risk of both SCCs and BCCs (46 participants, RR 0.40, 95% CI 0.19 to 0.85, p 0.02; RR 0.50, 95% CI 0.14 to 1.76)42 or development of a new skin cancer (19 participants, RR 0.22, 95% CI 0.06 to 0.90). Yet, there were no differences in the incidence of new SCCs detected. Astonishingly, one trial which was not included in the meta-analysis, revealed approximately a 50% reduction in the incidence of actinic keratosis which compared a high dose to a low dose of acitretin.
A well-known Australian trial of 22 renal transplant recipients studied nicotinamide came with the conclusion of an estimated relative rate difference of 0.35 (95% CI −0.62 to 0.74), 0.67 (95% CI −0.40 to 0.90) and 0.07 (95% CI −1.51 to 0.65) for NMSC, BCCs and SCCs respectively.
Discussion
Skin cancers are known to famous causes of morbidity and mortality in solid organ transplant recipients. Even though the trials of interventions to overcome this are still scarce in number (20 trials), small with half comprising of 50 patients or less, of short duration (48% have <12 months follow-up). Furthermore, 52% do not include incidence of skin cancer as an outcome.
This review precluded 22 reports of 20 trials involving 2295 transplant recipients mainly renal transplant recipients. Several studies were performed on a diverse range of interventions such as; behavioural to improve sun protection behaviour and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence without considering precancerous lesions or skin cancer incidence as important outcomes.
Up till now, the current evidence for interventions for skin cancer prevention in solid organ transplant recipients is of very low quality and is insufficient to guide decision-making and clinical practice. Another problem is the absence of long-term follow-up, large discontinuation rates owing to adverse events and variability in the doses of mTORis adds more uncertainty to the effectiveness of these strategy to overcome this. It is suggested that pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers) had shown marked reduction in precancerous lesions.
Previously performed reviews in other high risk populations especially outdoor workers, family history, personal history and phenotypic factors have found similar improvement in sun protective behaviours particularly the use of sunscreen, as well as a decreased incidence of keratoses.
Although behavioural change looks very simple strategy, yet long-term adherence is a bit challenging. It is suggested that maximum benefits of behavioural change should be associated with early implementation of education particularly prior to transplantation.
These interventions should best become integrated into routine appointments and tailored to meet the individual needs of patients. We also encourage performing additional large-scale and high-quality RCTs in order to demonstrate the effectiveness of interventions used to prevent skin cancer in transplant recipients in terms of patient important outcomes, especially morbidity and mortality associated with skin cancer. The level of evidence isLevel I (systematic review of randomized controlled trials). The difference between bias and errors
Bias is anerror in the study design or implementation that becomes associated with results that are in favour of one single direction against the others mostly due to nonrandom factors .whereas errors are mistakes occurring in the results because of the presence of random factors that could not be excluded.
This is a systemic review including 22 reports of 20 trials including 2295 transplanted patients, mainly kidney transplant. It evaluate the efficacy of behavioural or pharmaceutical interventions on behavioral change of skin cancer prevention.
Skin cancers including melanoma and non-melanoma skin cancer is the most frequently diagnosed malignancy complicating solid organ transplantation.
Sun exposure behaviours remain the most significant
and modifiable risk factor in the prevention of skin cancers in the general population. Pharmaceuticals have also been used to reduce and delay the development of skin cancer. Sun protective behaviours including use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days are potential
measures for skin cancer prevention. Also alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin
cancers in high-risk transplant recipients.
Results : Twenty trials were included. It is uncertain whether behavioural interventions
improve sun protection behaviour (n=3, n=414,
standardised mean difference (SMD) 0.89, 95% CI −0.84
to 2.62, I2=98%) and knowledge (n=4, n=489, SMD 0.50,
95% CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low. We are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of non-melanocytic
skin cancer (n=5, n=1080, relative risk 0.46, 95% CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low.
Conclusions : Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic
skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
This is systemic review of RCTs : level 1
Bias produces systemically prejudiced results while errors produce inaccurate results.
Introduction
Solid organ transplant recipients are at increased risk of skin cancer affecting around 50% of recipients.
melanoma and non-melanoma skin cancer (NMSC), is the most common malignancy among SOT recipients, incidence of NMSC increases with more time passing after transplantation, to reach 40%–80% at 20 years
Compared with the general population, there is a higher rate SCC to BCC, with an incidence of 65 to 250 times greater than matched general population.
In SOT recipient’s immunotherapy may be unsuitable due risk of graft rejection.
Risk of death due to metastatic skin cancer are three to nine times higher than general population, with 5-year overall survival of 30%.
avoid Sun exposure is a significant and modifiable risk factor in the prevention of skin cancers, but it is not effective alone and in case of SOT recipients, pharmaceuticals must be used reduce and delay the skin cancer.
preventive strategies on SOT recipients based on guidelines in the general population includes frequent skin self-examination, annual to biannual total body skin examination, use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days.
conversion to mTORi instead of CNI and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
Results and discussion
-This systematic review was done aiming to determine the effectiveness of interventions that promote behavioral change and skin cancer prevention in solid organ transplant recipients.
This review included reports of 20 trials on 2295 SOT recipients, mostly kidney transplant recipients. To evaluate the effect of different protective methods including :
behavioral changes to improve sun protection.
behavioral and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers).
effect of switching to mTORis
results showed:
-None of the behavioral intervention studies included precancerous lesions or skin cancer incidence as outcomes.
-Although interventions showed improvements to sun protection behaviors, precancerous lesion responses and cancer incidence, but still there was variability across intervention types, variability in outcomes assessed and outcome estimates.
-behavioral interventions improved sun protection attitude behavior, but the effect on skin cancer as an outcome was not documented in many of the studies.
-This review was unable to compare specific behavioral interventions (eg, mobile app vs written education) to detect the most effective method of delivering sun protection education.
– this review showed some benefits in the reduction of NMSC incidence among SOT recipients who were converted to mTORis compared with those on CNI maintenance.
-Pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers) showed a reduction in precancerous lesions compared with standard care or a comparator group.
– systematic review of the benefits of oral retinoids for the prevention of skin cancer on SOT recipients was inconclusive due to the small number of included trials.
Strengths and limitations of this study:
-A comprehensive review of twenty trials with Inclusion of a broad range of interventions, including either behavior only or behavior and pharmaceutical to improve sun protection to evaluate precancerous lesion response and cancer incidence.
-heterogeneity of the studies and high risk of bias.
– All studies of behavioral interventions were undertaken in USA, with four by the same authors, while most pharmacological intervention studies were conducted in Europe.
-large discontinuation rates due to adverse events in trials of mTORis.
-small number of studies included in the meta-analysis, we were unable to perform any detailed subgroup analyses to explore heterogeneity or assess for publication bias.
-Unable to perform detailed subgroup analyses or assess for publication bias due to small number of studies.
– Few trials included the important outcomes of skin cancer and none included melanoma or mortality.
Level of Evidence: This is a systematic review level of evidence 1
Introduction
Skin cancer is a frequently diagnosed malignancy among patients who have undergone solid organ transplantation. The incidence of non-melanoma skin cancer (NMSC) increases with time after transplantation. It is noted that squamous cell cancer (SCC) has a higher incidence than basal cell carcinoma (BCC), when compared with the general population. Management options are limited in post-transplant recipients once the cancer develops, as immunotherapy may lead to graft rejection. The mortality risk from invasive and metastatic skin cancer is 3 to 9 times higher in solid organ transplant recipients as compared to the general population. Some of the risk factors are modifiable, such as sun exposure, however, pharmaceutical agents have also been used to reduce and delay the development of skin cancer. Adjustment of the immune suppression medications have also been used in the management. The aim of the study was to determine the effectiveness of the interventions that promote behavioral change and skin cancer prevention in solid organ transplant recipients.
Methods
It was a systematic review that included randomized control trials (RCTs) or quasi RCTs of interventions of skin cancer (including melanoma and NMSC) in solid organ transplant recipients. Behavioral and pharmaceutical interventions to promote sun protective behaviors were included, as were studies that reported skin cancer-related outcomes as their primary outcomes. Studies that involved the interventions for skin cancer treatment were excluded. The outcome measures that were pre-specified were:
Incidence of precancerous and cancerous lesions
Sun protective behaviors
Use of sunscreen
Use of protective clothing
Sun avoidance
Knowledge and attitude
Skin self-examination
Sun exposure
Biological measures
Measurement of melanin index
Sun damage assessment
Results
22 reports with a total of 2295 participants, were included in the review, out of which 20 were RCTs. The medium follow-up duration was 10 months. The overall quality of the evidence was low for all the outcomes due to the limitations in the study design, the need for similarity in the interventions and outcome measures, the small sample size of individual studies and the small number of studies for each specific outcome.
The effect of behavioral interventions on sun protection outcomes
1.Sun protective behavior
Defined as hours spent outdoors per week, use of sunscreen , wearing protective clothing and seeking shade.
It was assessed in three trials
The outcome is uncertain due to the low quality of evidence.
2.Sun protection knowledge
It was assessed in 6 trials
It was noted that there was an improvement in knowledge score after the intervention of education.
3.Sun protection attitude
Three studies were assessed
There was an overall improvement in scores of concern about developing skin cancer
4.Skin complications and biologic measures
Two trials were assessed
The intervention group experienced a reduced incidence of skin irritation on sun exposed areas.
The effect of pharmaceutical interventions on skin cancer prevention
1.Topical/local interventions
Overall, a lower incidence of skin cancer was noted in patients who used the interventions
The interventions included:
5% imiquimod cream
Photodynamic therapy
Immune response modifiers
2.Systemic interventions
mTORis therapy reduced the incidence of NMSC compared with CNIs maintenance therapy
Discussion
Skin cancers are major causes of morbidity and mortality in solid organ transplant recipients. Trials aimed at preventing skin cancer in solid organ transplant recipients are few. Overall, the current evidence for interventions for skin cancer prevention in solid organ transplant recipients is of very low quality and is sufficient to guide decision-making and clinical practice.
It is an extensive review that was done using reliable methods to assess risk of bias and the certainty of evidence. It used a wide range of interventions to evaluate the response of lesions and the incidence of cancer.
Unfortunately, they encountered some difficulty in retrieving a summary of the overall outcomes. This was due to the various methods of analysis by the different studies included in the review. The number of studies available were also few, out of which even fewer included the outcomes of the patients diagnosed with skin cancer, and none included the mortality.
Level of Evidence: This is a systematic review of RCTs. LOE I
Difference between bias and errors:
A bias refers to a scenario where a system or model produces systematically prejudiced results. An error refers to anything that is inaccurate or incorrect
Biases occur systematically while errors occur randomly
Errors are identified through calculations while biases are identified through software packages
Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials Introduction
Skin cancer, including melanoma and nonmelanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post-transplantation recipients.
The cumulative incidence increases with time from 5%–10% at 2 years to 40%–80% at 20 years.
Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender-matched general population.
Once cancer develops, management options are limited as immunotherapy may be unsuitable as it may lead to graft rejection.
Inspite of improvement in survival , but there is greater risk of cancer development.
death from SCC and melanoma, are 3-9 nine times higher than the general population, with 5-year overall survival of <30%.6 12–15 Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population.16 However, with the dramatic increase in skin cancers in solid organ transplant recipients, pharmaceuticals have also been used to reduce and delay the development of skin cancer.16 17 Current recommendations for preventive strategies have often been extrapolated from guidelines in the general population, which may not be applicable to solid organ transplant recipients.18 19 For example, frequent skin self-examination and annual to biannual total body skin examination are generally recommended for the general population.18–20 Sun protective behaviours including use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days are potential measures for skin cancer prevention.3 4 14 Further, alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.20 The aim of this study is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients. Methods This systematic review followed a prespecified protocol registered in PROSPERO (CRD42017063962) and is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist.21The study was exempt from approval from an ethics’ board. Inclusion criteria All randomised controlled trials (RCTs) or quasi RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were included. Behavioural interventions defined as any strategy used to promote sun protective behaviour including passive (eg, pamphlets), active (eg, group workshops, counselling, dermatology clinic) and provision of sun protective equipment; and pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids) and studies that reported skin cancer-related outcomes as their primary outcomes were included. Studies that did not report these outcomes as primary endpoints were excluded. Studies of interventions for the treatment of skin cancer were excluded. Search strategies We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019 without language restriction, using search strategies designed by a specialist information manager (see Medline search strategy in online supplementary figure S1). Reference lists of included studies were also searched. Data extraction Titles and abstracts were reviewed by two independent authors (LJJ and LDWL) and those who did not meet the inclusion criteria were excluded. Full-text articles were reviewed by three independent reviewers (LJJ, VS, LDWL) and any disagreements were resolved by discussion. Data on study design, geographic location, sample size, type of transplant, measurement of interventions, interventions and comparators were extracted. We sought unclear or missing information from authors where possible. Outcome measures The prespecified outcome measures were incidence of precancerous and cancerous lesions, sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance), knowledge and attitude, skin selfexamination, sun exposure (including skin irritation, sunburn) and biologic measures (including measurement of melanin index and sun damage assessment). Risk of bias and quality of evidence The risk of bias was assessed independently by LJJ and VS using the Cochrane risk of bias tool.22 The domains included in the assessment were random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, trial registration and industry involvement. Each criterion was assigned a judgement of high, low or unclear risk of bias. Intention to treat and lost to follow-up were also assessed for each study. The quality of the evidence informing summary estimates for each outcome was then assessed by LJJ using the Grading of Recommendations Assessment Development and Evaluation (GRADE) guidelines.23 Data synthesis and statistical analyses Continuous outcomes were summarised as mean difference (MD) or standardised mean difference (SMD) and dichotomous outcomes as relative risk (RR). A MD/ SMD greater than 0 and/or a RR greater than 1 could be interpreted as favouring the intervention group relative to the control, unless specified elsewhere. Risk estimates were reported with 95% CIs, using random effects meta-analysis. We quantified the heterogeneity using the I² statistic. An I2 value of ><25% was considered to represent low heterogeneity and >75%. Factors to prevent in general population :
· frequent skin self-examination
· annual to biannual total body skin examination
· Sun protective behaviours including use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days
· alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis)
· secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients
The aim of this study is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients. Method
assessment of 79 studies found 22 eligible articles for inclusion . Studies characteristics
We included 22 reports of 20 RCTs, including 2295 participants . median follow-up duration was 10 months
All studies included kidney transplant recipients, with some also including heart transplant recipients, liver, heart, pancreas, lung, heart/lung and other transplants and lung and liver transplant recipients.
It is a meta-analyses.
assessment of reporting of sun protection behaviour and sun protection knowledge was not possible as outcomes were inconsistent and there was large diversity of interventions used (eg, written education material vs a mobile app programme).
formal testing of publication bias was not performed due to insufficient data. Interventions
The interventions in the included studies were grouped into three broad categories,
· behavioural
· switch to mTORis
· other pharmaceutical interventions photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide. Effect of behavioural interventions on sun protection outcomes:
We are uncertain of the effects of behavioural interventions on sun protection behaviour due to very low quality of evidence. Effect of pharmaceutical interventions on skin cancer prevention
These included the switch to mTORis , photodynamic therapy and immune response to current treatment . Discussion
Skin cancers (both non-melanoma and melanoma) are major causes of morbidity and mortality in solid organ transplant recipients.
Despite this, trials of interventions aimed at preventing skin cancer in solid organ transplant recipients are few in number
there is a high degree of uncertainty in the estimate of the effect of skin cancer prevention interventions.
Preventative measures: including behavioural, switch to mTORis and other pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients. However, the overall quality of evidence is very low and insufficient to guide decision-making and clinical practice.
Future robust studies that are well powered, have long-term follow-up and use clinical and patient important outcome measures in a consistent manner are required to therefore optimise outcomes for solid organ transplant recipients..
level of evidence 1a.
Skin cancer is a major concern for solid organ transplant recipients, affecting more than 50% of post-transplantation patients. The risk of developing skin cancer increases with time, and the incidence of squamous cell carcinoma is higher than in the general population. Cancer-related mortality is greater among transplant recipients. Sun exposure behaviors remain the most significant risk factor in skin cancer prevention, but pharmaceuticals have been used to reduce and delay cancer development.
Current recommendations for preventive strategies may not be applicable to solid organ transplant recipients, and this study aims to determine the effectiveness of interventions promoting behavioral change and skin cancer prevention in this population.
Systematic review that was conducted to evaluate interventions for preventing skin cancer (including melanoma and non-melanoma skin cancer) in solid organ transplant recipients. The review included randomized controlled trials or quasi-RCTs that examined behavioral interventions (such as promoting sun protective behavior) or pharmaceutical interventions (such as photodynamic therapy or oral retinoids) that reported skin cancer-related outcomes as their primary outcomes. Data were extracted and reviewed by multiple independent authors according to pre-specified inclusion criteria.
It is a systematic review and meta-analysis of randomized controlled trials (RCTs) on the effectiveness of interventions to prevent skin cancer in transplant recipients. The review identified 22 eligible studies, which included a total of 2,295 participants. The pre-specified outcome measures were the incidence of precancerous and cancerous lesions, sun protection behavior, knowledge and attitude, skin self-examination, sun exposure, and biologic measures. The interventions in the included studies were grouped into three broad categories: behavioral interventions, switch to mTORis, and other pharmaceutical interventions. The overall quality of the evidence was very low for all outcomes due to limitations in study design, heterogeneity in the intervention and outcome measures, small sample sizes, and a small number of studies for each specific outcome. The risk of bias was assessed independently by two reviewers using the Cochrane risk of bias tool, and the quality of the evidence was assessed using the Grading of Recommendations Assessment Development and Evaluation (GRADE) guidelines. The review found that there was insufficient evidence to support the effectiveness of any of the interventions in preventing skin cancer in transplant recipients.
Strengths:
The study was conducted using methods outlined by the Cochrane Collaboration
The review included a broad range of interventions, for comprehensive understanding of the effectiveness of different strategies for preventing skin cancer.
The use of the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework to assess risk of bias and evidence certainty is a rigorous method for evaluating the quality of evidence.
Limitations:
There was significant variability in the analytical methods and reporting in individual studies, which made it difficult to obtain an overall summary estimate for many outcomes.
The small number of studies prevented the authors from performing detailed subgroup analyses or assessing for publication bias.
The study did not include the important outcomes of skin cancer, melanoma, or mortality, which limits the applicability of the findings to these important clinical outcomes.
Q1- Please summarise this article.
Abstract Objectives: The study aim is to determine the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients. Study Design : Systematic review. Conclusions : Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
Introduction: Skin cancer, including melanoma and non-melanoma
skin cancer (NMSC), is the most frequently diagnosed malignancyamongsolid organ transplant recipients, affecting more than 50% of post-transplantation recipients.
(1 2) The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years.( 2–4 ) Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender-matched general population. (5–8 ) Once cancer develops, management options are limited as immunotherapy may be unsuitable as it may lead to graft rejection.
The excess risk of death from invasive and metastatic skin cancer, such as SCC and melanoma, are three to nine times higher than the general population, with 5-year overall survival of <30%.
Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population. However, with the dramatic increase in skin cancers in solid organ transplant recipients, pharmaceuticals have also been used to reduce and delay the development of skin cancer.
frequent skin self-examination and annual to biannual total body skin examination are generally recommended for the general population. Sun protective behaviours including use
of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days are potential measures for skin cancer prevention. alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients. Methods : A systematic review
The overall quality of the evidence was very low for all outcomes.
Sun protection behaviour, defined as hours spent outdoors per week, use of sunscreen, wearing protect tive clothing and seeking shade .
Systemic interventions
mTORis therapy reduced the incidence of NMSC compared with CNIs maintenance therapy . but , evidence was limited due to short follow-up periods, variability in dosing of mTORis and significant rates of loss to follow-up, and therefore the authers are uncertain of the effects of mTORis on skin cancer incidence due to very low quality of evidence. A single trial involving 21 patients reported a reduction in the overall incidence of SCC by 49% in the conversion arm, but reported a drop out rate of 77% and follow-uptime of less than 2 years. a single trial which compared mTORi conversion from CNI-based therapy reported a significant improvement in skin dysplasia
Discussion
Skin cancers (both non-melanoma and melanoma) are major causes of morbidity and mortality in solid organ transplant recipients.
Overall, the current evidence for interventions for skin cancer prevention in solid organ transplant recipients is of very low quality and is insufficient to guide decision-making and clinical practice.
Although behavioural interventions appeared to improve sun protection attitude, knowledge and behaviour, there were inconsistencies detected and none of these studies included skin cancer as an outcome.
While there may be some modest benefits in the reduction in cancer incidence (for NMSC) among solid organ transplant recipients who were converted to mTORis compared with those on CNI maintenance, there was substantial heterogeneity across the studies that was unable to be explained by subgroup analyses. Heterogeneity may be attributed to the absence of long-term follow-up, large discontinuation rates owing to adverse events and variability in the doses of mTORis.
Pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers) showed a reduction in precancerous lesions compared with standard care or a comparator group.
A systematic review of the benefits and harms of oral retinoids for the prevention of skin cancer among high-risk transplant recipients led to inconclusive results on the effect of acitretin due to the small number of included trials.
The use of pharmaceutical and immunosuppression therapy remains complex.
Not only has mTORi therapy shown benefits in lowering the risk of skin cancer, early conversion to mTORi therapy from CNIs has also shown promising effects in reducing cancer rates.
But overall mortality is higher and discontinuation following adverse events is more common in patients who receive mTORi therapy. Several RCTs showed a higher rate of patients reporting adverse events or drug discontinuation with sirolimus, demonstrating concern of its clinical usefulness. Nicotinamide may also offer benefits to reducing skin cancer incidence by 20% and is relatively safe with minimal side effects. The protective effect of nicotinamide on skin cancer incidence in kidney transplant recipients is currently being explored in a phase III RCT.
Although behavioural change is a simple strategy, long- term adherence remains challenging.
ncrease sun protective behaviours in non-transplant populations, there is no direct evidence to show that the behavioural change led to a reduction in morbidity and mortality.
Previous studies have suggested that transplant recipients do not practice sun protective behaviours regularly, were less likely to use sunscreen54 and that patients have to perceive skin cancer as being an important risk to be motivated to change behaviour.
Although recipients understand the importance of ongoing education for the ability to self-
Manage their disease, they may experience difficulty in concentrating and learning new knowledge, and are often unable to look beyond their graft and the anxiety fear of graft loss. Q2- What is the level of evidence provided by this article? Level 1 Q3- What is the difference between bias and errors?
Bias refers to the difference between the true or correct value of some quantity and a measurement or estimate of that quantity.
Error carries the flavour of mistake (something erroneous), at least in the context of measurement error and particularly when scientists are thinking about their data
The research question in this systematic review is whether Behavioral and pharmaceutical interventions can decrease incidence of skin cancer. Skin cancers are the most common malignancy diagnosed in Solid organ recipients, unfortunately very few studies are available in this regard.
This study was designed as a systematic review of RCTs that evaluated the effect of behavioral or pharmaceutical interventions on behavioral change or skin cancer prevention in solid organ transplant recipients. MEDLINE, Embase, CENTRAL and CINAHL databases were searched and relevant RCTs selected as per inclusion and exclusion criteria. The pre-specified outcome measures were incidence of precancerous and cancerous lesions, sun protection behavior, knowledge and attitude, skin self-examination, sun exposure and biologic measures.
The results were uncertain with regards to both behavioral therapy with regards to improving sun protection behavior and mTOR inhibitors with regards to decrease in incidence of skin cancers due to the quality of evidence being very low in both cases. Although behavioral interventions appeared to improve sun protection attitude, knowledge and behavior, there were inconsistencies detected and none of these studies included skin cancer as an outcome.
The researchers concluded that Behavioral and pharmaceutical interventions may decrease incidence of skin cancer but at present the quality of evidence is very low and insufficient to guide decision making and clinical practice at present.
The strength of this study was its design and data collection tools however the low number of RCTs included and the heterogeneity of all those RCTs was the biggest drawback as well leading to inconclusive results.
What is the level of evidence provided by this article?
Level of evidence for this article is Level I as it is a systematic review of multiple RCTs.
What is the difference between bias and errors?
In the simplest words the difference between bias and error is intent. Error can be of 2 types, Type I error (false positive) and type II error (false negative). If the error is introduced into research protocol to favor a pre-selected outcome then it is called a bias. Error can be identified by calculations whereas bias has to be identified manually.
Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials.
Introduction :
the most frequently diagnosed malignancy among solid organ transplant recipients is skin cancer including both melanoma and non- melanoma skin cancer.
there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma
(BCC) in comparison to the general population .As a result of improved transplan- tation techniques and management of immunosuppression, The registry data show improvement in survival rates of transplant recipients, but still there’s a greater risk of skin cancer incidence and mortality.
The aim of this study is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients. Design: systematic review study.
Data sources : MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
Inclusion criteria:
All randomised controlled trials (RCTs) or quasi RCTs of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were included.
Outcome measures :
The outcome include incidence of precancerous and cancerous lesions, sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance), knowledge and attitude, skin self- examination, sun exposure (including skin irritation, sunburn) and biologic measures (including measurement of melanin index and sun damage assessment).
risk of bias and quality of evidence :
The risk of bias was assessed independently by LJJ and VS using the Cochrane risk of bias tool.The quality of the evidence informing summary estimates for each outcome was then assessed by LJJ using the Grading of Recommendations Assessment Development and Evaluation (GRADE) guidelines.
Results : study selection
The literature search identified 1280 articles, of which, 1201 were excluded after abstract and title review. Full- text assessment of 79 studies found 22 eligible articles for inclusion .
studies characteristics
22 reports of 20 RCTs were included.including 2295 participants .The median number of participants was 44 (range 17–830) and the median follow-up duration was 10 months (range 1day to 60 months). All studies included kidney transplant recipients, with some also including heart transplant recipients (n=1), liver, heart, pancreas, lung, heart/lung and other transplants (n=1), and lung and liver transplant recipients (n=2).
risk of bias and quality of the evidence :
Overall studies had either high or unclear risk of bias for at least one domain .
The overall quality of the evidence was very low for all outcomes due to limitations in study design, heterogeneity in the intervention and outcome measures, the very small sample size of individual studies and the small number of studies for each specific outcome.
Interventions:
There are three broad categories of the intervention in the included studies: behavioural (n=6), switch to mTORis (n=6) and other pharmaceutical interventions (n=9, photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide). Studies of behavioural interventions used passive methods of delivery including written educational material (n=2), both written educational material and text messages (n=1), mobile app programmes (n=2) and a video (n=1).
All six studies of immunosuppression compared mTORis (sirolimus) to calcineurin inhibitors (CNIs) based therapies.
Effect of behavioural interventions on sun protection outcomes Sun protection behaviour
Patients who received behavioural interventions reported improved sun protection behaviour scores. But there is uncertainty of the effects of behavioural interventions on sun protection behaviour due to very low quality of evidence.
Sun protection knowledge
There was an improvement in knowledge scores .
Sun protection attitude
Compared with standard care, there was an overall improvement in scores of concern about developing cancer . There is uncertainty of the effects of behavioural interventions on sun protection attitude due to very low quality of evidence.
Skin complications and biologic measures
The intervention group experienced a reduced incidence of skin irritation or sunburn .They also had a decreased melanin index and reduced severity of sun damage on sun exposed areas .
Effect of pharmaceutical interventions on skin cancer prevention:
The incidence and responses of precancerous lesions were measured only in trials of pharmaceutical interventions .These included the switch to mTORis ,photodynamic therapy ,and immune response modifiers to current treatment or placebo.
Topical/local interventions :
One trial of 14 participants compared an immune response modifier, 5% imiquimod cream with placebo and found a reduction in the incidence of skin dysplasia ,skin atypia and viral warts
One Danish study of 26 kidney transplant recipients compared photodynamic therapy with no treatment and reported a relative reduction by approximately 40% in the incidence of NMSC on the treated area .a lower incidence of SCC was also reported in one trial comparing two areas of skin using an immune response modifier and placebo .Two trials comparing photodynamic therapy to an immune response modifier or photodynamic therapy to placebo in recipients with diagnosed keratoses reported a complete response rate of 60% compared with 24% in the control group There is uncertainty of the effects of photodynamic therapy on incidence of precancerous lesions due to very low quality of evidence.
Systemic interventions
mTORis therapy reduced the incidence of NMSC compared with CNIs maintenance therapy .However, evidence was limited due to short follow-up periods, variability in dosing of mTORis and significant rates of loss to follow-up, and therefore we are uncertain of the effects of mTORis on skin cancer incidence due to very low quality of evidence. Level of evidence:1
Bias : random
Error:non random
Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials
Summary
Introduction :
The most frequently diagnosed malignancy among solid organ transplant recipients is skin cancer, including melanoma and nonmelanoma skin cancer (NMSC), which affect more than 50% of post-transplantation recipients. The cumulative incidence of NMSC increases with time after transplantation with sun exposure being most significant modifiable risk factor.
Study design : systematic review
Sources : MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
Inclusion criteria :
This review includes all randomized controlled trials (RCTs) of interventions for skin cancer prevention in solid organ transplant recipients either behavioural interventions, pharmaceutical interventions, and studies that reported skin cancer-related outcomes as their primary endpoints.
It excludes studies of interventions for the treatment of skin cancer .
Data extraction and synthesis :
The quality of the evidence informing summary estimates for each outcome was assessed by LJJ using the Grading of Recommendations Assessment Development and Evaluation (GRADE) guidelines. Data synthesis and statistical analyses continuous outcomes were summarized as mean difference (MD) or standardized mean difference (SMD) and dichotomous outcomes as relative risk (RR). Risks of bias and evidence certainty were assessed using Cochrane and the Grading of Recommendations Assessment Development and Evaluation framework.
Result : The literature search identified 1280 articles for inclusion, of which 1201 were excluded after abstract and title review. 22 reports of 20 RCTs included 2295 participants, with median number of participants 44 and median follow-up duration 10 months.
Risk of bias and quality of evidence were high
Random sequence generation and allocation were unclear,
Blinding of participants was not done in most studies,
Intention to treat analyses used in 6 (30%) studies.
The overall quality of evidence was low due to limitations in study design, heterogeneity in the intervention and outcome measures, the small sample size of individual studies and the small number of studies for each outcome.
Discussion :
The current evidence for skin cancer prevention in solid organ transplant recipients is of low quality and insufficient to guide decision-making and clinical practice. Sun protection education may reduce cancer incidence among solid organ transplant recipients, but uncertainty exists in treatment effects. The use of pharmaceutical and immunosuppression therapy for skin cancer prevention is complex, with high risk of bias, potential for reporting bias, and uncertainty in estimates. Transplant recipients may benefit from early implementation of education to reduce skin cancer incidence and reduce morbidity and mortality.
Strength and limitations of the study :
This study was conducted using methods outlined by Cochrane Collaboration to assess risk of bias and evidence certainty. It included a broad range of interventions, including behavioural to improve sun protection behaviour and pharmaceuticals to evaluate precancerous lesions response and cancer incidence.
However, it was unable to obtain an overall summary estimate for many outcomes due to variability in the analytical methods and reporting in individual studies. Few trials included the important outcomes of skin cancer and none included melanoma or mortality.
What is the level of evidence provided by this article?
level 1
3.What is the difference between bias and errors? Baias are systematic errors that refer to deviations that are not due to chance alone also considered as an inclination of temperament , while error is a mistake, something you have done which is considered wrong, or which should not have been done .
Skin cancer is the most common malignancy seen in solid organ transplant recipients, occurs in more than 50% of post-transplantation recipients.
The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years.
Objective :
This study aimed to determine the effectiveness of interventions for behavioural changes for sun protection and prevention of skin cancer in solid organ transplant recipients.
Method:
All (RCTs) or quasi-RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients. Among interventions to prevent skin cancer post-transplantation are:
Use of sunscreen. Use of protective clothing. Limiting sun exposure during peak hours of high UV a few hours before and the mid-day sun Change to mammalian target of rapamycin inhibitors (mTOR is) Use of retinoid acitretin for the management of skin cancers in high-risk transplant recipients
Result: Twenty trial were included.
It is uncertain whether behavioural interventions improve sun protection behaviour. It is also uncertain whether the effects of mammalian target of rapamycin inhibitors on the incidence on non melanocytic skin cancer.
Conclusion :
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
Level of evidence provided by this article:
Level 1, Because i’s a systematic review
Difference between Bias and Errors:
Bias: is non random , can occur systematically.
Error: is random, can lead to inaccurate outcomes.
Behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients
Summary
Introduction
This article is based on the increased risk of skin cancer among solid organ transplant recipients, and the interventions that may aid in preventing the occurrence of these cancers.
The data has been obtained from randomized controlled trials.
Discussion
This is a systemic review. The motivation for this study is based on the fact that skin cancers of different kinds lead to significant morbidity and mortality in solid organ transplant recipients. Due to this, interventions that could possibly help preventing skin cancers in SOT recipients has been researched.
The interventions used in this study were grouped under three broad categories, namely, behavioral, switching to mTORi, and other pharmaceutical interventions.
Behavioral modifications included improved sun protection behaviour. Pharmaceutical measures included immunosuppression changes, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers. These interventions were able to produce some improvements in terms precancerous lesion response, and cancer incidence. However, this is of low quality and insufficient to guide decision making and clinical practice.
There is immense variability in interventions and their applications, and thus this provides space for different outcomes.
Early conversion to mTORi from CNIs can provide modest benefits at best in reducing the incidence of skin cancer in these patients.
However, the studies involved are heterogenous in nature, and have a high risk of bias, leading to imprecision in potential results.
Conclusions
Further studies are needed to back up evidence for interventions to prevent or reduce skin cancer incidence in SOT recipients. This can be obtained from high quality and large scale RCTs. In addition, patient preferences for prevention and management practices are to be taken into consideration to provide patient centric decisions and treatment. Long term follow up is also necessary so that these interventions can be put into clinical practice.
Level of evidence
Level of evidence is 1.
Difference between bias and errors
Bias refer to systematically prejudiced results while errors cause inaccurate results. Bias is conscious misrepresentation of values, i.e., shifting or straying from a true value. in contrast, error refers to fundamental or unmeasured randomness.
An example of bias is under-reporting.
An example of error is measurement error.
To determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients
Skin cancer is the most important complication after solid organ transplantation in general population basal cell carcinoma more common than squamous cell carcinoma but in patient with solid organ transplantation squamous cell carcinoma more than basal cell carcinoma (1.8:1) and the incidence increases after transplantation from 5-10% after the second year to about 40-80% after 20 years.
protection to prevent skin cancer post-transplantation are (use of sunblock, sun limitation, use cotton clothes for more sun protection, sunglasses, in high-risk patient early conversion of CNI to mTOR inhibitor)
Aim of study:
to determine behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients.
inclusion criteria;
All (RCTs) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients.
Behavioral therapies (including passive, active, and provision of sun protection devices) and pharmaceutical interventions
Studies that reported skin cancer-related outcomes as their primary outcomes. Exclusion Criteria;
Studies that didn’t include these results as their main objectives.
Studies of interventions for the management of skin cancer were excluded.
Conclusion:
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
2.What is the level of evidence provided by this article?
level 1 because its systematic review of randomized controlled trials.
3.What is the difference between bias and errors?
Bias: is non random , can occur systematically.
Error: is random, can lead to inaccurate outcomes
# The objective:
To determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
# Introduction:
*Different types of skin cancers (melanoma and non-melanoma) are commonly developed in patients with solid organ transplantation (more than 50%).
*The rate of NMSC elevated with post transplantation period, from 5%–10% at second years to 40%–80% at 20 years.
*The incidence of squamous cell carcinoma is higher than basal cell carcinoma compared to general population.
*In spite of advancement outcome of transplantation due to improvement in transplantation techniques and immunosuppression, there is a higher risk of skin cancer and cancer-related mortality.
*The mortality from invasive and metastatic skin cancer, are 3 to 9 times higher than the general population, with 5-year overall survival of <30%.
*Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population, but increase skin cancers in transplant recipients.
*pharmaceuticals have also been used to reduce and delay the development of skin cancer.
# The methods: *Design:
Systematic review. Data sources:
The study searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019. Including criteria:
All included randomised controlled trials that evaluated the effect of behavioural or pharmaceutical interventions on behavioural change or skin cancer prevention in solid organ transplant recipients. Data extraction and synthesis Risks of bias and evidence certainty were assessed using Cochrane and the Grading of Recommendations Assessment Development and Evaluation framework.
#The results:
Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour (n=3, n=414, standardised mean difference (SMD) 0.89, 95% CI −0.84 to 2.62, I2=98%) and knowledge (n=4, n=489, SMD 0.50, 95% CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low.
They are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of non-melanocytic skin cancer (n=5, n=1080, relative risk 0.46,
95% CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low.
# Strengths and limitations of the study:
*A comprehensive review conducted using methods outlined by Cochrane Collaboration including Grading of Recommendations Assessment Development and Evaluation to assess risk of bias and evidence certainty.
* Inclusion of a broad range of interventions, including behavioural to improve sun protection behaviour and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence.
*Difficulty obtaining an overall summary estimate for many outcomes due to the variability in the analytical methods and reporting in individual studies.
*Unable to perform detailed subgroup analyses or assess for publication bias due to small number of studies.
*Few trials included the important outcomes of skin cancer and none included melanoma or mortality.
#Conclusions:
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
# What is the level of evidence provided by this article? * Level (1)
# What is the difference between bias and errors?
*Error:
Always present in a sample when making statement about a population.
(Sample almost never be the same), so
Error: Always present
Can be control (by taking a large size of sample).
*Bias:
(systematic tendency to error)
Selecting from population with a non uniform probability.
Introduction:
Skin cancers are common post kidney Transplant reaching 50percent of the cases.
Both melanoma and nonmelanoma skin cancer (NMSC).
The aim of study:
is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipient.
Methods:
Systemic reviews.
Inclusion criteria :
All randomised controlled trials or quasi RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were include.
Behavioural interventions defined as any strategy used to promote sun protective behaviour including passive (eg, pamphlets), active (eg, group workshops
, counselling, dermatology clinic) and provision of sun protective equipment; and pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids) and studies that reported skin cancer-related outcomes as their primary outcomes were included.
Results & Outcomes:
1.These behavioral interventions reduced the incidence of Non-melanoma skin cancer. However, the analyzed evidence was of low quality to be applied in clinical practice.
2.There was a lot of bias.
3. Long term compliance on behavioral interventions is unpredicted.
4. Nicotinamide is beneficial to reduce cutaneous cancer by 20%.
5. m-TOR inhibitors may lower cutaneous cancer incidence compared to CNIs. however, their rate of stoppage was high because of side effects making the evidence weak.
Limitations:
1. This systematic review is full of heterogeneity especially variable non-specific behavioral interventions and high Bias of the analyzed studies.
2. Most of pharmaceutical interventions and behavioral interventions were in Europe and USA respectively. 4 of them were by the same author.
3. 10 studies included less than 50 patients.
4. m-TOR inhibitors were discontinued because of side effects in 2/2 studies.
5. 48% of studies have follow up less than 12 months.
6. Inability to analyze data for heterogeneity or publication bias.
Conclusions:
Due to the heterogeneity of the studies, the high risk of bias, the potential for reporting bias and imprecision in the point estimates of individual studies, there is a high degree of uncertainty in the estimate of the effect of skin cancer prevention interventions. Future randomized controlled studies are required to assess properly how effective these interventions in preventing skin cancer. These studies should be long term, with homogenous, validated and large samples data to help create true guidelines for clinical practice.
What is the level ofthis article? evidence provided by this article?
Level I evidence
What is the difference between bias and errors?
a)Error leads to inaccurate results and outcomes. Bias leads to prejudiced results.
b) Errors are classified into systematic or random. Bias equals systematic error. Random error is related to absent precision in the study conduction.
c) Error involves a single measurement. Bias is the average errors of repeated measurements.
d) Error can occur without Bias. Bias can cause an error. Bias expects an error to occur.
e) Bias can occur at any phase of the research: study design, data collection, data analysis and even publication.
study type – Systematic review of various RCT from open access journal (Open access online peer review)
Introduction, basis of study – Solid organ transplant recipients are at increased risk of skin cancers, affecting more than >50% of recipients.
Sun exposure behaviors remain the most significant modifiable risk factor in the prevention of skin cancers in the general population.
Due to dramatic increase in skin cancers in solid organ transplant recipients, pharmaceuticals have also been used to reduce and delay the development of skin cancer.
Current recommendations for preventive strategies extrapolated from guidelines in the general population like frequent skin self-examination and annual / biannual total body skin examination may not be applicable to solid organ transplant recipients.
Sun protective behaviors (use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days)
alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
Aim of this study is to determine the effectiveness of interventions that promote behavioral change and skin cancer prevention in solid organ transplant recipients.
methods – Systematic Review of RCTs on behavioral and pharmaceutical intervention for prevention of of skin cancer in Solid Organ transplant recipients was conducted.
20 RCT (2295 patients) with Primary end point of cancer related outcomes like behavioral skin protective strategies, pharmaceutical interventions were included.
Data on study design, geographic location, sample size, type of transplant, measurement of interventions, interventions and comparators were extracted.
Results;
Improvement in preventive behavioral measures with knowledge and attitudes in reducing sun exposure, use of high SPF sunscreen, wearing of sun protective cloth and googles etc helps in in reducing risk of skin cancer – but the evidence is low quality and inconclusive.
Pharmaceutical measures like change of mTOR inhibitors (SRL) in place of CNI; use of oral retinoid and nicotinamide – help in reducing precancerous lesions and skin cancer.
Early conversion of CsA to SRL is effective in prevention and treatment of skin cancer but large number of patients discontinued of SRL due to side effects.
Nicotinamide showed 20% effectiveness in reducing skin cancer with less side effects.
Conclusions:
Additional large-scale and high-quality RCTs are needed to demonstrate the effectiveness of interventions used to prevent skin cancer, and its associated morbidity and mortality.
Evidence of the efficacy of sun protective behavior interventions need to be strengthened, with use of measures that are homogeneous, reliable and validated.
Preventative measures like changing behavioral knowledge and attitude of patients, switch to mTORis and other pharmaceuticals may improve skin cancer prevention and outcomes for solid organ transplant recipients. However, the overall quality of evidence is very low and insufficient to guide decision-making and clinical practice.
