[Prevalence of burnout syndrome in physicians working in Spain: systematic review and meta-analysis]. / Prevalencia del síndrome de burnout en médicos que trabajan en España: revisión sistemática y metaanálisis.

OBJECTIVE: To analyze the prevalence of burnout syndrome in physicians working in Spain through a systematic review with meta-analysis METHOD: We searched PubMed/MEDLINE, Embase, and PsycINFO (up to June 2023). Observational studies conducted in Spain reporting the prevalence of burnout in physicians were included. From each study, methodological characteristics and results were extracted, and their quality was evaluated. We performed a narrative synthesis with random effects meta-analysis to calculate proportions. RESULTS: Sixty-seven studies with 16,076 participants were included. For the primary outcome, the meta-analysis revealed a global prevalence of burnout in physicians of 24% (95%CI: 19%-29%; 46 studies; 8821 participants; I2=97%). From subgroup analysis, differences were observed depending on the diagnostic criteria used: 18% (95%CI: 13%-23%) for three dimensions of burnout, 29% (95%CI: 24%-34%) for two dimensions and 51% (95%CI: 42%-60%) for one dimension. The heterogeneity between studies could not be fully explained through additional analyses where non-statistically significant differences were found with other variables (e.g., study quality, setting, professional category or medical specialty). CONCLUSIONS: A high prevalence of burnout syndrome was found in physicians working in Spain. These results can contribute to estimating the burden associated with burnout in physicians at a national level and to the design of future studies. Strategies appear to be necessary to prevent and mitigate this situation. PROTOCOL REGISTRATION: Open Science Framework: https://osf.io/b2h4m/.

Transparency, openness, and reproducible research practices are frequently underused in health economic evaluations.

OBJECTIVES: To investigate the extent to which articles of economic evaluations of healthcare interventions indexed in MEDLINE incorporate research practices that promote transparency, openness, and reproducibility. STUDY DESIGN AND SETTING: We evaluated a random sample of health economic evaluations indexed in MEDLINE during 2019. We included articles written in English reporting an incremental cost-effectiveness ratio in terms of costs per life years gained, quality-adjusted life years, and/or disability-adjusted life years. Reproducible research practices, openness, and transparency in each article were extracted in duplicate. We explored whether reproducible research practices were associated with self-report use of a guideline. RESULTS: We included 200 studies published in 147 journals. Almost half were published as open access articles (n = 93; 47%). Most studies (n = 150; 75%) were model-based economic evaluations. In 109 (55%) studies, authors self-reported use a guideline (e.g., for study conduct or reporting). Few studies (n = 31; 16%) reported working from a protocol. In 112 (56%) studies, authors reported the data needed to recreate the incremental cost-effectiveness ratio for the base case analysis. This percentage was higher in studies using a guideline than studies not using a guideline (72/109 [66%] with guideline vs. 40/91 [44%] without guideline; risk ratio 1.50, 95% confidence interval 1.15-1.97). Only 10 (5%) studies mentioned access to raw data and analytic code for reanalyses. CONCLUSION: Transparency, openness, and reproducible research practices are frequently underused in health economic evaluations. This study provides baseline data to compare future progress in the field.

[Vaccination coverage, beliefs, and attitudes in transplanted children and adolescents: a mixed-methods systematic review.] / Cobertura vacunal, creencias y actitudes en niños y adolescentes trasplantados: una revisión sistemática de métodos mixtos.

OBJECTIVE: Vaccine-preventable infectious diseases are a cause of morbidity and mortality in transplanted children. The main objective of this study was to synthesize the available evidence of vaccination coverage in children and adolescents who are candidates or transplant recipients and to analyze beliefs, attitudes, and experiences about vaccination. METHODS: A mixed-methods systematic review was performed (Open Science Framework registration: https://osf.io/auqn3/). Searches were conducted in PubMed/MEDLINE, EMBASE, IBECS and LILACS (from January 2000 to August 2021) and in gray literature. Quantitative and qualitative studies reported information on coverage, beliefs, attitudes and/or experiences about recommended vaccines in children who are candidates or recipients of solid organ or hematopoietic progenitor transplantation. Quality assessment was undertaken using Mixed Methods Appraisal Tool (MMAT). A narrative synthesis of the studies was carried out. RESULTS: A total of thirty-two studies in thirty-five publications were included. The most studied interventions were vaccines against measles (n=21; 66%) and hepatitis B (n=20; 62%). Vaccination rates showed a high variability for the most represented vaccines (specifically, 2%-100% for measles, 0.4%-100% for hepatitis B, diphtheria-tetanus-pertussis and rubella), with coverages lower than 90% in at least 70% of the studies. The lowest rates were reported in post-transplantation and hematopoietic stem cell transplantation. Only one qualitative study was identified reporting information on beliefs and/or attitudes, although nine quantitative studies explored cognitive aspects. CONCLUSIONS: This review shows a high variability in vaccination coverage in children and adolescents who are transplant candidates or recipients, with rates lower than those recommended. Further studies would be needed to identify beliefs and attitudes about immunization in this context.

