Association between dermatology follow-up and melanoma survival: A population-based cohort study.

BACKGROUND: Guidelines recommend that patients with melanoma undergo dermatologic examination at least annually. Adherence to follow-up and its impact on survival are unclear. OBJECTIVE: To determine the level of adherence to annual dermatologic follow-up in patients with primary cutaneous melanoma, identify predictors for better adherence, and evaluate whether adherence was associated with melanoma-related mortality. METHODS: Retrospective inception cohort analysis of adults with primary invasive melanoma in Ontario, Canada from 2010 to 2013 with follow-up until December 31, 2018. RESULTS: Adherence to dermatologic follow-up was variable with only 28.0% of patients seeing a dermatologist at least annually (median follow-up 5.0 years). Younger age, female sex, higher income, greater access to dermatology care, stage 2/3 melanoma, prior keratinocyte carcinoma, fewer comorbidities, and any outpatient visit in the 12 months prior to melanoma diagnosis were predictors for adherence. Greater adherence to annual dermatology visits was associated with reduced melanoma-specific mortality compared with lower levels of adherence (adjusted hazard ratio 0.64, 95% CI 0.52-0.78). LIMITATIONS: Observational study design and inability to identify skin examinations performed by non-dermatologists. CONCLUSION: Adherence to annual dermatology visits after melanoma diagnosis was low. Greater adherence may promote better patient survival but warrants confirmation in further research including randomized trials.

Characterizing the cutaneous late effects of allogeneic hematopoietic stem cell transplantation: A systematic review.

BACKGROUND: There is a well-documented risk of secondary cutaneous malignancies following allogeneic hematopoietic stem cell transplant (HSCT), but data on risk in pediatric populations are limited. The objective of this study is to perform a systematic review of reported features and outcomes of skin cancers in pediatric allogeneic HSCT recipients. METHODS: MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science were systematically searched (Prospero CRD42022342139). Studies reporting cutaneous cancer outcomes were included if the age at transplant was ≤19 years. Titles, abstracts, and full-text articles were screened in duplicate. RESULTS: Out of 824 citations that were screened, 12 articles were selected for analysis. The final sample included 67 pediatric HSCT recipients, comprising 65 allogeneic transplant recipients and 2 cases of HSCT with an unknown donor type. The median age at transplant and skin cancer diagnosis were 7.4 and 13 years, respectively. Out of the 67 pediatric HSCT recipients, some patients developed more than one lesion, resulting in 71 lesions. The most common skin cancer type was cutaneous squamous cell carcinoma (32 lesions), followed by basal cell carcinoma (25 lesions). The median latency period between HSCT and skin cancer diagnosis ranged from 0 to 29 years. Identified risk factors for skin cancers included younger age at the time of transplant, exposure to total body irradiation, prolonged post-transplant immunosuppression, graft versus host disease, and sunburn. CONCLUSION: Skin cancers are reported in pediatric allogeneic HSCT recipients, and the risk appears to be increased. More data are needed to better characterize this risk.

The risk of skin cancer in women who carry BRCA1 or BRCA2 mutations.

BACKGROUND: It has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations. METHODS: We report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations. Women were followed from the date of baseline questionnaire to the diagnosis of skin cancer, to age 80 years, death from any cause, or the date of last follow-up. RESULTS: During the mean follow-up period of eight years, 3.7% of women with a BRCA1 mutation (133 of 3,623) and 3.8% of women with a BRCA2 mutation (99 of 2,584) reported a diagnosis of skin cancer (including both keratinocyte carcinomas and melanoma). The cumulative risk of all types of skin cancer from age 20 to 80 years was 14.1% for BRCA1 carriers and 10.7% for BRCA2 carriers. The cumulative risk of melanoma was 2.5% for BRCA1 carriers and 2.3% for BRCA2 carriers, compared to 1.5% for women in the general population in the United States. The strongest risk factor for skin cancer was a prior diagnosis of skin cancer. CONCLUSION: The risk of non-melanoma skin cancer in women who carry a mutation in BRCA1 or BRCA2 is similar to that of non-carrier women. The risk of melanoma appears to be slightly elevated. We suggest that a referral to a dermatologist or primary care provider for BRCA mutation carriers for annual skin examination and counselling regarding limiting UV exposure, the use of sunscreen and recognizing the early signs of melanoma might be warranted, but further studies are necessary.

[Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extensionDiretrizes para protocolos de ensaios clínicos com intervenções que utilizam inteligência artificial: a extensão SPIRIT-AI]. / Directrices para los protocolos de ensayos clínicos de intervenciones con inteligencia artificial: la extensión SPIRIT-AI.

The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.