Future robust studies that are well powered, have long-term follow-up and use clinical and patient important outcome measures in a consistent manner are required to therefore optimize outcomes for solid organ transplant recipients.
Limitations of this study are. a. small sample size in majority of studies (only 1 with sample size >200)
b. short duration and non-homogenous follow up among the studies
c. no or inconclusive data on the incidence and outcome of skin cancer in some of studies.
d. bias factors
2.Level of evidence provided by this article?
Level of evidence is 1 ( systemic review of RCTs)
3.What is the difference between bias and errors?
Statistical bias is a systematic tendency which causes differences between results and facts, and may have a serious impact on results.
Statistical bias comes from all stages of data analysis. Source of the data (information bias, selection / sampling bias) the estimator chosen (estimator bias) the ways the data was analyzed (confounding bias).
e.g. various types of data selection bias Selection bias / sampling bias – individuals being more likely to be selected for study than others
Spectrum bias – evaluating diagnostic tests on biased patient samples, leads to an overestimate of the sensitivity and specificity of the test. Observer selection bias occurs when the evidence presented has been pre-filtered by observers, which is so-called anthropic principle.
Volunteer bias – volunteers have intrinsically different characteristics from the target population Funding bias may lead to the selection of outcomes, test samples, or test procedures that favor a study’s financial sponsor.[8] Attrition bias arises due to a loss of participants, e.g., loss of follow up during a study.[9] Recall bias arises due to differences in the accuracy or completeness of participant recollections of past events; for example, patients cannot recall how man
The error of an observation is the deviation of the observed value from the true value of a quantity of interest – which leads to wrong or inaccurate result. (sense of a deviation of a value from a hypothetical unobserved value)
Error in hypothesis testing: Type I error happens when the null hypothesis is correct but is rejected. Type II error happens when the null hypothesis is not correct but is accepted.
Sampling error incurs when statistical estimation of a population is estimated from the subset or selected sample of that population; can be controlled by size of the sample
The article is published in BMJ Openis an online peer review, open access journal, with Impact Factor: 3.007 Citescore: 3.9. As skin cancer increases many fold in solid organ transplant recipients with passage of time compared to age and gender matched general population. Systematic Review of RCTs on behavioral and pharmaceutical intervention for prevention of of skin cancer in Solid Organ transplant recipients was conducted with 20 RCTs and 2295 participants
All studies with Primary end point of cancer related outcomes like active and Passive behavioral skin protective strategies, pharmaceutical interventions were included were as studies that did not report these outcomes as primary endpoints and studies with interventions for the treatment of skin cancer were excluded Results; This study shows improvement of preventive measures in reduce risk of skin cancer by non pharmaceutical therapy with behavioral knowledge and behavioral attitudes in reducing sun exposure and use of high SPF sunscreen and wearing of sun protective materials but this evidence is low quality and inconclusive.
Pharmaceutical measures like use of mTOR inhibitors instead of Calcinurine inhibitors and oral retinoid and nicotinamide helps in reducing precancerous lesions and skin cancer.
Early Use of sirolimus (mTOR inhibitors), is effective in treatment of skin cancer but large number of patients discontinued of sirolimus due to adverse effects of therapy. Nicotinamide showed 20% effectiveness in reducing skin cancer with less side effects.
Limitations of this study are. a. small sample size in more than half of studies
b. short duration of follow up and heterogenicity of follow up. c. in some studies there is no data on the incidence and outcome of skin cancer. d. bias in few studies Conclusion:
Large scale of randomized clinical trials needed to strength evidence of behaviour, switching of CNI to mTOR inhibitors and other treatment measures in reducing risk of skin cancer.
Large, reported studies needed with homogeneous sample and follow up to demonstrate evidence of preventive measures to reduce risk of skin cancer. 2.What is the level of evidence provided by this article? Level of evidence is 1 ( systemic review)
3.What is the difference between bias and errors? Bias is systemic tendency to errors that results from inaccurate effects and associations. Selecting from population with non-uniform probability Type of bias ( information bias, selection bias and confounding bias). Error is inaccurate results. Always present in a sample when making statements about a population. As sample will never be same. So error will always be present and can be controlled by size of sample.types of error in statistics Type 1 error , type 2 error
Introduction : Skin cancer is the commonest malignancy seen in solid organ transplant recipients, occurs in > 50% of post-transplantation recipients. · The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years. Objective : This study aimed to detrmine the effectiveness of interventions for behavioral changes for sun protection and prevention of skin cancer in solid organ transplant recipients. Method: All (RCTs) or quasi-RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients. Among interventions to prevent skin cancer post-transplantation are: · use of sunscreen. · Use of protective clothing. · limiting sun exposure during peak hours of high UV a few hours before and the mid-day sun · change to mammalian target of rapamycin inhibitors (mTOR is) · use of retinoid acitretin for the management of skin cancers in high-risk transplant recipients. Result: Twenty trial were included. It is uncertain whether behavioural interventions improve sun protection behavior. It is also uncertain whether the effects of mammalian target of rapamycin inhibitors on the incidence on non melanocytic skin cancer. Conclusion :Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice. 2 .WHATS THE LEVEL OF EVIDENCE?
Level of evidence 1, as it’s a systematic review
3WHATS THE LEVEL BETWEEN BIAS AND ERROR?
Bias makes systematically prejudiced results
Errors produce inaccurate results.
Skin cancers, melanotic and non melanotic, are major causes of mortiality and morbidity in recipients of solid organ transplants. In these group of people, the rate of developing squamous cell carcinoma compared with basal cell carcinoma is markedly increased whein compared to the general population [when age and gender-matched]. the incidence is up to 65-250 times higher in the recipients of a solid organ transplant.
Development of a skin malignancy poses a problem, as management options are limited uppression in these population whose graft function and rejection depends onm immunosuppersssion. Hence measures to prevent the development of skin cancers post-=transplanmt are very important.
This study aimed to detrmine the effectiveness of interventions for behavioral changes for sun protection and prevention of skin cancer in solid organ transplant recipients. It is a syetematic review of several Randomized Control Trials that evaluate the effect of behavioural or pharmaceutical interventions on behavioural change or skin cancer prevention inrecipients of solid organ transplants.
The interventions studied were behavioural and pharmaceutical. Pharmaceutical involved the switch of the immunosuppression medication to mTORis or use of an immune-modulating agent.
The study found that these interventions did improve sun protective behaviour and knowledge, and reduced the incidence of non-melanocytic skin cancer. Hpwever, the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice
Level of Evidence: Level 1
Bias produces prejudiced results while errors produce inacurrate results
Bias can be can be identidfied manually or through software packages while errors are identified through calculations.
Bias occurs systematically while errors occur randomly.
It’s a Systematic Review of randomized control on behavioral and pharmaceutical intervention for the prevention of skin cancer in Solid Organ transplant recipients 20 RCTs and 2295 participants.
Skin cancer, including melanoma and non- melanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post- transplantation recipients.
The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years.2–4 Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender- matched general population.
Once cancer develops, management options are limited as immunotherapy may be unsuitable as it may lead to graft rejection.
-WHATS THE LEVEL OF EVIDENCE?
Level of evidence 1, as it’s a systematic review
-WHATS THE LEVEL BETWEEN BIAS AND ERROR?
Bias makes systematically prejudiced results
Errors produce inaccurate results.
It’s a Systematic Review of randomized control on behavioral and pharmaceutical intervention for the prevention of skin cancer in Solid Organ transplant recipients 20 RCTs and 2295 participants.
Introduction;
Among recipients of solid organ transplants, skin cancer, including melanoma and nonmelanoma skin cancer (NMSC), is the most common malignancy diagnosed. Once cancer has developed, there are few treatment options available since immunotherapy may be inappropriate and may cause graft rejection. Skin cancer and cancer-related death are also more prevalent.
Aim;
The aim is to evaluate the efficacy of behavioral change and skin cancer prevention interventions in solid organ transplant recipients.
Inclusion criteria;
All (RCTs) or quasi-RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients.
Behavioral therapies (including passive, active, and provision of sun protection devices) and pharmaceutical interventions
Studies that reported skin cancer-related outcomes as their primary outcomes.
Exclusion Criteria;
Studies that didn’t include these results as their main objectives.
Studies of interventions for the management of skin cancer were excluded.
Results;
Since the quality of evidence is very low. Uncertainty surrounds the effectiveness of behavioral interventions in enhancing sun protection behavior as well as the impact of mammalian target of rapamycin inhibitors on the prevalence of nonmelanocytic skin cancers.
Conclusion;
Although behavioral and pharmacological preventative treatments may increase awareness and behavior related to sun protection and decrease the incidence of non-melanocytic skin cancer, the overall quality of the evidence is comparatively low and insufficient to inform therapeutic practice.
What is the level of evidence provided by this article?
Level of evidence 1, as it’s a systematic review
Whatis the difference between bias and errors?
Bias makes systematically prejudiced results
Errors produce inaccurate results.
Introduction
· Skin cancer is the commonest malignancy seen in solid organ transplant recipients, occurs in > 50% of post-transplantation recipients.
· The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years
· squamous cell carcinoma (SCC) occurs in 65 to 250 times greater than the age and gender-matched general population.
· The increased risk of death from invasive and metastatic skin cancer are three to nine times higher than the general population, with 5-year overall survival of <30%
· Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population
The aim of this study
is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients. Inclusion criteria
· All randomised controlled trials (RCTs) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients.
· studies that reported skin cancer-related outcomes as their primary outcomes Exclusion criteria
· Studies that did not report these outcomes as primary endpoints
· Studies of interventions for the treatment of skin cancer Outcome measures
· incidence of precancerous and cancerous lesions
· sun protection behaviour
· knowledge and attitude
· skin self-examination
· sun exposure(including skin irritation, sunburn)
· biologic measures Interventions
· behavioural
· switch to mTORis
· other pharmaceutical (photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide) Discussion
· As skin cancers are an important case of morbidity and mortality in transplant recipients, but only few trials concerned about prevention of skin cancers in solid organ transplant recipients
· This review included 22 reports of 20 trials involving 2295 transplant recipients, who were predominately kidney transplant recipients.
· Interventions, included sun protection behaviour and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence.
· While there may be some modest benefits in the reduction in cancer incidence (for NMSC) among solid organ transplant recipients who were converted to mTORis compared with those on CNI maintenance, there was substantial heterogeneity across the studies that was unable to be explained by subgroup analyses.
· A systematic review of the benefits and harms of oral retinoids for the prevention of skin cancer among high-risk transplant recipients led to inconclusive results on the effect of acitretin due to the small number of included trials.
· Not only has mTORi therapy shown benefits in lowering the risk of skin cancer, early conversion to mTORi therapy from CNIs has also shown promising effects in reducing cancer rates
· overall mortality is higher and discontinuation following adverse events is more common in patients who receive mTORi therapy
· Nicotinamide may also offer benefits to reducing skin cancer incidence by 20% and is relatively safe with minimal side effects
· Additional large-scale and high-quality RCTs are needed to demonstrate the effectiveness of interventions used to prevent skin cancer in transplant recipients in terms of patient important outcomes, in particular morbidity and mortality associated with skin cancer. Limitations of this study
· Difficulty obtaining an overall summary estimate for many outcomes due to the variability in the analytical methods and reporting in individual studies.
· Unable to perform detailed subgroup analyses or assess for publication bias due to small number of studies.
· Few trials included the important outcomes of skin cancer and none included melanoma or mortality
Level of evidence 1 What is the difference between bias and errors? Bias produces systematically prejudiced results while errors produce inaccurate results.
Skin cancer is the most important complication after solid organ transplantation in general population basal cell carcinoma more common than squamous cell carcinoma but in patient with solid organ transplantation squamous cell carcinoma more than basal cell carcinoma (1.8:1) and the incidence increases after transplantation from 5-10% after the second year to about 40-80% after 20 years.
protection to prevent skin cancer post-transplantation are (use of sunblock, sun limitation, use cotton clothes for more sun protection, sunglasses, in high-risk patient early change CNI to mTOR inhibitor)
Aim of study:
to determine behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients.
Conclusion:
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
2.What is the level of evidence provided by this article? level 1 because its systematic review of randomized controlled trials.
3.What is the difference between bias and errors?
Bias: is non random , can occur systematically.
Error: is random, can lead to inaccurate outcomes.
SUMMARY Introduction Skincancer is the most common post-transplant malignancy among solid organ transplant recipients. Compared to the general population, the frequency of skin squamous cell carcinoma is more than basal cell and skin cancer incidence increases after transplantation from 5-10% after the second year to about 40-80% after 20 years Among interventions deployed to prevent skin cancer post-transplantation are: · use of sunscreen. · Use of protective clothing. · limiting sun exposure during peak hours of high UV a few hours before and the mid-day sun · change to mammalian target of rapamycin inhibitors (mTOR is) · use of retinoid acitretin for the management of skin cancers in high-risk transplant recipients Aim of the study · to determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients Method of the study · the study is a systemic review
Inclusion criteria
all RCT involving melanoma and NMSC
all studies that reported skin cancer as their primary outcome
Exclusion criteria
studies of interventions for the treatment of skin cancer
studies that did not report skin cancer as the primary outcome
Outcome measures
incidence of the precancerous and cancerous lesions
sun protection behaviour
knowledge and attitude
skin self-examination
sun exposure
biologic measure
Group of interventions done
Behavioural
switch to mTOR inhibitor
Pharmaceutical
Result/Discussion
Total of 20 RCTs comprising 2295 participants
The median number of participants and follow up 44 and 10 months respectively
The overall studies had either a high or unclear risk of bias
The blinding of participants was not done in most studies
The overall quality of evidence was low for all the outcomes
. Patients who received behavioural interventions reported improved sun protection behaviour scores (3 studies, 414 participants, SMD 0.89, 95%CI −0.84 to 2.62, I2 98%
mTOR inhibitors therapy reduced the incidence of NMSC compared with CNIs maintenance therapy (5 trials, 108 participants, RR 0.46, 95%CI 0.28 to 0.75, I2 72%,
Limitations of the study
small sample size
lack of long term follow up
high risk for bias due to the heterogenicity of the study
What is the level of evidence?
Level 1
Bias is said to have taken place when a systematic error is introduced into any stage of a study, either the sampling, selecting, or encouraging one outcome of the study over another
Error is an action that is inaccurate or not correct which can be detected through measures or calculations. It could be either a type 1 or 2 error
Summary of the article: This is a systemic review of level 1 of evidence Introduction: -Skin cancer is around 9 times more in solid organ transplant recipients than rest of population, this review article shows the effect of preventive measures in preventing skin cancer in transplant recipients. -This is a systematic review of randomized controlled trails that included 22 studies. Some studies showed that switch from CNI’s to mTORi or the use of immune response modifiers for non- melanoma skin cancers were beneficial. -It showed that behavioral and pharmaceutical measures may improve skin cancer outcomes for solid organ transplant. Bias which can occur at any phase of the research may lead to prejudiced results based on the average errors of repeated measurements Errors are either systematic or random, usually involving a single measure and may lead to inaccurate results and outcomes.
Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: 1-Please summarise this article: Introduction:
After solid organ transplantation, the chance of developing skin cancer including melanoma and nonmelanoma skin cancer (NMSC) greatly increases, and approximately 50% of the recipients develop it. Objectives: Goal of this systemic review is to evaluate the effectiveness of several preventive strategies for melanoma and non-melanoma skin cancer prevention in solid organ transplantation that have been investigated in various randomized controlled trials. Methods: -A systematic review of randomised controlled trials of interventions for skin cancer prevention in solid organ transplant cases ,involving behavioural actions either active or passive as well as pharmaceuticals. -Searching for RCT which include Behavioural interventions, pharmaceutical interventions and studies that reported skin cancer-related outcomes, total 22 reports of 20 RCTs, including 2295 participants with the median follow-up duration was 10 months. Strengths: -Extensive online review of many papers before selecting these 20 papers. -Inclusion of variable interventions, evaluation of precancerous lesion response and measuring the incidence of cutaneous cancer. Limitations: -Heterogeneity in the intervention and outcome measures.
-Small Sample size, and small number studies for each specific outcome. -Variability in the analytical methods and reporting in individual studies, with wide diversity of intervention used. -Publication bias was not performed due to insufficient data. -Almost half of the studies were with one year follow up, not sufficient to elaborate the long time effect. Conclusions:
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
2-What is the level of evidence provided by this article?
-This article is systematic review of randomised controlled trials (Level I)
3-What is the difference between bias and errors? -Bias; is non random , can occur systematically, can lead to prejudiced results ,identified manually or through available software programs.
–Error; is random, can lead to inaccurate outcomes ,identified through calculations and metrics.
Skin cancer is a common and potentially serious complication for solid organ transplant recipients. This is because transplant recipients have a higher risk of skin cancer due to the immunosuppressive medications they must take to prevent rejection of the transplanted organ.
This article is a systematic review of randomized controlled trials (RCTs) examining both behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients. The systematic review in the article aimed to evaluate the efficacy of various interventions for preventing skin cancers in this population.
The review analyzed data from several randomized controlled trials (RCTs), which are considered the gold standard for evaluating the effectiveness of medical interventions. The trials included in the review evaluated a range of interventions, including:
Behavioral interventions: such as regular skin self-examination and sun-safe behaviors, like wearing protective clothing and using sunscreen.
Pharmaceutical interventions: such as the use of oral or topical medications to prevent skin cancer. Such as switch to mTORis and other pharmaceutical interventions photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide).
The results of the review showed that some of the interventions, such as regular skin self-examination and sunscreen use, were effective in reducing the risk of skin cancer in solid organ transplant recipients. However, other interventions, such as photoprotective clothing and certain medications, had limited evidence of efficacy and more research is needed to determine their effectiveness. Although behavioural change is a simple strategy, long-term adherence remains challenging.
The authors concluded that a combination of behavioral and pharmaceutical interventions may be necessary to effectively reduce skin cancer risk in solid organ transplant recipients. However, more research is needed to determine the best approach to skin cancer prevention in this population.
In summary, the article provides evidence for the efficacy of certain interventions for preventing skin cancer in solid organ transplant recipients, and highlights the need for further research to determine the best approach to skin cancer prevention in this population.
Summary of article Title: Behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials.
Introduction: Skin cancer is the most common malignancy in solid organ transplant recipients as it accounts for more than half over post transplantation malignancies in the post transplantation population.
There is an excess risk of morbidity and mortality from skin malignancies and current treatment options are limited. Sun exposure is a major risk factor for skin cancers in solid organ recipients.
Hence, strategies to reduce exposure to ultraviolet radiations through behavioral changes and use of pharmaceuticals have been employed to reduce the risk of skin cancers.
James et al in this study aim to find the efficacy of interventions that encourage a behavioral change and skin cancer prevention in the recipients of organ transplants.
Methods: The study was a systematic review of both randomized controlled trials and quasi -randomized controlled trials of interventions for skin cancer prevention in solid organ transplant recipients using a prespecified protocol registered in PROSPERO. Twenty-two eligible articles from seventy-nine studies were found and assessed.
Behavioral interventions were defined as any method used to encourage reduced sun exposure behavior such as education (eg, use of pamphlets, training workshops, counselling sessions, dermatology clinic), provision of sun protective materials; and pharmaceutical interventions (change to mTOR inhibitors, nicotinamide, phototherapy, oral retinoids and immune response modifiers).
Variables measured includes incidence of precancerous and cancerous lesions, sun protection behavior such as application of sunscreen and protective materials (e.g., hats, sunglasses and shades), sun avoidance, knowledge and attitude of participants, skin self-examination, sun exposure (including skin irritation, sunburn) and biologic measures (including measurement of melanin index and sun damage assessment).
Results: Sun protection behavior: A positive effect of behavioral interventions on participants were found in three studies with 414 participants (SMD 0.89, 95%CI −0.84 to 2.62, I2 98%) and a single trial where standardized educational materials were used. However, due to low quality of evidence, authors believe the effects are uncertain.
Sun protection knowledge: Four studies reported improved sun protection knowledge in 489 participants (SMD 0.50, 95%CI 0.12 to 0.87, I2 76%) who were educated through workbooks, text messages, mobile app programs and videos. Another study found educational videos to be better than pamphlets.
Sun protection attitude: An improvement in participants’ concern about developing cancer was reported in three studies with 348 participants (SMD 1.85, 95%CI 1.59 to 2.11, I2 96%). There was also more awareness about personal risk of cancer in two studies involving 273 participants (SMD 0.61, 95%CI −0.60 to 1.82, I2 96%). Adherence to sun protection (SMD 0.77, 95%CI −0.14 to 1.68, I2 92%) and willingness or intention to change behavior (SMD 1.70, 95%CI −1.68 to 5.07, I2 99%) were also better. However, the low quality of evidence made the effects of behavioral interventions on sun protection attitude uncertain. Other studies show improvements in scores of abilities to recognize a potential skin cancer (MD 1.80, 95%CI 1.35 to 2.25), importance of skin self-examination (MD 1.05, 95%CI 0.61 to 1.49) and having a partner help for skin self-examination (MD 1.59, 95%CI 1.10 to 2.08).
Skin complications and biologic measures: Two trials tested the effect of behavioral intervention using a mobile app or an educational workbook and text messages on reported skin complications and biologic measures of sun exposure. The intervention arm experienced a lower rate of skin irritation (RR 1.00, 95%CI 0.89 to 1.13, I2 95%). A reduced melanin index was also found (right forearm, SMD −0.42, 95%CI −0.66 to −0.18; cheek SMD −0.25, 95%CI −0.64 to −0.15). The severity of sun damage also reduced (SMD −0.13, 95%CI −0.40 to 0.13) on sun exposed areas.
Topical/local interventions: A reduction in the rate of skin dysplasia (RR 2.14, 95%CI 0.31 to 14.65), skin atypia (RR 3.00, 95%CI 0.47 to 19.35), and viral warts (RR 7.00, 95%CI 0.46 to 106.10) was reported in a trial comparing 5% imiquimod cream with placebo. Other studies also found positive effects of photodynamic therapy and immune response modifiers on the incidence of non-melanoma skin cancer and precancerous skin lesions. However, due to low quality of evidence, authors believe the effects of photodynamic therapy on precancerous skin lesions were uncertain.
Systemic interventions: Five trials involving 1082 participants compared mTOR inhibitors with CNI maintenance therapy and found a reduced incidence of NMSC (RR 0.46, 95%CI 0.28 to 0.75, I2 72%). Due to various study limitations such as short follow-up period, a variable dosing of mTOR inhibitors, low quality of evidence etc., authors were uncertain of the effect of mTOR inhibitors on sin cancer incidence. Other studies also show a reduction in the incidence of SCC and other non-melanoma skin cancer with mTOR inhibitors when compared with CNI.
Conclusions: Trials ofintervention for skin cancer prevention are few and also do not include the incidence of skin cancer as an outcome. Additionally, there is low quality of evidence of intervention for skin cancer prevention which are insufficient to change clinical practice.
Level of evidence for this article is level 1 because its systematic review of randomized controlled trials.
Bias is a form of systematic error introduce into a study commonly due to a poor study design leading to distortion of the outcomes. The higher the bias, the lower the validity of the study. Although bias cannot be completely eliminated, it is to be reduced to the barest minimum. An error occurs when there is a difference between the measured and the true outcomes of a study.
Skin cancer, including melanoma and non- melanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post- transplantation recipients.
The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years.2–4 Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender- matched general population.
Once cancer develops, management options are limited as immunotherapy may be unsuitable as it may lead to graft rejection.
Effect of behavioural interventions on sun protection outcomes Sun protection behaviour
Sun protection behaviour, defined as hours spent outdoors per week, use of sunscreen, wearing protective clothing and seeking shade, was assessed in three trials.
Educational workbooks, educational workbooks and text messages31 and a mobile app program were compared with standard care. Patients who received behavioural interventions reported improved sun protection behaviour scores
Sun protection knowledge
The effectiveness of educational workbooks, text messages, mobile app programmes and videos on sun protection knowledge was assessed in six studies, four of which provided data for a meta- analysis. There was an improvement in knowledge scores Sun protection attitude
Three studies assessed sun protective attitude after receiving an educational workbook, text messages or a mobile app programme over a period of 0.5 months to 1.5 months.31–33 Compared with standard care, there was an overall improvement in scores of concern about developing cancer
Skin complications and biologic measures
Two trials of behavioural interventions in 271 kidney transplant recipients compared a mobile app or an educational workbook and text messages to standard care on reported skin complications and biologic measures of sun exposure. The intervention group experienced a reduced incidence of skin irritation (a culturally relevant term for sun exposure34 (RR 1.00, 95% CI 0.89 to 1.13, I2 95%) or sunburn (RR 3.19, 95% CI 2.47 to 4.10, I2 99%).
Previous systematic reviews have evaluated the impact of behavioural interventions on skin cancer prevention in the general population, and concluded that computer programmes may increase sun protective behaviours, and ‘appearance- focused’ interventions may decrease sun tanning and UV exposure in adolescents and young women, respectively.
Although behavioural change is a simple strategy, long- term adherence remains challenging. While behavioural counselling has been shown to increase sun protective behaviours in non- transplant populations there is no direct evidence to show that the behavioural change led to a reduction in morbidity and mortality.
Effect of pharmaceutical interventions on skin cancer prevention
The incidence and responses of precancerous lesions were measured only in trials of pharmaceutical interventions . These included the switch to mTORis (n=1),35 photodynamic therapy (n=2)36 37 and immune response modifiers (n=1)38 to current treatment or placebo. The incidence of NMSCs was assessed in nine pharmaceutical studies. None included melanoma as an outcome.
Topical/local interventions One trial of 14 participants compared an immune response modifier, 5% imiquimod cream with placebo and found a reduction in the incidence of skin dysplasia (RR 2.14, 95% CI 0.31 to 14.65), skin atypia (RR 3.00, 95% CI 0.47 to 19.35), and viral warts (RR 7.00, 95% CI 0.46 to 106.10).
Systemic interventions mTORis therapy reduced the incidence of NMSC compared with CNIs maintenance therapy (5 trials, 1082 participants, RR 0.46, 95% CI 0.28 to 0.75, I2 72%, However, evidence was limited due to short follow- up periods, variability in dosing of mTORis and significant rates of loss to follow- up, and therefore we are uncertain of the effects of mTORis on skin cancer incidence due to very low quality of evidence.
The use of pharmaceutical and immunosuppression therapy remains complex. Not only has mTORi therapy shown benefits in lowering the risk of skin cancer, early conversion to mTORi therapy from CNIs has also shown promising effects in reducing cancer rates.on the contrary, overall mortality is higher and discontinuation following adverse events is more common in patients who receive mTORi therapy.
Conclusion
We suggest that further strategies for skin cancer prevention in transplant recipients require a multifaceted and individualised approach. Transplant recipients are likely to benefit from early implementation of education, particularly before transplantation occurs and recipients may be preoccupied with other health needs related to transplantation. Although recipients understand the importance of ongoing education for the ability to self- manage their disease, they may experience difficulty in concentrating and learning new knowledge, and are often unable to look beyond their graft and the anxiety/ fear of graft loss.
Level I
Bias produces systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates
Introduction:
Skin cancers affecting more than 50% 0f post transplant recipients and cumulative risk increases with time after transplantation. As a result, there is a greater burden of skin cancer and cancer related mortality. Unfortunately, once cancer develops, management options are limited . Sun exposure is the most significant and modifiable risk factor for prevention of skin cancer. Use of sun screen, protective clothing and limited sun exposure during peak hour of high UV index are measures for skin cancer prevention. The aim of this study is to determine the effectiveness of interventions that promotes behavioural changes to prevent skin cancer.
Methods:
It is a systematic review.
Inclusion criteria:
All randomized control trial that evaluated the effect of behavioural change in skin cancer prevention in solid organ transplant recipients.
Data sources:
Searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and CINAHL from inception to November 2019.
Results:
Twenty trial were included. It is uncertain whether behavioural interventions improve sun protection behavior. It is also uncertain whether the effects of mammalian target of rapamycin inhibitors on the incidence on non melanocytic skin cancer.
Conclusion:
Behavioural and pharmaceutical interventions may improve sun protection behavior, but the overall quality of the evidence is low.
Skin cancer, including melanoma and nonmelanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post-transplantation recipients.
Further, alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
The aim of this study is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
Outcome measures
The prespecified outcome measures were incidence of precancerous and cancerous lesions, sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance), knowledge and attitude, skin selfexamination, sun exposure (including skin irritation, sunburn) and biologic measures (including measurement of melanin index and sun damage assessment).
Effect of behavioural interventions on sun protection outcomes Sun protection behavior
Sun protection behaviour, defined as hours spent outdoors per week, use of sunscreen, wearing protective clothing and seeking shade, was assessed in three trials. Educational workbooks, educational workbooks and text messages and a mobile app program were compared with standard care. Patients who received behavioural interventions reported improved sun protection behaviour scores .
Effect of pharmaceutical interventions on skin cancer prevention
the switch to mTORis ,photodynamic therapy and immune response modifiers to current treatment or placebo. The incidence of NMSCs was assessed in nine pharmaceutical studies. None included melanoma as an outcome.
5% imiquimod cream with placebo and found a reduction in the incidence of skin dysplasia ,skin atypia and viral warts .
Discussion
Skin cancers (both non-melanoma and melanoma) are major causes of morbidity and mortality in solid organ transplant recipients.
The studies covered a broad range of interventions, including behavioural to improve sun protection behaviour and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence.
Previous systematic reviews have evaluated the impact of behavioural interventions on skin cancer prevention in the general population, and concluded that computer programmes may increase sun protective behaviours, and ‘appearance-focused’ interventions may decrease sun tanning and UV exposure in adolescents and young women, respectively.
A systematic review of the benefits and harms of oral retinoids for the prevention of skin cancer among high-risk transplant recipients led to inconclusive results on the effect of acitretin due to the small number of included trials.
Preventative measures including behavioural, switch to mTORis and other pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients. However, the overall quality of evidence is very low and insufficient to guide decision-making and clinical practice. Future robust studies that are well powered, have long-term follow-up and use clinical and patient important outcome measures in a consistent manner are required to therefore optimise outcomes for solid organ transplant recipients.
SUMMARY Introduction.
Skin cancer (both melanoma and MMSC) is the most common malignancy diagnosed in solid organ recipients with increased incidence with increased duration post-transplantation. This is associated with increased mortality with 5 year overall survival <30%.
Immunotherapy in the transplant population is coupled with the risk of graft rejection.
The most significant and modifiable risk factor in the general population is sun exposure behaviour. The preventive measures in the transplant recipients are extrapolated from the general population.
The aim of this study was to determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients. Methodology
This was a systemic review of RCT and Quasi RCT of skin cancer prevention in solid organ transplant recipients.
Articles were reviewed by an independent party to remove selection bias of the articles.
Outcomes were: Incidence of precancerous and cancerous lesions, sun protection behaviours (sunscreen/ protective clothing/sun avoidance), knowledge and attitude, skin self-examination, biologic measures and sun exposure. Results
20 trials with 2295 participants were included.
All trials included kidney transplant recipients.
Median follow-up was 10 months.
Majority of the trials didn’t blind the participants (n=16), with half of the trials the outcome assessors were not blinded.
6 trials had high loss to followup
All trials had risk of selective reporting bias.
More than half the studies (n=11) had a small sample size(n=<50)
All interventions had reduced incidence of skin cancer and precancerous lesions; however they all had low quality of evidence thus thus making this results uncertain. Conclusion
Preventive measures including behavioural and pharmaceutical intervention may improve the outcome of skin cancer in solid organ recipients. However the quality of evidence is low thus insufficient to guide any clinical decisions. Strengths
This was a systemic review that included studies from various countries. Limitations
Majority of the studies had a small sample size
There was heterogeneity of the interventions and outcome measures.
LEVEL OF EVIDENCE
This is a systemic review of RCT making it level 1 of evidence.
ERROR VS BIAS
Bias produce systemic prejudice results which error lead to inaccurate results.
Q1: As there is an increasing risk of skin cancer among transplant recipients, this article determines the prevention of skin cancer by some intervention in form of a systematic review of RCTS.
Totally, twenty trials with 2295 recipients were studied.
The effect of behavioral and pharmaceutical interventions was uncertain for prevention of skin cancer became of low level of evidence.
In addition, the effects of MTOR inhibition on the incidence of NMSC is uncertain, because of low level of evidence.
Sun protection includes, skin examination, usage of sunscreens, protecting cloths, avoiding of exposure to mid-day and high UV index hours and days – pharmaceutical interventions includes: switching from CNIs to mTOR inhibitors, photo dynamic therapy nicotinamide and retinoid.
Q2
This is a systematic review with level of evidence of one.
Q3
Bias is a systematic error that results in incorrect estimate of association or effect.
Bias has three types: information selection and confounding.
The three types of error are: systematic, random and negligent.
Bias is identified manually or through software package and occurs systematically while error is identified through calculations and occurs randomly.
Please summarise this article Introduction
Skin cancer is common among solid organ transplant recipients and affects 50 % of patients
Sun exposure behaviours and pharmaceutical interventions may reduce and delay the development of skin cancer
The Aim of this study is to determine the effectiveness of behavioural and pharmaceutical interventions for the prevention of skin cancers Study design: systematic review Methods
All RCTs of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were included
Definition of behavioural interventions is any strategy used to promote sun protective behaviour including passive, active, and provision of sun protective equipment
Pharmaceutical interventions defined as switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids Results
Twenty trials (n=2295 participants) were included
The median follow- up duration was 10 months (range 1 day to 60 months)
All studies included kidney transplant recipients
The interventions were grouped into three broad categories, behavioural, switch to mTORis and other pharmaceutical interventions (photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide)
It is unclear if behavioural interventions improve sun protection behavior or not as the quality of evidence is very low
The effect of mammalian target of rapamaycin inhibitors on the incidence of non- melanocytic skin cancer is undecided as the quality of evidence is very low Discussion
This study included 22 reports of 20 trials involving 2295 transplant recipients, who were predominately kidney transplant recipients
The studies covered a broad range of interventions (including behavioural and pharmaceutical interventions)
The current evidence for interventions for skin cancer prevention in solid organ transplant recipients is of very low quality and is insufficient to guide decision- making and clinical practice Limitations
1. Difficulty obtaining an overall summary estimate for many outcomes due to the variability in the analytical methods
2. Failure to perform detailed subgroup analyses or assess for publication bias due to small number of studies
3. Few trials included the important outcomes of skin cancer and none included melanoma or mortality Strengths
Systemic review of randomized trials (20 trials) that include a broad range of interventions (behavioural and pharmaceutical) Conclusion
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non- melanocytic skin cancer. However, the overall quality of evidence is very low and insufficient to guide decision- making and clinical practice
Further robust studies are required What is the level of evidence provided by this article?
Level I (systematic review of randomised controlled trials) What is the difference between bias and errors? Error: a false or mistaken result obtained in a study or experiment. Generally produced by random error, random misclassification, bias, or confounding Bias: error in design or execution of a study, which produces results that are consistently distorted in one direction because of nonrandom factors
1. Please summarise this article
This systematic review of interventions randomised controlled trials or quasi RCTs for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients. Twenty trials (n=2295 participants) wereincluded. Prevention interventions implied are: 1-Behavioural including passive (eg, pamphlets), active (eg, group workshops, counselling, dermatology clinic) and provision of sun protective equipment, n=6 2-pharmaceutical interventions of switch to mTORi , n=6
3- other pharmaceutical interventions :photodynamic therapy, immune response modifiers,n nicotinamide and oral retinoids,n=9 Behavioural intervention were statistically significant in
1- behaviour of skin self examinatiom 1 month after visit, decreased daily outdoor hours, sun protection knowledge
2- attidude ofconcern about developing skin cancer, Knowledge of significance
of skin cancer, relevance of sun protection, risk of having a tan, Confidence in ability to recognise a skin cancer, Importance of skin self-examination, Importance of partner help for skin self-examination
3- complication and biologic measures of Sunburn (past week) and Melanin index—R forearm
(sun exposed)
Effect of pharmaceutical interventions on skin cancer prevention was significant in :
1- Switch to mTORis with Skin dysplasia of Any improvement, Cancerous lesions of SCC /BCC incidence
2- Photodynamic therapy in cases of No reduction
3- Oral retinoids in cases of >1 SCCor New skin cancer
The overall evidence is low
1. What is the level of evidence provided by this article? Level 1 2. What is the difference between bias and errors? Bias is shifting from a true value while error is the detection of findings that are different from true. Bias will result in prejudiced outcome while error result in inaccurate aoutcome. Bias can occour manually or through softwarebut the error is identified through calculations. The bias occur systematically while the error occur randomly.
(https://www.baeldung.com/cs/bias-vs-error)
Objective
In this sytematic review they include 20 RCTs (n=2295 participants) to study the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients. Methods
RCTs included from multicenter in europ ,usa and others. These RCTS had been published between 1995-2017 including either kidney transplantation (16) or multiple transplantations (4). Follow up duration in the included RCTs rang from <12 months to >24 months . the intervention used in these studies was Intervention type Behavioural 5 (25) Switch to mTORis 6 (30) Photodynamic therapy 4 (20) Oral retinoid 3 (15) Nictotinamide 1 (5) Topical immune response modifier 1 (5). They assessed the Risk of bias of included studies.using Cochrane bias risk assessment system Conclusion
Regarding Preventative measures including behavioural,it may improve the outcome for kidney transplant recipient but the evidence is very low
switch to mTORis and other pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients. However, the overall quality and insufficient to guide decision-making and clinical practice
level of evidence
1A Difference between Error and bias
Error :false o mistaken results obtained in a study it could be random error or systemic eror
Bias it is an error in the design of the study which affect the direction of the results it could be selection, informational or attrition bias
this was systemic review of 20 trials having 2295 participants.
the quality of evidence was low level 1.
because of low quality evidence the effect of mTOR on incidence of non-melanoma skin cancer were not very clear
to summarize it, the behaviors and pharmaceutical measures improves the prevention of skin cancers by sun protective measures.
but overall, the quality of evidence was low and insufficient to guide clinical practice.
Limitation
small sample size of studies
short follow up and loss of follow-up
difference between Bias and error
Error may be due to inaccurate measures. (lack of precision)
Bias is systemic errors due to inaccurate effects and association. (Prejudiced result)
Behavioural and pharmaceutical
interventions for the prevention of skin
cancers in solid organ transplant
recipients: a systematic review of
randomised controlled trials
A single study is less likely to give us the answer due to small sample size , short follow up. the systemic review is one of the best tool available at present on this topic
study population
all were post kidney transplant patient
variable but short follow up
heterogenous group without subgroup analysis ( this create low level evidence)
intervention studied
behaviour, knowledge and attitute
sun protection and limiting exposure
photodynamic therapy
oral retenoid
nicotinamid
CNI to mTOR change
end point intended to study but not a part of all the studies
incidence of NMSC
limitation
22 studies
short follow up 50% less than 12 mo
outcome and inferences
reducing sun exposure and its direct effect in reducing NMSC incidence is not yet proven in trials but found to be effective and need more study
phase 3 RCT on nicotinamide will answer pharmacology intervention on prevention od NMSC
melanoma is not studied
USA has all behaviour study
Europe has all pharmacology intervention trials on this topic
level of evidence is poor
level 1
BIAS/ERRORS
Bias is deep rooted in our psychology and can occur unknowingly at any stage of study
It is a choice of one thing over other without any apparent reason
error is more technical and can occur in measurement
use of technology can reduce it
Bias is more human characteristic
this study, is a meta analysis study explored the success of intervention made by improving sun protection behavior and pharmacological changes of immunosuppressants in post-transplant protocol on risk of skin cancer. Skin cancer: in the form of melanoma and non-melanotic skin cancer is frequently encountered with incidence hovers above 50% of transplant recipients. the accruing incidence of skin cancer is progressing with time from 5-10 %in 1st few years to 50-80% after 20 years post transplantation, there is higher incidence of squamous cell carcinoma to basal cell carcinoma and its general incidence is 60 to 250 times its level in general population. The main risk factor is sun exposure with heavy high UV light and immuno modulation inflicted by certain immunosuppressants such as calcineurin inhibitors. Preventive protocol:
Hence, sun exposure behavior improvement and switching CNi to mTORi were advocated as the main strategies to curtail the increasing incidence of skin cancers.
22 reports with 2295 patients were reviewed and included in the study with median follow up of 10 months (range between 2 and 60 months).
3 intervention limbs include sun protection, switching to mTORi and applying other pharmacological preparations such as Retinoid and Acitricin..
Conclusion:
the benefit of all mentioned strategies was not consistant and incnclusive throughout the studies examined.
level of evidence is 2as its a meta analysis
Bias is any deviation from truth in data collection, analysis, interpretation and publication. its intentional and incremental.
error is a false or mistaken result obtained in a study or experiment, its non-intentional and decremental.
The level of evidence that a meta-analysis of studies would provide is as good as the studies included. Hence, this would be 1A since RCTs are included.
But if it is a meta-analysis of cohort studies, then it would become 2A.
Ajay
This is understood that skin cancer is the most common cancer post-transplantation in recipients, it may account for >50% of cancer cases. The cumulative incidence of non-melanocytic skin cancers has increased with post-transplantation, from 5 to 10% at 2 years to 40 to 80% at 20 years.
The aim of this study was to determine the effectiveness of intervention that promote behavioral changes and skin cancer prevention in solid organ recipients.
This was a systemic review in which all randomized control trails for skin cancer prevention in solid organ recipient were included, the sources were MEDLINE, Embase, Cochrane Central registry of control trails and CINAHL, included number of trails were 22 reports of 20 RCTs and number of participant were 2295.
The eligibility criteria; was the evaluation of the effect of behavioral or pharmacological intervention on behavioral changes on skin cancer prevention in solid organ recipient.
Overall the quality of evidence was low, it was uncertain whether behavioral intervention improve sun protection, and second they were uncertain about the effect of mTOR inhibitor effects on skin cancers.
Sun protection behavior including use of sunscreen, protecting clothing, are potential measures for prevention.
Alteration of maitianence immunosuppression such as conversion to mTOR inhibitors.
Method used;
Systemic reviews and meta-analysis checklist.