OBJETIVO: Las enfermedades infecciosas prevenibles mediante vacunación son una causa de morbilidad y mortalidad en niños trasplantados. El objetivo principal de este estudio fue sintetizar la evidencia disponible de la cobertura vacunal en niños y adolescentes candidatos o receptores de trasplante y analizar las creencias, actitudes y experiencias acerca de la vacunación. METODOS: Se realizó una revisión sistemática de métodos mixtos (registro Open Science Framework: https://osf.io/auqn3/). Se llevaron a cabo búsquedas en PubMed/MEDLINE, EMBASE, IBECS y LILACS (desde enero de 2000 hasta agosto de 2021) y en literatura gris. Los estudios cuantitativos y cualitativos informaron sobre cobertura, creencias, actitudes y/o experiencias con respecto a cualquier vacuna recomendada en niños candidatos o receptores de trasplante de órganos sólidos y/o progenitores hematopoyéticos. Se evaluó la calidad metodológica mediante la herramienta MMAT (Mixed Methods Appraisal Tool). Se llevó a cabo una síntesis narrativa de los estudios. RESULTADOS: Se incluyeron treinta y dos estudios disponibles en treinta y cinco publicaciones. Las intervenciones más estudiadas fueron las vacunas frente a sarampión (n=21; 66%) y hepatitis B (n=20; 62%). Las tasas de inmunización mostraron una alta variabilidad para las vacunas más representadas (concretamente, 2%-100% en sarampión, 0,4%-100% en hepatitis B, difteria-tétanos-tosferina y rubeola), con coberturas inferiores al 90% en al menos el 70% de los estudios. Los valores más bajos se registraron en situación postrasplante y trasplante de progenitores hematopoyéticos. Sólo se identificó un estudio cualitativo que incluyó información sobre creencias y/o actitudes, aunque nueve estudios cuantitativos exploraron aspectos cognitivos. CONCLUSIONES: Esta revisión muestra una elevada variabilidad en la cobertura vacunal de niños candidatos o receptores de trasplante, con cifras generalmente inferiores a las recomendadas. Sería necesario desarrollar más estudios que contribuyan a identificar creencias y actitudes sobre inmunización en este contexto.

[Tumour necrosis factor (TNF) antagonist therapy for paediatric inflammatory bowel disease: A systematic review]. / Antagonistas del factor de necrosis tumoral (TNF) en la enfermedad inflamatoria intestinal pediátrica: Una revisión sistemática.

Inflammatory bowel disease includes two chronic inflammatory diseases, ulcerative colitis and Crohn's disease. The burden of disease is increasing worldwide. A few reviews evaluating the paediatric use of tumour necrosis factor (TNF) antagonists have been published, although these mostly include observational studies and do not consider economic evaluations. This systematic review evaluated the available evidence regarding the efficacy, safety, and cost-effectiveness of TNF antagonist therapy for paediatric inflammatory bowel disease. We searched PubMed/MEDLINE, Embase, and Cochrane Central (up to May 2022). Nine randomized clinical trials and four economic evaluations that examined any anti-TNF drugs (e.g., infliximab, adalimumab, golimumab, and certolizumab) against different alternatives were included. In studies evaluating the efficacy of anti-TNF drugs in Crohn's disease, most assessed the efficacy of maintenance regimen in patients who had previously responded to induction (response=28%-63%, and clinical remission=17%-83% depending on dose, drug, and follow-up). In ulcerative colitis, maintenance treatment with anti-TNF drugs reported clinical remission rates between 17% and 44%. Nine studies reported information on adverse events. No clinical trials comparing different anti-TNF drugs were found. The findings from this review suggest that maintenance treatment with anti-TNF drugs (such as infliximab and adalimumab) in paediatric inflammatory bowel disease is probably effective and safe. However, the economic evaluations reported contradictory results of the cost-effectiveness ratios. Protocol registry: Open Science Framework: https://osf.io/wjmvf.