A declaração SPIRIT 2013 tem como objetivo melhorar a integralidade dos relatórios dos protocolos de ensaios clínicos, fornecendo recomendações baseadas em evidências para o conjunto mínimo de itens que devem ser abordados. Essas orientações têm sido fundamentais para promover uma avaliação transparente de novas intervenções. Recentemente, tem-se reconhecido cada vez mais que intervenções que incluem inteligência artificial (IA) precisam ser submetidas a uma avaliação rigorosa e prospectiva para demonstrar seus impactos sobre os resultados de saúde. A extensão SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials - Artificial Intelligence) é uma nova diretriz de relatório para protocolos de ensaios clínicos que avaliam intervenções com um componente de IA. Essa diretriz foi desenvolvida em paralelo à sua declaração complementar para relatórios de ensaios clínicos, CONSORT-AI (Consolidated Standards of Reporting Trials - Artificial Intelligence). Ambas as diretrizes foram desenvolvidas por meio de um processo de consenso em etapas que incluiu revisão da literatura e consultas a especialistas para gerar 26 itens candidatos. Foram feitas consultas sobre esses itens a um grupo internacional composto por 103 interessados diretos, que participaram de uma pesquisa Delphi em duas etapas. Chegou-se a um acordo sobre os itens em uma reunião de consenso que incluiu 31 interessados diretos, e os itens foram refinados por meio de uma lista de verificação piloto que envolveu 34 participantes. A extensão SPIRIT-AI inclui 15 itens novos que foram considerados suficientemente importantes para os protocolos de ensaios clínicos com intervenções que utilizam IA. Esses itens novos devem constar dos relatórios de rotina, juntamente com os itens básicos da SPIRIT 2013. A SPIRIT-AI preconiza que os pesquisadores descrevam claramente a intervenção de IA, incluindo instruções e as habilidades necessárias para seu uso, o contexto no qual a intervenção de IA será integrada, considerações sobre o manuseio dos dados de entrada e saída, a interação humano-IA e a análise de casos de erro. A SPIRIT-AI ajudará a promover a transparência e a integralidade nos protocolos de ensaios clínicos com intervenções que utilizam IA. Seu uso ajudará editores e revisores, bem como leitores em geral, a entender, interpretar e avaliar criticamente o delineamento e o risco de viés de um futuro estudo clínico.

Development of consensus-driven SPIRIT and CONSORT extensions for early phase dose-finding trials: the DEFINE study.

BACKGROUND: Early phase dose-finding (EPDF) trials are crucial for the development of a new intervention and influence whether it should be investigated in further trials. Guidance exists for clinical trial protocols and completed trial reports in the SPIRIT and CONSORT guidelines, respectively. However, both guidelines and their extensions do not adequately address the characteristics of EPDF trials. Building on the SPIRIT and CONSORT checklists, the DEFINE study aims to develop international consensus-driven guidelines for EPDF trial protocols (SPIRIT-DEFINE) and reports (CONSORT-DEFINE). METHODS: The initial generation of candidate items was informed by reviewing published EPDF trial reports. The early draft items were refined further through a review of the published and grey literature, analysis of real-world examples, citation and reference searches, and expert recommendations, followed by a two-round modified Delphi process. Patient and public involvement and engagement (PPIE) was pursued concurrently with the quantitative and thematic analysis of Delphi participants' feedback. RESULTS: The Delphi survey included 79 new or modified SPIRIT-DEFINE (n = 36) and CONSORT-DEFINE (n = 43) extension candidate items. In Round One, 206 interdisciplinary stakeholders from 24 countries voted and 151 stakeholders voted in Round Two. Following Round One feedback, one item for CONSORT-DEFINE was added in Round Two. Of the 80 items, 60 met the threshold for inclusion (≥ 70% of respondents voted critical: 26 SPIRIT-DEFINE, 34 CONSORT-DEFINE), with the remaining 20 items to be further discussed at the consensus meeting. The parallel PPIE work resulted in the development of an EPDF lay summary toolkit consisting of a template with guidance notes and an exemplar. CONCLUSIONS: By detailing the development journey of the DEFINE study and the decisions undertaken, we envision that this will enhance understanding and help researchers in the development of future guidelines. The SPIRIT-DEFINE and CONSORT-DEFINE guidelines will allow investigators to effectively address essential items that should be present in EPDF trial protocols and reports, thereby promoting transparency, comprehensiveness, and reproducibility. TRIAL REGISTRATION: SPIRIT-DEFINE and CONSORT-DEFINE are registered with the EQUATOR Network ( https://www.equator-network.org/ ).

Incidence, Mortality, and Survival of Merkel Cell Carcinoma: A Systematic Review of Population Based-Studies.