Intervention;
The studies were grouped into three broad categories, behavioral, pharmacy article intervention, and switch to mTOR inhibitors.
Discussion and conclusion;
The articles covered broad range of interventions to change the behavior change to improve sun protection behavior and pharmaceutical including drug change, photodynamic therapy, oral retinoid, nicotinamide, and topical immune response modifier. Although, overall intervention showed improvement to sun protection behavior, but for skin cancer prevention in solid organ transplant recipient is of very low quality and is insufficient to lead to decision for clinical practice decision.
Level of evidence;
Level of evidence I.
1.Please summarise this article Introduction :Skin cancer affecting more than 50% of post-transplantation recipients.
-The cumulative incidence of non-melanoma skin cancer (NMSC ) increases from 5%–10% at 2 years to 40%–80% at 20 years.
-Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender-matched general population.
-The excess risk of death from invasive and metastatic skin cancer, such as SCC and melanoma, are three to nine times higher than the general population, with 5-year overall survival of <30%.
-Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population.
-Sun protective behaviours including use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days are potential
measures for skin cancer prevention.
– Alteration of maintenance immunosuppression such as
conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
–Objectives : They aimed to determine the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients.
–Design :Systematic review.
–Data sources :They searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL)and CINAHL from inception to November 2019.
– The review included 22 reports of 20 trials involving 2295 transplant recipients, who were predominately kidney transplant recipients.
– They covered a broad range of interventions, including behavioural to improve sun protection behaviour and pharmaceutical to evaluate precancerous lesion response and cancer incidence.
-The current evidence for interventions for skin cancer prevention in solid organ
transplant recipients is of very low quality and is insufficient to guide decision-making and clinical practice.
-Due to limited number of studies, They were unable to compare specific behavioural interventions (eg, mobile app vs written education) to ascertain the most effective method of delivering sun protection education. While there may
be some modest benefits in the reduction in cancer incidence (for NMSC) among solid organ transplant recipients who were converted to mTORis compared with those on CNI maintenance, there was substantial heterogeneity across the studies that was unable to be explained by subgroup analyses.
-Pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers) showed a reduction in precancerous lesions compared with standard care or a comparator group.
-Previous systematic reviews have evaluated the impact of behavioural interventions on skin cancer prevention in the general population, and concluded that computer programmes may increase sun protective behaviours,
and ‘appearance-focused’ interventions may decrease sun tanning and UV exposure in adolescents and young women, respectively.
-A systematic review of the benefits and harms of oral retinoids for the prevention of skin cancer among high-risk transplant recipients led to inconclusive results on the effect of acitretin due to the small number of included trials.
– Limitations: Due to the heterogeneity of the studies, the high risk of bias, there is a high degree of uncertainty in the estimate of the effect of skin cancer
prevention interventions.
-There were large discontinuation rates owing to adverse events in trials of mTORis.
Given the small number of studies included in the meta-analysis,
we were unable to perform any detailed subgroup analyses to explore heterogeneity or assess for publication bias.
-Few trials included patient important outcomes associated with skin cancer and
none included melanoma or mortality.
-Behavioural counselling has been shown to increase sun protective behaviours in non-transplant populations,there is no direct evidence to show that
the behavioural change led to a reduction in morbidity and mortality.
-Previous studies have suggested that transplant recipients do not practice sun protective behaviours regularly,were less likely to use sunscreen and
that patients have to perceive skin cancer as being an important risk to be motivated to change behaviour.
-Transplant recipients are likely to benefit from early implementation of education, particularly before transplantation occurs and recipients
may be preoccupied with other health needs related to transplantation. What is the level of evidence provided by this article? Level of evidence: 1 What is the difference between bias and errors?
Bias produces systematically prejudiced results while errors produce inaccurate results.
Summary of Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trialsIntroduction
Melanoma and non-melanoma skin cancer is the most frequently diagnosed malignancy among solid organ recipients and about more than 50% of the recipient.
Squamous cell CA is the most common skin CA than based cell CA.
The management of skin CA in Transplant recipients is limited as it leads to graft rejection. There are guidelines in the general population to reduce and delay the development of skin cancer which may not be applicable to solid organ transplant recipients.
The aim of this study determines the effectiveness of an intervention that promotes behavioural change and skin cancer prevention among organ transplant recipients. Method
Systemic Reviews and meta-analysis checklist. Inclusion criteria
1- Active behavioral strategies clinic visit and workshop.
2- Strategies for behavioral intervention include sun proactive equipment.
3- Pharmaceutical intervention strategies results.
1280 articles were identified and 1201 were excluded after the abstract. Full-text assessment of 79 studies found 22 eligible articles for inclusion.
Studies characteristics
22 Reports of 20 RCTS, including 22 95 participants and median followed up ten months limitation of this study:-
1- Heterogeneity in the intervention and outcome measure
2- Small size sample
3- Small number of studies for each specific outcome
4- Short time of following this study.
5- Formal testing of publication bias was not performed due to insufficient data. Intervention
Studies were grouped into three broad categories.
(1) Behavioural
(2) Switch to m TOR
(3) Pharmacy article intervention. Discussion
The studies covered a broad range of interventions including behavioural to improve protection behavior and pharmaceutical to evaluate precanerogenic lesions response and cancer incidence.
The current evidence for intervention for skin cancer prevention misdid organ transplant recipients is of very low quality and is insufficient to guide decision-making and clinical practice.
The use of mTORi therapy same benefits in lowering the risk of skin cancer, early conversation with mTOR therapy for CNI has shown promising effects in reclaiming the cancer rate.
There is no direct evidence to show that the behavioural charge led to a reduction in morbidity and mortality.
We suggest further strategies for skin cancer prevention in transplant recipients require a multifaceted and individualized approach. Conclusion
Preventive measures including a behavioural switch to mTORi and other pharmaceuticals many improve skin cancer outcomes for solid organ transplant recipients. The quality of evidence is very low and insufficient to guide disease-making and clinical practice. The level of evidence:-
This is retrospective about the level of evidence II
3) what are drawback when we use negative data?
1) bias in the collective data
2) participants lost follow upon long term
3) No control group
The level of evidence that a meta-analysis of studies would provide is as good as the studies included. Hence, this would be 1A since RCTs are included.
Ajay
This systematic review included twenty trials with a total of 2295 participants.
Because the quality of the evidence is so low, it is unclear whether behavioral interventions improve sun protection behavior (n = 3, n = 414) and knowledge (n = 4, n = 489).
The effects of mammalian-targeted rapamycin inhibitors on the incidence of non-melanocytic skin cancer (n = 5, n = 1080) are unknown due to the low quality of the evidence.
To summarize, while behavioral and pharmaceutical preventive interventions may improve sun protective behavior and knowledge while also decreasing the incidence of non-melanocytic skin cancer, the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
Strengths:
-To assess the risk of bias and evidence of certainty, a comprehensive review was conducted using methods outlined by the Cochrane Collaboration, including Grading of Recommendations Assessment Development and Evaluation.
– Inclusion of a wide range of interventions, including behavioral interventions to improve sun protection behavior and pharmaceutical interventions to assess precancerous lesion response and cancer incidence.
Limitations
Due to the variability in analytical methods and reporting in individual studies, it is difficult to obtain an overall summary estimate for many outcomes.
Due to the small number of studies, it was impossible to perform detailed subgroup analyses or assess publication bias.
Only a few trials included important skin cancer outcomes, and none included melanoma or mortality.
========================== 2. What is the level of evidence provided by this article? Level I ========================== 3. What is the difference between bias and errors?
Bias produces systematically biased results, whereas errors produce inaccurate results.
Errors are typically identified using calculations and metrics such as false positive rates, false negative rates, and root mean square error (RMSE).
Biases are detected manually or using software programs such as the What-If tool and AI Fairness 360.
I like your analysis of level of evidence, limitations and strengths of this study. I like your description of bias. Bias can happen at any stage of study: conceptualisation, planning, designing, performing, analysis and writing that study. Error may creep in due to inaccurate measurements.
Summary of the article BEHAVIOURAL AND PHARMACEUTICAL INTERVENTIONS FOR THE PREVENTION OF SKIN CANCERS IN SOLID ORGAN TRANSPLANT RECIPIENTS: A SYSTEMATIC REVIEW OF RANDOMISED CONTROLLED TRIALS
Skin cancer is frequently encountered in more than 50% of post-transplant recipient. In comparison to gender matched general population, the rate of SCC is higher than the rate of BCC.
This systematic review of RCTs studied the the behavioral and pharmaceutical intervention in the prevention of skin cancers in solid organ transplant.
The range of preventive intervention in this study included:
1.Sun protection behavior: • use of sunscreen. • wearing of protective clothing. • seeking shade. • Decreasing daily hours outdoors.
2.Pharmaceutical intervention: • Topical and local interventions. • Systemic intervention; shift to mTORi.
Study’s result • Currently, the evidence is of low quality regarding the protective interventions in skin cancers in solid organ transplant recipient. • Pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers) showed a reduction in precancerous lesions compared with standard care or a comparator group. • mTORi therapy shown benefits in lowering the risk of skin cancer. • Early conversion to mTORi therapy from CNIs has shown promising effects in reducing cancer rates. • Nicotinamide may offer benefits to reducing skin cancer incidence by 20%. • There is no direct evidence to show that the behavioural change led to a reduction in morbidity and mortality. What is the level of evidence provided by this article?
Systemic review of CRTs, level of evidence 1 What is the difference between bias and errors? Bias: is a systematic distortion of a statistical result due to a factor not allowed for in its derivation. Three types of bias can be identified; information bias, selection bias and confounding. Error: is a measure of the estimated difference between the observed or calculated value of a quantity and its true value.
I like your analysis of level of evidence, limitations and strengths of this study. I like your description of bias. Bias can happen at any stage of study: conceptualisation, planning, designing, performing, analysis and writing that study.Error may be due inaccurate measurements.
summary:
More than half of all people who get solid organ transplants will develop skin cancer in their lifetime. The purpose of this study was to investigate whether or not modifying the behaviour can successfully reduce the likelihood of developing post-transplant skin cancer. a systematic review of nearly twenty randomized controlled studies that investigated the effect of pharmaceutical treatments and lifestyle modifications on the incidence of skin cancer in patients with solid organ transplants. In terms of behavioural modifications that enhance awareness and sun protection behaviour, as well as mTOR inhibitors and skin cancer reduction, the conclusion was that Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice. level of evidence:
level I, a systematic review of a randomized controlled trial Error:
Error is the difference between actual and predicted or theoretical results.
Systematic errors and random errors are the two major types of errors.
Random errors can occur due to sampling or parameter variability.
Systematic errors (bias) are due to errors in the design of the study that can lead to incorrect results. can occur at any stage of the study. information bias, selection bias & confounding bias.
Please use bold or underline for heading or sub-headings. I like your analysis of level of evidence of this study. What are limitations and strengths of this study?
This article tries to reflect if there are changes in the outcome of behavioral and pharmaceutical interventions in changing the rate of skin cancer.
as we all know that post-transplant cancer is 50% , This study was a systemic review which included almost twenty randomized controlled trials that assessed pharmaceutical and behavioral changes which would affect the risk of skin cancers in solid transplant recipients. This review results were uncertain regarding behavioral changes that improve knowledge and sun protection behavior, the results were also uncertain about mTOR inhibitors and skin cancer reduction.
Method of this study:
A systematic review of 22 reports of 20 randomised controlled trials with 2295 participants.
What is the level of evidence provided by this article?
it is systemic review level 1
What is the difference between bias and errors? Biais systemic errors that results from inaccurate effects and associations. Error is inaccurate results. Bias is error but not all error is bias. There are 3 types of bias ( information bias, selection bias and confounding bias).
Please use bold or underline for heading or sub-headings. I like your analysis of level of evidence of this study. What are limitations and strengths of this study?
■ Summary: Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials
Introduction ▪︎ Solid organ transplant recipients are at increased risk of skin cancer, affecting more than 50% of recipients. ▪︎Skin cancer is the most frequently diagnosed malignancy among solid organ transplant patients. The cumulative incidence of non melanomas skin cancers (NMSC) increases with time after transplantation and there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), Once cancer develops, management options are limited as immunotherapy may be unsuitable as it may lead to graft rejection.
◇ Objectives of the study: to determine the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients.
◇ Design Systematic review. Data sources: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
◇ Eligibility criteria: the study included randomised controlled trials that evaluated the effect of behavioural or pharmaceutical interventions on behavioural change or skin cancer prevention in solid organ transplant recipients. ◇ Data extraction and synthesis:
Risks of bias and evidence certainty were assessed using Cochrane and the Grading of Recommendations Assessment Development and Evaluation framework. ◇ Results Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour. There were uncertainty of the effects of mammalian target of rapamaycin inhibitors on the incidence of nonmelanocytic skin cancer.
◇ Strength of the study: ▪︎Inclusion of a broad range of interventions, including behavioural to improve sun protection behaviour and pharmaceutical to evaluate precancerous lesion response and cancer incidence. ◇ Limitation of the study ▪︎ Diffculty obtaining an overall summary estimate for many outcomes due to the variability in the analytical methods and reporting in individual studies. ▪︎Unable to perform detailed subgroup analyses or assess for publication bias due to small number of studies. ▪︎Few trials included the important outcomes of skin cancer and none included melanoma or mortality
◇ Conclusions
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insuffcient to guide decision-making and clinical practic.
■ What is the level of evidence provided by this article? Level I
■ What is the difference between bias and errors?
Bias systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates and RMSE [1].
———–
Ref. [1] Emmanuella Badu. Differences Between Bias and Error. 2022
Summary:
More than 50% of solid organ transplant recipients are affected by skin malignancy. This study determined the effectiveness of behavioral changes which can reduce the risk of post-transplant skin cancers. This study was a systemic review which included almost twenty randomized controlled trials that assessed pharmaceutical and behavioral changes which would affect the risk of skin cancers in solid transplant recipients. This review results were uncertain regarding behavioral changes that improve knowledge and sun protection behavior, the results were also uncertain about mTOR inhibitors and skin cancer reduction.
Limitations.
1. Small sample size of individual studies.
2. Short follow-up period and loss of follow-up.
3. None of the studies included melanoma. Level of evidence: Level 1 What is the difference between bias and errors? Bias produces systematically prejudiced results while errors produce inaccurate results.
Introduction: Majority cases of solid organ transplant are at risk of skin cancer and account 50% of cases develop cancer in transplant patients.
Objective:
This study address Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients.
Method of this study:
a systematic review of 22 reports of 20 randomised controlled trials with 2295 participants.
Included Criteria: a. All melanoma and non melanoma skin cancer b. All passive and active behaviour measures of skin protection c. All studies with outcome of primary skin cancer
Excluded Criteria: Exclude all studies which address treatment of skin cancer and all studies not show outcome of primary skin cancer.
This study shows improvement of preventive measures in reduce risk of skin cancer by non pharmaceutical therapy with behavioral knowledge and behavioral attitudes in reduce sun exposure and use of high SPF sunscreen and wearing of sun protective materials but this evidence is low quality and non conclusive. Also pharmaceutical measures like use of mTOR inhibitors instead of Calcinurine inhibitors and oral retinoid and nicotinamide in reduce precancerous lesions and skin cancer but due to small number of studies shows not enough to benefit from using of retinoid management in preventing of skin cancer. However heterogeneous of studies shows large bias leading to miss estimate benefits of behaviour and pharmaceutical therapy in preventing skin cancer. Early Use of sirolimus (mTOR inhibitors), is effective in treatment of skin cancer but there’s large number of patients shows discontinuation of sirolimus due to adverse effects of therapy.Nicotinamide is effective in 20% to reduce skin cancer with less side effects.
Limitations of this study is a. small size b. short duration of fallow up and heterogeneocity of fallow up. c. there is no data on the incidence and outcome of skin cancer.
Conclusion: Large scale of randomised clinical trails needed to strength evidence of behaviour shift of CNI to mTOR inhibitors and other treatment measures in reduce risk of skin cancer. Large reported studies needed with homogeneous sample and fallow up to demonstrate evidence of preventive measures to reduce risk of skin cancer.
What is the level of evidence provided by this article?
Level of evidence is 1 ( systemic review)
What is the difference between bias and errors?
Bias is systemic errors that results from inaccurate effects and associations. Error is inaccurate results. Bias is error but not all error is bias. There are 3 types of bias ( information bias, selection bias and confounding bias).
You need not to type everything in bold or capitals. That amounts to ‘shouting’.
Use bold or underline for heading or sub-headings. I like your analysis of level of evidence, limitations and strengths of this study.
Systematic Review of RCTs on behavioral and pharmaceutical intervention for prevention of of skin cancer in Solid Organ transplant recipients 20 RCTs and 2295 participants.
1.Introdution;
Skin cancer increases many fold upto 9 times in solid organ transplant recipients with passage of time compared to age and gender matched general population. This review helps in understanding preventive strategies in prevention of skin cancers in SOT recipients 2.Inclusion criteria;
All studies with Primary end point of cancer related outcomes like,
Active behavioral strategies clinic visits and workshops
Passive behavioral strategies
Sun protective strategies
Pharmaceutical interventions
3.Exclusion Criteria;
Treatment related study
Primary Outcome without skin cancer.
4.Results;
This review suggests the decrease in skin malignancy with behavioral intervention but the quality of evidence is poor and it is difficult to infer solid evidence on affect of mTOR on skin malignancies.
5.Conclusion;
Preventive measures and pharmaceutical intervention not limited to CNI to mTOR switch may improve skin cancer in solid organ transplant receipts but this analysis provide very low quality of evidence.
No clinical judgment should be made based on this review.
6.Limitation;
Variability in analytical methods
Heterogeneity
Small sample size in included studies
Short follow up time of studies
What is the level of evidence provided by this article?
Level of evidence 1
What is the difference between bias and errors;
Bias——prejudiced results
Error—–lack of precision could be systematic or random
More than half of solid organ transplant (SOT) recipients get skin cancer. In the kidney transplant group, squamous cell carcinoma is more common than basal cell carcinoma; in the general population, the opposite is true. Despite advances in immunosuppressive therapy, the burden of skin cancer and cancer-related mortality remains significant. Skin cancer prevention strategies and immunosuppression modification are indicated in the treatment of skin cancer in transplant recipients. The study’s aim is to assess the efficacy of behavioral and pharmacological therapies in preventing skin cancer in SOT recipients. Systemic reviews
RCTs that assessed the efficacy of behavioral (passive or active) or pharmacological (mTORi usage, photodynamic treatment, oral retinoids) interventions on skin cancer prevention in SOT participants were eligible. MEDLINE, Embase, and Cochrane are examples of search engines. Outcome measures include precancerous and cancerous lesion incidence, sun protection behaviors, knowledge and attitude, skin self-examination, sun exposure, and biologic measurements.
Results
This systematic review comprised 20 RCTs with a total of 2295 individuals, the majority of whom were kidney transplant recipients. Although none of these researches included skin cancer as an endpoint, behavioral interventions enhanced sun protection behaviors. Precancerous lesions were reduced by pharmaceutical therapies. When compared to maintenance CNIs, the use of mTORi reduced cancer incidence (NMSC). Oral retinoids had no effect on the occurrence of new SCC. Limitations
-None of the research covered skin cancer as a result of inconsistencies in knowledge, attitude, and practice of non-medical approaches that hindered or compromised the quality of the results. -Subgroup analysis was unable to explain substantial heterogeneity between studies, probably due to a lack of long-term follow-up, a high dropout rate, and different MTOR dosages. Too few studies exist to permit the application of pharmaceutical intervention outcomes to clinical investigations. -All trials on non-pharmaceutical techniques, including four by the same authors, were conducted in the United States, whereas the pharmaceutical studies were conducted in Europe, increasing the possibility of bias. -Short follow-up duration insufficient to illustrate the long-term effects of pharmacological substances Level of evidence: Level 1 – Systemic review Difference between bias and error
Bias is typically used to refer to incorrect data collection, such as patient selection, allocation, concealment, blinding of patients and workers, blinding of outcome assessment, and selective outcome reporting. Typically, error is used to indicate errors in the statistical process, including the influence of introduced data on test findings.
That is an excellent summary and very well structured reply. I like your comment on limitation of sub-group analysis. I like your analysis of level of evidence, limitations and strengths of this study.
Systematic Review and Meta analysis of RCT and quasi RCT from inception till 2019
Research Question:
Are Behavioural change intenventions and pharmaceutical ones canimprove sun protection behaviour, knowledge and decrease inscidence of skin cancer?
Participants: all tranplant population, all oragams, all ages
Interventions:
Behavioral interventions defined as any strategy used to promote sun protective behavior including passive (eg, pamphlets), active (eg, group workshops, counselling, dermatology clinic) and provision of sun protective equipment.
Pharmaceutical interventions: switch to mTOR is and other pharmaceutical interventions (photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide)
Comparison:
For behavior intervention, it is compared with standard of care
Pharmaceutical intervention: Placebo or other immune supression
Outcome:
incidence of precancerous and cancerous lesions
sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance)
knowledge and attitude, skin self-examination, sun exposure (including skin irritation, sunburn)
biologic measures (including measurement of melanin index and sun damage assessment).
Results: Twenty trials (n=2295 participants) were included.
Behavioral interventions: There was no statistical difference to show that behavioral interventions can improve sun protection behavior and knowledge as the quality of evidence is very low.
mTor helped to decrease the incidence of nonmelanocytic skin cancer with relative risk 0.46 but the authors reported poor quality of evidence
heterogeneity : I2 for sun protection behavior and knowledge and switch to mTOR are 98 and 76, 71 respectively which indicate considerable heterogeneity (Ref 1)
POSITIVE:
It is good to try to collect the evidence with a nice review, the tables were very good and informative
NEGATIVES
The research question is too broad which I think it can be divided into many small reasonable questions.
Pharmaceutical interventions cannot be added together.
Too many inteventions with too many outcomes to follow which make the paper too hard to read and follow.
I find it difficult to understand their aim at the abstract section.
Included population, I presume included adult and children from their inclusion criteria which again too much data put together.
Duration of follow up was short, almost half of the studies had FU less than 12 months.
The authors graded the evidence as very poor, and they started metaanalysis. I think they should have stopped there rather wasting their time and ours .
The heterogeneity of the forest plot is considerably high between their included studies.
OVERALL, Too broad research question, nice tables, I would not rely on that paper in my practice.
What is the level of evidence provided by this article?
highest level of evidence but of very poor quality.
What is the difference between bias and errors?
Both are deviation from the truth that can affect data validitiy. Error is the bigger term which can be either random (due to change) or systematic. Bias is the systematic error in either results or inferences which can lead either over or underestimation of the effect.
That is a good summary. When you state that this evidence is of poor quality, how would you do this study better. Error may be due inaccurate measurements.
I. Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials
· Please summarise this article
Introduction
Skin cancer affects more than 50% of solid organ transplant (SOT) recipients. Squamous cell carcinoma is more common than basal cell carcinoma in the kidney transplant population, the reverse is true in the general population. The burden of skin cancer and cancer-related mortality remains high despite improvements in immunosuppressive therapy. Skin cancer prevention measures and modulation of immunosuppression are recommended in the management of skin malignancies in transplant recipients.
Study objectives
To determine the effectiveness of behavioural and pharmaceutical interventions in the prevention of skin malignancies in SOT recipients.
Methods
Systematic review
Inclusion criteria – RCTs that evaluated the effect of behavioural (passive or active) or pharmaceutical (mTORi use, photodynamic therapy, oral retinoids, noctinamide) interventions in prevention of skin cancers in SOT recipients.
Search engines – MEDLINE, Embase, Cochrane
Outcome measures – incidence of precancerous and cancerous lesions, sun protection behaviours, knowledge and attitude, skin self-examination, sun exposure, biologic measures
Results
This systematic review included 20 RCTs involving 2295 participants who were predominantly kidney transplant recipients. Behavioural interventions improved sun protective behaviours although none of these studies included skin cancer as an outcome. Pharmaceutical interventions demonstrated a reduction in precancerous lesions. Use of mTORi reduced cancer incidence (NMSC) compared to maintenance CNIs. Oral retinoids did not have an impact on incidence of new SCC.
Study strengths
Included a wide range of interventions, both behavioural and pharmaceutical.
Study limitations
Few trials included patient outcomes associated with skin malignancy
None of the trials included melanoma and mortality
Reporting bias
Large discontinuation rates due too adverse events experienced in the mTORi trials
Subgroup analyses could not be done due to the small number of studies included in the meta-analyses
Conclusion
Preventive measures including behavioural interventions and switch to mTORi may improve skin cancer outcomes in SOT recipients. However, the quality of evidence is low and cannot inform clinical practice, hence well powered studies are required to guide decision-making.
· What is the level of evidence provided by this article?
Level I evidence
· What is the difference between bias and errors?
Bias – occurs systematically, it produces prejudiced results and is identified manually or through software packages
Error – occurs randomly, it results in inaccurate results and is identified through calculations
That is an excellent summary and very well structured reply. I like your analysis of level of evidence, limitations and strengths of this study. I like your description of bias. Bias can happen at any stage of study: conceptualisation, planning, designing, performing, analysis and writing that study.
Amongst solid organ transplant recipients, skin malignancy is the commonest affecting more than half of the recipients. This includes both melanoma and non melanoma variants. Medical and non medical approaches have been applied to reduce the incidence of skin cancer post transplant with mixed outcomes.
STUDY OBJECTIVES.
To assess the efficacy of interventions that promote behavioral changes and skin cancer prevention in solid organ transplant recipients,
DESIGN.
Systemic review involving 22 RCTS with 2295 participants that met the inclusion criteria,
Inclusion criteria;
-All RCTS or Quasi RCTS of interventions to decrease skin cancer incidences in solid organ transplant recipients.
-Studies that reported skin cancer related outcomes as primary outcomes.
Exclusion criteria;
-Studies that did not report cancer related outcomes as primary end point.
-Studies of interventions for treatment of skin cancer.
RESULTS.
-Despite a high non compliance rate and drop out, it was noted that all behavioral approaches were beneficial.
-MTOR inhibitors were used for short period of time an aspect that limited the quality of evidence to inform clinical decision making, nevertheless they were beneficial in studied selected for this study.
STUDY LIMITATIONS.
-None of the studies included skin cancer as an outcome with inconsistencies in knowledge, attitude and practice of non medical approaches which hampered or affected the quality of results.
-Substantial heterogenicity across studies could not be explained by subgroup analysis possibly from lack of long term follow up, large drop out rate and varied MTOR doses.
-Too few studies to enable outcomes from pharmaceutical intervention be applied in clinical studies.
-All studies on non pharmaceutical approaches were done in USA with 4 by the same authors while the pharmaceutical ones were done in euro[e increasing risk of bias.
-Short follow up time insufficient to explain long term effects of pharmaceutical agents.
CONCLUSION.
–Preventive measures -medical and non medical decrease risk of skin cancer post solid organ transplant, however the quality of evidence is low.
-More studies, well powered and with a long term follow up are needed to provide more evidence to guide clinical decision making.
o Skin cancer is common among transplant recipients (about 50 % of cases) and increases with time after transplantation.
o It carries poor prognosis as it increases the mortality and also has bad impact on graft survival as minimization of immunosuppressive drugs increase incidence of rejection and graft loss.
o Prevention of skin cancer in general population mainly depends on avoiding sun exposure as avoidance of sun exposure around midday rime plus use of sunscreen and sun protective clothes.
o The current study included previous studies addressing the effectiveness of different protective methods as behavioral changes or drugs to prevent skin cancer (measured as incidence of precancerous skin lesions and skin cancer) among solid organ transplant recipients.
o Sun protective behavior and knowledge that are reflected thereafter on sun protective attitude were evaluated. In addition, biological effect of the sun as skin irritation or burn was studied.
o The current study found that in transplant patients, modification of immunosuppressive therapy (shift to mTORi as sirolimus) and additional drugs as retinoids and photodynamic therapy using methyl aminolevinate creams can prevent or delay occurrence of skin cancer.
o Use of sirolimus and early withdrawal of CNI may decrease incidence of skin cancer but increase risk of complications as proteinuria with discontinuation related to its side effects.
o Nicotinamide may be safe and effective in reduction of skin cancer.
o The available data and evidence is low and insufficient to support recommendations of above-mentioned behavioral and pharmacological therapies to prevent skin cancer in transplant patients. Hence, further studied are required to prove this.
· Level of evidence: it is systematic review but it is level I
· Difference ( ) errors and bias
o Errors are mistakes like miscalculation or using fabricated data or numbers that lead to inaccurate results.
o Bias include problems related to:
§ Selection bias in either randomization or allocation of cases in different study groups.
§ Performance bias: means unblinding regarding the intervention used so results are influenced by personal desire or industrial (financial) purpose.
§ Detection bias: unblinding regarding assessment of outcomes.
§ Attrition and reporting bias: means incomplete and selective reporting of the outcome data.
Skin cancers affect more than 50% of transplant recipients with the incidence of non-melanoma skin cancer (NMSC) increasing upto 80% at 20 years. The aim of this systemic review was to assess the effect of behavioural and pharmaceutical interventions on the prevention of skin cancer in transplant recipients.
Inclusion criteria: Randomized controlled trials (RCTs) in solid organ transplant recipients having skin cancer prevention using either behavioural (passive or active) or pharmaceutical (mTOR inhibitor switch, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids) interventions.
Results:
20 RCTs (22 reports) were included in the study, involving a total of 2295 recipients. 6 studies involved behavioural interventions, 6 pertained to mTOR inhibitor switch, while 9 studies dealt with other pharmaceutical interventions.
Behavioural interventions: Led to improved sun protection behaviour scores, and reduced incidence of skin irritation, sun damage and reduced melanin index. But the quality of evidence was very low.
Pharmaceutical interventions: Immune response modifier 5% imiquimod cream reduced incidence of skin dysplasia, atypia and viral warts. Positive effect of photodynamic therapy has very low-quality evidence. mTOR inhibitor switch from calcineurin inhibitors has shown modest benefit to reduce incidence of NMSC, but the quality of evidence is low due to short follow-up, variable doses, and increased rates of loss to follow-up. Use of oral retinoids did not have any effect on incidence of new squamous cell carcinoma.
Limitations: Participant blinding was not done in most studies, while blinding of outcome assessors was also reported in only 50% of the studies. Overall quality of evidence was very low for all outcomes. There was heterogeneity in intervention and outcome measures as weel as high risk of bias. Small sample size and small number of studies added to limitations. Large discontinuation rates in mTOR inhibitor studies. Precancerous lesions or skin cancer incidence as outcomes was not measured in the behavioural intervention studies.
Conclusions: Although the data suggests that behavioural and pharmaceutical interventions may improve sun-protective behaviour adoption by patients, reducing the incidence of NMSC, the quality of evidence is very low and hence guidelines cannot be laid on the basis of current evidence. A multifaceted and individualized approach is a must in this scenario.
2. What is the level of evidence provided by this article?
Systematic review: Level of evidence is Level 1
3. What is the difference between bias and errors?
A bias is a scenario in which the results are obtained in a prejudiced manner. It is due to a systemic flaw in the methodology.
An error is something which can occur randomly, resulting in inaccurate outcomes of the study.
A bias is an error, but every error is not a bias.
That is an excellent summary and very well structured reply. I like your analysis of level of evidence, limitations and strengths of this study. I like your description of bias. Bias can happen at any stage of study: conceptualisation, planning, designing, performing, analysis and writing that study.
Please summarise this article Introduction:
Skin cancer is the most common malignancy among SOT recipients, affecting more than 50% of post-transplantation recipients.
Sun exposure behaviors remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population.
The study aim:
Determine the effectiveness of interventions that promote behavioral change and SK prevention in SOT recipients
Methods: Design: SR included 22 studies included 2295 participants. Included studies:
-RCTs of interventions for skin cancer prevention in SOT recipients.
· Behavioral interventions: promote sun protective behavior and provision of sun protective equipment;
· Pharmaceutical interventions: switch to mTORi, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids
– Studies that reported skin cancer-related outcomes as their primary outcomes. Exclusion:
Studies that did not report these outcomes as primary endpoints.
Studies of interventions for the treatment of skin cancer.
Results:
-As the quality of evidence is very low, it is uncertain whether behavioral interventions improve:
– Sun protection behavior n=3, n=414, SMD 0.89.
– Knowledge n=4, n=489, SMD 0.50.
– Attitude n=3, n= 348, SMD 1.85
-As the quality of evidence is very low We are uncertain of the effects of:
– mTORi on the incidence of NMSK n=5, n=1080, RR 0.46.
– Photodynamic therapy on incidence of precancerous lesions.
Limitations:
-Heterogeneity in the intervention and outcome measures
-Very small sample size of individual studies and the small number of studies for each specific outcome.
-Short follow up period and considerable loss to follow-up for some studies
-Variability in the analytical methods and reporting in individual studies.
-None of the behavioral intervention studies included precancerous lesions or skin cancer incidence as outcomes.
-Reporting bias and imprecision in the point estimates of individual studies,
Conclusions:
Behavioral and pharmaceutical preventive interventions may improve sun protective behavior and knowledge, and reduce the incidence of NMSC , but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
What is the level of evidence provided by this article?
Level 1 What is the difference between bias and errors? Bias produces systematically prejudiced results, identified manually or through available software programs, and occurs systematically. Errors produce inaccurate results, identified through calculations and metrics, and occurs randomly.
Skin cancer, including melanoma and non- melanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post-transplantation recipients.
Objectives :
To determine the effectiveness of interventions for behavioral change for sun protection or skin cancer prevention in solid organ transplant recipients.
Design :
Systematic review.
Data sources :
Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
Inclusion criteria:
All randomized controlled trials (RCTs) or quasi RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients
pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids) and studies that reported skin cancer-related outcomes
Exclusion criteria :
Studies of interventions for the treatment of skin cancer.
Results:
Study selection
The literature search identified 1280 articles, of which, 1201 were excluded after abstract and title review.
Full-text assessment of 79 studies found 22 eligible articles for inclusion
Studies characteristics:
The median number of participants was 44 (range 17–830) and the median follow-up duration was 10 months (range 1day to 60 months).
All studies included kidney transplant recipients, with some also including heart transplant recipients (n=1), liver, heart, pancreas, lung, heart/lung and other transplants (n=1), and lung and liver transplant recipients (n=2).
In total, 15 (76%) of 21 studies provided sufficient data for the meta-analyses.
Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour (n=3, n=414, standardised mean difference (SMD) 0.89, 95%CI −0.84 to 2.62, I2 =98%) and knowledge (n=4, n=489, SMD 0.50, 95%CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low.
The effects of mammalian target of rapamaycin inhibitors on the incidence of non- melanocytic skin cancer (n=5, n=1080, relative risk 0.46, 95%CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low.
Risk of bias and quality of the evidence:
Overall studies had either high or unclear risk of bias for at least one domain.
Random sequence generation and allocation concealment were unclear in most studies (n=12, 60%).
Blinding of participants was not done in most studies (n=16, 80%) and blinding of outcome assessors was only reported in half of the studies (n=10).
Intention to treat analyses were used in 6 (30%) studies and 6 (30%) studies had a high loss to follow-up.
A total of 3 (15%) studies had incomplete outcome data, and all studies were at low risk for selective reporting.
Seven (35%) studies reported industry involvement in authorship, design or data anal- ysis, and of the 16 trials requiring trial registration, only 9 (56%) reported accordingly.
The overall quality of the evidence was very low for all outcomes
Strengths and limitations of this study:
► A comprehensive review .
► Inclusion of interventions, like ( sun protection behavior and pharmaceutical (immunosuppressant, photodynamic therapy, oral retinoid, nicotine amide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence.
► Difficulty obtaining an overall data.
► small number of studies.
► Few trials included the important outcomes of skin cancer and none included melanoma or mortality.
Conclusions :
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
level :1 systemic review study randomized controle
Bias produces systamatically prejudiced results while errors produce inaccurate results .Errors are usually identifed through calculations and metrics such as false positive rates ,negative rates and RMSE.
Behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: A systemic review of randomized controlled trials: Skin cancer is prevalent among transplant recipient patient, as a consequence of immunosuppressant medication, so it is an unavoidable but modifiable risk factor. Melanoma and non-skin melanoma affects more than 50% of transplant recipients, and the incidence increase as time increase post transplant, with 2 years incidence of 5% to 10% , while the rate is 40% to 80% in 20 years. The incidence is greater by 65 up to 250 times regarding the squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), compared to age-matched general population. This cancers related mortality make a burden on the outcome of kidney transplantation, although advances in transplantation technique and immunosuppressant medication and associated better outcome and survival in graft and patient life. In this sytemic trial will show modification and measures to reduce the incidence rate of transplantation-associated skin cancer. Modifications and measures against skin cancers:
Self-examination and yearly and twicw yearly total body examination.
Sun-protective behaviour , such as sunscreen, protective clothing, and reduce of sun exposure during the peak hours of UV light days.
Immunosuppressants modification, such as conversion to mTORis and secondary prevention using retinoids are recommended.
Effect of behavioural intervention on sun protection outcomes: Sun protection behaviour, attitude and knowledge using the following measures:
Outdoor time of sun exposure.
Use of sunscreen.
Wear of protective clothing.
Seeking shade.
All above mentioned measures was assessed in three trials, using an educational workbooks, educational workbook and messages, and a mobile phone program. With each of them noticed different participation committement and engagemnet, show the different improvement of the score of awareness. Effect of pharmaceutical intervention in skin cancer protection: Use the following modality:
Switch to mTORis.
Photodynamic therapy.
Immune modulators.
compare to current treatment or placebo, and by using whether topical apply or systemic intervention. Discussion: Although skin cancer associated solid organ transplantation are a major cause of comorbidity and mortality, only few number of trials done to prevent such complications and small study conclude the outcome, and all deficient in providing evident in clinical practice and outcome. Studies show improvement in awareness and attitude but deficient of outcome. Some study sustitude CNI by mTORis fail in final analysis of data, may be related to short duration of studies, doses variability, and participant commitment. Study limitation:
Short period of follow up.
Small number of participant.
Some studies deficent in outcome of cancer incidence.
Variabilities in participant commitment.
Due to all of the above, there was a high risk of bias:
Online supplementary.
Unclaear random sequence generation and allocation councealment in most studies.
Participant building was not done .
Outcome building assessed only of half of the studies.
High loss of follow up.
Industry authership involcement in some studies.
The quality of evidence is very law in most studies.
Difference between error and bias:
Error is the estimate of error of single measurement.
The bias is the average of errors in different measurements, it is a systemic error that lead to incorrect estimate of effect or association
-It is a SR of RCT assessing the impact of behavioral therapy intervention (either passive or active) and pharmaceutical therapy in skin cancer protection among SOT patients.
-Receiving behavioral intervention has been associated with improved sun protection behavior scores, sun protection knowledge score, and overall scores of concern about development of skin cancers. Also, it was associated with decreased incidence of skin irritation, sun burn, melanin index and severity of skin damage in the exposed areas.
-Pharmaceutical intervention effect on the incidence of precancerous lesions and its response to treatment:
Topical agents like immune modifier and photodynamic therapy reduced the incidence of skin dysplasia, atypia warts and NMSC and improved complete cure rate.
-Shifting to m-TOR inhibitors reduced the incidence of NMSC but the evidence is limited because of different limitations of the included studies. Use of retinoic reduced the risk of SCC and BCC.
Level of evidence:
According to the CEBM of oxoford: level of evidence is Ia
However, The overall quality of the evidence provided is very low for all outcomes due to limitations in study design, heterogeneity in the intervention and outcome measures, the very small sample size of individual studies and the small number of studies for each
specific outcome.
Difference between bias and error
Bias is usually used to describe the improper data collection including patient selection, allocation, concealment, blinding of patients and personnel, blinding of outcome measurement and selective outcome reporting.
Error is usually describe errors in the statistical process including the impact of introduced data on the results of the tests.
I like your analysis of level of evidence, limitations and strengths of this study. I like your description of bias. Bias can happen at any stage of study: conceptualisation, planning, designing, performing, analysis and writing that study. Error may creep in due to inaccurate measurements.
Please summarise this article: Introduction: It is known that skin cancer increases almost 9 folds in solid organ transplant recipient, this review article highlights the effect of preventive behavioral and pharmaceutical measures in preventing skin cancer in these patients. Systematic review of randomized controlled trails including 22 studies (2295 participants) with the proposed Inclusion criteria by the study group that are: – Interventions for skin cancer (melanoma and non-melanoma) prevention. a- Passive behavioral – pemphlets…etc b- Active behavioral – workshops , dermatology clinic visits,…etc. c- Sun UV wave protective equipments. d- Pharmaceutical interventions- oral retinoids, switch to m-TOR inhibitors…..etc. – Studies reported skin cancer related outcomes as primary endpoints. Exclusion criteria: – No skin cancer outcomes studies. – Treatment of skin cancer and interventions were excluded. Results: – All passive and active behavioral measures were beneficial in prevention of skin cancers, but with high dropout follow up and non compliance rate noticed. – Pharmaceutical measures in preventing only non-melanoma skin cancers, either switch to m-TOR, immune response modifiers, photodynamic therapy were of proven benefit but not in all studies. – m-TOR inhibitors may lower the incidence of skin cancer but studies were for short period, and there were a lot of discontinuation of drug in these studies due to side effects. Limitations: – heterogeneity in the intervention and outcome measures. – Small ample size, and small number studies for each specific outcome. – Variability in the analytical methods and reporting in individual studies, with wide diversity of intervention used. – Publication bias was not performed due to insufficient data. – Almost half of the studies were with one year follow up, not sufficient to elaborate the long time effect. Conclusion: Preventive behavioral and pharmaceutical measures including switching to m-TOR inhibitors may improve skin cancer outcomes for solid organ transplant recipients, however the quality of evidence is very low. Large randomized controlled trials for long times period of follow up are needed to guide clinical decision and practice.
What is the level of evidence provided by this article? Level of evidence 1 – review article of randomized trials.
What is the difference between bias and errors? Bias = systematically prejudiced results, identified manually or through software packages, occurs systematically. Errors = inaccurate or incorrect mathematically calculated results, occurs randomly.
Objectives
Skin cancer affects more than 50% of recipients of solid organ transplants, putting them at elevated risk.
In order to prevent skin cancer in solid organ transplant patients, we sought to evaluate the efficacy of behavioral change therapies.