Cobertura vacunal, creenciasy actitudes en niños y adolescentes trasplantados: una revisión sistemática de métodos mixtos / Vaccination coverage, beliefs, and attitudes in transplanted children and adolescents: a mixed-methods systematic review

Fundamentos: Las enfermedades infecciosas prevenibles mediante vacunación son una causa de morbilidad y mortalidaden niños trasplantados. El objetivo principal de este estudio fue sintetizar la evidencia disponible de la cobertura vacunal en niñosy adolescentes candidatos o receptores de trasplante y analizar las creencias, actitudes y experiencias acerca de la vacunación. Métodos: Se realizó una revisión sistemática de métodos mixtos (registro Open Science Framework:https://osf.io/auqn3/). Se lleva-ron a cabo búsquedas enPubMed/MEDLINE, EMBASE, IBECS yLILACS (desde enero de 2000 hasta agosto de 2021) y en literatura gris. Losestudios cuantitativos y cualitativos informaron sobre cobertura, creencias, actitudes y/o experiencias con respecto a cualquier vacunarecomendada en niños candidatos o receptores de trasplante de órganos sólidos y/o progenitores hematopoyéticos. Se evaluó la calidadmetodológica mediante la herramienta MMAT (Mixed Methods Appraisal Tool). Se llevó a cabo una síntesis narrativa de los estudios. Resultados: Se incluyeron treinta y dos estudios disponibles en treinta y cinco publicaciones. Las intervenciones más estu-diadas fueron las vacunas frente a sarampión (n=21; 66%) y hepatitis B (n=20; 62%). Las tasas de inmunización mostraron una altavariabilidad para las vacunas más representadas (concretamente, 2%-100% en sarampión, 0,4%-100% en hepatitis B, difteria-téta-nos-tosferina y rubeola), con coberturas inferiores al 90% en al menos el 70% de los estudios. Los valores más bajos se registraronen situación postrasplante y trasplante de progenitores hematopoyéticos. Sólo se identificó un estudio cualitativo que incluyó infor-mación sobre creencias y/o actitudes, aunque nueve estudios cuantitativos exploraron aspectos cognitivos. Conclusiones: Esta revisión muestra una elevada variabilidad en la cobertura vacunal de niños candidatos o receptores detrasplante, con cifras generalmente inferiores a las...(AU)

Background: Vaccine-preventable infectious diseases are a cause of morbidity and mortality in transplanted children. Themain objective of this study was to synthesize the available evidence of vaccination coverage in children and adolescents who arecandidates or transplant recipients and to analyze beliefs, attitudes, and experiences about vaccination. Methods: A mixed-methods systematic review was performed (Open Science Framework registration:https://osf.io/auqn3/). Sear-ches were conducted in PubMed/MEDLINE, EMBASE, IBECS and LILACS (from January 2000 to August 2021) and in gray literature. Quan-titative and qualitative studies reported information on coverage, beliefs, attitudes and/or experiences about recommended vaccines inchildren who are candidates or recipients of solid organ or hematopoietic progenitor transplantation. Quality assessment was undertakenusing Mixed Methods Appraisal Tool (MMAT). A narrative synthesis of the studies was carried out. Results: A total of thirty-two studies in thirty-five publications were included. The most studied interventions were vaccinesagainst measles (n=21; 66%) and hepatitis B (n=20; 62%). Vaccination rates showed a high variability for the most representedvaccines (specifically, 2%-100% for measles, 0.4%-100% for hepatitis B, diphtheria-tetanus-pertussis and rubella), with coverageslower than 90% in at least 70% of the studies. The lowest rates were reported in post-transplantation and hematopoietic stem celltransplantation. Only one qualitative study was identified reporting information on beliefs and/or attitudes, although nine quantitativestudies explored cognitive aspects. Conclusions: This review shows a high variability in vaccination coverage in children and adolescents who are transplantcandidates or recipients, with rates lower than those recommended. Further studies would be needed to identify beliefs and attitudesabout immunization in this context.(AU)

A cross-sectional analysis identified co-authorship networks and scientific collaboration on reporting guidelines for health research.

OBJECTIVES: To investigate scientific collaboration and citation metrics of reporting guidelines for health research. STUDY DESIGN AND SETTING: A cross-sectional analysis of published articles of reporting guidelines for health research. A search of the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network Library (from inception to January 21, 2021) was supplemented by searching websites of guideline developers. For each article, metadata (e.g., authors, institutions, countries, citations) were extracted from the Web of Science and Scopus (up to October 25, 2021). Descriptive analyses were conducted. Network analyses of collaborations were presented. RESULTS: We included 662 articles published in 332 journals. The BMJ (n = 50 articles; 8%), Annals of Internal Medicine (n = 29; 4%), and Journal of Clinical Epidemiology (n = 24; 4%) published the largest number of articles. Four thousand seven hundred twenty two authors, 1,647 institutions, and 83 countries were involved. The global productivity was led by the United States (n = 456 articles), the United Kingdom (n = 414), and Canada (n = 306). We found eight clusters of authors (e.g., one major group with 337 members) and three clusters of institutions (e.g., one major group with 256 members). The most prolific authors were affiliated with the Ottawa Hospital Research Institute (Canada), the University of Ottawa (Canada), the University of Oxford (the United Kingdom), and Stanford University (the United States). CONCLUSION: Our analysis identified key actors producing reporting guidelines, most intense collaborations, and 'citation classics' in the field. These results could potentially be used to strengthen collaborations for developing and disseminating reporting guidelines for health research.