BACKGROUND: Merkel Cell Carcinoma (MCC) is a rare, aggressive skin cancer that most commonly occurs in UV-exposed body sites. Its epidemiology in different geographies and populations is not well characterised. OBJECTIVE: The objective of this systematic review is to summarize evidence on the incidence, mortality, and survival rates of MCC from population-based studies. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from database inception to June 6th, 2023. No geographic, age or date exclusions were applied. We included population-based studies of MCC that reported the incidence, survival, or mortality rate, and considered systematic reviews. A data-charting form was created and validated to identify variables to extract. Two reviewers then independently charted the data for each included study with patient characteristics, and estimates of incidence rate, mortality rate, and survival rate and assessed the quality of included studies using the Joanna Briggs Institute Checklist for Prevalence studies, Newcastle-Ottawa Scale and Assessment of Multiple Systematic Reviews. We abstracted age-, sex-, stage- and race-stratified outcomes, and synthesized comparisons between strata narratively and using vote counting. We assessed the certainty of evidence for those comparisons using the Grading of Recommendations, Assessments, Developments and Evaluations framework. RESULTS: We identified 11,472 citations, of which 52 studies from 24 countries met our inclusion criteria. Stage 1 and the head and neck were the most frequently reported stage and location at diagnosis. The incidence of MCC is increasing over time (high certainty), with the highest reported incidences reported in Southern hemisphere countries (Australia [2.5 per 100,000], New Zealand [0.96 per 100,000]) (high certainty). Male patients generally had higher incidence rates compared to female patients (high certainty), although there were some variations over time periods. Survival rates varied, with lower survival and/or higher mortality associated with male sex (moderate certainty), higher stage at diagnosis (moderate-to-high certainty), older age (moderate certainty), and immunosuppression (low-to-moderate certainty). CONCLUSIONS: MCC is increasing in incidence and may increase further given the ageing population of many countries. The prognosis of MCC is poor, particularly for males, those who are immunosuppressed, and patients diagnosed at higher stages or at an older age.

Hydrochlorothiazide use and risk of keratinocyte carcinoma and melanoma: A multisite population-based cohort study.

BACKGROUND: The association between hydrochlorothiazide (HCTZ) and skin cancer remains controversial. OBJECTIVE: To determine whether HCTZ is associated with an increased risk of skin cancer compared with angiotensin-converting enzyme inhibitors and calcium channel blockers. METHODS: Two new-user, active comparator cohorts were assembled using 6 Canadian databases. Site-specific hazard ratios (HRs) with 95% CIs were estimated using standardized morbidity ratio weighted Cox proportional hazard models and pooled using random-effects meta-analysis. RESULTS: HCTZ was not associated with an overall increased risk of keratinocyte carcinoma compared with angiotensin-converting enzyme inhibitors or calcium channel blockers, although increased risks were observed with longer durations (≥10 years; HR: 1.12; 95% CI: 1.03-1.21) and higher cumulative doses (≥100,000 mg; HR: 1.49; 95% CI: 1.27-1.76). For melanoma, there was no association with angiotensin-converting enzyme inhibitors, but a 32% increased risk with calcium channel blockers (crude incidence rates: 64.2 vs 58.4 per 100,000 person-years; HR: 1.32; 95% CI: 1.19-1.46; estimated number needed to harm at 5 years of follow-up: 1627 patients), with increased risks with longer durations and cumulative doses. LIMITATIONS: Residual confounding due to the observational design. CONCLUSIONS: Increased risks of keratinocyte carcinoma and melanoma were observed with longer durations of use and higher cumulative doses of HCTZ.

Informing a Canadian Skin Science Trainee Program Based on the State of Trainee Programs Offered by International Academic Societies.

BACKGROUND: For dermatology to effectively address the ever-growing medical needs, longstanding communication barriers across investigators working in different research pillars and practicing clinicians must be improved. To address this problem, trainee-specific programs are now evolving to align their educational landscape across basic science, translational and clinical research programs. OBJECTIVES: To establish a Skin Investigation Network of Canada (SkIN Canada) training roadmap for the career and skill development of future clinicians, clinican scientists and basic scientists in Canada. This Working Group aims to strengthen and harmonize collaborations and capacity across the skin research community. METHODS: The Working Group conducted a search of established international academic societies which offered trainee programs with mandates similar to SkIN Canada. Societies' program items and meetings were evaluated by use of an interview survey and/or the collection of publicly available data. Program logistics, objectives and feedback were assessed for commonalities and factors reported or determined to improve trainee experience. RESULTS: Through the various factors explored, the Working Group discovered the need for increasing program accessibility, creating opportunities for soft skill development, emphasizing the importance of current challenges, collecting and responding to feedback, and improving knowledge sharing to bridge pillars of skin research. CONCLUSIONS: Although improvements have been made to trainee education in recent years, a plurality of approaches exist and many of the underlying roadblocks remain unresolved. To establish fundamental clinician-basic scientist collaboration and training efforts, this Working Group highlights important factors to include and consider in building a trainee program and emphasizes the importance of trainee education.