Eligibility criteria
The authors took into account randomized controlled trials that looked at how behavioral or pharmacological interventions affected skin cancer prevention or behavioral change in solid organ transplant recipients.
Results
There were 20 trials (n=2295 participants).
The quality of the evidence is quite poor, therefore it is unclear if behavioral interventions enhance sun protection knowledge (n=4, n=489) and behaviour (n=3, n=414, standardized mean difference (SMD) 0.89, 95% CI 0.84 to 2.62, I2=98%).
Method
This systematic review adhered to a predetermined procedure that was registered in PROSPERO (CRD42017063962), and it is documented in line with a checklist known as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The study was exempt from approval from an ethics’ board.
Recipients of solid organ transplants were included in all randomized controlled trials (RCTs) or quasi-RCTs evaluating treatments for preventing skin cancer.
Pharmaceutical therapies, studies that reported skin cancer-related outcomes as their primary outcomes, and behavioral interventions—defined as any technique used to promote sun protective behavior, including passive, active, and provision of sun protective equipment—were also included.
The author omitted studies that did not list these outcomes as primary endpoints.
Studies involving treatments for skin cancer were not included.
Results
Studying selection: After reviewing the title and abstract, 1201 of the 1280 items found by the literature search were eliminated.
22 publications were determined to be eligible for inclusion after full-text analysis of 79 research.
Characteristics of studies 22 papers from 20 RCTs with 2295 individuals were included.
All studies included kidney transplant recipients, and some also included recipients of liver, heart, pancreas, lung, heart/lung, and other transplants (n=1), liver and lung transplant recipients (n=2), and recipients of liver and heart transplants (n=1).
15 (or 76%) of the 21 studies offered enough information for the meta-analyses.
Six studies failed to meet the final requirements for meta-analysis because they used the same participant sample (n = 1)[24] or did not offer data that could be used for meta-analysis (n = 5).
Conclusion
Major causes of morbidity and mortality among recipients of solid organ transplants are skin malignancies.
There are only 20 trials of therapies to prevent skin cancer in solid organ transplant recipients. Half of these trials include 50 patients or less, are short-lived (48% have 12 months follow-up), and 52% do not include skin cancer incidence as an endpoint.
Studies on a wide range of interventions were conducted, including behavioural changes to increase sun protection behaviour and pharmaceutical tests to assess precancerous lesion response and cancer incidence.
Precancerous lesions or the incidence of skin cancer were not included as outcomes in any of the behavioural intervention studies.
There was a great deal of variation among intervention types, diversity in outcomes examined, and uncertainty in outcome estimates, although interventions showed reasonable increases in sun protection behaviours, precancerous lesion responses, and cancer incidence.
The available evidence for therapies to prevent skin cancer in people who have received solid organ transplants is of extremely poor quality and is insufficient to inform therapeutic practice.
2. Level 1
3. Bias produces systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates and RMSE. Biases are identified manually or through available software programs
Introduction:
Skin cancers are common post kidney Transplant reaching 50percent of the cases.
Both melanoma and nonmelanoma skin cancer (NMSC).
The aim of study:
is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipient.
Methods:
Systemic reviews.
Inclusion criteria :
All randomised controlled trials or quasi RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were include.
Behavioural interventions defined as any strategy used to promote sun protective behaviour including passive (eg, pamphlets), active (eg, group workshops
, counselling, dermatology clinic) and provision of sun protective equipment; and pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids) and studies that reported skin cancer-related outcomes as their primary outcomes were included.
Studies characteristics :
22 reports of 20 RCTs, including 2295 participants .
Effect of behavioural interventions on sun protection outcomes Sun protection behaviour:
Patients who received behavioural interventions reported improved sun protection behaviour
uncertain of the effects of behavioural interventions on sun protection behaviour due to very low quality of evidence.
Sun protection knowledge:
There was an improvement in knowledge scores in the intervention group compared with standard car.
One study compared an interactive visual representation of the educational programme with standard information pamphlets and found that knowledge of sun protection improved among those who received the educational video.
Sun protection attitude:
Compared with standard care, there was an overall improvement in scores of concern about developing cancer .improvement in scores of understanding the personal risk of skin cancer
There uncertain of the effects of behavioural interventions on sun protection attitude due to very low quality of evidence.
Effect of pharmaceutical interventions on skin cancer prevention:
5% imiquimod cream with placebo and found a reduction in the incidence of skin dysplasia (RR 2.14, skin atypia
One Danish study compared photodynamic therapy with no treatment and reported a relative reduction by approximately 40% in the incidence of NMSC ;A lower incidence of SCC was also reported in one trial comparing two areas of skin using an immune response modifier and placebo .
Two trials comparing photodynamic therapy to an immune response modifier or photodynamic therapy to placebo in recipients with diagnosed keratoses reported a complete response rate of 60% compared with 24% in the control group .
We are uncertain of the effects of photodynamic therapy on incidence of precancerous lesions due to very low quality of evidence.
Systemic interventions :
mTORis therapy reduced the incidence of NMSC compared with CNIs maintenance therapy ; However, evidence was limited due to short follow-up periods, variability in dosing of mTORis and significant rates of loss to follow-up, and therefore we are uncertain of the effects of mTORis on skin cancer incidence due to very low quality of evidence.
Limitations of the study:
small number of studies included in the meta-analysis, we were unable to perform any detailed subgroup analyses to explore heterogeneity or assess for publication bias.
Finally, few trials included patient important outcomes associated with skin cancer and none included melanoma or mortality.
Conclusions:
Due to the heterogeneity of the studies, the high risk of bias, the potential for reporting bias and imprecision in the point estimates of individual studies, there is a high degree of uncertainty in the estimate of the effect of skin cancer prevention interventions.
There were also large discontinuation rates owing to adverse events in trials of mTORi
Level of evidence 1.
Bias produce systematically prejudiced results while errors produce Inaccurate results.
Please summarise this article Aims Melanoma and non melanoma skin cancers are the most common malignancy post solid organ transplants. This is a systemic review to evaluate the efficacy of preventive measures for skin cancers in patients having solid organ transplants. Methodology In this systemic review search was done in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
Total RCTs- 22
no of patients- 2295
The following interventions were assessed.
Behavioural interventions included, less sun exposure, use of sunscreen, protective clothing, use of shade and self examinations.
Pharmaceutical measures included, use of nicotinamide, retinoids , immune modifiers and photodynamic therapy
Change of immune suppression to mTORi.
Results
Due to low quality of evidence it was possible to conclude that behavioural measures decreased the incidence of skin cancers. Due to poor quality of evidence , it was also not possible to draw a conclusion on the relationship of mTORi on non melanotic skin cancers.
Limitations
Variability in reporting and analytic methods
No subgroup analysis
No trial included melnoma and mortality Conclusions
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
What is the level of evidence provided by this article? Systemic review Level of evidence 1 What is the difference between bias and errors? Errors produce inaccurate results Bias can produce prejudiced results Bias can cause error while error can happen without bias
This is a systematic review of 20 randomized controlled trials that assessed the impact of behavioral or pharmaceutical interventions on prevention of cutaneous malignancy in recipients of solid organ transplant.
Cutaneous malignancy is the most common cancer in solid organ transplant recipients, its incidence is more than 50%.
Cutaneous malignancy includes Melanoma and non-melanoma skin cancer (NMSC).
Incidence of SCC is higher than BCC in solid organ transplant recipients where the incidence is 65-250 times higher than age matched general population. Malignant Melanomas carry the highest incidence of mortality among skin cancers.
Aim:
Assess the effectiveness of preventive interventions, including behavioral and pharmaceutical, against cutaneous cancer in solid organs recipients.
Methods:
2295 solid organ transplant recipients were included from 20 randomized controlled trials. With median follow up around 10 months.
Data were collected and analyzed regarding the following interventions:
1- Behavioral changes that include monthly cutaneous self-examination, 6-12 monthly cutaneous examination by dermatologist, avoidance of mid-day sun exposure, sun-screen use, protective clothes use and education about sun protection.
2- Medication changes that include topical, and systemic agents.
3- Use of m-TOR inhibitors instead of CNIs.
Exclusion criteria:
1-Trials without a primary endpoint.
2-Studies with cutaneous cancer treatment.
Results and outcomes:
1- These behavioral interventions reduced the incidence of Non-melanoma skin cancer. However, the analyzed evidence was of low quality to be applied in clinical practice.
2- There was a lot of bias.
3- Long term compliance on behavioral interventions is unpredicted.
4- Nicotinamide is beneficial to reduce cutaneous cancer by 20%.
5- m-TOR inhibitors may lower cutaneous cancer incidence compared to CNIs. however, their rate of stoppage was high because of side effects making the evidence weak.
Limitations:
1- This systematic review is full of heterogeneity especially variable non-specific behavioral interventions and high Bias of the analyzed studies.
2- Most of pharmaceutical interventions and behavioral interventions were in Europe and USA respectively. 4 of them were by the same author.
3- 10 studies included less than 50 patients.
4- m-TOR inhibitors were discontinued because of side effects in 2/2 studies.
5- 48% of studies have follow up less than 12 months.
6- Inability to analyze data for heterogeneity or publication bias.
Strengths:
Extensive online review of many papers before selecting these 20 papers.
Inclusion of variable interventions, evaluation of precancerous lesion response and measuring the incidence of cutaneous cancer.
Conclusion:
Behavioral and pharmaceutical interventions may reduce cutaneous cancer incidence in solid organ transplant recipients. However, the incidence is weak.
Future randomized controlled studies are required to assess properly how effective these interventions in preventing skin cancer. These studies should be long term, with homogenous, validated and large samples data to help create true guidelines for clinical practice.
2. What is the level of evidence provided by this article?
Level I evidence
3. What is the difference between bias and errors?
Error leads to inaccurate results and outcomes. Bias leads to prejudiced results.
Errors are classified into systematic or random. Bias equals systematic error. Random Error is related to absent precision in the study conduction.
Error involves a single measurement. Bias is the average errors of repeated measurements.
Error can occur without Bias. Bias can cause an error. Bias expects an error to occur.
Bias can occur at any phase of the research: study design, data collection, data analysis and even publication.
Errors and Bias can be reduced by large sample size and selection measures.
Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials
===================================================================
1- Please summarise this article
Introudction
Skin cancer is the most commonly diagnosed malignancy among organ transplant recipients, affecting more than 50% of post-transplantation patients.
The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years.
There is a high incidence of skin cancer in the US, with an estimated prevalence of up to 65 to 250 times higher than the age and gender-matched population.
Once cancer develops, management options are limited as immuno- therapy may be unsuitable as it may lead to rejection.
The risk of death from skin cancer in transplant patients is three to nine times higher than the general population, with 5-year overall survival of <30% for those with invasive and metastatic skin cancer, such as SCC and melanoma, according to the World Health Organization (WHO).
Drugs have been used to reduce and delay the development of skin cancer in people who have had solid organ transplants.
Sun exposure behaviours remain the most significant. modifiable risk factor in the prevention of skin cancers in the general population, but there has been an increase in skin cancers in transplant recipients.
The aim of this study is to determine whether interventions can promote behavioural change and skin cancer prevention in transplant recipients.
In total, 22 reports of 20 RCTs, including 2295 people, were found while looking for RCTs that included behavioral therapies, pharmacological interventions, and studies that reported outcomes linked to skin cancer.
The median follow-up period for these participants was 10 months.
================================================================== Effect of behavioural interventions on sun protection outcomes
1-Sun protection behaviour, defined as hours spent outdoors per week, use of sunscreen, wearing protec- tive clothing and seeking shade, was assessed in three trials.
Educational workbooks, 30 educational work- books and text messages 31 and a mobile app program 32 were compared with standard care.
Patients who received behavioural interventions for sun exposure reported improved sun protection behaviour scores 30–32 (3 studies, 414 participants, SMD 0.89, 95% CI 0.84 to 2.62, I 2 98).
One trial assessed a mobile app programme and reported a reduction in daily hours spent outdoors among the intervention group (170 participants, MD 6.12, 95% CI 5.13 to 7.13).
2- Sun protection knowledge
The effectiveness of educational workbooks, mobile app programmes and videos on sun protection was assessed in six studies.
There was an improvement in knowledge scores (4 studies, 489 participants, SMD 0.50, 95% CI 0.12 to 0.87, I2 76%) in the intervention group compared with standard care.
3- Sun protection attitude 4-Skin complications and biologic measures
Pharmacological therapies’ impact on preventing skin cancer
Only in studies of drug treatments were precancerous lesions’ incidence and responses assessed (table 4).
The switch to mTORis (n = 1), photodynamic treatment (n = 2), 36, 37, and immunological response were among them.
Skin cancer is a major cause of morbidity and mortality in solid organ transplant recipients, but trials of interventions to prevent skin cancer are few in number (20 trials) and of short duration.
Our review reviewed 22 reports of 20 trials involving 2295 transplant recipients, who were predominately kidney transplant patients.
Results showed plausible
improvements to sun-protection behaviours, precancerous lesion responses and cancer incidence but there was considerable variability across intervention types and outcomes.
Evidence for skin cancer prevention in solid organ transplant recipients is of very low quality and is insuffi- cient to guide decision-making and clinical practice.
None of the studies included skin cancer as an outcome, and behavioural interventions appeared to improve sun protection attitude, knowledge and behaviour.
MTORis treatment has shown modest benefits in reducing inci- dence (for NMSC) among solid organ transplant recipients who were converted to mTORis compared with those who were maintained on CNI maintenance.
Computer programs may increase sun protective behaviours and ‘appearance-focused’ interventions may decrease tanning and UV exposure in adolescents and young women.
Reviews conducted in other popu- lations at high-risk including outdoor workers, have found similar improvements in sun protective behaviour.
The results of this review are based on a comprehensive search for studies aimed at the prevention of skin cancer in solid organ transplant recipients.
There were large discon- tinuation rates owing to adverse events in trials of mTORis, but we were unable to perform a detailed subgroup analyses to explore for publication and reporting bias.
Nicotinamide may also offer the potential to reduce skin cancer incidence by 20% and is relatively safe with minimal side effects.
However, overall mortality is higher and discontinuation following adverse events is more common in patients who are treated with mTORi therapy.
The protective effect of nicotinamide on skin cancer incidence in kidney recipients is currently being explored in a phase III RCT.
Previous studies have suggested that trans- plant recipients do not practice sun protective behaviours and are therefore less likely to use sunscreen regularly, and may be at increased risk of developing skin cancer.
The quality of evidence on the effectiveness of drugs to prevent skin cancer in solid organ transplant recipients is very low.
Transplant recipients are likely to benefit from early implementation of education, particularly before transplantation.
Interventions should be integrated into routine appointments and tailored to meet the indi- vidual needs of patients.
This would be best achieved through a shared decision-making approach to iden- tify patient’s preferences and priorities.
1- Due to research variability, the effectiveness of skin cancer prevention measures is under dispute.
2-High potential for bias, potential for reporting bias, and imprecision in point estimations.
3-Most drug intervention trials took place in Europe, but all behavioral intervention studies—four of them by the same authors—were conducted there.
4-High mTOR negative effects include trial abandonment rates.
5-We were unable to conduct subgroup analyses to look at heterogeneity or publication bias since there weren’t enough papers included in the meta-analysis.
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, but they have limited clinical value, according to the World Health Organization (WHO).
What is the level of evidence provided by this article?
level 1 systamatic review
==================================================================== What is the difference between bias and errors?
Bias produces systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates and RMSE.
Introduction:
After solid organ transplantation, the chance of developing skin cancer greatly increases, and approximately 50% of the recipients develop it.
Objectives:
Goal of this systemic review is to evaluate the effectiveness of several preventive strategies for melanoma and non-melanoma skin cancer prevention in solid organ transplantation that have been investigated in various randomized controlled trials.
Methods:
Twenty randomized controlled trials (n = 2295 participants) were included. Types of different interventions analyzed in this systematic review:
a) Behavioral: by educating sun protection
b) Pharmaceutical: topical/local/systemic agents
c) Switching to mTOR inhibitor
Results:
Interventions may improve sun protection behavior and reduce the incidence of non-melanoma skin cancer, however this is insufficient to be implemented in clinical practice due to low quality of evidence analyzed in this research.
Conclusion:
The incidence of non-melanoma skin cancer may be decreased through behavioral and pharmaceutical preventive measures.
Level of evidence I, as this is a systematic review.
Bias results systemically prejudiced results; it means shifted from a true value. While errors are responsible for inaccurate results: it means wrong.
-The skin malignancy is most common malignancy occurs after solid organ transplantation, More than 50% of transplant recipients have at least one episode of skin cancer after transplantation, and the risk increase with increasing years of transplantation. -The SCC occur more commonly than BCC post organ tx. (although in general population BCC is more common) -Both SCC and melanoma have poor prognosis with the highest mortality observed with malignant melanoma
Aim : The purpose of this systematic review study is to assess the effectiveness of behavioural and pharmaceutical interventions for prevention of skin cancers that have been studied in various randomized controlled trials
Methods:
A systematic review including 2295 organ transplant recipients (mainly renal), collected from 20 randomized controlled trials Types of different interventions analyszed in this systematic review: . Behavioural: by educating sun protection behaviour like;=> Outdoor hours spent per week, Sunscreen use, Protective clothing, Use of shades, Skin self-examination & Concern about developing skin cancer through educating workbooks/mobile apps/videos/text messages/consultation
-From the low quality of evidence in the 20 studies reviewed, strong evidence resulted in the implementation of behaviorual and pharmaceutical intervention can improve sun protection, and subsequently reduce the incidence of NMSC, but with a lot of bias
-Behavioural intervention although appear easy but long term adherence is unpredicted & it is hard to say if behavioural treatments might help people learn how to protect themselves from the sun
-mTOR may reduce the incidence of skin cancer but the rate of discontinuation was high due to side effects, •but the evidence is week
-Nicotinamide is a safe drug that offer a benefits to reduce the incidence of skin cancer by 20% and is being assessed
-finally, interventions may enhance sun protection behaviour and decrease the incidence of non-melanoma skin cancer (NMSC), but this is not enough to be implemented in decision making or clinical practice.
Limitations:
-The impact of skin cancer preventive strategies is questionable due to studyheterogeneity, Heterogeneity & reporting High risk bias in the studies analyzed
-Most pharmaceutical intervention trials were in Europe, whereas all behavioural intervention studies were in the US, four by the same authors.
-Small patients in individual studies(10 studies comprising less than 50 patients)
-Discontinuation rates 2/2 SE of mTOR
-Short term follow( 48% studies have less than 12 months follow-up)
-Due to the insufficient number of papers in the meta-analysis, we were unable to undertake subgroup analyses to investigate heterogeneity or publication bias.
Conclusion:
– Preventative measures as behavioural & pharmaceutical interventions may improve sun protection and reduce the incidence off skin cancer but the evidence is week
–Large, well designed, properly powered, long term randomized studies using clinical and patient important outcome measure which is reliable, homogenous and validated are required to find importance of different interventions in preventing skin cancer in solid organ transplantation and to finally guide decision making in clinical practice.
-We hope in future quality RCT studies, With long-term follow-up & use clinical and patient outcome measures are required.
What is the level of evidence provided by this article?
-Because a systematic review (RCT) =level of evidence is 1A.
•What is the difference between bias and errors?
-Bias means expectation that an error may occur (is the average of errors of repeated measurements)
-Error means somtehing wrong happen=> inaccurate outcomes(a single measurement)
•(Finally =>Bias can cause an error, while an error can occur with no bias)
Behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials.
The aim of this systematic review is to determine the effectiveness of
interventions that promote behavioral change and skin cancer prevention in solid organ transplant recipients. Methods.
Searching for RCT which include Behavioural interventions,
pharmaceutical interventions and studies that reported skin cancer-related outcomes, total 22 reports of 20 RCTs, including 2295 participants with the median follow-up duration was 10 months. Results:
Effect of behavioural interventions on sun protection outcomes.
Patients who received behavioural interventions ((3 studies, 414 participants) reported improved sun protection but it is uncertain as the quality of evidence is very low.
Effect of pharmaceutical interventions on skin cancer prevention.
Determine the incidence of NMSCs in nine pharmaceutical studies , shown none included melanoma as an outcome and mTOR is therapy reduced the incidence of NMSC compared with CNIs maintenance therapy shown in (5 trials,1082 participants) but with low quality evidence as there is no long follow-up periods, variability in dosing of mTORis and significant rates of loss to follow-up.
Weakness points:
-Variability and non-specific behavioural interventions .
-Small studies with small number of participants .
-Most of the studies not included incidence of skin cancer as an outcome.
-Short follow up duration and large discontinuation rates. Conclusion:
Preventative measures such as behavioural and pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients.
But still high quality studies, have long-term follow-up and use clinical and patient outcome measures are required. level of evidence: Level 1(systematic review). What is the difference between bias and errors? A bias is the “obliquity or twisting of a thing to one side, or in the cut, or in the situation which might be cognitive, statistical, contextual, law enforcement bias, media bias, conflict of interest and even prejudice. Error can lead to inaccurate outcomes ,identified through calculations as false positive rates, false negative rates may be (randomised errors and systematic errors).
The most common malignancy encountered after solid organ transplantation is skin malignancy. More than half of transplant recipients have at least one episode of skin cancer after transplantation, and the risk increase with increasing years of transplantation.
In organ transplantation SCC occur more commonly than BCC (although in general population BCC is more common)
SCC and melanoma have poor prognosis with the highest mortality observed with malignant melanoma
The current study is a systematic review including 2295 organ transplant recipients (mainly renal) collected from 20 trials. The study is assessing the effectiveness of behavioural and pharmaceutical interventions for the prevention of skin cancers.
These interventions to prevent skin cancer includes :
Self-skin examination monthly and total skin examination by dermatologist /6-12 months
Avoiding sun exposure at mid-day
Use of sunscreen
Use of protective clothing
Modification of immunosuppression and the use of sirolimus instade of CNI
Use of chemoprophylaxis in the form of oral retinoid, nicotinamide and photodynamic therapy for secondary prophylaxis in recurrent cases of skin cancer
Results
No strong evidence (there is a lot of bias) that the implementation of behavioral and pharmaceutical intervention can improve sun protection, and subsequently reduce the incidence of NMSC
Behavioral intervention although appear easy but long term adherence is difficult
Sirolimuus may reduce the incidence of skin cancer but the rate of discontinuation was high due to side effects.
Nicotinamide is a safe drug that offer a benefits to reduce the incidence of skin cancer by 20% and is being assessed
Conclusion
Behavioral and pharmaceutical interventions may improve sun protection and reduce the incidence off skin cancer but the evidence is week
What is the level of evidence provided by this article?
This is a systematic review, level of evidence I
What is the difference between bias and errors?
Error and bias are related to each other but have different definitions
Bias means expectation that an error may occur while error means soothing wrong happen
Error involve a single measurement, while bias is the average of errors of repeated measurements
So bias can cause an error, while an error can occur with no bias
Introduction:
Both melanoma and non melanoma skin cancer(NMSC) are the commonest cancer after solid organ transplantation ( affect~ 50% of transplant recipients). NMSC risk increasing with time ( basal cell carcinoma more prevalent than squamous cell carcinoma). Different preventive methods used to reduce risk of post transplant skin cancer as sun screen, protective clothing, avoidance of sun exposure and changes in immunosuppression.
Aim of the study:
Assessment of interventional measures efficacy that promote behavioral changes and prevention of skin cancer in transplant recipients.
Method:
20 trails included in this review (2295 transplant recipients).
Any trail didn’t mention a primary endpoint as outcome excluded from this review, also studies with intervention of skin cancer treatment were excluded.
Behavioral changes mean any strategy used to optimized sun protection behavior including passive, active methods in addition to provision sun protective equipment.
Pharmacological intervention include change to mTOR-I, photodynamic therapy, immune response modifier, nicotanimide and oral retinoids.
The study outcome measure:
1. incidence of precancerous and cancerous lesion
2. Sun protective behavior e.g. sunscreen, protective clothing.
3.Knowledge and attitude.
4.Skin self examination.
5.Sun exposure.
6.Biological measures.
Discussion:
The evidence of interventional measures for skin cancer prevention in soils organ transplant recipients has very low quality and deficient to guide decision making in clinical practice.
Using mTOR-I or early change to mTOR show a benefit in reducing skin cancer incidence.
discontinuation of mTOR-I was high due to side effects.
nicotanimide can reduce skin cancer incidence by 20% with high safety and low side effects.
Limitations of this study:
Low number of trials included .
Short duration of follow-up (<12 months).
Half of studies not include the incidence of skin cancer as outcome.
high risk of bias due to heterogeneity of included studies.
Strength of the study:
Extensive review conducted using methods outline by Cochrane Collaboration.
inclusion of wide range of intervention measures & evaluate precancerous lesion response in addition to measurement of skin cancer incidence.
Level of evidence is 1
Bias: is a methodological errors that can lead to misrepresentation of study outcome.
Error: refer to difference between the prediction and ground truth value.
Introduction; the risk of skin cancer is significantly increased after solid organ transplantation and nearly half of the patients are affected by this disease.
Objectives; The objective of the study was to investigate how effective the interventions for behavioral change for sun protection or skin cancer prevention after solid organ transplantation
Methodology; this a systematic review of twenty studies(n=2295) from MEDLINE,Embase, CENTRAL and CINAHL. All RCTs under this topic were included and the risk of bias and evidence certainty were tested by Cochrane and the grading of recommendation assessment development and evaluation framework.
Results; there was no strong evidence that behavioral interventions enhance sun protection behavior. The effect of mTORi on non-melanoma skin cancer was not clear.
Conclusion; More evidence is needed to know the real effect of behavioral and therapeutic preventive interventions on the sun protective behavior
This is a systematic review and therefore the evidence is level I
In simple terms bias will give you systemic prejudiced results (systematic error) while errors (random errors)are responsible for inaccurate results
This study is a systematic review, classified as level 1.
This study selected 20 different studies with 2295 patients, but with high heterogeneity indices (I2) impacting the real quality of the study, whether due to subjective measurements or the difficulty of clinical and laboratory markers.
Skin cancers (regardless of melanoma or not) are quite common during the post-transplant period. Compared with the general population, the risk of transplanted patients is extremely high to develop this neoplasm and is related both to behavior (sun exposure and care) and immunosuppression (use of calcineurin inhibitors and absence of schemes with mTor inhibitors).
Prevention of sun exposure, self-examination, half-yearly/annual physical examinations by the assistant team, sun protection (specific clothing, sunscreen, exposure limit at times with a higher concentration of UVA/UVB rays), reducing the use of calcineurin inhibitors and increasing the use of mTor inhibitors were considered as measures to be included in this systematic review. Biological measurements for evaluation of skin lesions or sunburns were also included. The studies needed to be randomized, interventions in the prevention of skin cancer, active and passive protocols of sun protection, present equipment to protect against sunlight, pharmaceutical interventions and primary objectives aimed at prevention.
Of the 20 studies, 16 were specific for renal Tx and 4 were multiple. Eight studies were single center, 11 were multicenter and one did not make the model clear. Of the interventional studies, 5 were behavioral, 6 were switched to mTor, 4 were photodynamic therapy, 3 were oral retinoids, 1 was nicotinamide, and 1 was using immunomodulators.
The studies showed a lot of heterogeneity, with sun protection behavior having I2 98%, knowledge with sun protection with I2 76% for assessing the impact of knowledge about sun protection, probably due to discrepant questionnaires. In the attitudes taken for sun protection, the variability of heterogeneity ranged from 96 to 99%, even using clinical criteria for injury and sunburn.
Limited number of studies, different intervention models (applications, cell phone programs, written letters), lack of prolonged follow-up, patient discontinuation, different protocols in doses and mTor standards were problems that compromised the quality of the study, increasing its heterogeneity and precluding the ability to obtain adequate statistical values. The ideal would be I2 values below 25% and avoid values above 75%, unfortunately the latter occurred.
There is no doubt about the positive impact of using sun protection measures, replacing calcineurin inhibitors with mTor inhibitors and other pharmacological measures, but more elaborate studies are needed to define the statistical impact of each of these measures.
Aim:
The purpose of this systematic review is to determine the efficacy of various preventive interventions in skin cancer prevention (melanoma and non-melanoma) in solid organ transplantation that have been studied in various randomised controlled trials.
Methods:
Twenty randomised controlled trials (n = 2295 participants) were included from inception till November 2019.
Types of different interventions analysed in this systematic review:
1. Behavioural: by educating sun protection behaviour like
i. outdoor hours spent per week,
ii. sunscreen use,
iii. protective clothing,
iv. use of shades,
v. skin self-examination,
vi. concern about developing skin cancer
through educating workbooks/mobile apps/videos/text messages/consultation
2. Pharmaceutical(topical/local/systemic):
i. photodynamic therapy,
ii. immune response modifiers,
iii. oral retinoids
iv. nicotinamide
3. Switching to mTOR inhibitor
Results:
Due to the low quality of evidence in the studies reviewed, interventions may enhance sun protection behaviour and decrease the incidence of non-melanoma skin cancer (NMSC), but this is not enough to be implemented in decision making or clinical practice.
Limitations:
· Heterogenicity and reporting bias in the studies analysed
· Non-precise point estimates of skin prevention strategies
· Small patients in individual studies(10 studies comprising less than 50 patients)
· Short term follow( 48% studies have less than 12 months follow-up)
· Discontinuation of strategy due to adverse effects(especially in case of mTOR inhibitors)
· Few trials included skin cancer and none included melanoma as outcome measure
Conclusion:
Large, well designed, properly powered, long term randomised studies using clinical and patient important outcome measure which is reliable, homogenous and validated are required to find importance of different interventions in preventing skin cancer in solid organ transplantation and to finally guide decision making in clinical practice.
What is the level of evidence provided by this article?
It is a systematic review of randomised controlled trials and hence level of evidence is 1A.
What is the difference between bias and errors?
There are two types of errors(randomised errors and systematic errors/bias) in clinical research as elaborately mentioned in table as attachment(1)
Reference:
1. Gonzalez de la Cuesta DM. Errors and biases in clinical research. Enferm Intensiva (Engl Ed). 2021;32(4):220-3.
THE INTRODUCTION;
—————————————————————
Skin cancers (both non-melanoma and melanoma) are major causes of morbidity and mortality in solid organ transplant recipients. Despite this, trials of interventions aimed at preventing skin cancer in solid organ transplant recipients are few in number (20 trials), small with half comprising of 50 patients or less, of short duration (48% have <12 months follow-up) and 52% do not include incidence of skin cancer as an outcome.
THE STUDY DESIGN :
——————————————
Systematic review.
THE AIM O THE STUDY:
————————————————————–
The aim of this study is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
ETHICAL APPROVAL;
———————————————————
The study was exempt from approval from an ethics’ board.
THE OUTCOME MEASURES :
——————————————————————————-
1-Incidence of precancerous and cancerous lesions.
2- Sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance) .
2-Knowledge and attitude.
3- Skin self- examination .
4-Sun exposure (including skin irritation, sunburn).
5- Biologic measures (including measurement of melanin index and sun damage assessment).
THE POPULATION :
—————————————————–
2295 transplant recipients, who were predominately kidney transplant recipients.
THE INCLUSION CRITERIA :
—————————————————
All randomised controlled trials that evaluated the effect of behavioural or
pharmaceutical interventions on behavioural change or skin cancer prevention in solid organ transplant recipients.
THE EXCLUSION CRITERIA ;
———————————————————————-
1-Studies that did not report these outcomes as primary endpoints were excluded.
2- Studies of interventions for the treatment of skin cancer.
THE METHOD :
—————————————————————–
Risks of bias and evidence certainty were assessed using Cochrane and the
Grading of Recommendations Assessment Development and Evaluation framework.
THE RESULT ;
————————————————-
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
THE STRENGTH OF THE STUDIES :
——————————————————————
1-A comprehensive review conducted using methods outlined by Cochrane Collaboration including Grading of Recommendations Assessment Development and Evaluation to assess risk of bias and evidence certainty.
2-Inclusion of a broad range of interventions, including behavioural to improve sun protection behaviour and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence.
THE LIMITATION O THE STUDIES :
——————————————————–
1-Difficulty obtaining an overall summary estimate for many outcomes due to the variability in the analytical methods and reporting in individual studies.
2-Unable to perform detailed subgroup analyses or assess for publication bias due to small number of studies.
3-Few trials included the important outcomes of skin cancer and none included melanoma or mortality.
CONCLUSION :
————————————————–
1-The studies result suggest that further strategies for skin cancer prevention in transplant recipients require a multifaceted and individualised approach.
2-Transplant recipients are likely to benefit from early implementation of education, particularly before transplantation occurs and recipients may be preoccupied with other health needs related to transplantation.
3-Interventions should be integrated into routine appointments and tailored to meet the individual needs of patients.
4-Additional large-scale and high-quality RCTs are needed to demonstrate the effectiveness of interventions used to prevent skin cancer in transplant recipients in terms of patient important outcomes, in particular morbidity and mortality associated with skin cancer.
5-Determining patient’s preferences for prevention and management of skin cancer is also warranted to ensure interventions and outcomes for trials are relevant to patient needs and priorities and better support patient-centred treatment decisions.
6-Evidence of the efficacy of sun protective behaviour interventions need to be strengthened, with use of measures that are homogeneous, reliable and
validated.
7-Preventative measures including behavioural, switch to mTORis and other pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients. However, the overall quality of evidence is very low and insufficient to guide decision-making and clinical practice.
What is the level of evidence provided by this article?
LEVEL I
What is the difference between bias and errors?
Error is a specific instance of inaccurately sampling, such that the estimate does not represent the population, while a bias is a consistent error that affects multiple samples.
1-Summary Introduction
Non melanoma (NMSC) and melanoma skin cancers are the most common cancers occurring post solid organ transplantation, NMSC incidence increase with time.
Squamous cell carcinoma rate is higher than Basal cell carcinoma in solid organ transplant recipients compared to matched controls.
Although transplant recipients’ survival improved, skin cancer and cancer related mortality increased as well.
Sun exposure is a significant modifiable risk factor for skin cancer in general population.
Current recommendations for skin cancer preventive measures are for general population which can be unsuitable for solid organ transplant recipients.
Preventive measures include sun screen application, wearing protective clothes and avoiding direct sun exposure in peak UV light hours and shifting maintenance immunosuppression to m TOR for high risk cases.
Secondary skin cancer preventive measures include using retinoid acitretin.
The aim is to evaluate the effectiveness of behavioural change and pharmaceuticals for skin cancer prevention in solid organ transplantation. Methods
A systematic review of randomised controlled trials of interventions for skin cancer prevention in solid organ transplant cases ,involving behavioural actions either active or passive as well as pharmaceuticals.
The outcome measures included precancerous and cancerous lesions, sun protection
behaviour. Results
The study involved 22 reports including 20 RCT , all studies included kidney transplantation while others involved ,heart ,lung and liver transplantation.
Most studies had high or unclear bias risks also the quality of evidence was very low for all outcomes.
The interventions included were behavioural attitude, shifting to m TOR, pharmaceutical intervention. Behavioural interventions effect on sun protection outcomes Sun protection behaviour
Cases who had behavioural interventions had better patient sun prevention scores but this is not valid enough due to low evidence quality. Sun protection knowledge
It’s effectiveness either through workbooks , mobile apps ,messages ,videos was evaluated in 6 studies revealing favourable outcomes. Sun protection attitude
Educational workbook, text messages or a mobile app programme improved sun protection attitude in 3 studies but unconfirmed due to low quality of evidence. Skin complications and biologic measures
2 studies showed the effectiveness of behavioural intervention in the form of educational workbook, text messages or a mobile app programme compared to standard care regarding skin irritation, sun exposure , severity of sun damage and melanin index. Pharmaceutical interventions effects on skin cancer prevention
Involving switch to mTOR ,photodynamic therapy and immune response modifiers.
9 studies evaluated NMSC incidence and none included melanoma. Topical/local interventions
Immune response modifier, 5% imiquimod cream decreased skin dysplasia, atypia and viral warts in comparison to placebo in a study.
Photodynamic therapy reduced NMSC risk in a Danish study.
60% response rate of photodynamic therapy in recipients with diagnosed keratoses compared with 24% in the control group in 2 trials. Systemic interventions
5 trials revealed that mTOR decreased the incidence of NMSC compared to CNIs however quality of evidence was very low.
Oral retinoid and acitretin, compared to placebo lowered SCC and BCC risk in a study. Discussion
Behavioural intervention studies did not include precancerous lesions or skin cancer incidence as outcomes.
The evidence for interventions for skin cancer prevention in solid organ transplant recipients is of very low quality.
Behavioural interventions improved sun protection attitude, knowledge and behaviour, but these studies were inconsistent did not involve skin cancer as an outcome.
The best method for sun protection education was not detected due to small number of studies.
The shifting to m TORI compared to CNI maintenance was accompanied with less NMSC incidence but this was modest due to heterogenicity of the studies.
Pharmaceutical therapy decreased precancerous lesions but this was unconfirmed due to few trials, lack of follow up .
Previous systematic reviews stated that computer programmes can improve sun protective behaviours, and reduce UV light exposure.
Oral retinoids for the prevention of skin cancer among high-risk transplant recipients results were inconclusive due to lack of enough studies.
The effect of skin cancer prevention estimation is unconfirmed due to heterogeneity of the studies, the high risk of bias and discontinuation as with m TOR .
No study included melanoma outcome nor mortality.
Although m TOR conversion is associated with lower cancer risk on the other hand it is associated with higher mortality rates , more discontinuation due to adverse events.
Nicotinamide reduced cancer risk by 20%.
There is no evidence that behavioural therapy can decrease morbidity or mortality.
Skin cancer prevention in transplant recipients need a multifaceted and individualised approach.
Large RCTs are needed to evaluate the effectiveness of interventions used to prevent skin cancer in transplant recipients.
Preventative measures as behavioural, switch to mTOR and pharmaceuticals can improve
skin cancer outcomes in solid organ transplant recipients.
2- level of evidence is 1
3-Bias is non random , can occur systematically, can lead to prejudiced results ,identified manually or through available software programs
-Error is random, can lead to inaccurate outcomes ,identified through calculations as false positive rates, false negative rates
Patients who have had solid organ transplants are at a greater risk of developing skin cancer, which affects more than half of all recipients.
The aim of the study is:
In solid organ transplant patients, the purpose of this research is to investigate the efficacy of treatments that promote behavioral change and skin cancer prevention.
Design:
systematic review. There were a total of twenty trials with a total of 2295 participants.
Conditions for eligibility We looked at randomized, controlled studies that looked at how well drugs or behavior treatments prevented skin cancer in people who had solid organ transplants. These interventions might be either behavioral or pharmacological.
Results :
There were a total of twenty trials, with a total of 2295 participants. Due to the low quality of the evidence, it is hard to say if behavioral treatments might help people learn how to protect themselves from the sun.
Due to the poor quality of the data, we are unable to draw any conclusions on the effects of the mammalian target of rapamycin inhibitors on the incidence of nonmelanocytic skin cancer.
Limitations:
-The impact of skin cancer preventive strategies is questionable due to study heterogeneity.
-high risk of bias, the possibility for reporting bias, and imprecision in point estimates.
-Most pharmaceutical intervention trials were in Europe, whereas all behavioral intervention studies were in the US, four by the same authors.
-Adverse effects caused by high mTOR is trial discontinuation rates.
-Due to the insufficient number of papers in the meta-analysis, we were unable to undertake subgroup analyses to investigate heterogeneity or publication bias.
Conclusions :
Behavioral and pharmaceutical preventive interventions may improve sun protective behavior and knowledge, and reduce the incidence of non-melanocytic skin cancer; however, the overall quality of the evidence is very low, and it is insufficient to guide decision-making and clinical practice. Even so, there is a chance that these interventions will help people learn and act more sun-safely.
What is the level of evidence provided by this article?
Level 1, systematic review
What is the difference between bias and errors?
bias refers to deviations that are not due to chance alone. tendency to deviate from the norm. and can be considered systematic errors. Error: an unintentional deviation from truth or accuracy that fails to achieve what should be done.
Skin cancer either melanoma and non-melanoma skin cancer NMSC are frequently seen in more than 50% of transplant recipient and its incidence is cumulative as it increases by the time post-transplant.
This has a risk of graft rejection, as its diagnosis of course will affect course of immunosuppressive drugs because it should be handled and reduced so it carries the risk of graft rejection and failure.
The mortality is higher from skin cancer in transplant recipient than general population.
Direct sun exposure is important factor that increase the risk of skin cancer in general population and especially post solid organ transplant, this factor is behavioral factor which means that counselling of the patient regarding sun exposure and protection from ultraviolet rays A and B is very important.
Sun protection behavior, defined as hours spent outdoors per week, use of sunscreen, wearing protective clothing and seeking shade. Educational workbooks, educational workbooks and text messages and a mobile app program were compared with standard care.
Sun protection knowledge The effectiveness of educational workbooks, text messages, mobile app programmes and videos on sun protection knowledge.
Sun protection attitude sun protective attitude after receiving an educational workbook, text messages or a mobile app programme over a period.
Sun protection attitude changed to the better one after inclusion of sun protection knowledge through the patient’s behavior.
Also, pharmaceutical interventions affect the precancerous lesions like conversion to sirolimus, photodynamic treatment and immune response modifiers can decrease incidence of skin cancer.
The adherence of the patients to behavioral changes against sun exposure is not well practiced, also conversion to sirolimus is associated with adverse effects and also should be done as early as possible before appearance of any precancerous lesion.
it is level 1 evidence
error in research can be systematic or random, systematic error is called bias , and random error is introduced by a lack of precision in conducting the study
defined in terms of the null hypothesis, which is no difference between the intervention group and the control group
reduced by meticulous technique and by large sample size
Bias is defined as any tendency which prevents unprejudiced consideration of a question 6. In research, bias occurs when “systematic error [is] introduced into sampling or testing by selecting or encouraging one outcome or answer over others” 7. Bias can occur at any phase of research, including study design or data collection, as well as in the process of data analysis and publication.
Skin cancer affects more than 50% of post-transplant patients. There is a higher rate of squamous cell carcinoma to basal cell carcinoma in comparison to general population with an incidence of 65 to 250 times higher than general population.
Once skin cancer developed, management options are limited.