Evaluating the online impact of reporting guidelines for randomised trial reports and protocols: a cross-sectional web-based data analysis of CONSORT and SPIRIT initiatives.

Reporting guidelines are tools to help improve the transparency, completeness, and clarity of published articles in health research. Specifically, the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statements provide evidence-based guidance on what to include in randomised trial articles and protocols to guarantee the efficacy of interventions. These guidelines are subsequently described and discussed in journal articles and used to produce checklists. Determining the online impact (i.e., number and type of links received) of these articles can provide insights into the dissemination of reporting guidelines in broader environments (web-at-large) than simply that of the scientific publications that cite them. To address the technical limitations of link analysis, here the Debug-Validate-Access-Find (DVAF) method is designed and implemented to measure different facets of the guidelines' online impact. A total of 65 articles related to 38 reporting guidelines are taken as a baseline, providing 240,128 URL citations, which are then refined, analysed, and categorised using the DVAF method. A total of 15,582 links to journal articles related to the CONSORT and SPIRIT initiatives were identified. CONSORT 2010 and SPIRIT 2013 were the reporting guidelines that received most links (URL citations) from other online objects (5328 and 2190, respectively). Overall, the online impact obtained is scattered (URL citations are received by different article URL IDs, mainly from link-based DOIs), narrow (limited number of linking domain names, half of articles are linked from fewer than 29 domain names), concentrated (links come from just a few academic publishers, around 60% from publishers), non-reputed (84% of links come from dubious websites and fake domain names) and highly decayed (89% of linking domain names were not accessible at the time of the analysis). In light of these results, it is concluded that the online impact of these guidelines could be improved, and a set of recommendations are proposed to this end. Supplementary Information: The online version contains supplementary material available at 10.1007/s11192-022-04542-z.

Design and methodological characteristics of studies using observational routinely collected health data for investigating the link between cancer and neurodegenerative diseases: protocol for a meta-research study.

INTRODUCTION: Health services generate large amounts of routine health data (eg, administrative databases, disease registries and electronic health records), which have important secondary uses for research. Increases in the availability and the ability to access and analyse large amounts of data represent a major opportunity for conducting studies on the possible relationships between complex diseases. The objective of this study will be to evaluate the design, methods and reporting of studies conducted using observational routinely collected health data for investigating the link between cancer and neurodegenerative diseases. METHODS AND ANALYSIS: This is the protocol for a meta-research study. We registered the study protocol within the Open Science Framework: https://osf.io/h2qjg. We will evaluate observational studies (eg, cohort and case-control) conducted using routinely collected health data for investigating the associations between cancer and neurodegenerative diseases (such as Alzheimer's disease, amyotrophic lateral sclerosis/motor neuron disease, Huntington's disease, multiple sclerosis and Parkinson's disease). The following electronic databases will be searched (from their inception onwards): MEDLINE, Embase and Web of Science Core Collection. Screening and selection of articles will be conducted by at least two researchers. Potential discrepancies will be resolved via discussion. Design, methods and reporting characteristics in each article will be extracted using a standardised data extraction form. Information on general, methodological and transparency items will be reported. We will summarise our findings with tables and graphs (eg, bar charts, forest plots). ETHICS AND DISSEMINATION: Due to the nature of the proposed study, no ethical approval will be required. We plan to publish the full study in an open access peer-reviewed journal and disseminate the findings at scientific conferences and via social media. All data will be deposited in a cross-disciplinary public repository.

Mortality in Persons With Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis.