Top Ten Research Priorities for Psoriasis, Atopic Dermatitis and Hidradenitis Suppurativa: The SkIN Canada Priority Setting Initiative.

BACKGROUND: The Skin Investigation Network of Canada (SkIN Canada) is a new national skin research network. To shape the research landscape and ensure its value to patient care, research priorities that are important to patients, caregivers, and health care providers must be identified. OBJECTIVES: To identify the Top Ten research priorities for 9 key skin conditions. METHODS: We first surveyed health care providers and researchers to select the top skin conditions for future research within the categories of inflammatory skin disease, skin cancers (other than melanoma), and wound healing. For those selected skin conditions, we conducted scoping reviews to identify previous priority setting exercises. We combined the results of those scoping reviews with a survey of patients, health care providers, and researchers to generate lists of knowledge gaps for each condition. We then surveyed patients and health care providers to create preliminary rankings to prioritize those knowledge gaps. Finally, we conducted workshops of patients and health care providers to create the final Top Ten lists of research priorities for each condition. RESULTS: Overall, 538 patients, health care providers, and researchers participated in at least one survey or workshop. Psoriasis, atopic dermatitis and hidradenitis suppurativa (inflammatory skin disease); chronic wounds, burns and scars (wound healing); and basal cell, squamous cell and Merkel cell carcinoma (skin cancer) were selected as priority skin conditions. Top Ten lists of knowledge gaps for inflammatory skin conditions encompassed a range of issues relevant to patient care, including questions on pathogenesis, prevention, non-pharmacologic and pharmacologic management. CONCLUSIONS: Research priorities derived from patients and health care providers should be used to guide multidisciplinary research networks, funders, and policymakers in Canada and internationally.

[Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extensionDiretrizes para protocolos de ensaios clínicos com intervenções que utilizam inteligência artificial: a extensão SPIRIT-AI]. / Directrices para los protocolos de ensayos clínicos de intervenciones con inteligencia artificial: la extensión SPIRIT-AI.

The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.

A declaração SPIRIT 2013 tem como objetivo melhorar a integralidade dos relatórios dos protocolos de ensaios clínicos, fornecendo recomendações baseadas em evidências para o conjunto mínimo de itens que devem ser abordados. Essas orientações têm sido fundamentais para promover uma avaliação transparente de novas intervenções. Recentemente, tem-se reconhecido cada vez mais que intervenções que incluem inteligência artificial (IA) precisam ser submetidas a uma avaliação rigorosa e prospectiva para demonstrar seus impactos sobre os resultados de saúde. A extensão SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials - Artificial Intelligence) é uma nova diretriz de relatório para protocolos de ensaios clínicos que avaliam intervenções com um componente de IA. Essa diretriz foi desenvolvida em paralelo à sua declaração complementar para relatórios de ensaios clínicos, CONSORT-AI (Consolidated Standards of Reporting Trials - Artificial Intelligence). Ambas as diretrizes foram desenvolvidas por meio de um processo de consenso em etapas que incluiu revisão da literatura e consultas a especialistas para gerar 26 itens candidatos. Foram feitas consultas sobre esses itens a um grupo internacional composto por 103 interessados diretos, que participaram de uma pesquisa Delphi em duas etapas. Chegou-se a um acordo sobre os itens em uma reunião de consenso que incluiu 31 interessados diretos, e os itens foram refinados por meio de uma lista de verificação piloto que envolveu 34 participantes. A extensão SPIRIT-AI inclui 15 itens novos que foram considerados suficientemente importantes para os protocolos de ensaios clínicos com intervenções que utilizam IA. Esses itens novos devem constar dos relatórios de rotina, juntamente com os itens básicos da SPIRIT 2013. A SPIRIT-AI preconiza que os pesquisadores descrevam claramente a intervenção de IA, incluindo instruções e as habilidades necessárias para seu uso, o contexto no qual a intervenção de IA será integrada, considerações sobre o manuseio dos dados de entrada e saída, a interação humano-IA e a análise de casos de erro. A SPIRIT-AI ajudará a promover a transparência e a integralidade nos protocolos de ensaios clínicos com intervenções que utilizam IA. Seu uso ajudará editores e revisores, bem como leitores em geral, a entender, interpretar e avaliar criticamente o delineamento e o risco de viés de um futuro estudo clínico.

[Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extensionDiretrizes para protocolos de ensaios clínicos com intervenções que utilizam inteligência artificial: a extensão SPIRIT-AI]. / Directrices para los protocolos de ensayos clínicos de intervenciones con inteligencia artificial: la extensión SPIRIT-AI.

The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.

A declaração SPIRIT 2013 tem como objetivo melhorar a integralidade dos relatórios dos protocolos de ensaios clínicos, fornecendo recomendações baseadas em evidências para o conjunto mínimo de itens que devem ser abordados. Essas orientações têm sido fundamentais para promover uma avaliação transparente de novas intervenções. Recentemente, tem-se reconhecido cada vez mais que intervenções que incluem inteligência artificial (IA) precisam ser submetidas a uma avaliação rigorosa e prospectiva para demonstrar seus impactos sobre os resultados de saúde. A extensão SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials - Artificial Intelligence) é uma nova diretriz de relatório para protocolos de ensaios clínicos que avaliam intervenções com um componente de IA. Essa diretriz foi desenvolvida em paralelo à sua declaração complementar para relatórios de ensaios clínicos, CONSORT-AI (Consolidated Standards of Reporting Trials - Artificial Intelligence). Ambas as diretrizes foram desenvolvidas por meio de um processo de consenso em etapas que incluiu revisão da literatura e consultas a especialistas para gerar 26 itens candidatos. Foram feitas consultas sobre esses itens a um grupo internacional composto por 103 interessados diretos, que participaram de uma pesquisa Delphi em duas etapas. Chegou-se a um acordo sobre os itens em uma reunião de consenso que incluiu 31 interessados diretos, e os itens foram refinados por meio de uma lista de verificação piloto que envolveu 34 participantes. A extensão SPIRIT-AI inclui 15 itens novos que foram considerados suficientemente importantes para os protocolos de ensaios clínicos com intervenções que utilizam IA. Esses itens novos devem constar dos relatórios de rotina, juntamente com os itens básicos da SPIRIT 2013. A SPIRIT-AI preconiza que os pesquisadores descrevam claramente a intervenção de IA, incluindo instruções e as habilidades necessárias para seu uso, o contexto no qual a intervenção de IA será integrada, considerações sobre o manuseio dos dados de entrada e saída, a interação humano-IA e a análise de casos de erro. A SPIRIT-AI ajudará a promover a transparência e a integralidade nos protocolos de ensaios clínicos com intervenções que utilizam IA. Seu uso ajudará editores e revisores, bem como leitores em geral, a entender, interpretar e avaliar criticamente o delineamento e o risco de viés de um futuro estudo clínico.

Reporting of Factorial Randomized Trials: Extension of the CONSORT 2010 Statement.

Importance: Transparent reporting of randomized trials is essential to facilitate critical appraisal and interpretation of results. Factorial trials, in which 2 or more interventions are assessed in the same set of participants, have unique methodological considerations. However, reporting of factorial trials is suboptimal. Objective: To develop a consensus-based extension to the Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement for factorial trials. Design: Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the CONSORT extension for factorial trials was developed by (1) generating a list of reporting recommendations for factorial trials using a scoping review of methodological articles identified using a MEDLINE search (from inception to May 2019) and supplemented with relevant articles from the personal collections of the authors; (2) a 3-round Delphi survey between January and June 2022 to identify additional items and assess the importance of each item, completed by 104 panelists from 14 countries; and (3) a hybrid consensus meeting attended by 15 panelists to finalize the selection and wording of items for the checklist. Findings: This CONSORT extension for factorial trials modifies 16 of the 37 items in the CONSORT 2010 checklist and adds 1 new item. The rationale for the importance of each item is provided. Key recommendations are (1) the reason for using a factorial design should be reported, including whether an interaction is hypothesized, (2) the treatment groups that form the main comparisons should be clearly identified, and (3) for each main comparison, the estimated interaction effect and its precision should be reported. Conclusions and Relevance: This extension of the CONSORT 2010 Statement provides guidance on the reporting of factorial randomized trials and should facilitate greater understanding of and transparency in their reporting.

Picosecond Infrared Laser Mass Spectrometry Identifies a Metabolite Array for 10 s Diagnosis of Select Skin Cancer Types: A Proof-of-Concept Feasibility Study.