There is greater burden of skin cancer and cancer related mortality. The risk of death from invasive and metastatic skin cancer is three to nine times higher than general population.
Current recommendations for prevention as frequent skin self examination and annual to biannual total body skin examination ,sun protective measures ( use of sunscreens, protective clothing and limiting sun exposure during peak hours of high ultraviolet index days) and alteration of immunosuppression
May not be applicable to solid organ transplant patients.
Aim of study: Determine the effectiveness of interventions that promote behavioral changes and skin cancer prevention in solid organ transplant.
Method
Study design: systematic review
Inclusion criteria: All randomized controlled trials or quasi RCTs of interventions for skin cancer prevention in solid organ transplant patients.
Exclusion criteria: Titles and abstracts were reviewed and those who didn’t meet the Inclusion criteria were discarded.
Data extraction and synthesis: Risks of bias and evidence of certainty were assessed using Cochrane and the Grading of recommendations Assessment Development and Evaluation framework.
Results : 20 trials including 2295 participants. It is uncertain whether behavioral interventions improve sun protection behavior and knowledge as the quality of evidence is very low.
It is uncertain of the effect of mTOR inhibitors on the incidence of non melanocytic skin cancer as the quality of evidence is very low.
Conclusion
Behavioral and pharmaceutical preventive interventions may improve sun protective behavior and knowledge and reduce the incidence of non melanocytic skin cancer, but the overall quality of the evidence is very low to guide decision-making and clinical practice.
What is the level of evidence
Level of evidence 1
What is the difference between errors and bias?
Bias produces systematically prejudiced results. Biases are identified manually or through available software programs.
Errors produce inaccurate results. Errors are identified through calculations and metrics such as false positive rates.
Introduction
Skin cancer is a very common post-renal transplant affecting around 50% of transplant recipients.
Squamous cell carcinoma increased by 65 to 250 folds greater than aged match general populations. This affects patient survival. Immune therapy may not be suitable as it may induce rejection, limiting treatment options for this group of patients. Preventive measures recommended for the general population have not been tested and validated in transplant recipients, such as sunscreen, protective cloths and avoidance of sun exposure during peak UV light.
Methods
This is a systematic review and meta-analysis.
Inclusion criteria
All randomized controlled trials (RCTs) or quasi-RCTs of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were included.
Outcome measures
The prespecified outcome measures were incidence of precancerous and cancerous lesions, sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance), knowledge and attitude, skin self-examination, sun exposure (including skin irritation, sunburn) and biologic measures (including measurement of melanin index and sun damage assessment).
Result:
They identified 1280 articles, 1201 were excluded after abstract and title review. After further assessment of 79 studies, 22 reports were found eligible articles for inclusion. Twenty of them were RCT (n=2295 participants) were included.
It is uncertain whether behavioural interventions improve sun protection behaviour as the quality of evidence is very low.
We are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of non melanocytic skin cancer (n=5, n=1080, relative risk 0.46, 95%CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low
Conclusion
Preventative measures including behavioural, switch to mTORis and other pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients. However with low quality level.
Level 1
An error is a term used to refer to anything that is incorrect and inaccurate. In machine learning, errors give insight into how accurate predictions are. Alternatively, errors can also refer to the difference between the predictions and the ground truth value.
Bias produces systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates and RMSE. Biases are identified manually or through available software programs.
Please summarise this article
Introduction
Skin cancer, including melanoma and nonmelanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post-transplantation recipients.Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC).Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population.Sun protective behaviours including use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days are potential measures for skin cancer prevention.Further, alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
Methods
This systematic review followed a prespecified protocol registered in PROSPERO and is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist.
Inclusion criteria –
All randomised controlled trials (RCTs) or quasi RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were included. Behavioural interventions defined as any strategy used to promote sun protective behaviour including passive (eg, pamphlets), active (eg, group workshops, counselling, dermatology clinic) and provision of sun protective equipment; and pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoid.
RESULTS-
Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour (n=3, n=414, standardised mean difference (SMD) 0.89, 95%CI −0.84 to 2.62, I2 =98%) and knowledge (n=4, n=489, SMD 0.50, 95%CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low. We are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of nonmelanocytic skin cancer (n=5, n=1080, relative risk 0.46, 95%CI 0.28).
Conclusions
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
What is the level of evidence provided by this article?
Level 1
What is the difference between bias and errors?
Bias produces systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates and RMSE. Biases are identified manually or through available software programs.
Introduction
Solid organ transplantation (SOT) is known to be the definitive treatment for almost end organ failure, yet among the most irritating disadvantage is the relation between heavy immunosuppression and increased incidence of malignancies. Up to our knowledge Skin cancer, including melanoma and non-melanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among SOT recipients more than 50%. The cumulative incidence of NMSC is elevating with time after transplantation from 5%–10% at 2 years to 40%–80% at 20 years. There is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender-matched general population.
The development of malignant conditions affects markedly the immunosuppressive regimen for such patients, being less than the proper doses needed leads to more exposure to rejection episodes. Recently registry data show progress in survival rates of transplant recipients as a result of improved transplantation techniques as well as better management of immunosuppression reduction, yet there is still a great burden of skin cancer and cancer-related mortality.
We still face the excess risk of death after invasive and metastatic skin cancer, such as SCC and melanoma are encountered by three to nine times higher than the general population, with 5-year overall survival of <30%. One known factor can be identified which is sun exposure behaviour being the most significant modifiable factor in the prevention of skin cancers in the general population. So preventative strategies are being suggested as frequent skin self-examination and annual to biannual total body skin examination. Other strategies include using proper sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days. Tailoring of maintenance immunosuppression by switching to mammalian target of rapamaycin inhibitors (mTORis) and administration of retinoid acitretin are crucial for management of skin cancers in high-risk transplant recipients.
The study aims to assess the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
Methods
It is a systematic review, including all randomised controlled trials (RCTs) till November 2019 concerned by interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients.
Outcome measures the incidence of precancerous, cancerous lesions and sun protection behaviour.
Results
There were 22 eligible articles only for the study to be included with total 20 RCTs of 2295 participants. The median number of participants was 44 (range 17–830) and the median follow-up duration was 10 months (range 1 day to 60 months). Finally a total of 15 (76%) of 21 studies supplied sufficient data for the meta-analyses.
Limitations
Main obstacles were the poor overall quality of the evidence for all outcomes, limitations in study design, heterogeneity in the intervention, outcome measures, the very small sample size of individual studies and the small number of studies for each specific outcome.
Moreover, the assessment of reporting of sun protection behaviour and sun protection knowledge was not possible as outcomes were inconsistent owing to the large diversity of interventions used.
Interventions
Three classified groups according to the intervention applied ether behavioural or shifting to mTORi or other including photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide categories.
Effect of behavioural interventions on sun protection outcomes
Sun protection behaviour
It is best described by as total hours spent outdoors per week, use of sunscreen, wearing protective clothing and seeking shade. Sun protection is assessed in three trials. Fortunately, those patients who adopted behavioural interventions reported improved sun protection behaviour scores (3 studies, 414 participants, SMD 0.89, 95% CI −0.84 to 2.62, I2 98%).
Only a single trial was concerned by self-skin examination reported improvement after 1 month (75 participants, RR 4.14, 95% CI 2.22 to 7.72).
Also one trial was minded by the reduction of total number of hours spent outdoors which was also improved (170 participants, MD −6.12, 95% CI −711 to −5.13).
Sun protection knowledge
Six trials were concerned by the improvement of the sun protection knowledge whereas the knowledge scores were raised (4 studies, 489 participants, SMD 0.50, 95% CI 0.12 to 0.87, I2 76%).
Sun protection attitude
The study expressed an overall improvement in scores of concern about developing cancer (3 studies, 348 participants, SMD 1.85, 95% CI 1.59 to 2.11, I2 96%).
Two studies included 273 participants estimated improvement in scores of understanding the personal risk of skin cancer by (SMD 0.61, 95% CI −0.60 to 1.82, I2 96%), adherence to sun protection (SMD 0.77, 95% CI −0.14 to 1.68, I2 92%) as well as the intention to change behaviour (SMD 1.70, 95% CI −1.68 to 5.07, I2 99%).
To our knowledge one study included 75 participants reported an improvement in scores of ability to recognise a potential skin cancer (MD 1.80, 95% CI 1.35 to 2.25), importance of skin self-examination (MD 1.05, 95% CI 0.61 to 1.49) and having a partner help for skin self-examination (MD 1.59, 95% CI1.10 to 2.08).
Also one single study reported better improvement in the necessity of engaging in sun protection (measured using 5-point Likert scale, 101 participants, MD 7.00, 95% CI 2.94 to 11.06).
Skin complications and biologic measures
A total of 271 renal transplant recipients were encountered in two trials concerned by the behavioural interventions. The intervention group exhibited reduction of the incidence of skin irritation by (RR 1.00, 95% CI 0.89 to 1.13, I2 95%) as well as sunburn by (RR 3.19, 95% CI 2.47 to 4.10, I2 99%).
Fortunately a significant decrease in melanin index (right forearm, SMD −0.42, 95% CI −0.66 to −0.18; cheek SMD −0.25, 95% CI −0.64 to −0.15) besides reduced severity of sun damage (SMD −0.13, 95% CI −0.40 to 0.13) on sun exposed areas.
Effect of pharmaceutical interventions on skin cancer prevention
Topical/local interventions
A trial of 14 participants assessed an immune response modifier revealed a reduction in the incidence of skin dysplasia (RR 2.14, 95% CI 0.31 to 14.65), skin atypia (RR 3.00, 95% CI 0.47 to 19.35), and viral warts (RR 7.00, 95% CI 0.46 to 106.10).
A famous Danish study consisted of 26 renal transplant recipients concerned by the use of photodynamic therapy documented a relative reduction by nearly 40% in the incidence of NMSC on the treated area (RR 0.59, 95% CI 0.34 to 21.03, p 0.06).
A significant lower incidence of SCC was reported in one trial after using an immune response modifier (14 participants, RR 0.09, 95% CI 0.0.01 to 1.70). Furthermore, Two trials studied both photodynamic therapy as well as immune response modifiers in recipients with diagnosed keratoses revealed a complete response rate of 60% compared with 24% in the control group (50 participants, RR 5.03, 95% CI 0.14 to 176.17, I2 85%).
However the effects of photodynamic therapy on the incidence of precancerous lesions couldn’t be assessed owing to the very low quality of evidence.
It is wise to mention that a trial which was not included in the meta-analysis, reported a higher cumulative incidence of actinic keratosis lesions in untreated skin (63%) compared with skin treated by photodynamic therapy (28%).
Systemic interventions
A number of 5 trials studied the role of mTORis therapy in reduction of the incidence of NMSC in comparison to CNIs maintenance therapy (5 trials, 1082 participants, RR 0.46, 95% CI 0.28 to 0.75, I2 72%). Unfortunately, there was lack of evidence because of short follow-up periods, variability in dosing of mTORis and significant rates of loss to follow-up.
A single trial considered switching from CNI to mTORi therapy reported marked improvement in skin dysplasia (32 participants, RR 24.35, 95% CI 1.55 to 381.99).
Two trials assessing the use of an oral retinoid, acitretin reported an improved lower risk of both SCCs and BCCs (46 participants, RR 0.40, 95% CI 0.19 to 0.85, p 0.02; RR 0.50, 95% CI 0.14 to 1.76)42 or development of a new skin cancer (19 participants, RR 0.22, 95% CI 0.06 to 0.90). Yet, there were no differences in the incidence of new SCCs detected. Astonishingly, one trial which was not included in the meta-analysis, revealed approximately a 50% reduction in the incidence of actinic keratosis which compared a high dose to a low dose of acitretin.
A well-known Australian trial of 22 renal transplant recipients studied nicotinamide came with the conclusion of an estimated relative rate difference of 0.35 (95% CI −0.62 to 0.74), 0.67 (95% CI −0.40 to 0.90) and 0.07 (95% CI −1.51 to 0.65) for NMSC, BCCs and SCCs respectively.
Discussion
Skin cancers are known to famous causes of morbidity and mortality in solid organ transplant recipients. Even though the trials of interventions to overcome this are still scarce in number (20 trials), small with half comprising of 50 patients or less, of short duration (48% have <12 months follow-up). Furthermore, 52% do not include incidence of skin cancer as an outcome.
This review precluded 22 reports of 20 trials involving 2295 transplant recipients mainly renal transplant recipients. Several studies were performed on a diverse range of interventions such as; behavioural to improve sun protection behaviour and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence without considering precancerous lesions or skin cancer incidence as important outcomes.
Up till now, the current evidence for interventions for skin cancer prevention in solid organ transplant recipients is of very low quality and is insufficient to guide decision-making and clinical practice. Another problem is the absence of long-term follow-up, large discontinuation rates owing to adverse events and variability in the doses of mTORis adds more uncertainty to the effectiveness of these strategy to overcome this. It is suggested that pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers) had shown marked reduction in precancerous lesions.
Previously performed reviews in other high risk populations especially outdoor workers, family history, personal history and phenotypic factors have found similar improvement in sun protective behaviours particularly the use of sunscreen, as well as a decreased incidence of keratoses.
Although behavioural change looks very simple strategy, yet long-term adherence is a bit challenging. It is suggested that maximum benefits of behavioural change should be associated with early implementation of education particularly prior to transplantation.
These interventions should best become integrated into routine appointments and tailored to meet the individual needs of patients. We also encourage performing additional large-scale and high-quality RCTs in order to demonstrate the effectiveness of interventions used to prevent skin cancer in transplant recipients in terms of patient important outcomes, especially morbidity and mortality associated with skin cancer.
The level of evidence is Level I (systematic review of randomized controlled trials).
The difference between bias and errors
Bias is an error in the study design or implementation that becomes associated with results that are in favour of one single direction against the others mostly due to nonrandom factors .whereas errors are mistakes occurring in the results because of the presence of random factors that could not be excluded.
This is a systemic review including 22 reports of 20 trials including 2295 transplanted patients, mainly kidney transplant. It evaluate the efficacy of behavioural or pharmaceutical interventions on behavioral change of skin cancer prevention.
Skin cancers including melanoma and non-melanoma skin cancer is the most frequently diagnosed malignancy complicating solid organ transplantation.
Sun exposure behaviours remain the most significant
and modifiable risk factor in the prevention of skin cancers in the general population. Pharmaceuticals have also been used to reduce and delay the development of skin cancer. Sun protective behaviours including use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days are potential
measures for skin cancer prevention. Also alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin
cancers in high-risk transplant recipients.
Results : Twenty trials were included. It is uncertain whether behavioural interventions
improve sun protection behaviour (n=3, n=414,
standardised mean difference (SMD) 0.89, 95% CI −0.84
to 2.62, I2=98%) and knowledge (n=4, n=489, SMD 0.50,
95% CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low. We are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of non-melanocytic
skin cancer (n=5, n=1080, relative risk 0.46, 95% CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low.
Conclusions : Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic
skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
This is systemic review of RCTs : level 1
Bias produces systemically prejudiced results while errors produce inaccurate results.
Introduction
Solid organ transplant recipients are at increased risk of skin cancer affecting around 50% of recipients.
melanoma and non-melanoma skin cancer (NMSC), is the most common malignancy among SOT recipients, incidence of NMSC increases with more time passing after transplantation, to reach 40%–80% at 20 years
Compared with the general population, there is a higher rate SCC to BCC, with an incidence of 65 to 250 times greater than matched general population.
In SOT recipient’s immunotherapy may be unsuitable due risk of graft rejection.
Risk of death due to metastatic skin cancer are three to nine times higher than general population, with 5-year overall survival of 30%.
avoid Sun exposure is a significant and modifiable risk factor in the prevention of skin cancers, but it is not effective alone and in case of SOT recipients, pharmaceuticals must be used reduce and delay the skin cancer.
preventive strategies on SOT recipients based on guidelines in the general population includes frequent skin self-examination, annual to biannual total body skin examination, use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days.
conversion to mTORi instead of CNI and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
Results and discussion
-This systematic review was done aiming to determine the effectiveness of interventions that promote behavioral change and skin cancer prevention in solid organ transplant recipients.
This review included reports of 20 trials on 2295 SOT recipients, mostly kidney transplant recipients. To evaluate the effect of different protective methods including :
behavioral changes to improve sun protection.
behavioral and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers).
effect of switching to mTORis
results showed:
-None of the behavioral intervention studies included precancerous lesions or skin cancer incidence as outcomes.
-Although interventions showed improvements to sun protection behaviors, precancerous lesion responses and cancer incidence, but still there was variability across intervention types, variability in outcomes assessed and outcome estimates.
-behavioral interventions improved sun protection attitude behavior, but the effect on skin cancer as an outcome was not documented in many of the studies.
-This review was unable to compare specific behavioral interventions (eg, mobile app vs written education) to detect the most effective method of delivering sun protection education.
– this review showed some benefits in the reduction of NMSC incidence among SOT recipients who were converted to mTORis compared with those on CNI maintenance.
-Pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers) showed a reduction in precancerous lesions compared with standard care or a comparator group.
– systematic review of the benefits of oral retinoids for the prevention of skin cancer on SOT recipients was inconclusive due to the small number of included trials.
Strengths and limitations of this study:
-A comprehensive review of twenty trials with Inclusion of a broad range of interventions, including either behavior only or behavior and pharmaceutical to improve sun protection to evaluate precancerous lesion response and cancer incidence.
-heterogeneity of the studies and high risk of bias.
– All studies of behavioral interventions were undertaken in USA, with four by the same authors, while most pharmacological intervention studies were conducted in Europe.
-large discontinuation rates due to adverse events in trials of mTORis.
-small number of studies included in the meta-analysis, we were unable to perform any detailed subgroup analyses to explore heterogeneity or assess for publication bias.
-Unable to perform detailed subgroup analyses or assess for publication bias due to small number of studies.
– Few trials included the important outcomes of skin cancer and none included melanoma or mortality.
Level of Evidence: This is a systematic review level of evidence 1
Introduction
Skin cancer is a frequently diagnosed malignancy among patients who have undergone solid organ transplantation. The incidence of non-melanoma skin cancer (NMSC) increases with time after transplantation. It is noted that squamous cell cancer (SCC) has a higher incidence than basal cell carcinoma (BCC), when compared with the general population. Management options are limited in post-transplant recipients once the cancer develops, as immunotherapy may lead to graft rejection. The mortality risk from invasive and metastatic skin cancer is 3 to 9 times higher in solid organ transplant recipients as compared to the general population. Some of the risk factors are modifiable, such as sun exposure, however, pharmaceutical agents have also been used to reduce and delay the development of skin cancer. Adjustment of the immune suppression medications have also been used in the management. The aim of the study was to determine the effectiveness of the interventions that promote behavioral change and skin cancer prevention in solid organ transplant recipients.
Methods
It was a systematic review that included randomized control trials (RCTs) or quasi RCTs of interventions of skin cancer (including melanoma and NMSC) in solid organ transplant recipients. Behavioral and pharmaceutical interventions to promote sun protective behaviors were included, as were studies that reported skin cancer-related outcomes as their primary outcomes. Studies that involved the interventions for skin cancer treatment were excluded. The outcome measures that were pre-specified were:
Use of sunscreen
Use of protective clothing
Sun avoidance
Measurement of melanin index
Sun damage assessment
Results
22 reports with a total of 2295 participants, were included in the review, out of which 20 were RCTs. The medium follow-up duration was 10 months. The overall quality of the evidence was low for all the outcomes due to the limitations in the study design, the need for similarity in the interventions and outcome measures, the small sample size of individual studies and the small number of studies for each specific outcome.
The effect of behavioral interventions on sun protection outcomes
1.Sun protective behavior
2.Sun protection knowledge
3.Sun protection attitude
4.Skin complications and biologic measures
The effect of pharmaceutical interventions on skin cancer prevention
1.Topical/local interventions
Overall, a lower incidence of skin cancer was noted in patients who used the interventions
The interventions included:
2.Systemic interventions
mTORis therapy reduced the incidence of NMSC compared with CNIs maintenance therapy
Discussion
Skin cancers are major causes of morbidity and mortality in solid organ transplant recipients. Trials aimed at preventing skin cancer in solid organ transplant recipients are few. Overall, the current evidence for interventions for skin cancer prevention in solid organ transplant recipients is of very low quality and is sufficient to guide decision-making and clinical practice.
It is an extensive review that was done using reliable methods to assess risk of bias and the certainty of evidence. It used a wide range of interventions to evaluate the response of lesions and the incidence of cancer.
Unfortunately, they encountered some difficulty in retrieving a summary of the overall outcomes. This was due to the various methods of analysis by the different studies included in the review. The number of studies available were also few, out of which even fewer included the outcomes of the patients diagnosed with skin cancer, and none included the mortality.
Level of Evidence: This is a systematic review of RCTs. LOE I
Difference between bias and errors:
Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials
Introduction
Skin cancer, including melanoma and nonmelanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post-transplantation recipients.
The cumulative incidence increases with time from 5%–10% at 2 years to 40%–80% at 20 years.
Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender-matched general population.
Once cancer develops, management options are limited as immunotherapy may be unsuitable as it may lead to graft rejection.
Inspite of improvement in survival , but there is greater risk of cancer development.
death from SCC and melanoma, are 3-9 nine times higher than the general population, with 5-year overall survival of <30%.6 12–15 Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population.16 However, with the dramatic increase in skin cancers in solid organ transplant recipients, pharmaceuticals have also been used to reduce and delay the development of skin cancer.16 17 Current recommendations for preventive strategies have often been extrapolated from guidelines in the general population, which may not be applicable to solid organ transplant recipients.18 19 For example, frequent skin self-examination and annual to biannual total body skin examination are generally recommended for the general population.18–20 Sun protective behaviours including use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days are potential measures for skin cancer prevention.3 4 14 Further, alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.20 The aim of this study is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients. Methods This systematic review followed a prespecified protocol registered in PROSPERO (CRD42017063962) and is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist.21The study was exempt from approval from an ethics’ board. Inclusion criteria All randomised controlled trials (RCTs) or quasi RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were included. Behavioural interventions defined as any strategy used to promote sun protective behaviour including passive (eg, pamphlets), active (eg, group workshops, counselling, dermatology clinic) and provision of sun protective equipment; and pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids) and studies that reported skin cancer-related outcomes as their primary outcomes were included. Studies that did not report these outcomes as primary endpoints were excluded. Studies of interventions for the treatment of skin cancer were excluded. Search strategies We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019 without language restriction, using search strategies designed by a specialist information manager (see Medline search strategy in online supplementary figure S1). Reference lists of included studies were also searched. Data extraction Titles and abstracts were reviewed by two independent authors (LJJ and LDWL) and those who did not meet the inclusion criteria were excluded. Full-text articles were reviewed by three independent reviewers (LJJ, VS, LDWL) and any disagreements were resolved by discussion. Data on study design, geographic location, sample size, type of transplant, measurement of interventions, interventions and comparators were extracted. We sought unclear or missing information from authors where possible. Outcome measures The prespecified outcome measures were incidence of precancerous and cancerous lesions, sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance), knowledge and attitude, skin selfexamination, sun exposure (including skin irritation, sunburn) and biologic measures (including measurement of melanin index and sun damage assessment). Risk of bias and quality of evidence The risk of bias was assessed independently by LJJ and VS using the Cochrane risk of bias tool.22 The domains included in the assessment were random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, trial registration and industry involvement. Each criterion was assigned a judgement of high, low or unclear risk of bias. Intention to treat and lost to follow-up were also assessed for each study. The quality of the evidence informing summary estimates for each outcome was then assessed by LJJ using the Grading of Recommendations Assessment Development and Evaluation (GRADE) guidelines.23 Data synthesis and statistical analyses Continuous outcomes were summarised as mean difference (MD) or standardised mean difference (SMD) and dichotomous outcomes as relative risk (RR). A MD/ SMD greater than 0 and/or a RR greater than 1 could be interpreted as favouring the intervention group relative to the control, unless specified elsewhere. Risk estimates were reported with 95% CIs, using random effects meta-analysis. We quantified the heterogeneity using the I² statistic. An I2 value of ><25% was considered to represent low heterogeneity and >75%.
Factors to prevent in general population :
· frequent skin self-examination
· annual to biannual total body skin examination
· Sun protective behaviours including use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days
· alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis)
· secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients
The aim of this study is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
Method
assessment of 79 studies found 22 eligible articles for inclusion .
Studies characteristics
We included 22 reports of 20 RCTs, including 2295 participants . median follow-up duration was 10 months
All studies included kidney transplant recipients, with some also including heart transplant recipients, liver, heart, pancreas, lung, heart/lung and other transplants and lung and liver transplant recipients.
It is a meta-analyses.
assessment of reporting of sun protection behaviour and sun protection knowledge was not possible as outcomes were inconsistent and there was large diversity of interventions used (eg, written education material vs a mobile app programme).
formal testing of publication bias was not performed due to insufficient data.
Interventions
The interventions in the included studies were grouped into three broad categories,
· behavioural
· switch to mTORis
· other pharmaceutical interventions photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide.
Effect of behavioural interventions on sun protection outcomes:
We are uncertain of the effects of behavioural interventions on sun protection behaviour due to very low quality of evidence.
Effect of pharmaceutical interventions on skin cancer prevention
These included the switch to mTORis , photodynamic therapy and immune response to current treatment .
Discussion
Skin cancers (both non-melanoma and melanoma) are major causes of morbidity and mortality in solid organ transplant recipients.
Despite this, trials of interventions aimed at preventing skin cancer in solid organ transplant recipients are few in number
there is a high degree of uncertainty in the estimate of the effect of skin cancer prevention interventions.
Preventative measures: including behavioural, switch to mTORis and other pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients. However, the overall quality of evidence is very low and insufficient to guide decision-making and clinical practice.
Future robust studies that are well powered, have long-term follow-up and use clinical and patient important outcome measures in a consistent manner are required to therefore optimise outcomes for solid organ transplant recipients..
level of evidence 1a.
Skin cancer is a major concern for solid organ transplant recipients, affecting more than 50% of post-transplantation patients. The risk of developing skin cancer increases with time, and the incidence of squamous cell carcinoma is higher than in the general population. Cancer-related mortality is greater among transplant recipients. Sun exposure behaviors remain the most significant risk factor in skin cancer prevention, but pharmaceuticals have been used to reduce and delay cancer development.
Current recommendations for preventive strategies may not be applicable to solid organ transplant recipients, and this study aims to determine the effectiveness of interventions promoting behavioral change and skin cancer prevention in this population.
Systematic review that was conducted to evaluate interventions for preventing skin cancer (including melanoma and non-melanoma skin cancer) in solid organ transplant recipients. The review included randomized controlled trials or quasi-RCTs that examined behavioral interventions (such as promoting sun protective behavior) or pharmaceutical interventions (such as photodynamic therapy or oral retinoids) that reported skin cancer-related outcomes as their primary outcomes. Data were extracted and reviewed by multiple independent authors according to pre-specified inclusion criteria.
It is a systematic review and meta-analysis of randomized controlled trials (RCTs) on the effectiveness of interventions to prevent skin cancer in transplant recipients. The review identified 22 eligible studies, which included a total of 2,295 participants. The pre-specified outcome measures were the incidence of precancerous and cancerous lesions, sun protection behavior, knowledge and attitude, skin self-examination, sun exposure, and biologic measures. The interventions in the included studies were grouped into three broad categories: behavioral interventions, switch to mTORis, and other pharmaceutical interventions. The overall quality of the evidence was very low for all outcomes due to limitations in study design, heterogeneity in the intervention and outcome measures, small sample sizes, and a small number of studies for each specific outcome. The risk of bias was assessed independently by two reviewers using the Cochrane risk of bias tool, and the quality of the evidence was assessed using the Grading of Recommendations Assessment Development and Evaluation (GRADE) guidelines. The review found that there was insufficient evidence to support the effectiveness of any of the interventions in preventing skin cancer in transplant recipients.
Strengths:
Limitations:
level of evidence is V
Q1- Please summarise this article.
Abstract
Objectives: The study aim is to determine the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients.
Study Design : Systematic review.
Conclusions : Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
Introduction: Skin cancer, including melanoma and non- melanoma
skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post-transplantation recipients.
(1 2) The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years.( 2–4 ) Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender-matched general population. (5–8 ) Once cancer develops, management options are limited as immunotherapy may be unsuitable as it may lead to graft rejection.
The excess risk of death from invasive and metastatic skin cancer, such as SCC and melanoma, are three to nine times higher than the general population, with 5-year overall survival of <30%.
Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population. However, with the dramatic increase in skin cancers in solid organ transplant recipients, pharmaceuticals have also been used to reduce and delay the development of skin cancer.
frequent skin self-examination and annual to biannual total body skin examination are generally recommended for the general population. Sun protective behaviours including use
of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days are potential measures for skin cancer prevention. alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
Methods : A systematic review
The overall quality of the evidence was very low for all outcomes.
Sun protection behaviour, defined as hours spent outdoors per week, use of sunscreen, wearing protect tive clothing and seeking shade .
Systemic interventions
mTORis therapy reduced the incidence of NMSC compared with CNIs maintenance therapy . but , evidence was limited due to short follow-up periods, variability in dosing of mTORis and significant rates of loss to follow-up, and therefore the authers are uncertain of the effects of mTORis on skin cancer incidence due to very low quality of evidence. A single trial involving 21 patients reported a reduction in the overall incidence of SCC by 49% in the conversion arm, but reported a drop out rate of 77% and follow-uptime of less than 2 years. a single trial which compared mTORi conversion from CNI-based therapy reported a significant improvement in skin dysplasia
Discussion
Skin cancers (both non-melanoma and melanoma) are major causes of morbidity and mortality in solid organ transplant recipients.
Overall, the current evidence for interventions for skin cancer prevention in solid organ transplant recipients is of very low quality and is insufficient to guide decision-making and clinical practice.
Although behavioural interventions appeared to improve sun protection attitude, knowledge and behaviour, there were inconsistencies detected and none of these studies included skin cancer as an outcome.
While there may be some modest benefits in the reduction in cancer incidence (for NMSC) among solid organ transplant recipients who were converted to mTORis compared with those on CNI maintenance, there was substantial heterogeneity across the studies that was unable to be explained by subgroup analyses. Heterogeneity may be attributed to the absence of long-term follow-up, large discontinuation rates owing to adverse events and variability in the doses of mTORis.
Pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers) showed a reduction in precancerous lesions compared with standard care or a comparator group.
A systematic review of the benefits and harms of oral retinoids for the prevention of skin cancer among high-risk transplant recipients led to inconclusive results on the effect of acitretin due to the small number of included trials.
The use of pharmaceutical and immunosuppression therapy remains complex.
Not only has mTORi therapy shown benefits in lowering the risk of skin cancer, early conversion to mTORi therapy from CNIs has also shown promising effects in reducing cancer rates.
But overall mortality is higher and discontinuation following adverse events is more common in patients who receive mTORi therapy. Several RCTs showed a higher rate of patients reporting adverse events or drug discontinuation with sirolimus, demonstrating concern of its clinical usefulness. Nicotinamide may also offer benefits to reducing skin cancer incidence by 20% and is relatively safe with minimal side effects. The protective effect of nicotinamide on skin cancer incidence in kidney transplant recipients is currently being explored in a phase III RCT.
Although behavioural change is a simple strategy, long- term adherence remains challenging.
ncrease sun protective behaviours in non-transplant populations, there is no direct evidence to show that the behavioural change led to a reduction in morbidity and mortality.
Previous studies have suggested that transplant recipients do not practice sun protective behaviours regularly, were less likely to use sunscreen54 and that patients have to perceive skin cancer as being an important risk to be motivated to change behaviour.
Although recipients understand the importance of ongoing education for the ability to self-
Manage their disease, they may experience difficulty in concentrating and learning new knowledge, and are often unable to look beyond their graft and the anxiety fear of graft loss.
Q2- What is the level of evidence provided by this article?
Level 1
Q3- What is the difference between bias and errors?
Bias refers to the difference between the true or correct value of some quantity and a measurement or estimate of that quantity.
Error carries the flavour of mistake (something erroneous), at least in the context of measurement error and particularly when scientists are thinking about their data
Please summarize this article
The research question in this systematic review is whether Behavioral and pharmaceutical interventions can decrease incidence of skin cancer. Skin cancers are the most common malignancy diagnosed in Solid organ recipients, unfortunately very few studies are available in this regard.
This study was designed as a systematic review of RCTs that evaluated the effect of behavioral or pharmaceutical interventions on behavioral change or skin cancer prevention in solid organ transplant recipients. MEDLINE, Embase, CENTRAL and CINAHL databases were searched and relevant RCTs selected as per inclusion and exclusion criteria. The pre-specified outcome measures were incidence of precancerous and cancerous lesions, sun protection behavior, knowledge and attitude, skin self-examination, sun exposure and biologic measures.
The results were uncertain with regards to both behavioral therapy with regards to improving sun protection behavior and mTOR inhibitors with regards to decrease in incidence of skin cancers due to the quality of evidence being very low in both cases. Although behavioral interventions appeared to improve sun protection attitude, knowledge and behavior, there were inconsistencies detected and none of these studies included skin cancer as an outcome.
The researchers concluded that Behavioral and pharmaceutical interventions may decrease incidence of skin cancer but at present the quality of evidence is very low and insufficient to guide decision making and clinical practice at present.
The strength of this study was its design and data collection tools however the low number of RCTs included and the heterogeneity of all those RCTs was the biggest drawback as well leading to inconclusive results.
What is the level of evidence provided by this article?
Level of evidence for this article is Level I as it is a systematic review of multiple RCTs.
What is the difference between bias and errors?
In the simplest words the difference between bias and error is intent. Error can be of 2 types, Type I error (false positive) and type II error (false negative). If the error is introduced into research protocol to favor a pre-selected outcome then it is called a bias. Error can be identified by calculations whereas bias has to be identified manually.
Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials.
Introduction :
the most frequently diagnosed malignancy among solid organ transplant recipients is skin cancer including both melanoma and non- melanoma skin cancer.
there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma
(BCC) in comparison to the general population .As a result of improved transplan- tation techniques and management of immunosuppression, The registry data show improvement in survival rates of transplant recipients, but still there’s a greater risk of skin cancer incidence and mortality.
The aim of this study is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
Design: systematic review study.
Data sources : MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
Inclusion criteria:
All randomised controlled trials (RCTs) or quasi RCTs of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were included.
Outcome measures :
The outcome include incidence of precancerous and cancerous lesions, sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance), knowledge and attitude, skin self- examination, sun exposure (including skin irritation, sunburn) and biologic measures (including measurement of melanin index and sun damage assessment).
risk of bias and quality of evidence :
The risk of bias was assessed independently by LJJ and VS using the Cochrane risk of bias tool.The quality of the evidence informing summary estimates for each outcome was then assessed by LJJ using the Grading of Recommendations Assessment Development and Evaluation (GRADE) guidelines.
Results :
study selection
The literature search identified 1280 articles, of which, 1201 were excluded after abstract and title review. Full- text assessment of 79 studies found 22 eligible articles for inclusion .
studies characteristics
22 reports of 20 RCTs were included.including 2295 participants .The median number of participants was 44 (range 17–830) and the median follow-up duration was 10 months (range 1day to 60 months). All studies included kidney transplant recipients, with some also including heart transplant recipients (n=1), liver, heart, pancreas, lung, heart/lung and other transplants (n=1), and lung and liver transplant recipients (n=2).
risk of bias and quality of the evidence :
Overall studies had either high or unclear risk of bias for at least one domain .
The overall quality of the evidence was very low for all outcomes due to limitations in study design, heterogeneity in the intervention and outcome measures, the very small sample size of individual studies and the small number of studies for each specific outcome.
Interventions:
There are three broad categories of the intervention in the included studies: behavioural (n=6), switch to mTORis (n=6) and other pharmaceutical interventions (n=9, photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide). Studies of behavioural interventions used passive methods of delivery including written educational material (n=2), both written educational material and text messages (n=1), mobile app programmes (n=2) and a video (n=1).
All six studies of immunosuppression compared mTORis (sirolimus) to calcineurin inhibitors (CNIs) based therapies.
Effect of behavioural interventions on sun protection outcomes
Sun protection behaviour
Patients who received behavioural interventions reported improved sun protection behaviour scores. But there is uncertainty of the effects of behavioural interventions on sun protection behaviour due to very low quality of evidence.
Sun protection knowledge
There was an improvement in knowledge scores .
Sun protection attitude
Compared with standard care, there was an overall improvement in scores of concern about developing cancer . There is uncertainty of the effects of behavioural interventions on sun protection attitude due to very low quality of evidence.
Skin complications and biologic measures
The intervention group experienced a reduced incidence of skin irritation or sunburn .They also had a decreased melanin index and reduced severity of sun damage on sun exposed areas .
Effect of pharmaceutical interventions on skin cancer prevention:
The incidence and responses of precancerous lesions were measured only in trials of pharmaceutical interventions .These included the switch to mTORis ,photodynamic therapy ,and immune response modifiers to current treatment or placebo.
Topical/local interventions :
One trial of 14 participants compared an immune response modifier, 5% imiquimod cream with placebo and found a reduction in the incidence of skin dysplasia ,skin atypia and viral warts
One Danish study of 26 kidney transplant recipients compared photodynamic therapy with no treatment and reported a relative reduction by approximately 40% in the incidence of NMSC on the treated area .a lower incidence of SCC was also reported in one trial comparing two areas of skin using an immune response modifier and placebo .Two trials comparing photodynamic therapy to an immune response modifier or photodynamic therapy to placebo in recipients with diagnosed keratoses reported a complete response rate of 60% compared with 24% in the control group There is uncertainty of the effects of photodynamic therapy on incidence of precancerous lesions due to very low quality of evidence.
Systemic interventions
mTORis therapy reduced the incidence of NMSC compared with CNIs maintenance therapy .However, evidence was limited due to short follow-up periods, variability in dosing of mTORis and significant rates of loss to follow-up, and therefore we are uncertain of the effects of mTORis on skin cancer incidence due to very low quality of evidence.
Level of evidence:1
Bias : random
Error:non random
Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials
Summary
Introduction :
The most frequently diagnosed malignancy among solid organ transplant recipients is skin cancer, including melanoma and nonmelanoma skin cancer (NMSC), which affect more than 50% of post-transplantation recipients. The cumulative incidence of NMSC increases with time after transplantation with sun exposure being most significant modifiable risk factor.
Study design : systematic review
Sources : MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
Inclusion criteria :
Data extraction and synthesis :
The quality of the evidence informing summary estimates for each outcome was assessed by LJJ using the Grading of Recommendations Assessment Development and Evaluation (GRADE) guidelines.
Data synthesis and statistical analyses continuous outcomes were summarized as mean difference (MD) or standardized mean difference (SMD) and dichotomous outcomes as relative risk (RR).
Risks of bias and evidence certainty were assessed using Cochrane and the Grading of Recommendations Assessment Development and Evaluation framework.
Result :
The literature search identified 1280 articles for inclusion, of which 1201 were excluded after abstract and title review. 22 reports of 20 RCTs included 2295 participants, with median number of participants 44 and median follow-up duration 10 months.
The overall quality of evidence was low due to limitations in study design, heterogeneity in the intervention and outcome measures, the small sample size of individual studies and the small number of studies for each outcome.
Discussion :
The current evidence for skin cancer prevention in solid organ transplant recipients is of low quality and insufficient to guide decision-making and clinical practice. Sun protection education may reduce cancer incidence among solid organ transplant recipients, but uncertainty exists in treatment effects.
The use of pharmaceutical and immunosuppression therapy for skin cancer prevention is complex, with high risk of bias, potential for reporting bias, and uncertainty in estimates. Transplant recipients may benefit from early implementation of education to reduce skin cancer incidence and reduce morbidity and mortality.
Strength and limitations of the study :
level 1
3.What is the difference between bias and errors?
Baias are systematic errors that refer to deviations that are not due to chance alone also considered as an inclination of temperament , while error is a mistake, something you have done which is considered wrong, or which should not have been done .
Summary of the Article :
Skin cancer is the most common malignancy seen in solid organ transplant recipients, occurs in more than 50% of post-transplantation recipients.
The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years.
Objective :
This study aimed to determine the effectiveness of interventions for behavioural changes for sun protection and prevention of skin cancer in solid organ transplant recipients.
Method:
All (RCTs) or quasi-RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients. Among interventions to prevent skin cancer post-transplantation are:
Use of sunscreen.
Use of protective clothing.
Limiting sun exposure during peak hours of high UV a few hours before and the mid-day sun
Change to mammalian target of rapamycin inhibitors (mTOR is)
Use of retinoid acitretin for the management of skin cancers in high-risk transplant recipients
Result:
Twenty trial were included.
It is uncertain whether behavioural interventions improve sun protection behaviour. It is also uncertain whether the effects of mammalian target of rapamycin inhibitors on the incidence on non melanocytic skin cancer.
Conclusion :
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
Level of evidence provided by this article:
Level 1, Because i’s a systematic review
Difference between Bias and Errors:
Bias: is non random , can occur systematically.
Error: is random, can lead to inaccurate outcomes.
Behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients
Summary
Introduction
This article is based on the increased risk of skin cancer among solid organ transplant recipients, and the interventions that may aid in preventing the occurrence of these cancers.
The data has been obtained from randomized controlled trials.
Discussion
This is a systemic review. The motivation for this study is based on the fact that skin cancers of different kinds lead to significant morbidity and mortality in solid organ transplant recipients. Due to this, interventions that could possibly help preventing skin cancers in SOT recipients has been researched.
The interventions used in this study were grouped under three broad categories, namely, behavioral, switching to mTORi, and other pharmaceutical interventions.
Behavioral modifications included improved sun protection behaviour. Pharmaceutical measures included immunosuppression changes, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers. These interventions were able to produce some improvements in terms precancerous lesion response, and cancer incidence. However, this is of low quality and insufficient to guide decision making and clinical practice.
There is immense variability in interventions and their applications, and thus this provides space for different outcomes.
Early conversion to mTORi from CNIs can provide modest benefits at best in reducing the incidence of skin cancer in these patients.
However, the studies involved are heterogenous in nature, and have a high risk of bias, leading to imprecision in potential results.