IMPORTANCE: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are childhood-onset disorders that may persist into adulthood. Several studies have suggested that they may be associated with an increased risk of mortality; however, the results are inconsistent. OBJECTIVE: To assess the risk of mortality among persons with ASD or ADHD and their first-degree relatives. DATA SOURCES: A search of MEDLINE, Embase, Scopus, Web of Science, and PsycINFO (published from inception to April 1, 2021) was supplemented by searching reference lists of the retrieved articles. STUDY SELECTION: Cohort and case-control studies that reported mortality rate ratios (RRs) in persons with ASD or ADHD and/or their first-degree relatives compared with the general population or those without ASD/ADHD were included. DATA EXTRACTION AND SYNTHESIS: Screening, data extraction, and quality assessment were performed by at least 2 researchers independently. A random-effects model was used to meta-analyze individual studies and assessed heterogeneity (I2). MAIN OUTCOMES AND MEASURES: All-cause mortality in association with ASD or ADHD. Secondary outcome was cause-specific mortality. RESULTS: Twenty-seven studies were included, with a total of 642 260 individuals. All-cause mortality was found to be higher for persons with ASD (154 238 participants; 12 studies; RR, 2.37; 95% CI, 1.97-2.85; I2, 89%; moderate confidence) and persons with ADHD (396 488 participants; 8 studies; RR, 2.13; 95% CI, 1.13-4.02; I2, 98%; low confidence) than for the general population. Among persons with ASD, deaths from natural causes (4 studies; RR, 3.80; 95% CI, 2.06-7.01; I2, 96%; low confidence) and deaths from unnatural causes were increased (6 studies; RR, 2.50; 95% CI, 1.49-4.18; I2, 95%; low confidence). Among persons with ADHD, deaths from natural causes were not significantly increased (4 studies; RR, 1.62; 95% CI, 0.89-2.96; I2, 88%; low confidence), but deaths from unnatural causes were higher than expected (10 studies; RR, 2.81; 95% CI, 1.73-4.55; I2, 92%; low confidence). CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found that ASD and ADHD are associated with a significantly increased risk of mortality. Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups. The substantial heterogeneity between studies should be explored further.

Citation impact was highly variable for reporting guidelines of health research: a citation analysis.

OBJECTIVES: Over 400 reporting guidelines are currently published, but the frequency of their use by authors to accurately and transparently report research remains unclear. This study examined citation counts of reporting guidelines and characteristics contributing to their citation impact. STUDY DESIGN AND SETTING: Web of Science database was searched for citation counts of all reporting guidelines with a minimum citation age of 5 years. The total citation impact, mean citation impact and the factors contributing to 2- and 5-year citation rate were established. RESULTS: The search identified 296 articles of reporting guidelines from 1995 to 2013. The mean citations per year was 32.4 (95% confidence interval, 22.3-42.4 citations). The factors associated with 2- and 5-year citation performance of reporting guidelines included the following: open access to the reporting guideline, field of the publishing journal (general vs. specialized medical journal), impact factor of the publishing journal, simultaneous publication in multiple journals, and a male first author. CONCLUSION: The citation rate across reporting guidelines varied with journal impact factor, open access publication, field of the publishing journal, simultaneous publications, and a male first author. Gaps in citations highlight opportunities to increase visibility and encourage author use of reporting guidelines.

Reporting guidelines of health research studies are frequently used inappropriately.

OBJECTIVES: Appropriate use of reporting guidelines of health research ensures that articles present readers with a consistent representation of study relevance, methodology, and results. This study evaluated the use of major reporting guidelines. STUDY DESIGN AND SETTING: A cross-sectional analysis of health research articles citing four major reporting guidelines indexed in the Web of Science Core Collection (up to June 24, 2018). Two independent reviews were performed in a random sample of 200 articles, including clinical trials (N = 50), economic evaluations (N = 50), systematic reviews (N = 50), and animal research studies (N = 50). The use of reporting guidelines to guide the reporting of research studies was considered appropriate. Inappropriate uses included the use of the reporting guidelines as a tool to assess the methodological quality of studies or as a guideline on how to design and conduct the studies. RESULTS: Across all selected reporting guidelines, appropriate use of reporting guidelines was observed in only 39% (95% CI: 32-46%; 78/200) of articles. By contrast, inappropriate use was observed in 41% (95% CI: 34-48%; 82/200), and unclear/other use was observed in 20% (95% CI: 15-26%; 40/200). CONCLUSIONS: Reporting guidelines of health research studies are frequently used inappropriately. Authors may require further education around appropriate use of the reporting guidelines in research reporting.

Hyperosmolar therapy for acute brain injury: study protocol for an umbrella review of meta-analyses and an evidence mapping.