Currently, a large number of skin biopsies are taken for each true skin cancer case detected, creating a need for a rapid, high sensitivity, and specificity skin cancer detection tool to reduce the number of unnecessary biopsies taken from benign tissue. Picosecond infrared laser mass spectrometry (PIRL-MS) using a hand-held sampling probe is reported to detect and classify melanoma, squamous cell carcinoma, and normal skin with average sensitivity and specificity values of 86-95% and 91-98%, respectively (at a 95% confidence level) solely requiring 10 s or less of total data collection and analysis time. Classifications are not adversely affected by specimen's quantity of melanin pigments and are mediated by a number of metabolic lipids, further identified herein as potential biomarkers for skin cancer-type differentiation, 19 of which were sufficient here (as a fully characterized metabolite array) to provide high specificity and sensitivity classification of skin cancer types. In situ detection was demonstrated in an intradermal melanoma mouse model wherein in vivo sampling did not cause significant discomfort. PIRL-MS sampling is further shown to be compatible with downstream gross histopathologic evaluations despite loss of tissue from the immediate laser sampling site(s) and can be configured using selective laser pulses to avoid thermal damage to normal skin. Therefore, PIRL-MS may be employed as a decision-support tool to reduce both the subjectivity of clinical diagnosis and the number of unnecessary biopsies currently required for skin cancer screening.

Outcomes of skin cancers in pediatric solid organ transplant patients: A systematic review.

BACKGROUND: The most frequently reported malignancies after solid organ transplant are cutaneous, but data on the risk in pediatric populations varies across studies. OBJECTIVES: To perform a systematic review including reported features and outcomes of skin cancers in pediatric solid organ transplant recipients. METHODS: EMBASE and MEDLINE were systematically searched (Prospero CRD42020201659). RESULTS: The review summarizes data from 20 studies on 337 patients, with a median age ranging from 15.0 to 19.5 years as reported in 4 studies, who developed skin malignancies after pediatric solid organ transplantation. Median ages at transplant and skin cancer diagnosis ranged from 1.5 to 17.0 years and 15.3 to 33.5 years, respectively. Squamous cell carcinoma (SCC) was most commonly reported (218 cases), followed by basal cell carcinoma (BCC) (91 cases), melanoma (18 cases), and unspecified keratinocyte carcinomas (2 cases). The median latency period between transplantation and cancer diagnosis ranged from 2.2 to 21.0 years. Overall, 4 studies reported 17 cases of metastasis in total, and recurrence was reported in one case. Six deaths were reported in one study related to SCC and melanoma metastases. The incidence rate of skin cancer after pediatric transplantation per 100 person-years of follow-up was 2.1 based on 5 studies. CONCLUSION: The most frequent post-transplant malignancy in pediatric organ transplant recipients was SCC.

Guidelines for Reporting Outcomes in Trial Reports: The CONSORT-Outcomes 2022 Extension.

Importance: Clinicians, patients, and policy makers rely on published results from clinical trials to help make evidence-informed decisions. To critically evaluate and use trial results, readers require complete and transparent information regarding what was planned, done, and found. Specific and harmonized guidance as to what outcome-specific information should be reported in publications of clinical trials is needed to reduce deficient reporting practices that obscure issues with outcome selection, assessment, and analysis. Objective: To develop harmonized, evidence- and consensus-based standards for reporting outcomes in clinical trial reports through integration with the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement. Evidence Review: Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the CONSORT-Outcomes 2022 extension of the CONSORT 2010 statement was developed by (1) generation and evaluation of candidate outcome reporting items via consultation with experts and a scoping review of existing guidance for reporting trial outcomes (published within the 10 years prior to March 19, 2018) identified through expert solicitation, electronic database searches of MEDLINE and the Cochrane Methodology Register, gray literature searches, and reference list searches; (2) a 3-round international Delphi voting process (November 2018-February 2019) completed by 124 panelists from 22 countries to rate and identify additional items; and (3) an in-person consensus meeting (April 9-10, 2019) attended by 25 panelists to identify essential items for the reporting of outcomes in clinical trial reports. Findings: The scoping review and consultation with experts identified 128 recommendations relevant to reporting outcomes in trial reports, the majority (83%) of which were not included in the CONSORT 2010 statement. All recommendations were consolidated into 64 items for Delphi voting; after the Delphi survey process, 30 items met criteria for further evaluation at the consensus meeting and possible inclusion in the CONSORT-Outcomes 2022 extension. The discussions during and after the consensus meeting yielded 17 items that elaborate on the CONSORT 2010 statement checklist items and are related to completely defining and justifying the trial outcomes, including how and when they were assessed (CONSORT 2010 statement checklist item 6a), defining and justifying the target difference between treatment groups during sample size calculations (CONSORT 2010 statement checklist item 7a), describing the statistical methods used to compare groups for the primary and secondary outcomes (CONSORT 2010 statement checklist item 12a), and describing the prespecified analyses and any outcome analyses not prespecified (CONSORT 2010 statement checklist item 18). Conclusions and Relevance: This CONSORT-Outcomes 2022 extension of the CONSORT 2010 statement provides 17 outcome-specific items that should be addressed in all published clinical trial reports and may help increase trial utility, replicability, and transparency and may minimize the risk of selective nonreporting of trial results.