Conclusions
Further studies are needed to back up evidence for interventions to prevent or reduce skin cancer incidence in SOT recipients. This can be obtained from high quality and large scale RCTs. In addition, patient preferences for prevention and management practices are to be taken into consideration to provide patient centric decisions and treatment. Long term follow up is also necessary so that these interventions can be put into clinical practice.
Level of evidence
Level of evidence is 1.
Difference between bias and errors
Bias refer to systematically prejudiced results while errors cause inaccurate results. Bias is conscious misrepresentation of values, i.e., shifting or straying from a true value. in contrast, error refers to fundamental or unmeasured randomness.
An example of bias is under-reporting.
An example of error is measurement error.
The objective:
Skin cancer is the most important complication after solid organ transplantation in general population basal cell carcinoma more common than squamous cell carcinoma but in patient with solid organ transplantation squamous cell carcinoma more than basal cell carcinoma (1.8:1) and the incidence increases after transplantation from 5-10% after the second year to about 40-80% after 20 years.
protection to prevent skin cancer post-transplantation are (use of sunblock, sun limitation, use cotton clothes for more sun protection, sunglasses, in high-risk patient early conversion of CNI to mTOR inhibitor)
Aim of study:
to determine behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients.
inclusion criteria;
All (RCTs) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients.
Behavioral therapies (including passive, active, and provision of sun protection devices) and pharmaceutical interventions
Studies that reported skin cancer-related outcomes as their primary outcomes.
Exclusion Criteria;
Studies that didn’t include these results as their main objectives.
Studies of interventions for the management of skin cancer were excluded.
Conclusion:
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
2.What is the level of evidence provided by this article?
level 1 because its systematic review of randomized controlled trials.
3.What is the difference between bias and errors?
Bias: is non random , can occur systematically.
Error: is random, can lead to inaccurate outcomes
# Please summarise this article
# The objective:
To determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
# Introduction:
*Different types of skin cancers (melanoma and non-melanoma) are commonly developed in patients with solid organ transplantation (more than 50%).
*The rate of NMSC elevated with post transplantation period, from 5%–10% at second years to 40%–80% at 20 years.
*The incidence of squamous cell carcinoma is higher than basal cell carcinoma compared to general population.
*In spite of advancement outcome of transplantation due to improvement in transplantation techniques and immunosuppression, there is a higher risk of skin cancer and cancer-related mortality.
*The mortality from invasive and metastatic skin cancer, are 3 to 9 times higher than the general population, with 5-year overall survival of <30%.
*Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population, but increase skin cancers in transplant recipients.
*pharmaceuticals have also been used to reduce and delay the development of skin cancer.
# The methods:
*Design:
Systematic review.
Data sources:
The study searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
Including criteria:
All included randomised controlled trials that evaluated the effect of behavioural or pharmaceutical interventions on behavioural change or skin cancer prevention in solid organ transplant recipients.
Data extraction and synthesis Risks of bias and evidence certainty were assessed using Cochrane and the Grading of Recommendations Assessment Development and Evaluation framework.
#The results:
Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour (n=3, n=414, standardised mean difference (SMD) 0.89, 95% CI −0.84 to 2.62, I2=98%) and knowledge (n=4, n=489, SMD 0.50, 95% CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low.
They are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of non-melanocytic skin cancer (n=5, n=1080, relative risk 0.46,
95% CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low.
# Strengths and limitations of the study:
*A comprehensive review conducted using methods outlined by Cochrane Collaboration including Grading of Recommendations Assessment Development and Evaluation to assess risk of bias and evidence certainty.
* Inclusion of a broad range of interventions, including behavioural to improve sun protection behaviour and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence.
*Difficulty obtaining an overall summary estimate for many outcomes due to the variability in the analytical methods and reporting in individual studies.
*Unable to perform detailed subgroup analyses or assess for publication bias due to small number of studies.
*Few trials included the important outcomes of skin cancer and none included melanoma or mortality.
#Conclusions:
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
# What is the level of evidence provided by this article?
* Level (1)
# What is the difference between bias and errors?
*Error:
Always present in a sample when making statement about a population.
(Sample almost never be the same), so
Error: Always present
Can be control (by taking a large size of sample).
*Bias:
(systematic tendency to error)
Selecting from population with a non uniform probability.
Introduction:
Skin cancers are common post kidney Transplant reaching 50percent of the cases.
Both melanoma and nonmelanoma skin cancer (NMSC).
The aim of study:
is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipient.
Methods:
Systemic reviews.
Inclusion criteria :
All randomised controlled trials or quasi RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were include.
Behavioural interventions defined as any strategy used to promote sun protective behaviour including passive (eg, pamphlets), active (eg, group workshops
, counselling, dermatology clinic) and provision of sun protective equipment; and pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids) and studies that reported skin cancer-related outcomes as their primary outcomes were included.
Results & Outcomes:
1.These behavioral interventions reduced the incidence of Non-melanoma skin cancer. However, the analyzed evidence was of low quality to be applied in clinical practice.
2.There was a lot of bias.
3. Long term compliance on behavioral interventions is unpredicted.
4. Nicotinamide is beneficial to reduce cutaneous cancer by 20%.
5. m-TOR inhibitors may lower cutaneous cancer incidence compared to CNIs. however, their rate of stoppage was high because of side effects making the evidence weak.
Limitations:
1. This systematic review is full of heterogeneity especially variable non-specific behavioral interventions and high Bias of the analyzed studies.
2. Most of pharmaceutical interventions and behavioral interventions were in Europe and USA respectively. 4 of them were by the same author.
3. 10 studies included less than 50 patients.
4. m-TOR inhibitors were discontinued because of side effects in 2/2 studies.
5. 48% of studies have follow up less than 12 months.
6. Inability to analyze data for heterogeneity or publication bias.
Conclusions:
Due to the heterogeneity of the studies, the high risk of bias, the potential for reporting bias and imprecision in the point estimates of individual studies, there is a high degree of uncertainty in the estimate of the effect of skin cancer prevention interventions.
Future randomized controlled studies are required to assess properly how effective these interventions in preventing skin cancer. These studies should be long term, with homogenous, validated and large samples data to help create true guidelines for clinical practice.
Level I evidence
a)Error leads to inaccurate results and outcomes. Bias leads to prejudiced results.
b) Errors are classified into systematic or random. Bias equals systematic error. Random error is related to absent precision in the study conduction.
c) Error involves a single measurement. Bias is the average errors of repeated measurements.
d) Error can occur without Bias. Bias can cause an error. Bias expects an error to occur.
e) Bias can occur at any phase of the research: study design, data collection, data analysis and even publication.
study type – Systematic review of various RCT from open access journal (Open access online peer review)
Introduction, basis of study –
Solid organ transplant recipients are at increased risk of skin cancers, affecting more than >50% of recipients.
Sun exposure behaviors remain the most significant modifiable risk factor in the prevention of skin cancers in the general population.
Due to dramatic increase in skin cancers in solid organ transplant recipients, pharmaceuticals have also been used to reduce and delay the development of skin cancer.
Current recommendations for preventive strategies extrapolated from guidelines in the general population like frequent skin self-examination and annual / biannual total body skin examination may not be applicable to solid organ transplant recipients.
Sun protective behaviors (use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days)
alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
Aim of this study is to determine the effectiveness of interventions that promote behavioral change and skin cancer prevention in solid organ transplant recipients.
methods –
Systematic Review of RCTs on behavioral and pharmaceutical intervention for prevention of of skin cancer in Solid Organ transplant recipients was conducted.
20 RCT (2295 patients) with Primary end point of cancer related outcomes like behavioral skin protective strategies, pharmaceutical interventions were included.
Data on study design, geographic location, sample size, type of transplant, measurement of interventions, interventions and comparators were extracted.
Results;
Improvement in preventive behavioral measures with knowledge and attitudes in reducing sun exposure, use of high SPF sunscreen, wearing of sun protective cloth and googles etc helps in in reducing risk of skin cancer – but the evidence is low quality and inconclusive.
Pharmaceutical measures like change of mTOR inhibitors (SRL) in place of CNI; use of oral retinoid and nicotinamide – help in reducing precancerous lesions and skin cancer.
Early conversion of CsA to SRL is effective in prevention and treatment of skin cancer but large number of patients discontinued of SRL due to side effects.
Nicotinamide showed 20% effectiveness in reducing skin cancer with less side effects.
Conclusions:
Additional large-scale and high-quality RCTs are needed to demonstrate the effectiveness of interventions used to prevent skin cancer, and its associated morbidity and mortality.
Evidence of the efficacy of sun protective behavior interventions need to be strengthened, with use of measures that are homogeneous, reliable and validated.
Preventative measures like changing behavioral knowledge and attitude of patients, switch to mTORis and other pharmaceuticals may improve skin cancer prevention and outcomes for solid organ transplant recipients. However, the overall quality of evidence is very low and insufficient to guide decision-making and clinical practice.
Future robust studies that are well powered, have long-term follow-up and use clinical and patient important outcome measures in a consistent manner are required to therefore optimize outcomes for solid organ transplant recipients.
Limitations of this study are.
a. small sample size in majority of studies (only 1 with sample size >200)
b. short duration and non-homogenous follow up among the studies
c. no or inconclusive data on the incidence and outcome of skin cancer in some of studies.
d. bias factors
2.Level of evidence provided by this article?
Level of evidence is 1 ( systemic review of RCTs)
3.What is the difference between bias and errors?
Statistical bias is a systematic tendency which causes differences between results and facts, and may have a serious impact on results.
Statistical bias comes from all stages of data analysis.
Source of the data (information bias, selection / sampling bias)
the estimator chosen (estimator bias)
the ways the data was analyzed (confounding bias).
e.g. various types of data selection bias
Selection bias / sampling bias – individuals being more likely to be selected for study than others
Spectrum bias – evaluating diagnostic tests on biased patient samples, leads to an overestimate of the sensitivity and specificity of the test.
Observer selection bias occurs when the evidence presented has been pre-filtered by observers, which is so-called anthropic principle.
Volunteer bias – volunteers have intrinsically different characteristics from the target population
Funding bias may lead to the selection of outcomes, test samples, or test procedures that favor a study’s financial sponsor.[8]
Attrition bias arises due to a loss of participants, e.g., loss of follow up during a study.[9]
Recall bias arises due to differences in the accuracy or completeness of participant recollections of past events; for example, patients cannot recall how man
The error of an observation is the deviation of the observed value from the true value of a quantity of interest – which leads to wrong or inaccurate result.
(sense of a deviation of a value from a hypothetical unobserved value)
Error in hypothesis testing:
Type I error happens when the null hypothesis is correct but is rejected.
Type II error happens when the null hypothesis is not correct but is accepted.
Sampling error incurs when statistical estimation of a population is estimated from the subset or selected sample of that population; can be controlled by size of the sample
1. Please summarise this article
The article is published in BMJ Openis an online peer review, open access journal, with Impact Factor: 3.007 Citescore: 3.9.
As skin cancer increases many fold in solid organ transplant recipients with passage of time compared to age and gender matched general population. Systematic Review of RCTs on behavioral and pharmaceutical intervention for prevention of of skin cancer in Solid Organ transplant recipients was conducted with 20 RCTs and 2295 participants
All studies with Primary end point of cancer related outcomes like active and Passive behavioral skin protective strategies, pharmaceutical interventions were included were as studies that did not report these outcomes as primary endpoints and studies with interventions for the treatment of skin cancer were excluded
Results;
This study shows improvement of preventive measures in reduce risk of skin cancer by non pharmaceutical therapy with behavioral knowledge and behavioral attitudes in reducing sun exposure and use of high SPF sunscreen and wearing of sun protective materials but this evidence is low quality and inconclusive.
Pharmaceutical measures like use of mTOR inhibitors instead of Calcinurine inhibitors and oral retinoid and nicotinamide helps in reducing precancerous lesions and skin cancer.
Early Use of sirolimus (mTOR inhibitors), is effective in treatment of skin cancer but large number of patients discontinued of sirolimus due to adverse effects of therapy. Nicotinamide showed 20% effectiveness in reducing skin cancer with less side effects.
Limitations of this study are.
a. small sample size in more than half of studies
b. short duration of follow up and heterogenicity of follow up.
c. in some studies there is no data on the incidence and outcome of skin cancer.
d. bias in few studies
Conclusion:
Large scale of randomized clinical trials needed to strength evidence of behaviour, switching of CNI to mTOR inhibitors and other treatment measures in reducing risk of skin cancer.
Large, reported studies needed with homogeneous sample and follow up to demonstrate evidence of preventive measures to reduce risk of skin cancer.
2.What is the level of evidence provided by this article?
Level of evidence is 1 ( systemic review)
3.What is the difference between bias and errors?
Bias is systemic tendency to errors that results from inaccurate effects and associations. Selecting from population with non-uniform probability
Type of bias ( information bias, selection bias and confounding bias).
Error is inaccurate results. Always present in a sample when making statements about a population. As sample will never be same. So error will always be present and can be controlled by size of sample.types of error in statistics
Type 1 error , type 2 error
Introduction : Skin cancer is the commonest malignancy seen in solid organ transplant recipients, occurs in > 50% of post-transplantation recipients.
· The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years. Objective : This study aimed to detrmine the effectiveness of interventions for behavioral changes for sun protection and prevention of skin cancer in solid organ transplant recipients. Method: All (RCTs) or quasi-RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients. Among interventions to prevent skin cancer post-transplantation are:
· use of sunscreen.
· Use of protective clothing.
· limiting sun exposure during peak hours of high UV a few hours before and the mid-day sun
· change to mammalian target of rapamycin inhibitors (mTOR is)
· use of retinoid acitretin for the management of skin cancers in high-risk transplant recipients. Result: Twenty trial were included. It is uncertain whether behavioural interventions improve sun protection behavior. It is also uncertain whether the effects of mammalian target of rapamycin inhibitors on the incidence on non melanocytic skin cancer. Conclusion :Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice. 2 .WHATS THE LEVEL OF EVIDENCE?
Level of evidence 1, as it’s a systematic review
3WHATS THE LEVEL BETWEEN BIAS AND ERROR?
Bias makes systematically prejudiced results
Errors produce inaccurate results.
Skin cancers, melanotic and non melanotic, are major causes of mortiality and morbidity in recipients of solid organ transplants. In these group of people, the rate of developing squamous cell carcinoma compared with basal cell carcinoma is markedly increased whein compared to the general population [when age and gender-matched]. the incidence is up to 65-250 times higher in the recipients of a solid organ transplant.
Development of a skin malignancy poses a problem, as management options are limited uppression in these population whose graft function and rejection depends onm immunosuppersssion. Hence measures to prevent the development of skin cancers post-=transplanmt are very important.
This study aimed to detrmine the effectiveness of interventions for behavioral changes for sun protection and prevention of skin cancer in solid organ transplant recipients. It is a syetematic review of several Randomized Control Trials that evaluate the effect of behavioural or pharmaceutical interventions on behavioural change or skin cancer prevention inrecipients of solid organ transplants.
The interventions studied were behavioural and pharmaceutical. Pharmaceutical involved the switch of the immunosuppression medication to mTORis or use of an immune-modulating agent.
The study found that these interventions did improve sun protective behaviour and knowledge, and reduced the incidence of non-melanocytic skin cancer. Hpwever, the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice
Level of Evidence: Level 1
Bias produces prejudiced results while errors produce inacurrate results
Bias can be can be identidfied manually or through software packages while errors are identified through calculations.
Bias occurs systematically while errors occur randomly.
-SUMMARY OF THE ARTICLE:
It’s a Systematic Review of randomized control on behavioral and pharmaceutical intervention for the prevention of skin cancer in Solid Organ transplant recipients 20 RCTs and 2295 participants.
Skin cancer, including melanoma and non- melanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post- transplantation recipients.
The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years.2–4 Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender- matched general population.
Once cancer develops, management options are limited as immunotherapy may be unsuitable as it may lead to graft rejection.
-WHATS THE LEVEL OF EVIDENCE?
Level of evidence 1, as it’s a systematic review
-WHATS THE LEVEL BETWEEN BIAS AND ERROR?
Bias makes systematically prejudiced results
Errors produce inaccurate results.
Please summarize this article;
It’s a Systematic Review of randomized control on behavioral and pharmaceutical intervention for the prevention of skin cancer in Solid Organ transplant recipients 20 RCTs and 2295 participants.
Introduction;
Among recipients of solid organ transplants, skin cancer, including melanoma and nonmelanoma skin cancer (NMSC), is the most common malignancy diagnosed. Once cancer has developed, there are few treatment options available since immunotherapy may be inappropriate and may cause graft rejection. Skin cancer and cancer-related death are also more prevalent.
Aim;
The aim is to evaluate the efficacy of behavioral change and skin cancer prevention interventions in solid organ transplant recipients.
Inclusion criteria;
All (RCTs) or quasi-RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients.
Behavioral therapies (including passive, active, and provision of sun protection devices) and pharmaceutical interventions
Studies that reported skin cancer-related outcomes as their primary outcomes.
Exclusion Criteria;
Studies that didn’t include these results as their main objectives.
Studies of interventions for the management of skin cancer were excluded.
Results;
Since the quality of evidence is very low. Uncertainty surrounds the effectiveness of behavioral interventions in enhancing sun protection behavior as well as the impact of mammalian target of rapamycin inhibitors on the prevalence of nonmelanocytic skin cancers.
Conclusion;
Although behavioral and pharmacological preventative treatments may increase awareness and behavior related to sun protection and decrease the incidence of non-melanocytic skin cancer, the overall quality of the evidence is comparatively low and insufficient to inform therapeutic practice.
What is the level of evidence provided by this article?
Level of evidence 1, as it’s a systematic review
What is the difference between bias and errors?
Bias makes systematically prejudiced results
Errors produce inaccurate results.
Introduction
· Skin cancer is the commonest malignancy seen in solid organ transplant recipients, occurs in > 50% of post-transplantation recipients.
· The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years
· squamous cell carcinoma (SCC) occurs in 65 to 250 times greater than the age and gender-matched general population.
· The increased risk of death from invasive and metastatic skin cancer are three to nine times higher than the general population, with 5-year overall survival of <30%
· Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population
The aim of this study
is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
Inclusion criteria
· All randomised controlled trials (RCTs) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients.
· studies that reported skin cancer-related outcomes as their primary outcomes
Exclusion criteria
· Studies that did not report these outcomes as primary endpoints
· Studies of interventions for the treatment of skin cancer
Outcome measures
· incidence of precancerous and cancerous lesions
· sun protection behaviour
· knowledge and attitude
· skin self-examination
· sun exposure(including skin irritation, sunburn)
· biologic measures
Interventions
· behavioural
· switch to mTORis
· other pharmaceutical (photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide)
Discussion
· As skin cancers are an important case of morbidity and mortality in transplant recipients, but only few trials concerned about prevention of skin cancers in solid organ transplant recipients
· This review included 22 reports of 20 trials involving 2295 transplant recipients, who were predominately kidney transplant recipients.
· Interventions, included sun protection behaviour and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence.
· While there may be some modest benefits in the reduction in cancer incidence (for NMSC) among solid organ transplant recipients who were converted to mTORis compared with those on CNI maintenance, there was substantial heterogeneity across the studies that was unable to be explained by subgroup analyses.
· A systematic review of the benefits and harms of oral retinoids for the prevention of skin cancer among high-risk transplant recipients led to inconclusive results on the effect of acitretin due to the small number of included trials.
· Not only has mTORi therapy shown benefits in lowering the risk of skin cancer, early conversion to mTORi therapy from CNIs has also shown promising effects in reducing cancer rates
· overall mortality is higher and discontinuation following adverse events is more common in patients who receive mTORi therapy
· Nicotinamide may also offer benefits to reducing skin cancer incidence by 20% and is relatively safe with minimal side effects
· Additional large-scale and high-quality RCTs are needed to demonstrate the effectiveness of interventions used to prevent skin cancer in transplant recipients in terms of patient important outcomes, in particular morbidity and mortality associated with skin cancer.
Limitations of this study
· Difficulty obtaining an overall summary estimate for many outcomes due to the variability in the analytical methods and reporting in individual studies.
· Unable to perform detailed subgroup analyses or assess for publication bias due to small number of studies.
· Few trials included the important outcomes of skin cancer and none included melanoma or mortality
Level of evidence 1
What is the difference between bias and errors?
Bias produces systematically prejudiced results while errors produce inaccurate results.
Skin cancer is the most important complication after solid organ transplantation in general population basal cell carcinoma more common than squamous cell carcinoma but in patient with solid organ transplantation squamous cell carcinoma more than basal cell carcinoma (1.8:1) and the incidence increases after transplantation from 5-10% after the second year to about 40-80% after 20 years.
protection to prevent skin cancer post-transplantation are (use of sunblock, sun limitation, use cotton clothes for more sun protection, sunglasses, in high-risk patient early change CNI to mTOR inhibitor)
Aim of study:
to determine behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients.
Conclusion:
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
2.What is the level of evidence provided by this article?
level 1 because its systematic review of randomized controlled trials.
3.What is the difference between bias and errors?
Bias: is non random , can occur systematically.
Error: is random, can lead to inaccurate outcomes.
SUMMARY
Introduction
Skin cancer is the most common post-transplant malignancy among solid organ transplant recipients. Compared to the general population, the frequency of skin squamous cell carcinoma is more than basal cell and skin cancer incidence increases after transplantation from 5-10% after the second year to about 40-80% after 20 years
Among interventions deployed to prevent skin cancer post-transplantation are:
· use of sunscreen.
· Use of protective clothing.
· limiting sun exposure during peak hours of high UV a few hours before and the mid-day sun
· change to mammalian target of rapamycin inhibitors (mTOR is)
· use of retinoid acitretin for the management of skin cancers in high-risk transplant recipients
Aim of the study
· to determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients
Method of the study
· the study is a systemic review
Inclusion criteria
Exclusion criteria
Outcome measures
Group of interventions done
Result/Discussion
Limitations of the study
What is the level of evidence?
Bias is said to have taken place when a systematic error is introduced into any stage of a study, either the sampling, selecting, or encouraging one outcome of the study over another
Error is an action that is inaccurate or not correct which can be detected through measures or calculations. It could be either a type 1 or 2 error
Summary of the article:
This is a systemic review of level 1 of evidence
Introduction:
-Skin cancer is around 9 times more in solid organ transplant recipients than rest of population, this review article shows the effect of preventive measures in preventing skin cancer in transplant recipients.
-This is a systematic review of randomized controlled trails that included 22 studies. Some studies showed that switch from CNI’s to mTORi or the use of immune response modifiers for non- melanoma skin cancers were beneficial.
-It showed that behavioral and pharmaceutical measures may improve skin cancer outcomes for solid organ transplant.
Bias which can occur at any phase of the research may lead to prejudiced results based on the average errors of repeated measurements
Errors are either systematic or random, usually involving a single measure and may lead to inaccurate results and outcomes.
Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients:
1-Please summarise this article:
Introduction:
After solid organ transplantation, the chance of developing skin cancer including melanoma and nonmelanoma skin cancer (NMSC) greatly increases, and approximately 50% of the recipients develop it.
Objectives:
Goal of this systemic review is to evaluate the effectiveness of several preventive strategies for melanoma and non-melanoma skin cancer prevention in solid organ transplantation that have been investigated in various randomized controlled trials.
Methods:
-A systematic review of randomised controlled trials of interventions for skin cancer prevention in solid organ transplant cases ,involving behavioural actions either active or passive as well as pharmaceuticals.
-Searching for RCT which include Behavioural interventions, pharmaceutical interventions and studies that reported skin cancer-related outcomes, total 22 reports of 20 RCTs, including 2295 participants with the median follow-up duration was 10 months.
Strengths:
-Extensive online review of many papers before selecting these 20 papers.
-Inclusion of variable interventions, evaluation of precancerous lesion response and measuring the incidence of cutaneous cancer.
Limitations:
-Heterogeneity in the intervention and outcome measures.
-Small Sample size, and small number studies for each specific outcome.
-Variability in the analytical methods and reporting in individual studies, with wide diversity of intervention used.
-Publication bias was not performed due to insufficient data.
-Almost half of the studies were with one year follow up, not sufficient to elaborate the long time effect.
Conclusions:
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
2-What is the level of evidence provided by this article?
-This article is systematic review of randomised controlled trials (Level I)
3-What is the difference between bias and errors?
-Bias; is non random , can occur systematically, can lead to prejudiced results ,identified manually or through available software programs.
–Error; is random, can lead to inaccurate outcomes ,identified through calculations and metrics.
1- Summary:
Skin cancer is a common and potentially serious complication for solid organ transplant recipients. This is because transplant recipients have a higher risk of skin cancer due to the immunosuppressive medications they must take to prevent rejection of the transplanted organ.
This article is a systematic review of randomized controlled trials (RCTs) examining both behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients. The systematic review in the article aimed to evaluate the efficacy of various interventions for preventing skin cancers in this population.
The review analyzed data from several randomized controlled trials (RCTs), which are considered the gold standard for evaluating the effectiveness of medical interventions. The trials included in the review evaluated a range of interventions, including:
Behavioral interventions: such as regular skin self-examination and sun-safe behaviors, like wearing protective clothing and using sunscreen.
Pharmaceutical interventions: such as the use of oral or topical medications to prevent skin cancer. Such as switch to mTORis and other pharmaceutical interventions photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide).
The results of the review showed that some of the interventions, such as regular skin self-examination and sunscreen use, were effective in reducing the risk of skin cancer in solid organ transplant recipients. However, other interventions, such as photoprotective clothing and certain medications, had limited evidence of efficacy and more research is needed to determine their effectiveness. Although behavioural change is a simple strategy, long-term adherence remains challenging.
The authors concluded that a combination of behavioral and pharmaceutical interventions may be necessary to effectively reduce skin cancer risk in solid organ transplant recipients. However, more research is needed to determine the best approach to skin cancer prevention in this population.
In summary, the article provides evidence for the efficacy of certain interventions for preventing skin cancer in solid organ transplant recipients, and highlights the need for further research to determine the best approach to skin cancer prevention in this population.
2- type-1 evidence
Summary of article
Title: Behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials.
Introduction: Skin cancer is the most common malignancy in solid organ transplant recipients as it accounts for more than half over post transplantation malignancies in the post transplantation population.
There is an excess risk of morbidity and mortality from skin malignancies and current treatment options are limited. Sun exposure is a major risk factor for skin cancers in solid organ recipients.
Hence, strategies to reduce exposure to ultraviolet radiations through behavioral changes and use of pharmaceuticals have been employed to reduce the risk of skin cancers.
James et al in this study aim to find the efficacy of interventions that encourage a behavioral change and skin cancer prevention in the recipients of organ transplants.
Methods: The study was a systematic review of both randomized controlled trials and quasi -randomized controlled trials of interventions for skin cancer prevention in solid organ transplant recipients using a prespecified protocol registered in PROSPERO. Twenty-two eligible articles from seventy-nine studies were found and assessed.
Behavioral interventions were defined as any method used to encourage reduced sun exposure behavior such as education (eg, use of pamphlets, training workshops, counselling sessions, dermatology clinic), provision of sun protective materials; and pharmaceutical interventions (change to mTOR inhibitors, nicotinamide, phototherapy, oral retinoids and immune response modifiers).
Variables measured includes incidence of precancerous and cancerous lesions, sun protection behavior such as application of sunscreen and protective materials (e.g., hats, sunglasses and shades), sun avoidance, knowledge and attitude of participants, skin self-examination, sun exposure (including skin irritation, sunburn) and biologic measures (including measurement of melanin index and sun damage assessment).
Results:
Sun protection behavior: A positive effect of behavioral interventions on participants were found in three studies with 414 participants (SMD 0.89, 95%CI −0.84 to 2.62, I2 98%) and a single trial where standardized educational materials were used. However, due to low quality of evidence, authors believe the effects are uncertain.
Sun protection knowledge: Four studies reported improved sun protection knowledge in 489 participants (SMD 0.50, 95%CI 0.12 to 0.87, I2 76%) who were educated through workbooks, text messages, mobile app programs and videos. Another study found educational videos to be better than pamphlets.
Sun protection attitude: An improvement in participants’ concern about developing cancer was reported in three studies with 348 participants (SMD 1.85, 95%CI 1.59 to 2.11, I2 96%). There was also more awareness about personal risk of cancer in two studies involving 273 participants (SMD 0.61, 95%CI −0.60 to 1.82, I2 96%). Adherence to sun protection (SMD 0.77, 95%CI −0.14 to 1.68, I2 92%) and willingness or intention to change behavior (SMD 1.70, 95%CI −1.68 to 5.07, I2 99%) were also better. However, the low quality of evidence made the effects of behavioral interventions on sun protection attitude uncertain. Other studies show improvements in scores of abilities to recognize a potential skin cancer (MD 1.80, 95%CI 1.35 to 2.25), importance of skin self-examination (MD 1.05, 95%CI 0.61 to 1.49) and having a partner help for skin self-examination (MD 1.59, 95%CI 1.10 to 2.08).
Skin complications and biologic measures: Two trials tested the effect of behavioral intervention using a mobile app or an educational workbook and text messages on reported skin complications and biologic measures of sun exposure. The intervention arm experienced a lower rate of skin irritation (RR 1.00, 95%CI 0.89 to 1.13, I2 95%). A reduced melanin index was also found (right forearm, SMD −0.42, 95%CI −0.66 to −0.18; cheek SMD −0.25, 95%CI −0.64 to −0.15). The severity of sun damage also reduced (SMD −0.13, 95%CI −0.40 to 0.13) on sun exposed areas.
Topical/local interventions: A reduction in the rate of skin dysplasia (RR 2.14, 95%CI 0.31 to 14.65), skin atypia (RR 3.00, 95%CI 0.47 to 19.35), and viral warts (RR 7.00, 95%CI 0.46 to 106.10) was reported in a trial comparing 5% imiquimod cream with placebo. Other studies also found positive effects of photodynamic therapy and immune response modifiers on the incidence of non-melanoma skin cancer and precancerous skin lesions. However, due to low quality of evidence, authors believe the effects of photodynamic therapy on precancerous skin lesions were uncertain.
Systemic interventions: Five trials involving 1082 participants compared mTOR inhibitors with CNI maintenance therapy and found a reduced incidence of NMSC (RR 0.46, 95%CI 0.28 to 0.75, I2 72%). Due to various study limitations such as short follow-up period, a variable dosing of mTOR inhibitors, low quality of evidence etc., authors were uncertain of the effect of mTOR inhibitors on sin cancer incidence. Other studies also show a reduction in the incidence of SCC and other non-melanoma skin cancer with mTOR inhibitors when compared with CNI.
Conclusions: Trials of intervention for skin cancer prevention are few and also do not include the incidence of skin cancer as an outcome. Additionally, there is low quality of evidence of intervention for skin cancer prevention which are insufficient to change clinical practice.
Level of evidence for this article is level 1 because its systematic review of randomized controlled trials.
Bias is a form of systematic error introduce into a study commonly due to a poor study design leading to distortion of the outcomes. The higher the bias, the lower the validity of the study. Although bias cannot be completely eliminated, it is to be reduced to the barest minimum. An error occurs when there is a difference between the measured and the true outcomes of a study.
Introduction
Skin cancer, including melanoma and non- melanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post- transplantation recipients.
The cumulative incidence of NMSC increases with time after transplantation, from 5%–10% at 2 years to 40%–80% at 20 years.2–4 Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender- matched general population.
Once cancer develops, management options are limited as immunotherapy may be unsuitable as it may lead to graft rejection.
Effect of behavioural interventions on sun protection outcomes Sun protection behaviour
Sun protection behaviour, defined as hours spent outdoors per week, use of sunscreen, wearing protective clothing and seeking shade, was assessed in three trials.
Educational workbooks, educational workbooks and text messages31 and a mobile app program were compared with standard care. Patients who received behavioural interventions reported improved sun protection behaviour scores
Sun protection knowledge
The effectiveness of educational workbooks, text messages, mobile app programmes and videos on sun protection knowledge was assessed in six studies, four of which provided data for a meta- analysis. There was an improvement in knowledge scores
Sun protection attitude
Three studies assessed sun protective attitude after receiving an educational workbook, text messages or a mobile app programme over a period of 0.5 months to 1.5 months.31–33 Compared with standard care, there was an overall improvement in scores of concern about developing cancer
Skin complications and biologic measures
Two trials of behavioural interventions in 271 kidney transplant recipients compared a mobile app or an educational workbook and text messages to standard care on reported skin complications and biologic measures of sun exposure. The intervention group experienced a reduced incidence of skin irritation (a culturally relevant term for sun exposure34 (RR 1.00, 95% CI 0.89 to 1.13, I2 95%) or sunburn (RR 3.19, 95% CI 2.47 to 4.10, I2 99%).
Previous systematic reviews have evaluated the impact of behavioural interventions on skin cancer prevention in the general population, and concluded that computer programmes may increase sun protective behaviours, and ‘appearance- focused’ interventions may decrease sun tanning and UV exposure in adolescents and young women, respectively.
Although behavioural change is a simple strategy, long- term adherence remains challenging. While behavioural counselling has been shown to increase sun protective behaviours in non- transplant populations there is no direct evidence to show that the behavioural change led to a reduction in morbidity and mortality.
Effect of pharmaceutical interventions on skin cancer prevention
The incidence and responses of precancerous lesions were measured only in trials of pharmaceutical interventions . These included the switch to mTORis (n=1),35 photodynamic therapy (n=2)36 37 and immune response modifiers (n=1)38 to current treatment or placebo. The incidence of NMSCs was assessed in nine pharmaceutical studies. None included melanoma as an outcome.
Topical/local interventions One trial of 14 participants compared an immune response modifier, 5% imiquimod cream with placebo and found a reduction in the incidence of skin dysplasia (RR 2.14, 95% CI 0.31 to 14.65), skin atypia (RR 3.00, 95% CI 0.47 to 19.35), and viral warts (RR 7.00, 95% CI 0.46 to 106.10).
Systemic interventions
mTORis therapy reduced the incidence of NMSC compared with CNIs maintenance therapy (5 trials, 1082 participants, RR 0.46, 95% CI 0.28 to 0.75, I2 72%, However, evidence was limited due to short follow- up periods, variability in dosing of mTORis and significant rates of loss to follow- up, and therefore we are uncertain of the effects of mTORis on skin cancer incidence due to very low quality of evidence.
The use of pharmaceutical and immunosuppression therapy remains complex. Not only has mTORi therapy shown benefits in lowering the risk of skin cancer, early conversion to mTORi therapy from CNIs has also shown promising effects in reducing cancer rates.on the contrary, overall mortality is higher and discontinuation following adverse events is more common in patients who receive mTORi therapy.
Conclusion
We suggest that further strategies for skin cancer prevention in transplant recipients require a multifaceted and individualised approach. Transplant recipients are likely to benefit from early implementation of education, particularly before transplantation occurs and recipients may be preoccupied with other health needs related to transplantation. Although recipients understand the importance of ongoing education for the ability to self- manage their disease, they may experience difficulty in concentrating and learning new knowledge, and are often unable to look beyond their graft and the anxiety/ fear of graft loss.
Level I
Bias produces systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates
Introduction:
Skin cancers affecting more than 50% 0f post transplant recipients and cumulative risk increases with time after transplantation. As a result, there is a greater burden of skin cancer and cancer related mortality. Unfortunately, once cancer develops, management options are limited . Sun exposure is the most significant and modifiable risk factor for prevention of skin cancer. Use of sun screen, protective clothing and limited sun exposure during peak hour of high UV index are measures for skin cancer prevention. The aim of this study is to determine the effectiveness of interventions that promotes behavioural changes to prevent skin cancer.
Methods:
It is a systematic review.
Inclusion criteria:
All randomized control trial that evaluated the effect of behavioural change in skin cancer prevention in solid organ transplant recipients.
Data sources:
Searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and CINAHL from inception to November 2019.
Results:
Twenty trial were included. It is uncertain whether behavioural interventions improve sun protection behavior. It is also uncertain whether the effects of mammalian target of rapamycin inhibitors on the incidence on non melanocytic skin cancer.
Conclusion:
Behavioural and pharmaceutical interventions may improve sun protection behavior, but the overall quality of the evidence is low.
Skin cancer, including melanoma and nonmelanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post-transplantation recipients.
Further, alteration of maintenance immunosuppression such as conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
The aim of this study is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
Outcome measures
The prespecified outcome measures were incidence of precancerous and cancerous lesions, sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance), knowledge and attitude, skin selfexamination, sun exposure (including skin irritation, sunburn) and biologic measures (including measurement of melanin index and sun damage assessment).
Effect of behavioural interventions on sun protection outcomes
Sun protection behavior
Sun protection behaviour, defined as hours spent outdoors per week, use of sunscreen, wearing protective clothing and seeking shade, was assessed in three trials. Educational workbooks, educational workbooks and text messages and a mobile app program were compared with standard care. Patients who received behavioural interventions reported improved sun protection behaviour scores .
Effect of pharmaceutical interventions on skin cancer prevention
the switch to mTORis ,photodynamic therapy and immune response modifiers to current treatment or placebo. The incidence of NMSCs was assessed in nine pharmaceutical studies. None included melanoma as an outcome.
5% imiquimod cream with placebo and found a reduction in the incidence of skin dysplasia ,skin atypia and viral warts .
Discussion
Skin cancers (both non-melanoma and melanoma) are major causes of morbidity and mortality in solid organ transplant recipients.
The studies covered a broad range of interventions, including behavioural to improve sun protection behaviour and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence.
Previous systematic reviews have evaluated the impact of behavioural interventions on skin cancer prevention in the general population, and concluded that computer programmes may increase sun protective behaviours, and ‘appearance-focused’ interventions may decrease sun tanning and UV exposure in adolescents and young women, respectively.
A systematic review of the benefits and harms of oral retinoids for the prevention of skin cancer among high-risk transplant recipients led to inconclusive results on the effect of acitretin due to the small number of included trials.
Preventative measures including behavioural, switch to mTORis and other pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients. However, the overall quality of evidence is very low and insufficient to guide decision-making and clinical practice. Future robust studies that are well powered, have long-term follow-up and use clinical and patient important outcome measures in a consistent manner are required to therefore optimise outcomes for solid organ transplant recipients.
level of evidence 1
Bias systemic errors
SUMMARY
Introduction.
Skin cancer (both melanoma and MMSC) is the most common malignancy diagnosed in solid organ recipients with increased incidence with increased duration post-transplantation. This is associated with increased mortality with 5 year overall survival <30%.
Immunotherapy in the transplant population is coupled with the risk of graft rejection.
The most significant and modifiable risk factor in the general population is sun exposure behaviour. The preventive measures in the transplant recipients are extrapolated from the general population.
The aim of this study was to determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
Methodology
This was a systemic review of RCT and Quasi RCT of skin cancer prevention in solid organ transplant recipients.
Articles were reviewed by an independent party to remove selection bias of the articles.
Outcomes were: Incidence of precancerous and cancerous lesions, sun protection behaviours (sunscreen/ protective clothing/sun avoidance), knowledge and attitude, skin self-examination, biologic measures and sun exposure.
Results
20 trials with 2295 participants were included.
All trials included kidney transplant recipients.
Median follow-up was 10 months.
Majority of the trials didn’t blind the participants (n=16), with half of the trials the outcome assessors were not blinded.
6 trials had high loss to followup
All trials had risk of selective reporting bias.
More than half the studies (n=11) had a small sample size(n=<50)
All interventions had reduced incidence of skin cancer and precancerous lesions; however they all had low quality of evidence thus thus making this results uncertain.
Conclusion
Preventive measures including behavioural and pharmaceutical intervention may improve the outcome of skin cancer in solid organ recipients. However the quality of evidence is low thus insufficient to guide any clinical decisions.
Strengths
This was a systemic review that included studies from various countries.
Limitations
Majority of the studies had a small sample size
There was heterogeneity of the interventions and outcome measures.
LEVEL OF EVIDENCE
This is a systemic review of RCT making it level 1 of evidence.
ERROR VS BIAS
Bias produce systemic prejudice results which error lead to inaccurate results.
Q1: As there is an increasing risk of skin cancer among transplant recipients, this article determines the prevention of skin cancer by some intervention in form of a systematic review of RCTS.
Totally, twenty trials with 2295 recipients were studied.
The effect of behavioral and pharmaceutical interventions was uncertain for prevention of skin cancer became of low level of evidence.
In addition, the effects of MTOR inhibition on the incidence of NMSC is uncertain, because of low level of evidence.
Sun protection includes, skin examination, usage of sunscreens, protecting cloths, avoiding of exposure to mid-day and high UV index hours and days – pharmaceutical interventions includes: switching from CNIs to mTOR inhibitors, photo dynamic therapy nicotinamide and retinoid.
Q2
This is a systematic review with level of evidence of one.
Q3
Bias is a systematic error that results in incorrect estimate of association or effect.
Bias has three types: information selection and confounding.
The three types of error are: systematic, random and negligent.
Bias is identified manually or through software package and occurs systematically while error is identified through calculations and occurs randomly.
Please summarise this article
Introduction
Skin cancer is common among solid organ transplant recipients and affects 50 % of patients
Sun exposure behaviours and pharmaceutical interventions may reduce and delay the development of skin cancer
The Aim of this study is to determine the effectiveness of behavioural and pharmaceutical interventions for the prevention of skin cancers
Study design: systematic review
Methods
All RCTs of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were included
Definition of behavioural interventions is any strategy used to promote sun protective behaviour including passive, active, and provision of sun protective equipment
Pharmaceutical interventions defined as switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids
Results
Twenty trials (n=2295 participants) were included
The median follow- up duration was 10 months (range 1 day to 60 months)
All studies included kidney transplant recipients
The interventions were grouped into three broad categories, behavioural, switch to mTORis and other pharmaceutical interventions (photodynamic therapy, immune response modifiers, oral retinoids and nicotinamide)
It is unclear if behavioural interventions improve sun protection behavior or not as the quality of evidence is very low
The effect of mammalian target of rapamaycin inhibitors on the incidence of non- melanocytic skin cancer is undecided as the quality of evidence is very low
Discussion
This study included 22 reports of 20 trials involving 2295 transplant recipients, who were predominately kidney transplant recipients
The studies covered a broad range of interventions (including behavioural and pharmaceutical interventions)
The current evidence for interventions for skin cancer prevention in solid organ transplant recipients is of very low quality and is insufficient to guide decision- making and clinical practice
Limitations
1. Difficulty obtaining an overall summary estimate for many outcomes due to the variability in the analytical methods
2. Failure to perform detailed subgroup analyses or assess for publication bias due to small number of studies
3. Few trials included the important outcomes of skin cancer and none included melanoma or mortality
Strengths
Systemic review of randomized trials (20 trials) that include a broad range of interventions (behavioural and pharmaceutical)
Conclusion
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non- melanocytic skin cancer. However, the overall quality of evidence is very low and insufficient to guide decision- making and clinical practice
Further robust studies are required
What is the level of evidence provided by this article?