INTRODUCTION: Acute brain injury is a challenging public health problem worldwide. Elevated intracranial pressure is a common complication after acute brain injury. Hyperosmolar therapy is one of the main therapeutic strategies for the management of intracranial hypertension. This study protocol outlines an umbrella review of meta-analyses which will investigate the benefits and harms of hyperosmolar therapy routinely used for the management of acute brain injury in the intensive care. METHODS AND ANALYSIS: We will search PubMed/MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. We will include meta-analyses of primary research studies (eg, randomised controlled trials, observational studies or both) that evaluate one or more hyperosmolar solutions (including hypertonic saline and/or mannitol) for the treatment of adult patients with acute brain injury of any severity. Two researchers will independently screen all citations, full-text articles and abstract data. Potential conflicts will be resolved through discussion with a third researcher. Primary outcomes will be mortality and neurological outcomes at discharge. Secondary outcomes will include control of intracranial pressure, cerebral perfusion pressure, length of stay (in hospital an intensive care unit) and any adverse event. Quality of the included meta-analyses will be assessed using the AMSTAR-2 tool. An overall summary of methods and results will be performed using tabular and graphical approaches and will be supplemented by narrative description. We will analyse whether published meta-analyses present an outline of available evidence (eg, cited, described and discussed any previous meta-analysis). Where objectives from two or more meta-analyses overlap, we will assess the causes of any noted discrepancies between meta-analyses. ETHICS AND DISSEMINATION: No ethical approval will be required. Findings from this study will be published in a peer-reviewed journal. All data will be deposited in a cross-disciplinary public repository. PROSPERO REGISTRATION NUMBER: CRD42019148152.

Reproducible research practices, openness and transparency in health economic evaluations: study protocol for a cross-sectional comparative analysis.

INTRODUCTION: There has been a growing awareness of the need for rigorously and transparent reported health research, to ensure the reproducibility of studies by future researchers. Health economic evaluations, the comparative analysis of alternative interventions in terms of their costs and consequences, have been promoted as an important tool to inform decision-making. The objective of this study will be to investigate the extent to which articles of economic evaluations of healthcare interventions indexed in MEDLINE incorporate research practices that promote transparency, openness and reproducibility. METHODS AND ANALYSIS: This is the study protocol for a cross-sectional comparative analysis. We registered the study protocol within the Open Science Framework (osf.io/gzaxr). We will evaluate a random sample of 600 cost-effectiveness analysis publications, a specific form of health economic evaluations, indexed in MEDLINE during 2012 (n=200), 2019 (n=200) and 2022 (n=200). We will include published papers written in English reporting an incremental cost-effectiveness ratio in terms of costs per life years gained, quality-adjusted life years and/or disability-adjusted life years. Screening and selection of articles will be conducted by at least two researchers. Reproducible research practices, openness and transparency in each article will be extracted using a standardised data extraction form by multiple researchers, with a 33% random sample (n=200) extracted in duplicate. Information on general, methodological and reproducibility items will be reported, stratified by year, citation of the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement and journal. Risk ratios with 95% CIs will be calculated to represent changes in reporting between 2012-2019 and 2019-2022. ETHICS AND DISSEMINATION: Due to the nature of the proposed study, no ethical approval will be required. All data will be deposited in a cross-disciplinary public repository. It is anticipated the study findings could be relevant to a variety of audiences. Study findings will be disseminated at scientific conferences and published in peer-reviewed journals.

Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis.

BACKGROUND: Randomised controlled trials (RCTs) provide the most reliable information to inform clinical practice and patient care. We aimed to map global clinical research publication activity through RCT-related articles in high-impact-factor medical journals over the past five decades. METHODS: We conducted a cross-sectional analysis of articles published in the highest ranked medical journals with an impact factor > 10 (according to Journal Citation Reports published in 2017). We searched PubMed/MEDLINE (from inception to December 31, 2017) for all RCT-related articles (e.g. primary RCTs, secondary analyses and methodology papers) published in high-impact-factor medical journals. For each included article, raw metadata were abstracted from the Web of Science. A process of standardization was conducted to unify the different terms and grammatical variants and to remove typographical, transcription and/or indexing errors. Descriptive analyses were conducted (including the number of articles, citations, most prolific authors, countries, journals, funding sources and keywords). Network analyses of collaborations between countries and co-words are presented. RESULTS: We included 39,305 articles (for the period 1965-2017) published in forty journals. The Lancet (n = 3593; 9.1%), the Journal of Clinical Oncology (n = 3343; 8.5%) and The New England Journal of Medicine (n = 3275 articles; 8.3%) published the largest number of RCTs. A total of 154 countries were involved in the production of articles. The global productivity ranking was led by the United States (n = 18,393 articles), followed by the United Kingdom (n = 8028 articles), Canada (n = 4548 articles) and Germany (n = 4415 articles). Seventeen authors who had published 100 or more articles were identified; the most prolific authors were affiliated with Duke University (United States), Harvard University (United States) and McMaster University (Canada). The main funding institutions were the National Institutes of Health (United States), Hoffmann-La Roche (Switzerland), Pfizer (United States), Merck Sharp & Dohme (United States) and Novartis (Switzerland). The 100 most cited RCTs were published in nine journals, led by The New England Journal of Medicine (n = 78 articles), The Lancet (n = 9 articles) and JAMA (n = 7 articles). These landmark contributions focused on novel methodological approaches (e.g. the "Bland-Altman method") and trials on the management of chronic conditions (e.g. diabetes control, hormone replacement therapy in postmenopausal women, multiple therapies for diverse cancers, cardiovascular therapies such as lipid-lowering statins, antihypertensive medications, and antiplatelet and antithrombotic therapy). CONCLUSIONS: Our analysis identified authors, countries, funding institutions, landmark contributions and high-impact-factor medical journals publishing RCTs. Over the last 50 years, publication production in leading medical journals has increased, with Western countries leading in research but with low- and middle-income countries showing very limited representation.