Guidelines for Reporting Outcomes in Trial Protocols: The SPIRIT-Outcomes 2022 Extension.

Importance: Complete information in a trial protocol regarding study outcomes is crucial for obtaining regulatory approvals, ensuring standardized trial conduct, reducing research waste, and providing transparency of methods to facilitate trial replication, critical appraisal, accurate reporting and interpretation of trial results, and knowledge synthesis. However, recommendations on what outcome-specific information should be included are diverse and inconsistent. To improve reporting practices promoting transparent and reproducible outcome selection, assessment, and analysis, a need for specific and harmonized guidance as to what outcome-specific information should be addressed in clinical trial protocols exists. Objective: To develop harmonized, evidence- and consensus-based standards for describing outcomes in clinical trial protocols through integration with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement. Evidence Review: Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement was developed by (1) generation and evaluation of candidate outcome reporting items via consultation with experts and a scoping review of existing guidance for reporting trial outcomes (published within the 10 years prior to March 19, 2018) identified through expert solicitation, electronic database searches of MEDLINE and the Cochrane Methodology Register, gray literature searches, and reference list searches; (2) a 3-round international Delphi voting process (November 2018-February 2019) completed by 124 panelists from 22 countries to rate and identify additional items; and (3) an in-person consensus meeting (April 9-10, 2019) attended by 25 panelists to identify essential items for outcome-specific reporting to be addressed in clinical trial protocols. Findings: The scoping review and consultation with experts identified 108 recommendations relevant to outcome-specific reporting to be addressed in trial protocols, the majority (72%) of which were not included in the SPIRIT 2013 statement. All recommendations were consolidated into 56 items for Delphi voting; after the Delphi survey process, 19 items met criteria for further evaluation at the consensus meeting and possible inclusion in the SPIRIT-Outcomes 2022 extension. The discussions during and after the consensus meeting yielded 9 items that elaborate on the SPIRIT 2013 statement checklist items and are related to completely defining and justifying the choice of primary, secondary, and other outcomes (SPIRIT 2013 statement checklist item 12) prospectively in the trial protocol, defining and justifying the target difference between treatment groups for the primary outcome used in the sample size calculations (SPIRIT 2013 statement checklist item 14), describing the responsiveness of the study instruments used to assess the outcome and providing details on the outcome assessors (SPIRIT 2013 statement checklist item 18a), and describing any planned methods to account for multiplicity relating to the analyses or interpretation of the results (SPIRIT 2013 statement checklist item 20a). Conclusions and Relevance: This SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement provides 9 outcome-specific items that should be addressed in all trial protocols and may help increase trial utility, replicability, and transparency and may minimize the risk of selective nonreporting of trial results.

Guidelines for cellular and molecular pathology content in clinical trial protocols: the SPIRIT-Path extension.

The 2013 SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Statement provides evidence-based recommendations for the minimum content to be included in a clinical trial protocol. Assessment of biospecimens is often required for trial eligibility or as part of an outcome evaluation, and precision molecular approaches are increasingly used in trial design. However, cellular and molecular pathology practices within trials have not been codified or formalised. We developed international consensus reporting guidelines for cellular and molecular pathology content in clinical trial protocols (the SPIRIT-Path extension) using an international Delphi process, which assesses candidate items generated from a previous systematic review, followed by an expert consensus meeting. 74 individuals from five continents responded, including clinicians, statisticians, laboratory scientists, patient advocates, funders, industry representatives, journal editors, and regulators. The SPIRIT-Path guidelines recommend 14 additional items (seven extensions to the SPIRIT checklist and seven elaborations) that should be addressed in trial protocols containing pathology content, alongside the SPIRIT 2013 Statement items. SPIRIT-Path recommends that protocols should document the individuals, processes, and standards for all cellular and molecular pathology components of the trial, including all stages of the specimen pathway and any digital pathology methods, with specific consideration of the value of trial data and biological tissues for additional translational studies.

Incidence and mortality rates of keratinocyte carcinoma from 1998-2017: a population-based study of sex differences in Ontario, Canada.