Level I (systematic review of randomised controlled trials)
What is the difference between bias and errors?
Error: a false or mistaken result obtained in a study or experiment. Generally produced by random error, random misclassification, bias, or confounding
Bias: error in design or execution of a study, which produces results that are consistently distorted in one direction because of nonrandom factors
1. Please summarise this article
This systematic review of interventions randomised controlled trials or quasi RCTs for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients. Twenty trials (n=2295 participants) wereincluded.
Prevention interventions implied are:
1-Behavioural including passive (eg, pamphlets), active (eg, group workshops, counselling,
dermatology clinic) and provision of sun protective equipment, n=6
2-pharmaceutical interventions of switch to mTORi , n=6
3- other pharmaceutical interventions :photodynamic therapy, immune response modifiers,n nicotinamide and oral retinoids,n=9
Behavioural intervention were statistically significant in
1- behaviour of skin self examinatiom 1 month after visit, decreased daily outdoor hours, sun protection knowledge
2- attidude ofconcern about developing skin cancer, Knowledge of significance
of skin cancer, relevance of sun protection, risk of having a tan, Confidence in ability to recognise a skin cancer, Importance of skin self-examination, Importance of partner help for skin self-examination
3- complication and biologic measures of Sunburn (past week) and Melanin index—R forearm
(sun exposed)
Effect of pharmaceutical interventions on skin cancer prevention was significant in :
1- Switch to mTORis with Skin dysplasia of Any improvement, Cancerous lesions of SCC /BCC incidence
2- Photodynamic therapy in cases of No reduction
3- Oral retinoids in cases of >1 SCCor New skin cancer
The overall evidence is low
1. What is the level of evidence provided by this article?
Level 1
2. What is the difference between bias and errors?
Bias is shifting from a true value while error is the detection of findings that are different from true.
Bias will result in prejudiced outcome while error result in inaccurate aoutcome. Bias can occour manually or through softwarebut the error is identified through calculations. The bias occur systematically while the error occur randomly.
(https://www.baeldung.com/cs/bias-vs-error)
Objective
In this sytematic review they include 20 RCTs (n=2295 participants) to study the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients.
Methods
RCTs included from multicenter in europ ,usa and others. These RCTS had been published between 1995-2017 including either kidney transplantation (16) or multiple transplantations (4). Follow up duration in the included RCTs rang from <12 months to >24 months . the intervention used in these studies was Intervention type Behavioural 5 (25) Switch to mTORis 6 (30) Photodynamic therapy 4 (20) Oral retinoid 3 (15) Nictotinamide 1 (5) Topical immune response modifier 1 (5). They assessed the Risk of bias of included studies.using Cochrane bias risk assessment system
Conclusion
Regarding Preventative measures including behavioural,it may improve the outcome for kidney transplant recipient but the evidence is very low
switch to mTORis and other pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients. However, the overall quality and insufficient to guide decision-making and clinical practice
level of evidence
1A
Difference between Error and bias
Error :false o mistaken results obtained in a study it could be random error or systemic eror
Bias it is an error in the design of the study which affect the direction of the results it could be selection, informational or attrition bias
summarise article;
this was systemic review of 20 trials having 2295 participants.
the quality of evidence was low level 1.
because of low quality evidence the effect of mTOR on incidence of non-melanoma skin cancer were not very clear
to summarize it, the behaviors and pharmaceutical measures improves the prevention of skin cancers by sun protective measures.
but overall, the quality of evidence was low and insufficient to guide clinical practice.
Limitation
small sample size of studies
short follow up and loss of follow-up
difference between Bias and error
Error may be due to inaccurate measures. (lack of precision)
Bias is systemic errors due to inaccurate effects and association. (Prejudiced result)
Behavioural and pharmaceutical
interventions for the prevention of skin
cancers in solid organ transplant
recipients: a systematic review of
randomised controlled trials
A single study is less likely to give us the answer due to small sample size , short follow up. the systemic review is one of the best tool available at present on this topic
study population
all were post kidney transplant patient
variable but short follow up
heterogenous group without subgroup analysis ( this create low level evidence)
intervention studied
behaviour, knowledge and attitute
sun protection and limiting exposure
photodynamic therapy
oral retenoid
nicotinamid
CNI to mTOR change
end point intended to study but not a part of all the studies
incidence of NMSC
limitation
22 studies
short follow up 50% less than 12 mo
outcome and inferences
reducing sun exposure and its direct effect in reducing NMSC incidence is not yet proven in trials but found to be effective and need more study
phase 3 RCT on nicotinamide will answer pharmacology intervention on prevention od NMSC
melanoma is not studied
USA has all behaviour study
Europe has all pharmacology intervention trials on this topic
level of evidence is poor
level 1
BIAS/ERRORS
Bias is deep rooted in our psychology and can occur unknowingly at any stage of study
It is a choice of one thing over other without any apparent reason
error is more technical and can occur in measurement
use of technology can reduce it
Bias is more human characteristic
I like your analysis of level of evidence, limitations and strengths of this study.
I like your description of bias vs error.
this study, is a meta analysis study explored the success of intervention made by improving sun protection behavior and pharmacological changes of immunosuppressants in post-transplant protocol on risk of skin cancer.
Skin cancer: in the form of melanoma and non-melanotic skin cancer is frequently encountered with incidence hovers above 50% of transplant recipients. the accruing incidence of skin cancer is progressing with time from 5-10 %in 1st few years to 50-80% after 20 years post transplantation, there is higher incidence of squamous cell carcinoma to basal cell carcinoma and its general incidence is 60 to 250 times its level in general population. The main risk factor is sun exposure with heavy high UV light and immuno modulation inflicted by certain immunosuppressants such as calcineurin inhibitors.
Preventive protocol:
Hence, sun exposure behavior improvement and switching CNi to mTORi were advocated as the main strategies to curtail the increasing incidence of skin cancers.
22 reports with 2295 patients were reviewed and included in the study with median follow up of 10 months (range between 2 and 60 months).
3 intervention limbs include sun protection, switching to mTORi and applying other pharmacological preparations such as Retinoid and Acitricin..
Conclusion:
the benefit of all mentioned strategies was not consistant and incnclusive throughout the studies examined.
level of evidence is 2as its a meta analysis
Bias is any deviation from truth in data collection, analysis, interpretation and publication. its intentional and incremental.
error is a false or mistaken result obtained in a study or experiment, its non-intentional and decremental.
Sorry, level of evidence is 1 and not 2 as its meta analysis
The level of evidence that a meta-analysis of studies would provide is as good as the studies included. Hence, this would be 1A since RCTs are included.
But if it is a meta-analysis of cohort studies, then it would become 2A.
Ajay
This is understood that skin cancer is the most common cancer post-transplantation in recipients, it may account for >50% of cancer cases. The cumulative incidence of non-melanocytic skin cancers has increased with post-transplantation, from 5 to 10% at 2 years to 40 to 80% at 20 years.
The aim of this study was to determine the effectiveness of intervention that promote behavioral changes and skin cancer prevention in solid organ recipients.
This was a systemic review in which all randomized control trails for skin cancer prevention in solid organ recipient were included, the sources were MEDLINE, Embase, Cochrane Central registry of control trails and CINAHL, included number of trails were 22 reports of 20 RCTs and number of participant were 2295.
The eligibility criteria; was the evaluation of the effect of behavioral or pharmacological intervention on behavioral changes on skin cancer prevention in solid organ recipient.
Overall the quality of evidence was low, it was uncertain whether behavioral intervention improve sun protection, and second they were uncertain about the effect of mTOR inhibitor effects on skin cancers.
Sun protection behavior including use of sunscreen, protecting clothing, are potential measures for prevention.
Alteration of maitianence immunosuppression such as conversion to mTOR inhibitors.
Method used;
Systemic reviews and meta-analysis checklist.
Intervention;
The studies were grouped into three broad categories, behavioral, pharmacy article intervention, and switch to mTOR inhibitors.
Discussion and conclusion;
The articles covered broad range of interventions to change the behavior change to improve sun protection behavior and pharmaceutical including drug change, photodynamic therapy, oral retinoid, nicotinamide, and topical immune response modifier. Although, overall intervention showed improvement to sun protection behavior, but for skin cancer prevention in solid organ transplant recipient is of very low quality and is insufficient to lead to decision for clinical practice decision.
Level of evidence;
Level of evidence I.
Please use bold or underline for heading or sub-headings.
I like your analysis of level of evidence, limitations and strengths of this study.
1. Please summarise this article
Introduction :Skin cancer affecting more than 50% of post-transplantation recipients.
-The cumulative incidence of non-melanoma skin cancer (NMSC ) increases from 5%–10% at 2 years to 40%–80% at 20 years.
-Compared with the general population, there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), with an incidence of 65 to 250 times greater than the age and gender-matched general population.
-The excess risk of death from invasive and metastatic skin cancer, such as SCC and melanoma, are three to nine times higher than the general population, with 5-year overall survival of <30%.
-Sun exposure behaviours remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population.
-Sun protective behaviours including use of sunscreen, protective clothing and limiting sun exposure during peak hours of high UV index days are potential
measures for skin cancer prevention.
– Alteration of maintenance immunosuppression such as
conversion to mammalian target of rapamaycin inhibitors (mTORis) and secondary prevention using retinoid acitretin are recommended for management of skin cancers in high-risk transplant recipients.
–Objectives : They aimed to determine the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients.
–Design :Systematic review.
–Data sources :They searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL)and CINAHL from inception to November 2019.
– The review included 22 reports of 20 trials involving 2295 transplant recipients, who were predominately kidney transplant recipients.
– They covered a broad range of interventions, including behavioural to improve sun protection behaviour and pharmaceutical to evaluate precancerous lesion response and cancer incidence.
-The current evidence for interventions for skin cancer prevention in solid organ
transplant recipients is of very low quality and is insufficient to guide decision-making and clinical practice.
-Due to limited number of studies, They were unable to compare specific behavioural interventions (eg, mobile app vs written education) to ascertain the most effective method of delivering sun protection education. While there may
be some modest benefits in the reduction in cancer incidence (for NMSC) among solid organ transplant recipients who were converted to mTORis compared with those on CNI maintenance, there was substantial heterogeneity across the studies that was unable to be explained by subgroup analyses.
-Pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers) showed a reduction in precancerous lesions compared with standard care or a comparator group.
-Previous systematic reviews have evaluated the impact of behavioural interventions on skin cancer prevention in the general population, and concluded that computer programmes may increase sun protective behaviours,
and ‘appearance-focused’ interventions may decrease sun tanning and UV exposure in adolescents and young women, respectively.
-A systematic review of the benefits and harms of oral retinoids for the prevention of skin cancer among high-risk transplant recipients led to inconclusive results on the effect of acitretin due to the small number of included trials.
– Limitations: Due to the heterogeneity of the studies, the high risk of bias, there is a high degree of uncertainty in the estimate of the effect of skin cancer
prevention interventions.
-There were large discontinuation rates owing to adverse events in trials of mTORis.
Given the small number of studies included in the meta-analysis,
we were unable to perform any detailed subgroup analyses to explore heterogeneity or assess for publication bias.
-Few trials included patient important outcomes associated with skin cancer and
none included melanoma or mortality.
-Behavioural counselling has been shown to increase sun protective behaviours in non-transplant populations,there is no direct evidence to show that
the behavioural change led to a reduction in morbidity and mortality.
-Previous studies have suggested that transplant recipients do not practice sun protective behaviours regularly,were less likely to use sunscreen and
that patients have to perceive skin cancer as being an important risk to be motivated to change behaviour.
-Transplant recipients are likely to benefit from early implementation of education, particularly before transplantation occurs and recipients
may be preoccupied with other health needs related to transplantation.
What is the level of evidence provided by this article?
Level of evidence: 1
What is the difference between bias and errors?
Bias produces systematically prejudiced results while errors produce inaccurate results.
I like your analysis of level of evidence, limitations and strengths of this study.
I like your description of bias vs error.
Summary of Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trialsIntroduction
Melanoma and non-melanoma skin cancer is the most frequently diagnosed malignancy among solid organ recipients and about more than 50% of the recipient.
Squamous cell CA is the most common skin CA than based cell CA.
The management of skin CA in Transplant recipients is limited as it leads to graft rejection. There are guidelines in the general population to reduce and delay the development of skin cancer which may not be applicable to solid organ transplant recipients.
The aim of this study determines the effectiveness of an intervention that promotes behavioural change and skin cancer prevention among organ transplant recipients.
Method
Systemic Reviews and meta-analysis checklist.
Inclusion criteria
1- Active behavioral strategies clinic visit and workshop.
2- Strategies for behavioral intervention include sun proactive equipment.
3- Pharmaceutical intervention strategies results.
1280 articles were identified and 1201 were excluded after the abstract. Full-text assessment of 79 studies found 22 eligible articles for inclusion.
Studies characteristics
22 Reports of 20 RCTS, including 22 95 participants and median followed up ten months
limitation of this study:-
1- Heterogeneity in the intervention and outcome measure
2- Small size sample
3- Small number of studies for each specific outcome
4- Short time of following this study.
5- Formal testing of publication bias was not performed due to insufficient data.
Intervention
Studies were grouped into three broad categories.
(1) Behavioural
(2) Switch to m TOR
(3) Pharmacy article intervention.
Discussion
The studies covered a broad range of interventions including behavioural to improve protection behavior and pharmaceutical to evaluate precanerogenic lesions response and cancer incidence.
The current evidence for intervention for skin cancer prevention misdid organ transplant recipients is of very low quality and is insufficient to guide decision-making and clinical practice.
The use of mTORi therapy same benefits in lowering the risk of skin cancer, early conversation with mTOR therapy for CNI has shown promising effects in reclaiming the cancer rate.
There is no direct evidence to show that the behavioural charge led to a reduction in morbidity and mortality.
We suggest further strategies for skin cancer prevention in transplant recipients require a multifaceted and individualized approach.
Conclusion
Preventive measures including a behavioural switch to mTORi and other pharmaceuticals many improve skin cancer outcomes for solid organ transplant recipients. The quality of evidence is very low and insufficient to guide disease-making and clinical practice.
The level of evidence:-
This is retrospective about the level of evidence II
3) what are drawback when we use negative data?
1) bias in the collective data
2) participants lost follow upon long term
3) No control group
The level of evidence that a meta-analysis of studies would provide is as good as the studies included. Hence, this would be 1A since RCTs are included.
Ajay
1. Please summarise this article
Strengths:
Limitations
==========================
2. What is the level of evidence provided by this article?
Level I
==========================
3. What is the difference between bias and errors?
I like your analysis of level of evidence, limitations and strengths of this study.
I like your description of bias. Bias can happen at any stage of study: conceptualisation, planning, designing, performing, analysis and writing that study. Error may creep in due to inaccurate measurements.
Summary of the article
BEHAVIOURAL AND PHARMACEUTICAL INTERVENTIONS FOR THE PREVENTION OF SKIN CANCERS IN SOLID ORGAN TRANSPLANT RECIPIENTS: A SYSTEMATIC REVIEW OF RANDOMISED CONTROLLED TRIALS
Skin cancer is frequently encountered in more than 50% of post-transplant recipient. In comparison to gender matched general population, the rate of SCC is higher than the rate of BCC.
This systematic review of RCTs studied the the behavioral and pharmaceutical intervention in the prevention of skin cancers in solid organ transplant.
The range of preventive intervention in this study included:
1.Sun protection behavior:
• use of sunscreen.
• wearing of protective clothing.
• seeking shade.
• Decreasing daily hours outdoors.
2.Pharmaceutical intervention:
• Topical and local interventions.
• Systemic intervention; shift to mTORi.
Study’s result
• Currently, the evidence is of low quality regarding the protective interventions in skin cancers in solid organ transplant recipient.
• Pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers) showed a reduction in precancerous lesions compared with standard care or a comparator group.
• mTORi therapy shown benefits in lowering the risk of skin cancer.
• Early conversion to mTORi therapy from CNIs has shown promising effects in reducing cancer rates.
• Nicotinamide may offer benefits to reducing skin cancer incidence by 20%.
• There is no direct evidence to show that the behavioural change led to a reduction in morbidity and mortality.
What is the level of evidence provided by this article?
Systemic review of CRTs, level of evidence 1
What is the difference between bias and errors?
Bias: is a systematic distortion of a statistical result due to a factor not allowed for in its derivation. Three types of bias can be identified; information bias, selection bias and confounding.
Error: is a measure of the estimated difference between the observed or calculated value of a quantity and its true value.
I like your analysis of level of evidence, limitations and strengths of this study.
I like your description of bias. Bias can happen at any stage of study: conceptualisation, planning, designing, performing, analysis and writing that study.Error may be due inaccurate measurements.
summary:
More than half of all people who get solid organ transplants will develop skin cancer in their lifetime. The purpose of this study was to investigate whether or not modifying the behaviour can successfully reduce the likelihood of developing post-transplant skin cancer. a systematic review of nearly twenty randomized controlled studies that investigated the effect of pharmaceutical treatments and lifestyle modifications on the incidence of skin cancer in patients with solid organ transplants. In terms of behavioural modifications that enhance awareness and sun protection behaviour, as well as mTOR inhibitors and skin cancer reduction, the conclusion was that Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
level of evidence:
level I, a systematic review of a randomized controlled trial
Error:
Error is the difference between actual and predicted or theoretical results.
Systematic errors and random errors are the two major types of errors.
Random errors can occur due to sampling or parameter variability.
Systematic errors (bias) are due to errors in the design of the study that can lead to incorrect results. can occur at any stage of the study. information bias, selection bias & confounding bias.
Please use bold or underline for heading or sub-headings.
I like your analysis of level of evidence of this study.
What are limitations and strengths of this study?
This article tries to reflect if there are changes in the outcome of behavioral and pharmaceutical interventions in changing the rate of skin cancer.
as we all know that post-transplant cancer is 50% , This study was a systemic review which included almost twenty randomized controlled trials that assessed pharmaceutical and behavioral changes which would affect the risk of skin cancers in solid transplant recipients. This review results were uncertain regarding behavioral changes that improve knowledge and sun protection behavior, the results were also uncertain about mTOR inhibitors and skin cancer reduction.
Method of this study:
A systematic review of 22 reports of 20 randomised controlled trials with 2295 participants.
What is the level of evidence provided by this article?
it is systemic review level 1
What is the difference between bias and errors?
Biais systemic errors that results from inaccurate effects and associations.
Error is inaccurate results.
Bias is error but not all error is bias.
There are 3 types of bias ( information bias, selection bias and confounding bias).
Please use bold or underline for heading or sub-headings.
I like your analysis of level of evidence of this study.
What are limitations and strengths of this study?
■ Summary:
Behavioural and pharmaceutical interventions for the prevention of skin
cancers in solid organ transplant recipients: a systematic review of
randomised controlled trials
Introduction
▪︎ Solid organ transplant recipients are at increased risk of skin cancer, affecting more than 50% of recipients.
▪︎Skin cancer is the most frequently diagnosed malignancy among solid organ transplant patients. The cumulative incidence of non melanomas skin cancers (NMSC) increases with time after transplantation and there is a higher rate of squamous cell carcinoma (SCC) to basal cell carcinoma (BCC), Once cancer develops, management options are limited as immunotherapy may be unsuitable as it may lead to graft rejection.
◇ Objectives of the study: to determine the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients.
◇ Design Systematic review.
Data sources: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
◇ Eligibility criteria: the study included randomised controlled trials that evaluated the effect of behavioural or pharmaceutical interventions on behavioural change or
skin cancer prevention in solid organ transplant recipients.
◇ Data extraction and synthesis:
Risks of bias and evidence certainty were assessed using Cochrane and the
Grading of Recommendations Assessment Development and Evaluation framework.
◇ Results Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions
improve sun protection behaviour.
There were uncertainty of the effects of mammalian target of rapamaycin inhibitors on the incidence of nonmelanocytic skin cancer.
◇ Strength of the study:
▪︎ Inclusion of a broad range of interventions, including behavioural to improve sun protection behaviour and
pharmaceutical to evaluate precancerous
lesion response and cancer incidence.
◇ Limitation of the study
▪︎ Diffculty obtaining an overall summary estimate for
many outcomes due to the variability in the analytical methods and reporting in individual studies.
▪︎Unable to perform detailed subgroup analyses or
assess for publication bias due to small number of
studies.
▪︎ Few trials included the important outcomes of skin cancer and none included melanoma or mortality
◇ Conclusions
Behavioural and pharmaceutical preventive
interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insuffcient to guide decision-making and clinical practic.
■ What is the level of evidence provided by this article? Level I
■ What is the difference between bias and errors?
Bias systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates and RMSE [1].
———–
Ref. [1] Emmanuella Badu. Differences Between Bias and Error. 2022
Please use bold or underline for heading or sub-headings.
I like your analysis of level of evidence, limitations and strengths of this study.
Summary:
More than 50% of solid organ transplant recipients are affected by skin malignancy. This study determined the effectiveness of behavioral changes which can reduce the risk of post-transplant skin cancers. This study was a systemic review which included almost twenty randomized controlled trials that assessed pharmaceutical and behavioral changes which would affect the risk of skin cancers in solid transplant recipients. This review results were uncertain regarding behavioral changes that improve knowledge and sun protection behavior, the results were also uncertain about mTOR inhibitors and skin cancer reduction.
Limitations.
1. Small sample size of individual studies.
2. Short follow-up period and loss of follow-up.
3. None of the studies included melanoma.
Level of evidence: Level 1
What is the difference between bias and errors?
Bias produces systematically prejudiced results while errors produce inaccurate results.
When you state that this evidence is of poor quality, how would you do this study better.
Error may be due inaccurate measurements.
Introduction:
Majority cases of solid organ transplant are at risk of skin cancer and account 50% of cases develop cancer in transplant patients.
Objective:
This study address Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients.
Method of this study:
a systematic review of 22 reports of 20 randomised controlled trials with 2295 participants.
Included Criteria:
a. All melanoma and non melanoma skin cancer
b. All passive and active behaviour measures of skin protection
c. All studies with outcome of primary skin cancer
Excluded Criteria:
Exclude all studies which address treatment of skin cancer and all studies not show outcome of primary skin cancer.
This study shows improvement of preventive measures in reduce risk of skin cancer by non pharmaceutical therapy with behavioral knowledge and behavioral attitudes in reduce sun exposure and use of high SPF sunscreen and wearing of sun protective materials but this evidence is low quality and non conclusive.
Also pharmaceutical measures like use of mTOR inhibitors instead of Calcinurine inhibitors and oral retinoid and nicotinamide in reduce precancerous lesions and skin cancer but due to small number of studies shows not enough to benefit from using of retinoid management in preventing of skin cancer. However heterogeneous of studies shows large bias leading to miss estimate benefits of behaviour and pharmaceutical therapy in preventing skin cancer.
Early Use of sirolimus (mTOR inhibitors), is effective in treatment of skin cancer but there’s large number of patients shows discontinuation of sirolimus due to adverse effects of therapy.Nicotinamide is effective in 20% to reduce skin cancer with less side effects.
Limitations of this study is
a. small size
b. short duration of fallow up and heterogeneocity of fallow up.
c. there is no data on the incidence and outcome of skin cancer.
Conclusion:
Large scale of randomised clinical trails needed to strength evidence of behaviour shift of CNI to mTOR inhibitors and other treatment measures in reduce risk of skin cancer.
Large reported studies needed with homogeneous sample and fallow up to demonstrate evidence of preventive measures to reduce risk of skin cancer.
Level of evidence is 1 ( systemic review)
Bias is systemic errors that results from inaccurate effects and associations.
Error is inaccurate results.
Bias is error but not all error is bias.
There are 3 types of bias ( information bias, selection bias and confounding bias).
You need not to type everything in bold or capitals. That amounts to ‘shouting’.
Use bold or underline for heading or sub-headings.
I like your analysis of level of evidence, limitations and strengths of this study.
Please summaries this article;
Systematic Review of RCTs on behavioral and pharmaceutical intervention for prevention of of skin cancer in Solid Organ transplant recipients 20 RCTs and 2295 participants.
1.Introdution;
Skin cancer increases many fold upto 9 times in solid organ transplant recipients with passage of time compared to age and gender matched general population. This review helps in understanding preventive strategies in prevention of skin cancers in SOT recipients
2.Inclusion criteria;
All studies with Primary end point of cancer related outcomes like,
3.Exclusion Criteria;
4.Results;
This review suggests the decrease in skin malignancy with behavioral intervention but the quality of evidence is poor and it is difficult to infer solid evidence on affect of mTOR on skin malignancies.
5.Conclusion;
Preventive measures and pharmaceutical intervention not limited to CNI to mTOR switch may improve skin cancer in solid organ transplant receipts but this analysis provide very low quality of evidence.
No clinical judgment should be made based on this review.
6.Limitation;
What is the level of evidence provided by this article?
Level of evidence 1
What is the difference between bias and errors;
Bias——prejudiced results
Error—–lack of precision could be systematic or random
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations and strengths of this study.
Introduction
More than half of solid organ transplant (SOT) recipients get skin cancer. In the kidney transplant group, squamous cell carcinoma is more common than basal cell carcinoma; in the general population, the opposite is true. Despite advances in immunosuppressive therapy, the burden of skin cancer and cancer-related mortality remains significant. Skin cancer prevention strategies and immunosuppression modification are indicated in the treatment of skin cancer in transplant recipients.
The study’s aim is to assess the efficacy of behavioral and pharmacological therapies in preventing skin cancer in SOT recipients.
Systemic reviews
RCTs that assessed the efficacy of behavioral (passive or active) or pharmacological (mTORi usage, photodynamic treatment, oral retinoids) interventions on skin cancer prevention in SOT participants were eligible.
MEDLINE, Embase, and Cochrane are examples of search engines.
Outcome measures include precancerous and cancerous lesion incidence, sun protection behaviors, knowledge and attitude, skin self-examination, sun exposure, and biologic measurements.
Results
This systematic review comprised 20 RCTs with a total of 2295 individuals, the majority of whom were kidney transplant recipients. Although none of these researches included skin cancer as an endpoint, behavioral interventions enhanced sun protection behaviors. Precancerous lesions were reduced by pharmaceutical therapies. When compared to maintenance CNIs, the use of mTORi reduced cancer incidence (NMSC). Oral retinoids had no effect on the occurrence of new SCC.
Limitations
-None of the research covered skin cancer as a result of inconsistencies in knowledge, attitude, and practice of non-medical approaches that hindered or compromised the quality of the results.
-Subgroup analysis was unable to explain substantial heterogeneity between studies, probably due to a lack of long-term follow-up, a high dropout rate, and different MTOR dosages.
Too few studies exist to permit the application of pharmaceutical intervention outcomes to clinical investigations.
-All trials on non-pharmaceutical techniques, including four by the same authors, were conducted in the United States, whereas the pharmaceutical studies were conducted in Europe, increasing the possibility of bias.
-Short follow-up duration insufficient to illustrate the long-term effects of pharmacological substances
Level of evidence: Level 1 – Systemic review
Difference between bias and error
Bias is typically used to refer to incorrect data collection, such as patient selection, allocation, concealment, blinding of patients and workers, blinding of outcome assessment, and selective outcome reporting.
Typically, error is used to indicate errors in the statistical process, including the influence of introduced data on test findings.
That is an excellent summary and very well structured reply. I like your comment on limitation of sub-group analysis.
I like your analysis of level of evidence, limitations and strengths of this study.
Please summarise this article
Systematic Review and Meta analysis of RCT and quasi RCT from inception till 2019
Research Question:
Participants: all tranplant population, all oragams, all ages
Interventions:
Comparison:
Outcome:
Results: Twenty trials (n=2295 participants) were included.
POSITIVE:
NEGATIVES
OVERALL, Too broad research question, nice tables, I would not rely on that paper in my practice.
References:
What is the level of evidence provided by this article?
What is the difference between bias and errors?
That is a good summary.
When you state that this evidence is of poor quality, how would you do this study better.
Error may be due inaccurate measurements.
I. Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials
· Please summarise this article
Introduction
Skin cancer affects more than 50% of solid organ transplant (SOT) recipients. Squamous cell carcinoma is more common than basal cell carcinoma in the kidney transplant population, the reverse is true in the general population. The burden of skin cancer and cancer-related mortality remains high despite improvements in immunosuppressive therapy. Skin cancer prevention measures and modulation of immunosuppression are recommended in the management of skin malignancies in transplant recipients.
Study objectives
To determine the effectiveness of behavioural and pharmaceutical interventions in the prevention of skin malignancies in SOT recipients.
Methods
Systematic review
Inclusion criteria – RCTs that evaluated the effect of behavioural (passive or active) or pharmaceutical (mTORi use, photodynamic therapy, oral retinoids, noctinamide) interventions in prevention of skin cancers in SOT recipients.
Search engines – MEDLINE, Embase, Cochrane
Outcome measures – incidence of precancerous and cancerous lesions, sun protection behaviours, knowledge and attitude, skin self-examination, sun exposure, biologic measures
Results
This systematic review included 20 RCTs involving 2295 participants who were predominantly kidney transplant recipients. Behavioural interventions improved sun protective behaviours although none of these studies included skin cancer as an outcome. Pharmaceutical interventions demonstrated a reduction in precancerous lesions. Use of mTORi reduced cancer incidence (NMSC) compared to maintenance CNIs. Oral retinoids did not have an impact on incidence of new SCC.
Study strengths
Included a wide range of interventions, both behavioural and pharmaceutical.
Study limitations
Few trials included patient outcomes associated with skin malignancy
None of the trials included melanoma and mortality
Reporting bias
Large discontinuation rates due too adverse events experienced in the mTORi trials
Subgroup analyses could not be done due to the small number of studies included in the meta-analyses
Conclusion
Preventive measures including behavioural interventions and switch to mTORi may improve skin cancer outcomes in SOT recipients. However, the quality of evidence is low and cannot inform clinical practice, hence well powered studies are required to guide decision-making.
· What is the level of evidence provided by this article?
Level I evidence
· What is the difference between bias and errors?
Bias – occurs systematically, it produces prejudiced results and is identified manually or through software packages
Error – occurs randomly, it results in inaccurate results and is identified through calculations
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations and strengths of this study.
I like your description of bias. Bias can happen at any stage of study: conceptualisation, planning, designing, performing, analysis and writing that study.
Well noted Professor, thank you.
SUMMARISE THE ARTICLE.
INTRODUCTION.
Amongst solid organ transplant recipients, skin malignancy is the commonest affecting more than half of the recipients. This includes both melanoma and non melanoma variants. Medical and non medical approaches have been applied to reduce the incidence of skin cancer post transplant with mixed outcomes.
STUDY OBJECTIVES.
To assess the efficacy of interventions that promote behavioral changes and skin cancer prevention in solid organ transplant recipients,
DESIGN.
Systemic review involving 22 RCTS with 2295 participants that met the inclusion criteria,
Inclusion criteria;
-All RCTS or Quasi RCTS of interventions to decrease skin cancer incidences in solid organ transplant recipients.
-Studies that reported skin cancer related outcomes as primary outcomes.
Exclusion criteria;
-Studies that did not report cancer related outcomes as primary end point.
-Studies of interventions for treatment of skin cancer.
RESULTS.
-Despite a high non compliance rate and drop out, it was noted that all behavioral approaches were beneficial.
-MTOR inhibitors were used for short period of time an aspect that limited the quality of evidence to inform clinical decision making, nevertheless they were beneficial in studied selected for this study.
STUDY LIMITATIONS.
-None of the studies included skin cancer as an outcome with inconsistencies in knowledge, attitude and practice of non medical approaches which hampered or affected the quality of results.
-Substantial heterogenicity across studies could not be explained by subgroup analysis possibly from lack of long term follow up, large drop out rate and varied MTOR doses.
-Too few studies to enable outcomes from pharmaceutical intervention be applied in clinical studies.
-All studies on non pharmaceutical approaches were done in USA with 4 by the same authors while the pharmaceutical ones were done in euro[e increasing risk of bias.
-Short follow up time insufficient to explain long term effects of pharmaceutical agents.
CONCLUSION.
–Preventive measures -medical and non medical decrease risk of skin cancer post solid organ transplant, however the quality of evidence is low.
-More studies, well powered and with a long term follow up are needed to provide more evidence to guide clinical decision making.
LEVEL OF EVIDENCE.
Level 1 – Systemic review of all relevant RCT.
BIAS VS ERROR.
Bias – Produces predetermined/one sided/discriminatory results.
Error – Produces wrong/incorrect results.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations and strengths of this study.
· Summary
o Skin cancer is common among transplant recipients (about 50 % of cases) and increases with time after transplantation.
o It carries poor prognosis as it increases the mortality and also has bad impact on graft survival as minimization of immunosuppressive drugs increase incidence of rejection and graft loss.
o Prevention of skin cancer in general population mainly depends on avoiding sun exposure as avoidance of sun exposure around midday rime plus use of sunscreen and sun protective clothes.
o The current study included previous studies addressing the effectiveness of different protective methods as behavioral changes or drugs to prevent skin cancer (measured as incidence of precancerous skin lesions and skin cancer) among solid organ transplant recipients.
o Sun protective behavior and knowledge that are reflected thereafter on sun protective attitude were evaluated. In addition, biological effect of the sun as skin irritation or burn was studied.
o The current study found that in transplant patients, modification of immunosuppressive therapy (shift to mTORi as sirolimus) and additional drugs as retinoids and photodynamic therapy using methyl aminolevinate creams can prevent or delay occurrence of skin cancer.
o Use of sirolimus and early withdrawal of CNI may decrease incidence of skin cancer but increase risk of complications as proteinuria with discontinuation related to its side effects.
o Nicotinamide may be safe and effective in reduction of skin cancer.
o The available data and evidence is low and insufficient to support recommendations of above-mentioned behavioral and pharmacological therapies to prevent skin cancer in transplant patients. Hence, further studied are required to prove this.
· Level of evidence: it is systematic review but it is level I
· Difference ( ) errors and bias
o Errors are mistakes like miscalculation or using fabricated data or numbers that lead to inaccurate results.
o Bias include problems related to:
§ Selection bias in either randomization or allocation of cases in different study groups.
§ Performance bias: means unblinding regarding the intervention used so results are influenced by personal desire or industrial (financial) purpose.
§ Detection bias: unblinding regarding assessment of outcomes.
§ Attrition and reporting bias: means incomplete and selective reporting of the outcome data.
That is a good summary.
When you state that this evidence is low, how would you do this study better.
Error may be due inaccurate measurements.
1. Please summarise this article
Skin cancers affect more than 50% of transplant recipients with the incidence of non-melanoma skin cancer (NMSC) increasing upto 80% at 20 years. The aim of this systemic review was to assess the effect of behavioural and pharmaceutical interventions on the prevention of skin cancer in transplant recipients.
Inclusion criteria: Randomized controlled trials (RCTs) in solid organ transplant recipients having skin cancer prevention using either behavioural (passive or active) or pharmaceutical (mTOR inhibitor switch, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids) interventions.
Results:
20 RCTs (22 reports) were included in the study, involving a total of 2295 recipients. 6 studies involved behavioural interventions, 6 pertained to mTOR inhibitor switch, while 9 studies dealt with other pharmaceutical interventions.
Behavioural interventions: Led to improved sun protection behaviour scores, and reduced incidence of skin irritation, sun damage and reduced melanin index. But the quality of evidence was very low.
Pharmaceutical interventions: Immune response modifier 5% imiquimod cream reduced incidence of skin dysplasia, atypia and viral warts. Positive effect of photodynamic therapy has very low-quality evidence. mTOR inhibitor switch from calcineurin inhibitors has shown modest benefit to reduce incidence of NMSC, but the quality of evidence is low due to short follow-up, variable doses, and increased rates of loss to follow-up. Use of oral retinoids did not have any effect on incidence of new squamous cell carcinoma.
Limitations: Participant blinding was not done in most studies, while blinding of outcome assessors was also reported in only 50% of the studies. Overall quality of evidence was very low for all outcomes. There was heterogeneity in intervention and outcome measures as weel as high risk of bias. Small sample size and small number of studies added to limitations. Large discontinuation rates in mTOR inhibitor studies. Precancerous lesions or skin cancer incidence as outcomes was not measured in the behavioural intervention studies.
Conclusions: Although the data suggests that behavioural and pharmaceutical interventions may improve sun-protective behaviour adoption by patients, reducing the incidence of NMSC, the quality of evidence is very low and hence guidelines cannot be laid on the basis of current evidence. A multifaceted and individualized approach is a must in this scenario.
2. What is the level of evidence provided by this article?
Systematic review: Level of evidence is Level 1
3. What is the difference between bias and errors?
A bias is a scenario in which the results are obtained in a prejudiced manner. It is due to a systemic flaw in the methodology.
An error is something which can occur randomly, resulting in inaccurate outcomes of the study.
A bias is an error, but every error is not a bias.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations and strengths of this study.
I like your description of bias. Bias can happen at any stage of study: conceptualisation, planning, designing, performing, analysis and writing that study.
Please summarise this article
Introduction:
Skin cancer is the most common malignancy among SOT recipients, affecting more than 50% of post-transplantation recipients.
Sun exposure behaviors remain the most significant and modifiable risk factor in the prevention of skin cancers in the general population.
The study aim:
Determine the effectiveness of interventions that promote behavioral change and SK prevention in SOT recipients
Methods:
Design: SR included 22 studies included 2295 participants.
Included studies:
-RCTs of interventions for skin cancer prevention in SOT recipients.
· Behavioral interventions: promote sun protective behavior and provision of sun protective equipment;
· Pharmaceutical interventions: switch to mTORi, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids
– Studies that reported skin cancer-related outcomes as their primary outcomes.
Exclusion:
Studies that did not report these outcomes as primary endpoints.
Studies of interventions for the treatment of skin cancer.
Results:
-As the quality of evidence is very low, it is uncertain whether behavioral interventions improve:
– Sun protection behavior n=3, n=414, SMD 0.89.
– Knowledge n=4, n=489, SMD 0.50.
– Attitude n=3, n= 348, SMD 1.85
-As the quality of evidence is very low We are uncertain of the effects of:
– mTORi on the incidence of NMSK n=5, n=1080, RR 0.46.
– Photodynamic therapy on incidence of precancerous lesions.
Limitations:
-Heterogeneity in the intervention and outcome measures
-Very small sample size of individual studies and the small number of studies for each specific outcome.
-Short follow up period and considerable loss to follow-up for some studies
-Variability in the analytical methods and reporting in individual studies.
-None of the behavioral intervention studies included precancerous lesions or skin cancer incidence as outcomes.
-Reporting bias and imprecision in the point estimates of individual studies,
Conclusions:
Behavioral and pharmaceutical preventive interventions may improve sun protective behavior and knowledge, and reduce the incidence of NMSC , but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
What is the level of evidence provided by this article?
Level 1
What is the difference between bias and errors?
Bias produces systematically prejudiced results, identified manually or through available software programs, and occurs systematically.
Errors produce inaccurate results, identified through calculations and metrics, and occurs randomly.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations and strengths of this study.
Introduction:
Skin cancer, including melanoma and non- melanoma skin cancer (NMSC), is the most frequently diagnosed malignancy among solid organ transplant recipients, affecting more than 50% of post-transplantation recipients.
Objectives :
To determine the effectiveness of interventions for behavioral change for sun protection or skin cancer prevention in solid organ transplant recipients.
Design :
Systematic review.
Data sources :
Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
Inclusion criteria:
All randomized controlled trials (RCTs) or quasi RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients
pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids) and studies that reported skin cancer-related outcomes
Exclusion criteria :
Studies of interventions for the treatment of skin cancer.
Results:
Study selection
The literature search identified 1280 articles, of which, 1201 were excluded after abstract and title review.
Full-text assessment of 79 studies found 22 eligible articles for inclusion
Studies characteristics:
The median number of participants was 44 (range 17–830) and the median follow-up duration was 10 months (range 1day to 60 months).
All studies included kidney transplant recipients, with some also including heart transplant recipients (n=1), liver, heart, pancreas, lung, heart/lung and other transplants (n=1), and lung and liver transplant recipients (n=2).
In total, 15 (76%) of 21 studies provided sufficient data for the meta-analyses.
Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour (n=3, n=414, standardised mean difference (SMD) 0.89, 95%CI −0.84 to 2.62, I2 =98%) and knowledge (n=4, n=489, SMD 0.50, 95%CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low.
The effects of mammalian target of rapamaycin inhibitors on the incidence of non- melanocytic skin cancer (n=5, n=1080, relative risk 0.46, 95%CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low.
Risk of bias and quality of the evidence:
Overall studies had either high or unclear risk of bias for at least one domain.
Random sequence generation and allocation concealment were unclear in most studies (n=12, 60%).
Blinding of participants was not done in most studies (n=16, 80%) and blinding of outcome assessors was only reported in half of the studies (n=10).
Intention to treat analyses were used in 6 (30%) studies and 6 (30%) studies had a high loss to follow-up.
A total of 3 (15%) studies had incomplete outcome data, and all studies were at low risk for selective reporting.
Seven (35%) studies reported industry involvement in authorship, design or data anal- ysis, and of the 16 trials requiring trial registration, only 9 (56%) reported accordingly.
The overall quality of the evidence was very low for all outcomes
Strengths and limitations of this study:
► A comprehensive review .
► Inclusion of interventions, like ( sun protection behavior and pharmaceutical (immunosuppressant, photodynamic therapy, oral retinoid, nicotine amide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence.
► Difficulty obtaining an overall data.
► small number of studies.
► Few trials included the important outcomes of skin cancer and none included melanoma or mortality.