Association of Anorexia Nervosa With Risk of Cancer: A Systematic Review and Meta-analysis.

Importance: Anorexia nervosa is recognized as an important cause of morbidity in young people. However, the risk of cancer in people with anorexia nervosa remains uncertain. Objective: To evaluate the association of anorexia nervosa with the risk of developing or dying of cancer. Data Sources: MEDLINE, Scopus, Embase, and Web of Science from database inception to January 9, 2019. Study Selection: Published observational studies in humans examining the risk of cancer in people with anorexia nervosa compared with the general population or those without anorexia nervosa. Studies needed to report incidence or mortality rate ratios (RRs). Data Extraction and Synthesis: Screening, data extraction, and methodological quality assessment were performed by at least 2 researchers independently. A random-effects model was used to synthesize individual studies. Heterogeneity (I2) was assessed and 95% prediction intervals (PIs) were calculated. Main Outcomes and Measures: All cancer incidence and cancer mortality associated with anorexia nervosa. Secondary outcomes were site-specific cancer incidence and mortality. Results: Seven cohort studies published in 10 articles (42 602 participants with anorexia nervosa) were included. Anorexia nervosa was not associated with risk of developing any cancer (4 studies in women; RR, 0.97; 95% CI, 0.89-1.06; P = .53; I2, 0%; 95% PI, 0.80-1.18; moderate confidence). Anorexia nervosa was associated with decreased breast cancer incidence (5 studies in women; RR, 0.60; 95% CI, 0.50-0.80; P < .001; I2, 0%; 95% PI, 0.44-0.83; high confidence). Conversely, anorexia nervosa was associated with increased risk of developing lung cancer (3 studies in women; RR, 1.50; 95% CI, 1.06-2.12; P = .001; I2, 0%; 95% PI, 0.19-16.46; low confidence) and esophageal cancer (2 studies in women; RR, 6.10; 95% CI, 2.30-16.18; P < .001; I2, 0%; low confidence). Conclusions and Relevance: Among people with anorexia nervosa, risk of developing cancer did not differ compared with the general population, but a significantly reduced risk of breast cancer was observed. Understanding the mechanisms underlying these associations could have important preventive potential.

Prevalence and comorbidity of autism spectrum disorder in Spain: study protocol for a systematic review and meta-analysis of observational studies.

BACKGROUND: Autism spectrum disorder (ASD) is a complex developmental disorder characterised by impaired social interaction and communication, and restrictive and repetitive behaviour. Previous systematic reviews have traditionally assessed the prevalence of ASD on global or regional context, with very few meta-analyses at the country level. The objective of this study will be to systematically evaluate published and unpublished observational studies that present prevalence and comorbidity of ASD among children, adolescent and adult population in Spain. METHODS/DESIGN: We designed and registered a study protocol for a systematic review and meta-analysis of descriptive epidemiology data. Observational studies (cohort, cross-sectional) reporting the prevalence of ASD and conducted in a wide range of people (e.g. general population, outpatient and/or school settings) will be included. The primary outcome will be the prevalence of ASD. Secondary outcomes will be the prevalence of any physical or mental comorbidity in association with ASD. No limitations will be imposed on publication status, study conduct period, and language of dissemination. Comprehensive literature searches will be conducted in seven electronic databases (from January 1980 onwards), including PubMed/MEDLINE, EMBASE, Scopus, Web of Science, PsycINFO, IME-Spanish Medical Index and IBECS-Spanish Bibliographic Index of Health Sciences. Grey literature will be identified through searching dissertation databases, Google Scholar and conference abstracts. Two team members will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct random effects meta-analysis of observational data. Prevalence estimates will be stratified according to gender, age and geographical location. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g. methodological quality, sample size, diagnostic criteria). DISCUSSION: This systematic review and meta-analysis of observational data will identify, evaluate and integrate the epidemiological knowledge underlying the prevalence of ASD in Spain. The results of this study will be of interest to multiple audiences including patients, their families, caregivers, healthcare professional, scientists and policy makers. Results will be published in a peer-reviewed journal. Implications for future epidemiological research will be discussed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018090372.