BACKGROUND: Keratinocyte carcinoma is the most common malignant disease, but it is not captured in major registries. We aimed to describe differences by sex in the incidence and mortality rates of keratinocyte carcinoma in Ontario, Canada. METHODS: We conducted a population-based retrospective study of adults residing in Ontario between Jan. 1, 1998, and Dec. 31, 2017, using linked health administrative databases. We identified the first diagnosis of keratinocyte carcinoma using a validated algorithm of health insurance claims, and deaths related to keratinocyte carcinoma from death certificates. We calculated the incidence and mortality rates of keratinocyte carcinoma, stratified by sex, age and income quintile. We evaluated trends using the average annual percentage change (AAPC) based on joinpoint regression. RESULTS: After decreasing from 1998 to 2003, the incidence rate of keratinocyte carcinoma increased by 30% to 369 per 100 000 males and 345 per 100 000 females in 2017 (AAPC 1.9%, 95% confidence interval [CI] 1.7 to 2.1 from 2003 to 2017). The incidence rate was higher in females younger than 55 years, but higher in males aged 55 years or older. Between 2008 and 2017, the incidence rate rose faster in females than males aged 45-54 years (AAPC 1.2% v. 0.5%, p = 0.01) and 55-64 years (1.2% v. 0.1%, p < 0.01). The incidence was higher in males than females in the higher income quintiles. Between 1998 and 2017, the mortality rate of keratinocyte carcinoma was 1.8 times higher in males than females, on average, and rose 4.8-fold overall (AAPC 8.9%, 95% CI 6.4 to 11.4 in males; 8.0%, 95% CI 5.3-10.8 in females). INTERPRETATION: The population burden of keratinocyte carcinoma is growing, and the incidence and mortality rates rose disproportionately among certain sex- and age-specific groups. This warrants further investigation into causal factors and renewed preventive public health measures.

Association between antihypertensive medications and risk of skin cancer in people older than 65 years: a population-based study.

BACKGROUND: The risk of skin cancer associated with antihypertensive medication use is unclear, although thiazides have been implicated in regulatory safety warnings. We aimed to assess whether use of thiazides and other antihypertensives is associated with increased rates of keratinocyte carcinoma and melanoma. METHODS: We conducted a population-based inception cohort study using linked administrative health data from Ontario, 1998-2017. We matched adults aged ≥ 66 years with a first prescription for an antihypertensive medication (thiazides, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, ß-blockers) by age and sex to 2 unexposed adults who were prescribed a non-antihypertensive medication within 30 days of the index date. We evaluated each antihypertensive class in a separate cohort study. Our primary exposure was the cumulative dose within each class, standardized according to the World Health Organization's Defined Daily Dose. Outcomes were time to first keratinocyte carcinoma, advanced keratinocyte carcinoma and melanoma. RESULTS: The inception cohorts included a total of 302 634 adults prescribed an antihypertensive medication and 605 268 unexposed adults. Increasing thiazide exposure was associated with an increased rate of incident keratinocyte carcinoma (adjusted hazard ratios [HRs] per 1 Defined Annual Dose unit 1.08, 95% confidence interval [CI] 1.03-1.14), advanced keratinocyte carcinoma (adjusted HR 1.07, 95% CI 0.93-1.23) and melanoma (adjusted HR 1.34, 95% CI 1.01-1.78). We found no consistent evidence of association between other antihypertensive classes and keratinocyte carcinoma or melanoma. INTERPRETATION: Higher cumulative exposure to thiazides was associated with increased rates of incident skin cancer in people aged 66 years and older. Consideration of other antihypertensive treatments in patients at high risk of skin cancer may be warranted.

Outcomes of Staged Excision With Circumferential en Face Margin Control for Lentigo Maligna of the Head and Neck.

BACKGROUND: Treatment practices vary for lentigo maligna (LM). Staged excision with circumferential margin control (SECMC) has the potential to achieve low recurrence rates. OBJECTIVES: To evaluate the clinical outcomes of SECMC using permanent, paraffin-embedded sections and delayed reconstruction. METHODS: We conducted a retrospective, uncontrolled, observational cohort study involving patients who underwent staged excision for LM of the head and neck at Women's College Hospital in Toronto, Canada, from September 2010 to March 2013. Recurrence and infection rates were ascertained from patient charts and postal surveys. RESULTS: One hundred and two patients (45 female, 57 male) were included with a median follow-up time of 1410.5 (IQR 260-1756) days. The median age was 69 (IQR 61-79) years. Approximately one-fifth (21%, 21/102) of patients required greater than 0.5 cm margins to achieve histological clearance. One patient (1/102) upstaged to invasive melanoma based on the initial stage of excision. The infection rate was 6% (6/102) and the 5-year cumulative recurrence rate was 1.4% (95% CI 0.2-9.6%). CONCLUSION: SECMC using permanent sections and delayed reconstruction appears to be a safe and effective treatment method for LM on the head and neck. Randomized trials are needed to help define the optimal treatment.