Conclusions :
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
level :1 systemic review study randomized controle
Bias produces systamatically prejudiced results while errors produce inaccurate results .Errors are usually identifed through calculations and metrics such as false positive rates ,negative rates and RMSE.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations and strengths of this study.
Behavioral and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients:
A systemic review of randomized controlled trials:
Skin cancer is prevalent among transplant recipient patient, as a consequence of immunosuppressant medication, so it is an unavoidable but modifiable risk factor.
Melanoma and non-skin melanoma affects more than 50% of transplant recipients, and the incidence increase as time increase post transplant, with 2 years incidence of 5% to 10% , while the rate is 40% to 80% in 20 years.
The incidence is greater by 65 up to 250 times regarding the squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), compared to age-matched general population.
This cancers related mortality make a burden on the outcome of kidney transplantation, although advances in transplantation technique and immunosuppressant medication and associated better outcome and survival in graft and patient life.
In this sytemic trial will show modification and measures to reduce the incidence rate of transplantation-associated skin cancer.
Modifications and measures against skin cancers:
Effect of behavioural intervention on sun protection outcomes:
Sun protection behaviour, attitude and knowledge using the following measures:
All above mentioned measures was assessed in three trials, using an educational workbooks, educational workbook and messages, and a mobile phone program.
With each of them noticed different participation committement and engagemnet, show the different improvement of the score of awareness.
Effect of pharmaceutical intervention in skin cancer protection:
Use the following modality:
compare to current treatment or placebo, and by using whether topical apply or systemic intervention.
Discussion:
Although skin cancer associated solid organ transplantation are a major cause of comorbidity and mortality, only few number of trials done to prevent such complications and small study conclude the outcome, and all deficient in providing evident in clinical practice and outcome.
Studies show improvement in awareness and attitude but deficient of outcome.
Some study sustitude CNI by mTORis fail in final analysis of data, may be related to short duration of studies, doses variability, and participant commitment.
Study limitation:
Due to all of the above, there was a high risk of bias:
Difference between error and bias:
Level of evidence :
Systemic, randomized controll trial (I)
-It is a SR of RCT assessing the impact of behavioral therapy intervention (either passive or active) and pharmaceutical therapy in skin cancer protection among SOT patients.
-Receiving behavioral intervention has been associated with improved sun protection behavior scores, sun protection knowledge score, and overall scores of concern about development of skin cancers. Also, it was associated with decreased incidence of skin irritation, sun burn, melanin index and severity of skin damage in the exposed areas.
-Pharmaceutical intervention effect on the incidence of precancerous lesions and its response to treatment:
Topical agents like immune modifier and photodynamic therapy reduced the incidence of skin dysplasia, atypia warts and NMSC and improved complete cure rate.
-Shifting to m-TOR inhibitors reduced the incidence of NMSC but the evidence is limited because of different limitations of the included studies. Use of retinoic reduced the risk of SCC and BCC.
According to the CEBM of oxoford: level of evidence is Ia
However, The overall quality of the evidence provided is very low for all outcomes due to limitations in study design, heterogeneity in the intervention and outcome measures, the very small sample size of individual studies and the small number of studies for each
specific outcome.
Bias is usually used to describe the improper data collection including patient selection, allocation, concealment, blinding of patients and personnel, blinding of outcome measurement and selective outcome reporting.
Error is usually describe errors in the statistical process including the impact of introduced data on the results of the tests.
I like your analysis of level of evidence, limitations and strengths of this study.
I like your description of bias. Bias can happen at any stage of study: conceptualisation, planning, designing, performing, analysis and writing that study. Error may creep in due to inaccurate measurements.
Please summarise this article:
Introduction:
It is known that skin cancer increases almost 9 folds in solid organ transplant recipient, this review article highlights the effect of preventive behavioral and pharmaceutical measures in preventing skin cancer in these patients.
Systematic review of randomized controlled trails including 22 studies (2295 participants) with the proposed Inclusion criteria by the study group that are:
– Interventions for skin cancer (melanoma and non-melanoma) prevention.
a- Passive behavioral – pemphlets…etc
b- Active behavioral – workshops , dermatology clinic visits,…etc.
c- Sun UV wave protective equipments.
d- Pharmaceutical interventions- oral retinoids, switch to m-TOR inhibitors…..etc.
– Studies reported skin cancer related outcomes as primary endpoints.
Exclusion criteria:
– No skin cancer outcomes studies.
– Treatment of skin cancer and interventions were excluded.
Results:
– All passive and active behavioral measures were beneficial in prevention of skin cancers, but with high dropout follow up and non compliance rate noticed.
– Pharmaceutical measures in preventing only non-melanoma skin cancers, either switch to m-TOR, immune response modifiers, photodynamic therapy were of proven benefit but not in all studies.
– m-TOR inhibitors may lower the incidence of skin cancer but studies were for short period, and there were a lot of discontinuation of drug in these studies due to side effects.
Limitations:
– heterogeneity in the intervention and outcome measures.
– Small ample size, and small number studies for each specific outcome.
– Variability in the analytical methods and reporting in individual studies, with wide diversity of intervention used.
– Publication bias was not performed due to insufficient data.
– Almost half of the studies were with one year follow up, not sufficient to elaborate the long time effect.
Conclusion:
Preventive behavioral and pharmaceutical measures including switching to m-TOR inhibitors may improve skin cancer outcomes for solid organ transplant recipients, however the quality of evidence is very low.
Large randomized controlled trials for long times period of follow up are needed to guide clinical decision and practice.
What is the level of evidence provided by this article?
Level of evidence 1 – review article of randomized trials.
What is the difference between bias and errors?
Bias = systematically prejudiced results, identified manually or through software packages, occurs systematically.
Errors = inaccurate or incorrect mathematically calculated results, occurs randomly.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence.
Objectives
Skin cancer affects more than 50% of recipients of solid organ transplants, putting them at elevated risk.
In order to prevent skin cancer in solid organ transplant patients, we sought to evaluate the efficacy of behavioral change therapies.
Eligibility criteria
The authors took into account randomized controlled trials that looked at how behavioral or pharmacological interventions affected skin cancer prevention or behavioral change in solid organ transplant recipients.
Results
There were 20 trials (n=2295 participants).
The quality of the evidence is quite poor, therefore it is unclear if behavioral interventions enhance sun protection knowledge (n=4, n=489) and behaviour (n=3, n=414, standardized mean difference (SMD) 0.89, 95% CI 0.84 to 2.62, I2=98%).
Method
This systematic review adhered to a predetermined procedure that was registered in PROSPERO (CRD42017063962), and it is documented in line with a checklist known as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The study was exempt from approval from an ethics’ board.
Recipients of solid organ transplants were included in all randomized controlled trials (RCTs) or quasi-RCTs evaluating treatments for preventing skin cancer.
Pharmaceutical therapies, studies that reported skin cancer-related outcomes as their primary outcomes, and behavioral interventions—defined as any technique used to promote sun protective behavior, including passive, active, and provision of sun protective equipment—were also included.
The author omitted studies that did not list these outcomes as primary endpoints.
Studies involving treatments for skin cancer were not included.
Results
Studying selection: After reviewing the title and abstract, 1201 of the 1280 items found by the literature search were eliminated.
22 publications were determined to be eligible for inclusion after full-text analysis of 79 research.
Characteristics of studies 22 papers from 20 RCTs with 2295 individuals were included.
All studies included kidney transplant recipients, and some also included recipients of liver, heart, pancreas, lung, heart/lung, and other transplants (n=1), liver and lung transplant recipients (n=2), and recipients of liver and heart transplants (n=1).
15 (or 76%) of the 21 studies offered enough information for the meta-analyses.
Six studies failed to meet the final requirements for meta-analysis because they used the same participant sample (n = 1)[24] or did not offer data that could be used for meta-analysis (n = 5).
Conclusion
Major causes of morbidity and mortality among recipients of solid organ transplants are skin malignancies.
There are only 20 trials of therapies to prevent skin cancer in solid organ transplant recipients. Half of these trials include 50 patients or less, are short-lived (48% have 12 months follow-up), and 52% do not include skin cancer incidence as an endpoint.
Studies on a wide range of interventions were conducted, including behavioural changes to increase sun protection behaviour and pharmaceutical tests to assess precancerous lesion response and cancer incidence.
Precancerous lesions or the incidence of skin cancer were not included as outcomes in any of the behavioural intervention studies.
There was a great deal of variation among intervention types, diversity in outcomes examined, and uncertainty in outcome estimates, although interventions showed reasonable increases in sun protection behaviours, precancerous lesion responses, and cancer incidence.
The available evidence for therapies to prevent skin cancer in people who have received solid organ transplants is of extremely poor quality and is insufficient to inform therapeutic practice.
2. Level 1
3. Bias produces systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates and RMSE. Biases are identified manually or through available software programs
That is a good summary and an interesting analysis. Please type headings and sub-headings in bold or in underline.
Ajay
Introduction:
Skin cancers are common post kidney Transplant reaching 50percent of the cases.
Both melanoma and nonmelanoma skin cancer (NMSC).
The aim of study:
is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipient.
Methods:
Systemic reviews.
Inclusion criteria :
All randomised controlled trials or quasi RCTs (allocated to trial arms by investigators) of interventions for skin cancer prevention (both melanoma and NMSC) in solid organ transplant recipients were include.
Behavioural interventions defined as any strategy used to promote sun protective behaviour including passive (eg, pamphlets), active (eg, group workshops
, counselling, dermatology clinic) and provision of sun protective equipment; and pharmaceutical interventions (switch to mTORis, photodynamic therapy, immune response modifiers, nicotinamide and oral retinoids) and studies that reported skin cancer-related outcomes as their primary outcomes were included.
Studies characteristics :
22 reports of 20 RCTs, including 2295 participants .
Effect of behavioural interventions on sun protection outcomes Sun protection behaviour:
Patients who received behavioural interventions reported improved sun protection behaviour
uncertain of the effects of behavioural interventions on sun protection behaviour due to very low quality of evidence.
Sun protection knowledge:
There was an improvement in knowledge scores in the intervention group compared with standard car.
One study compared an interactive visual representation of the educational programme with standard information pamphlets and found that knowledge of sun protection improved among those who received the educational video.
Sun protection attitude:
Compared with standard care, there was an overall improvement in scores of concern about developing cancer .improvement in scores of understanding the personal risk of skin cancer
There uncertain of the effects of behavioural interventions on sun protection attitude due to very low quality of evidence.
Effect of pharmaceutical interventions on skin cancer prevention:
5% imiquimod cream with placebo and found a reduction in the incidence of skin dysplasia (RR 2.14, skin atypia
One Danish study compared photodynamic therapy with no treatment and reported a relative reduction by approximately 40% in the incidence of NMSC ;A lower incidence of SCC was also reported in one trial comparing two areas of skin using an immune response modifier and placebo .
Two trials comparing photodynamic therapy to an immune response modifier or photodynamic therapy to placebo in recipients with diagnosed keratoses reported a complete response rate of 60% compared with 24% in the control group .
We are uncertain of the effects of photodynamic therapy on incidence of precancerous lesions due to very low quality of evidence.
Systemic interventions :
mTORis therapy reduced the incidence of NMSC compared with CNIs maintenance therapy ; However, evidence was limited due to short follow-up periods, variability in dosing of mTORis and significant rates of loss to follow-up, and therefore we are uncertain of the effects of mTORis on skin cancer incidence due to very low quality of evidence.
Limitations of the study:
small number of studies included in the meta-analysis, we were unable to perform any detailed subgroup analyses to explore heterogeneity or assess for publication bias.
Finally, few trials included patient important outcomes associated with skin cancer and none included melanoma or mortality.
Conclusions:
Due to the heterogeneity of the studies, the high risk of bias, the potential for reporting bias and imprecision in the point estimates of individual studies, there is a high degree of uncertainty in the estimate of the effect of skin cancer prevention interventions.
There were also large discontinuation rates owing to adverse events in trials of mTORi
Level of evidence 1.
Bias produce systematically prejudiced results while errors produce Inaccurate results.
That is a good summary and an interesting analysis. Please type headings and sub-headings in bold or in underline.
Ajay
Please summarise this article
Aims
Melanoma and non melanoma skin cancers are the most common malignancy post solid organ transplants. This is a systemic review to evaluate the efficacy of preventive measures for skin cancers in patients having solid organ transplants.
Methodology
In this systemic review search was done in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.
Total RCTs- 22
no of patients- 2295
The following interventions were assessed.
Behavioural interventions included, less sun exposure, use of sunscreen, protective clothing, use of shade and self examinations.
Pharmaceutical measures included, use of nicotinamide, retinoids , immune modifiers and photodynamic therapy
Change of immune suppression to mTORi.
Results
Due to low quality of evidence it was possible to conclude that behavioural measures decreased the incidence of skin cancers. Due to poor quality of evidence , it was also not possible to draw a conclusion on the relationship of mTORi on non melanotic skin cancers.
Limitations
Variability in reporting and analytic methods
No subgroup analysis
No trial included melnoma and mortality
Conclusions
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
What is the level of evidence provided by this article?
Systemic review
Level of evidence 1
What is the difference between bias and errors?
Errors produce inaccurate results
Bias can produce prejudiced results
Bias can cause error while error can happen without bias
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence.
1. Please summarize this article
Introduction:
This is a systematic review of 20 randomized controlled trials that assessed the impact of behavioral or pharmaceutical interventions on prevention of cutaneous malignancy in recipients of solid organ transplant.
Cutaneous malignancy is the most common cancer in solid organ transplant recipients, its incidence is more than 50%.
Cutaneous malignancy includes Melanoma and non-melanoma skin cancer (NMSC).
Incidence of SCC is higher than BCC in solid organ transplant recipients where the incidence is 65-250 times higher than age matched general population. Malignant Melanomas carry the highest incidence of mortality among skin cancers.
Aim:
Assess the effectiveness of preventive interventions, including behavioral and pharmaceutical, against cutaneous cancer in solid organs recipients.
Methods:
2295 solid organ transplant recipients were included from 20 randomized controlled trials. With median follow up around 10 months.
Data were collected and analyzed regarding the following interventions:
1- Behavioral changes that include monthly cutaneous self-examination, 6-12 monthly cutaneous examination by dermatologist, avoidance of mid-day sun exposure, sun-screen use, protective clothes use and education about sun protection.
2- Medication changes that include topical, and systemic agents.
3- Use of m-TOR inhibitors instead of CNIs.
Exclusion criteria:
1-Trials without a primary endpoint.
2-Studies with cutaneous cancer treatment.
Results and outcomes:
1- These behavioral interventions reduced the incidence of Non-melanoma skin cancer. However, the analyzed evidence was of low quality to be applied in clinical practice.
2- There was a lot of bias.
3- Long term compliance on behavioral interventions is unpredicted.
4- Nicotinamide is beneficial to reduce cutaneous cancer by 20%.
5- m-TOR inhibitors may lower cutaneous cancer incidence compared to CNIs. however, their rate of stoppage was high because of side effects making the evidence weak.
Limitations:
1- This systematic review is full of heterogeneity especially variable non-specific behavioral interventions and high Bias of the analyzed studies.
2- Most of pharmaceutical interventions and behavioral interventions were in Europe and USA respectively. 4 of them were by the same author.
3- 10 studies included less than 50 patients.
4- m-TOR inhibitors were discontinued because of side effects in 2/2 studies.
5- 48% of studies have follow up less than 12 months.
6- Inability to analyze data for heterogeneity or publication bias.
Strengths:
Conclusion:
Behavioral and pharmaceutical interventions may reduce cutaneous cancer incidence in solid organ transplant recipients. However, the incidence is weak.
Future randomized controlled studies are required to assess properly how effective these interventions in preventing skin cancer. These studies should be long term, with homogenous, validated and large samples data to help create true guidelines for clinical practice.
2. What is the level of evidence provided by this article?
Level I evidence
3. What is the difference between bias and errors?
Error leads to inaccurate results and outcomes. Bias leads to prejudiced results.
Errors are classified into systematic or random. Bias equals systematic error. Random Error is related to absent precision in the study conduction.
Error involves a single measurement. Bias is the average errors of repeated measurements.
Error can occur without Bias. Bias can cause an error. Bias expects an error to occur.
Bias can occur at any phase of the research: study design, data collection, data analysis and even publication.
Errors and Bias can be reduced by large sample size and selection measures.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence.
Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials
===================================================================
1- Please summarise this article
Introudction
====================================================================
Methods
==================================================================
Effect of behavioural interventions on sun protection
outcomes
1-Sun protection behaviour, defined as hours spent outdoors per week, use of sunscreen, wearing protec- tive clothing and seeking shade, was assessed in three trials.
2- Sun protection knowledge
3- Sun protection attitude
4-Skin complications and biologic measures
Discussion:
Results showed plausible
Limitations
1- Due to research variability, the effectiveness of skin cancer prevention measures is under dispute.
2-High potential for bias, potential for reporting bias, and imprecision in point estimations.
3-Most drug intervention trials took place in Europe, but all behavioral intervention studies—four of them by the same authors—were conducted there.
4-High mTOR negative effects include trial abandonment rates.
5-We were unable to conduct subgroup analyses to look at heterogeneity or publication bias since there weren’t enough papers included in the meta-analysis.
====================================================================
Conclusion
===================================================================
What is the level of evidence provided by this article?
level 1 systamatic review
====================================================================
What is the difference between bias and errors?
Bias produces systematically prejudiced results while errors produce inaccurate results. Errors are usually identified through calculations and metrics such as false positive rates, false negative rates and RMSE.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence.
Thaks very much Prof.Sharma
Summary:
Introduction:
After solid organ transplantation, the chance of developing skin cancer greatly increases, and approximately 50% of the recipients develop it.
Objectives:
Goal of this systemic review is to evaluate the effectiveness of several preventive strategies for melanoma and non-melanoma skin cancer prevention in solid organ transplantation that have been investigated in various randomized controlled trials.
Methods:
Twenty randomized controlled trials (n = 2295 participants) were included. Types of different interventions analyzed in this systematic review:
a) Behavioral: by educating sun protection
b) Pharmaceutical: topical/local/systemic agents
c) Switching to mTOR inhibitor
Results:
Interventions may improve sun protection behavior and reduce the incidence of non-melanoma skin cancer, however this is insufficient to be implemented in clinical practice due to low quality of evidence analyzed in this research.
Conclusion:
The incidence of non-melanoma skin cancer may be decreased through behavioral and pharmaceutical preventive measures.
Level of evidence I, as this is a systematic review.
Bias results systemically prejudiced results; it means shifted from a true value. While errors are responsible for inaccurate results: it means wrong.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence.
Summary for this article:
-The skin malignancy is most common malignancy occurs after solid organ transplantation, More than 50% of transplant recipients have at least one episode of skin cancer after transplantation, and the risk increase with increasing years of transplantation.
-The SCC occur more commonly than BCC post organ tx. (although in general population BCC is more common)
-Both SCC and melanoma have poor prognosis with the highest mortality observed with malignant melanoma
Aim :
The purpose of this systematic review study is to assess the effectiveness of behavioural and pharmaceutical interventions for prevention of skin cancers that have been studied in various randomized controlled trials
Methods:
A systematic review including 2295 organ transplant recipients (mainly renal), collected from 20 randomized controlled trials Types of different interventions analyszed in this systematic review:
. Behavioural: by educating sun protection behaviour like;=> Outdoor hours spent per week, Sunscreen use, Protective clothing, Use of shades, Skin self-examination & Concern about developing skin cancer through educating workbooks/mobile apps/videos/text messages/consultation
. Pharmaceutical(topical/local/systemic) =>Photodynamic therapy, Immune response modifiers, Oral retinoids, Nicotinamide
. Switching to mTOR inhibitor
Result:
-From the low quality of evidence in the 20 studies reviewed, strong evidence resulted in the implementation of behaviorual and pharmaceutical intervention can improve sun protection, and subsequently reduce the incidence of NMSC, but with a lot of bias
-Behavioural intervention although appear easy but long term adherence is unpredicted & it is hard to say if behavioural treatments might help people learn how to protect themselves from the sun
-mTOR may reduce the incidence of skin cancer but the rate of discontinuation was high due to side effects, •but the evidence is week
-Nicotinamide is a safe drug that offer a benefits to reduce the incidence of skin cancer by 20% and is being assessed
-finally, interventions may enhance sun protection behaviour and decrease the incidence of non-melanoma skin cancer (NMSC), but this is not enough to be implemented in decision making or clinical practice.
Limitations:
-The impact of skin cancer preventive strategies is questionable due to study heterogeneity, Heterogeneity & reporting High risk bias in the studies analyzed
-Most pharmaceutical intervention trials were in Europe, whereas all behavioural intervention studies were in the US, four by the same authors.
-Small patients in individual studies(10 studies comprising less than 50 patients)
-Discontinuation rates 2/2 SE of mTOR
-Short term follow( 48% studies have less than 12 months follow-up)
-Due to the insufficient number of papers in the meta-analysis, we were unable to undertake subgroup analyses to investigate heterogeneity or publication bias.
Conclusion:
– Preventative measures as behavioural & pharmaceutical interventions may improve sun protection and reduce the incidence off skin cancer but the evidence is week
–Large, well designed, properly powered, long term randomized studies using clinical and patient important outcome measure which is reliable, homogenous and validated are required to find importance of different interventions in preventing skin cancer in solid organ transplantation and to finally guide decision making in clinical practice.
-We hope in future quality RCT studies, With long-term follow-up & use clinical and patient outcome measures are required.
What is the level of evidence provided by this article?
-Because a systematic review (RCT) =level of evidence is 1A.
•What is the difference between bias and errors?
-Bias means expectation that an error may occur (is the average of errors of repeated measurements)
-Error means somtehing wrong happen=> inaccurate outcomes(a single measurement)
•(Finally =>Bias can cause an error, while an error can occur with no bias)
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence.
Behavioral and pharmaceutical interventions for the prevention of skin
cancers in solid organ transplant recipients: a systematic review of
randomized controlled trials.
The aim of this systematic review is to determine the effectiveness of
interventions that promote behavioral change and skin cancer prevention in solid organ transplant recipients.
Methods.
Searching for RCT which include Behavioural interventions,
pharmaceutical interventions and studies that reported skin cancer-related outcomes, total 22 reports of 20 RCTs, including 2295 participants with the median follow-up duration was 10 months.
Results:
Effect of behavioural interventions on sun protection outcomes.
Patients who received behavioural interventions ((3 studies, 414 participants) reported improved sun protection but it is uncertain as the quality of evidence is very low.
Effect of pharmaceutical interventions on skin cancer prevention.
Determine the incidence of NMSCs in nine pharmaceutical studies , shown none included melanoma as an outcome and mTOR is therapy reduced the incidence of NMSC compared with CNIs maintenance therapy shown in (5 trials,1082 participants) but with low quality evidence as there is no long follow-up periods, variability in dosing of mTORis and significant rates of loss to follow-up.
Weakness points:
-Variability and non-specific behavioural interventions .
-Small studies with small number of participants .
-Most of the studies not included incidence of skin cancer as an outcome.
-Short follow up duration and large discontinuation rates.
Conclusion:
Preventative measures such as behavioural and pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients.
But still high quality studies, have long-term follow-up and use clinical and patient outcome measures are required.
level of evidence: Level 1(systematic review).
What is the difference between bias and errors?
A bias is the “obliquity or twisting of a thing to one side, or in the cut, or in the situation which might be cognitive, statistical, contextual, law enforcement bias, media bias, conflict of interest and even prejudice.
Error can lead to inaccurate outcomes ,identified through calculations as false positive rates, false negative rates may be (randomised errors and systematic errors).
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence.
Please summarise this article
The most common malignancy encountered after solid organ transplantation is skin malignancy. More than half of transplant recipients have at least one episode of skin cancer after transplantation, and the risk increase with increasing years of transplantation.
In organ transplantation SCC occur more commonly than BCC (although in general population BCC is more common)
SCC and melanoma have poor prognosis with the highest mortality observed with malignant melanoma
The current study is a systematic review including 2295 organ transplant recipients (mainly renal) collected from 20 trials. The study is assessing the effectiveness of behavioural and pharmaceutical interventions for the prevention of skin cancers.
These interventions to prevent skin cancer includes :
Results
Conclusion
What is the level of evidence provided by this article?
What is the difference between bias and errors?
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence.
Introduction:
Both melanoma and non melanoma skin cancer(NMSC) are the commonest cancer after solid organ transplantation ( affect~ 50% of transplant recipients). NMSC risk increasing with time ( basal cell carcinoma more prevalent than squamous cell carcinoma). Different preventive methods used to reduce risk of post transplant skin cancer as sun screen, protective clothing, avoidance of sun exposure and changes in immunosuppression.
Aim of the study:
Assessment of interventional measures efficacy that promote behavioral changes and prevention of skin cancer in transplant recipients.
Method:
1. incidence of precancerous and cancerous lesion
2. Sun protective behavior e.g. sunscreen, protective clothing.
3.Knowledge and attitude.
4.Skin self examination.
5.Sun exposure.
6.Biological measures.
Discussion:
Level of evidence is 1
Bias: is a methodological errors that can lead to misrepresentation of study outcome.
Error: refer to difference between the prediction and ground truth value.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence.
That is a good summary.
I like your analysis of level of evidence.
This study is a systematic review, classified as level 1.
This study selected 20 different studies with 2295 patients, but with high heterogeneity indices (I2) impacting the real quality of the study, whether due to subjective measurements or the difficulty of clinical and laboratory markers.
Skin cancers (regardless of melanoma or not) are quite common during the post-transplant period. Compared with the general population, the risk of transplanted patients is extremely high to develop this neoplasm and is related both to behavior (sun exposure and care) and immunosuppression (use of calcineurin inhibitors and absence of schemes with mTor inhibitors).
Prevention of sun exposure, self-examination, half-yearly/annual physical examinations by the assistant team, sun protection (specific clothing, sunscreen, exposure limit at times with a higher concentration of UVA/UVB rays), reducing the use of calcineurin inhibitors and increasing the use of mTor inhibitors were considered as measures to be included in this systematic review. Biological measurements for evaluation of skin lesions or sunburns were also included. The studies needed to be randomized, interventions in the prevention of skin cancer, active and passive protocols of sun protection, present equipment to protect against sunlight, pharmaceutical interventions and primary objectives aimed at prevention.
Of the 20 studies, 16 were specific for renal Tx and 4 were multiple. Eight studies were single center, 11 were multicenter and one did not make the model clear. Of the interventional studies, 5 were behavioral, 6 were switched to mTor, 4 were photodynamic therapy, 3 were oral retinoids, 1 was nicotinamide, and 1 was using immunomodulators.
The studies showed a lot of heterogeneity, with sun protection behavior having I2 98%, knowledge with sun protection with I2 76% for assessing the impact of knowledge about sun protection, probably due to discrepant questionnaires. In the attitudes taken for sun protection, the variability of heterogeneity ranged from 96 to 99%, even using clinical criteria for injury and sunburn.
Limited number of studies, different intervention models (applications, cell phone programs, written letters), lack of prolonged follow-up, patient discontinuation, different protocols in doses and mTor standards were problems that compromised the quality of the study, increasing its heterogeneity and precluding the ability to obtain adequate statistical values. The ideal would be I2 values below 25% and avoid values above 75%, unfortunately the latter occurred.
There is no doubt about the positive impact of using sun protection measures, replacing calcineurin inhibitors with mTor inhibitors and other pharmacological measures, but more elaborate studies are needed to define the statistical impact of each of these measures.
Please use bold or underline for heading or sub-headings. I like your analysis of level of evidence, limitations and strengths of this study.
Please summarise this article
Aim:
The purpose of this systematic review is to determine the efficacy of various preventive interventions in skin cancer prevention (melanoma and non-melanoma) in solid organ transplantation that have been studied in various randomised controlled trials.
Methods:
Twenty randomised controlled trials (n = 2295 participants) were included from inception till November 2019.
Types of different interventions analysed in this systematic review:
1. Behavioural: by educating sun protection behaviour like
i. outdoor hours spent per week,
ii. sunscreen use,
iii. protective clothing,
iv. use of shades,
v. skin self-examination,
vi. concern about developing skin cancer
through educating workbooks/mobile apps/videos/text messages/consultation
2. Pharmaceutical(topical/local/systemic):
i. photodynamic therapy,
ii. immune response modifiers,
iii. oral retinoids
iv. nicotinamide
3. Switching to mTOR inhibitor
Results:
Due to the low quality of evidence in the studies reviewed, interventions may enhance sun protection behaviour and decrease the incidence of non-melanoma skin cancer (NMSC), but this is not enough to be implemented in decision making or clinical practice.
Limitations:
· Heterogenicity and reporting bias in the studies analysed
· Non-precise point estimates of skin prevention strategies
· Small patients in individual studies(10 studies comprising less than 50 patients)
· Short term follow( 48% studies have less than 12 months follow-up)
· Discontinuation of strategy due to adverse effects(especially in case of mTOR inhibitors)
· Few trials included skin cancer and none included melanoma as outcome measure
Conclusion:
Large, well designed, properly powered, long term randomised studies using clinical and patient important outcome measure which is reliable, homogenous and validated are required to find importance of different interventions in preventing skin cancer in solid organ transplantation and to finally guide decision making in clinical practice.
What is the level of evidence provided by this article?
It is a systematic review of randomised controlled trials and hence level of evidence is 1A.
What is the difference between bias and errors?
There are two types of errors(randomised errors and systematic errors/bias) in clinical research as elaborately mentioned in table as attachment(1)
Reference:
1. Gonzalez de la Cuesta DM. Errors and biases in clinical research. Enferm Intensiva (Engl Ed). 2021;32(4):220-3.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence.
Thank You
THE INTRODUCTION;
—————————————————————
Skin cancers (both non-melanoma and melanoma) are major causes of morbidity and mortality in solid organ transplant recipients. Despite this, trials of interventions aimed at preventing skin cancer in solid organ transplant recipients are few in number (20 trials), small with half comprising of 50 patients or less, of short duration (48% have <12 months follow-up) and 52% do not include incidence of skin cancer as an outcome.
THE STUDY DESIGN :
——————————————
Systematic review.
THE AIM O THE STUDY:
————————————————————–
The aim of this study is determine the effectiveness of interventions that promote behavioural change and skin cancer prevention in solid organ transplant recipients.
ETHICAL APPROVAL;
———————————————————
The study was exempt from approval from an ethics’ board.
THE OUTCOME MEASURES :
——————————————————————————-
1-Incidence of precancerous and cancerous lesions.
2- Sun protection behaviour (including use of sunscreen, use of protective clothing including hats and sunglasses, shade and sun avoidance) .
2-Knowledge and attitude.
3- Skin self- examination .
4-Sun exposure (including skin irritation, sunburn).
5- Biologic measures (including measurement of melanin index and sun damage assessment).
THE POPULATION :
—————————————————–
2295 transplant recipients, who were predominately kidney transplant recipients.
THE INCLUSION CRITERIA :
—————————————————
All randomised controlled trials that evaluated the effect of behavioural or
pharmaceutical interventions on behavioural change or skin cancer prevention in solid organ transplant recipients.
THE EXCLUSION CRITERIA ;
———————————————————————-
1-Studies that did not report these outcomes as primary endpoints were excluded.
2- Studies of interventions for the treatment of skin cancer.
THE METHOD :
—————————————————————–
Risks of bias and evidence certainty were assessed using Cochrane and the
Grading of Recommendations Assessment Development and Evaluation framework.
THE RESULT ;
————————————————-
Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.
THE STRENGTH OF THE STUDIES :
——————————————————————
1-A comprehensive review conducted using methods outlined by Cochrane Collaboration including Grading of Recommendations Assessment Development and Evaluation to assess risk of bias and evidence certainty.
2-Inclusion of a broad range of interventions, including behavioural to improve sun protection behaviour and pharmaceutical (immunosuppression, photodynamic therapy, oral retinoid, nicotinamide and topical immune response modifiers) to evaluate precancerous lesion response and cancer incidence.
THE LIMITATION O THE STUDIES :
——————————————————–
1-Difficulty obtaining an overall summary estimate for many outcomes due to the variability in the analytical methods and reporting in individual studies.
2-Unable to perform detailed subgroup analyses or assess for publication bias due to small number of studies.
3-Few trials included the important outcomes of skin cancer and none included melanoma or mortality.
CONCLUSION :
————————————————–
1-The studies result suggest that further strategies for skin cancer prevention in transplant recipients require a multifaceted and individualised approach.
2-Transplant recipients are likely to benefit from early implementation of education, particularly before transplantation occurs and recipients may be preoccupied with other health needs related to transplantation.
3-Interventions should be integrated into routine appointments and tailored to meet the individual needs of patients.
4-Additional large-scale and high-quality RCTs are needed to demonstrate the effectiveness of interventions used to prevent skin cancer in transplant recipients in terms of patient important outcomes, in particular morbidity and mortality associated with skin cancer.
5-Determining patient’s preferences for prevention and management of skin cancer is also warranted to ensure interventions and outcomes for trials are relevant to patient needs and priorities and better support patient-centred treatment decisions.
6-Evidence of the efficacy of sun protective behaviour interventions need to be strengthened, with use of measures that are homogeneous, reliable and
validated.
7-Preventative measures including behavioural, switch to mTORis and other pharmaceuticals may improve skin cancer outcomes for solid organ transplant recipients. However, the overall quality of evidence is very low and insufficient to guide decision-making and clinical practice.
What is the level of evidence provided by this article?
LEVEL I
What is the difference between bias and errors?
Error is a specific instance of inaccurately sampling, such that the estimate does not represent the population, while a bias is a consistent error that affects multiple samples.
That is an excellent summary.
I like your analysis of level of evidence.
1-Summary
Introduction
Non melanoma (NMSC) and melanoma skin cancers are the most common cancers occurring post solid organ transplantation, NMSC incidence increase with time.
Squamous cell carcinoma rate is higher than Basal cell carcinoma in solid organ transplant recipients compared to matched controls.
Although transplant recipients’ survival improved, skin cancer and cancer related mortality increased as well.
Sun exposure is a significant modifiable risk factor for skin cancer in general population.
Current recommendations for skin cancer preventive measures are for general population which can be unsuitable for solid organ transplant recipients.
Preventive measures include sun screen application, wearing protective clothes and avoiding direct sun exposure in peak UV light hours and shifting maintenance immunosuppression to m TOR for high risk cases.
Secondary skin cancer preventive measures include using retinoid acitretin.
The aim is to evaluate the effectiveness of behavioural change and pharmaceuticals for skin cancer prevention in solid organ transplantation.
Methods
A systematic review of randomised controlled trials of interventions for skin cancer prevention in solid organ transplant cases ,involving behavioural actions either active or passive as well as pharmaceuticals.
The outcome measures included precancerous and cancerous lesions, sun protection
behaviour.
Results
The study involved 22 reports including 20 RCT , all studies included kidney transplantation while others involved ,heart ,lung and liver transplantation.
Most studies had high or unclear bias risks also the quality of evidence was very low for all outcomes.
The interventions included were behavioural attitude, shifting to m TOR, pharmaceutical intervention.
Behavioural interventions effect on sun protection outcomes
Sun protection behaviour
Cases who had behavioural interventions had better patient sun prevention scores but this is not valid enough due to low evidence quality.
Sun protection knowledge
It’s effectiveness either through workbooks , mobile apps ,messages ,videos was evaluated in 6 studies revealing favourable outcomes.
Sun protection attitude
Educational workbook, text messages or a mobile app programme improved sun protection attitude in 3 studies but unconfirmed due to low quality of evidence.
Skin complications and biologic measures
2 studies showed the effectiveness of behavioural intervention in the form of educational workbook, text messages or a mobile app programme compared to standard care regarding skin irritation, sun exposure , severity of sun damage and melanin index.
Pharmaceutical interventions effects on skin cancer prevention
Involving switch to mTOR ,photodynamic therapy and immune response modifiers.
9 studies evaluated NMSC incidence and none included melanoma.
Topical/local interventions
Immune response modifier, 5% imiquimod cream decreased skin dysplasia, atypia and viral warts in comparison to placebo in a study.
Photodynamic therapy reduced NMSC risk in a Danish study.
60% response rate of photodynamic therapy in recipients with diagnosed keratoses compared with 24% in the control group in 2 trials.
Systemic interventions
5 trials revealed that mTOR decreased the incidence of NMSC compared to CNIs however quality of evidence was very low.
Oral retinoid and acitretin, compared to placebo lowered SCC and BCC risk in a study.
Discussion
Behavioural intervention studies did not include precancerous lesions or skin cancer incidence as outcomes.
The evidence for interventions for skin cancer prevention in solid organ transplant recipients is of very low quality.
Behavioural interventions improved sun protection attitude, knowledge and behaviour, but these studies were inconsistent did not involve skin cancer as an outcome.
The best method for sun protection education was not detected due to small number of studies.
The shifting to m TORI compared to CNI maintenance was accompanied with less NMSC incidence but this was modest due to heterogenicity of the studies.
Pharmaceutical therapy decreased precancerous lesions but this was unconfirmed due to few trials, lack of follow up .
Previous systematic reviews stated that computer programmes can improve sun protective behaviours, and reduce UV light exposure.
Oral retinoids for the prevention of skin cancer among high-risk transplant recipients results were inconclusive due to lack of enough studies.
The effect of skin cancer prevention estimation is unconfirmed due to heterogeneity of the studies, the high risk of bias and discontinuation as with m TOR .
No study included melanoma outcome nor mortality.
Although m TOR conversion is associated with lower cancer risk on the other hand it is associated with higher mortality rates , more discontinuation due to adverse events.
Nicotinamide reduced cancer risk by 20%.
There is no evidence that behavioural therapy can decrease morbidity or mortality.
Skin cancer prevention in transplant recipients need a multifaceted and individualised approach.
Large RCTs are needed to evaluate the effectiveness of interventions used to prevent skin cancer in transplant recipients.
Preventative measures as behavioural, switch to mTOR and pharmaceuticals can improve
skin cancer outcomes in solid organ transplant recipients.
2- level of evidence is 1
3-Bias is non random , can occur systematically, can lead to prejudiced results ,identified manually or through available software programs
-Error is random, can lead to inaccurate outcomes ,identified through calculations as false positive rates, false negative rates
That is a excellent summary.
I like your analysis of level of evidence.
Patients who have had solid organ transplants are at a greater risk of developing skin cancer, which affects more than half of all recipients.
The aim of the study is:
In solid organ transplant patients, the purpose of this research is to investigate the efficacy of treatments that promote behavioral change and skin cancer prevention.
Design:
systematic review. There were a total of twenty trials with a total of 2295 participants.
Conditions for eligibility We looked at randomized, controlled studies that looked at how well drugs or behavior treatments prevented skin cancer in people who had solid organ transplants. These interventions might be either behavioral or pharmacological.
Results :
There were a total of twenty trials, with a total of 2295 participants. Due to the low quality of the evidence, it is hard to say if behavioral treatments might help people learn how to protect themselves from the sun.
Due to the poor quality of the data, we are unable to draw any conclusions on the effects of the mammalian target of rapamycin inhibitors on the incidence of nonmelanocytic skin cancer.
Limitations:
-The impact of skin cancer preventive strategies is questionable due to study heterogeneity.
-high risk of bias, the possibility for reporting bias, and imprecision in point estimates.
-Most pharmaceutical intervention trials were in Europe, whereas all behavioral intervention studies were in the US, four by the same authors.
-Adverse effects caused by high mTOR is trial discontinuation rates.
-Due to the insufficient number of papers in the meta-analysis, we were unable to undertake subgroup analyses to investigate heterogeneity or publication bias.
Conclusions :
Behavioral and pharmaceutical preventive interventions may improve sun protective behavior and knowledge, and reduce the incidence of non-melanocytic skin cancer; however, the overall quality of the evidence is very low, and it is insufficient to guide decision-making and clinical practice. Even so, there is a chance that these interventions will help people learn and act more sun-safely.
What is the level of evidence provided by this article?
Level 1, systematic review
What is the difference between bias and errors?
bias refers to deviations that are not due to chance alone. tendency to deviate from the norm. and can be considered systematic errors.
Error: an unintentional deviation from truth or accuracy that fails to achieve what should be done.
That is a good summary, I wish you could have typed headings in bold, or underline or in italics.
I like your analysis of level of evidence.
Skin cancer either melanoma and non-melanoma skin cancer NMSC are frequently seen in more than 50% of transplant recipient and its incidence is cumulative as it increases by the time post-transplant.
This has a risk of graft rejection, as its diagnosis of course will affect course of immunosuppressive drugs because it should be handled and reduced so it carries the risk of graft rejection and failure.
The mortality is higher from skin cancer in transplant recipient than general population.
Direct sun exposure is important factor that increase the risk of skin cancer in general population and especially post solid organ transplant, this factor is behavioral factor which means that counselling of the patient regarding sun exposure and protection from ultraviolet rays A and B is very important.
Sun protection behavior, defined as hours spent outdoors per week, use of sunscreen, wearing protective clothing and seeking shade. Educational workbooks, educational workbooks and text messages and a mobile app program were compared with standard care.
Sun protection knowledge The effectiveness of educational workbooks, text messages, mobile app programmes and videos on sun protection knowledge.
Sun protection attitude sun protective attitude after receiving an educational workbook, text messages or a mobile app programme over a period.
Sun protection attitude changed to the better one after inclusion of sun protection knowledge through the patient’s behavior.
Also, pharmaceutical interventions affect the precancerous lesions like conversion to sirolimus, photodynamic treatment and immune response modifiers can decrease incidence of skin cancer.
The adherence of the patients to behavioral changes against sun exposure is not well practiced, also conversion to sirolimus is associated with adverse effects and also should be done as early as possible before appearance of any precancerous lesion.
it is level 1 evidence
Bias is defined as any tendency which prevents unprejudiced consideration of a question 6. In research, bias occurs when “systematic error [is] introduced into sampling or testing by selecting or encouraging one outcome or answer over others” 7. Bias can occur at any phase of research, including study design or data collection, as well as in the process of data analysis and publication.
Christopher J. Pannucci, Edwin G. Wilkins. Identifying and Avoiding Bias in Research. Plast Reconstr Surg. 2010 Aug; 126(2): 619–625.
Chris Nickson. Error in Research. LIFE IN THE FASTLANE.2020
That is a good summary, I wish you could have added headings.
I like your analysis of level of evidence.