Apoyo a las guías de publicación para estudios de evaluación económica por parte de las revistas biomédicas españolas / Endorsement of guidelines for reporting economic evaluation studies by Spanish biomedical journals

Objetivo: Examinar el apoyo a las guías de publicación para estudios de evaluación económica, como la declaración CHEERS (Consolidated Health Economic Evaluation Reporting Standards), por parte de las revistas biomédicas españolas. Método: Análisis transversal de las normas de autoría de las revistas biomédicas españolas incluidas en Journal Citation Reports 2017. Dos autores examinaron y extrajeron la siguiente información: mención de alguna guía de publicación, declaración CHEERS, recomendaciones del International Committee of Medical Journal Editors (ICMJE) e iniciativa Enhancing the QUAlity and Transparency Of health Research (EQUATOR). Resultados: De las 28 revistas incluidas, 23 (82,1%; intervalo de confianza del 95% [IC95%]: 63,1-93,9%) mencionaron alguna guía. Una única revista mencionó la declaración CHEERS para estudios de evaluación económica. Veinticuatro revistas (85,7%; IC95%: 67,3-96,0%) mencionaron las recomendaciones del ICMJE y 8 (28,6%; IC95%: 13,2-48,7%) la red EQUATOR. La declaración CONSORT (Consolidated Standards of Reporting Trials) para ensayos clínicos fue la guía más mencionada (n=21; 75,0%; IC95%: 55,1-89,3%). Discusión: La mayoría de las normas de autoría no incorporan información sobre cómo presentar evaluaciones económicas. Las revistas deberían apoyar el cumplimiento de las guías de publicación por parte de las personas autoras y revisoras

Objective: To examine the endorsement of reporting guidelines for economic evaluation studies, such as the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) statement, by Spanish biomedical journals. Method: Cross-sectional analysis of the instructions to authors of Spanish biomedical journals included in the Journal Citation Reports 2017. Two authors examined and extracted the following information: mention of any reporting guideline, the CHEERS statement, the recommendations of the International Committee of Medical Journal Directors (ICMJE) and the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network. Results: Of the 28 journals included, 23 (82.1%; 95% confidence interval [95%CI]: 63.1-93.9%) mentioned at least one reporting guideline in the instructions to authors. Only one journal mentioned the CHEERS statement for health economic evaluations. Twenty-four journals (85.7%; 95%CI: 67.3-96.0%) mentioned the ICMJE recommendations and 8 (28.6%; 95%CI: 13.2-48.7%) mentioned the EQUATOR network. The CONSORT (Consolidated Standards of Reporting Trials) statement for clinical trials was the most- mentioned reporting guideline (n=21; 75.0%; 95%CI: 55.1-89.3%). Discussion: Most of the instructions to authors do not provide guidance on how to report economic evaluations. Journals should support compliance with reporting guidelines by authors and peer-reviewers

Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer.

Background: Epidemiological and clinical evidence points to cancer as a comorbidity in people with autism spectrum disorders (ASD). A significant overlap of genes and biological processes between both diseases has also been reported. Methods: Here, for the first time, we compared the gene expression profiles of ASD frontal cortex tissues and 22 cancer types obtained by differential expression meta-analysis and report gene, pathway, and drug set-based overlaps between them. Results: Four cancer types (brain, thyroid, kidney, and pancreatic cancers) presented a significant overlap in gene expression deregulations in the same direction as ASD whereas two cancer types (lung and prostate cancers) showed differential expression profiles significantly deregulated in the opposite direction from ASD. Functional enrichment and LINCS L1000 based drug set enrichment analyses revealed the implication of several biological processes and pathways that were affected jointly in both diseases, including impairments of the immune system, and impairments in oxidative phosphorylation and ATP synthesis among others. Our data also suggest that brain and kidney cancer have patterns of transcriptomic dysregulation in the PI3K/AKT/MTOR axis that are similar to those found in ASD. Conclusions: Comparisons of ASD and cancer differential gene expression meta-analysis results suggest that brain, kidney, thyroid, and pancreatic cancers are candidates for direct comorbid associations with ASD. On the other hand, lung and prostate cancers are candidates for inverse comorbid associations with ASD. Joint perturbations in a set of specific biological processes underlie these associations which include several pathways previously implicated in both cancer and ASD encompassing immune system alterations, impairments of energy metabolism, cell cycle, and signaling through PI3K and G protein-coupled receptors among others. These findings could help to explain epidemiological observations pointing towards direct and inverse comorbid associations between ASD and specific cancer types and depict a complex scenario regarding the molecular patterns of association between ASD and cancer.