[Potential sponsorship bias in cost-effectiveness analyses of healthcare interventions: A cross-sectional analysis]. / Potencial sesgo de patrocinio en los análisis coste-efectividad de intervenciones sanitarias: un análisis transversal.

OBJECTIVE: To examine the relationship between the funding source of cost-effectiveness analyses of healthcare interventions published in Spain and study conclusions. DESIGN: Descriptive cross-sectional study. LOCATION: Scientific literature databases (until December 2014). PARTICIPANTS (ANALYSIS UNITS): Cohort of cost-effectiveness analysis of healthcare interventions published in Spain between 1989-2014 (n=223) presenting quality-adjusted life years (QALYs) as the outcome measure. MAIN MEASUREMENTS: The relationship between qualitative conclusions of the studies and the type of funding source were established using Fisher's exact test in contingency tables. Distributions of the incremental cost-effectiveness ratios by source of funding in relation to hypothetical willingness to pay thresholds between €30,000-€50,000 per QALY were explored. RESULTS: A total of 136 (61.0%) studies were funded by industry. The industry-funded studies were less likely to report unfavorable or neutral conclusions than studies non-funded by industry (2.2% vs. 23.0%; P<.0001), largely driven by studies evaluating drugs (0.9% vs. 21.4%; P<.0001). The incremental cost-effectiveness ratios in studies funded by industry were more likely to be below the hypothetical willingness to pay threshold of €30,000 (73.8% vs. 56.3%; P<.0001) and €50,000 (89.4% vs. 68.2%; P<.0001) per QALY. CONCLUSIONS: This study reveals a potential sponsorship bias in cost-effectiveness analyses of healthcare interventions. Studies funded by industry could be favoring the efficiency profile of their products.

Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses.

BACKGROUND: Medications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes. METHODS AND FINDINGS: Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84). No significant differences were showed between ACE inhibitors and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, ESRD, or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies. Potential inconsistency was identified in network meta-analyses of stroke and angina pectoris, limiting the conclusiveness of findings for these single endpoints. CONCLUSIONS: In adults with diabetes, comparisons of different RAS blockers showed similar effects of ACE inhibitors and ARBs on major cardiovascular and renal outcomes. Compared with monotherapies, the combination of an ACE inhibitor and an ARB failed to provide significant benefits on major outcomes. Clinicians should discuss the balance between benefits, costs, and potential harms with individual diabetes patients before starting treatment. REVIEW REGISTRATION: PROSPERO CRD42014014404.

Female authorship positions in health economic evaluations: a cross-sectional analysis.

OBJECTIVE: To investigate the gender of the authors who publish articles of health economic evaluations in medicine and healthcare journals. METHOD: We evaluated a random sample of economic evaluations indexed in MEDLINE during 2019. Gender of the first, last and corresponding author was determined by review of the author's first name. Data were summarized as frequency and percentage for categorical items and median and interquartile range (IQR) for continuous items. We also calculated the index of authors per paper. RESULTS: We included 200 studies with 1365 authors (median of 6 authors per paper; IQR: 4-9). Gender identification was possible for all authors in the study sample: 802 (59%) were men and 563 (41%) were women. The number of female first, last, and corresponding authors respectively were 78 (39%), 68 (34%), and 80 (40%) for health economic evaluations. DISCUSSION: Female scientists were underrepresented as co-authors and in prominent authorship positions in health economic evaluations. This study serves as a call to action for the scientific community to actively work towards equity and inclusion.

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.

Risk of cancer development associated with disease-modifying therapies for multiple sclerosis: study protocol for a systematic review and meta-analysis of randomised and non-randomised studies.

BACKGROUND: The association between cancer and multiple sclerosis has long been investigated. Several studies and reviews have examined the risk of cancer among patients with multiple sclerosis treated with disease-modifying therapies (DMTs) but with conflicting results. This study will aim to investigate the association between DMTs for multiple sclerosis and subsequent cancer risk using research synthesis methods. METHODS/DESIGN: We designed and registered a study protocol for a systematic review and meta-analysis. We will include randomised and non-randomised trials, prospective or retrospective cohort studies, and case-control studies of treatment with DMTs compared with placebo, no treatment, or another active agent. The primary outcome will be the risk of cancer (all-malignant neoplasms) in association with the exposure of DMTs. Secondary outcomes will include site-specific cancers (e.g. breast cancer). Literature searches will be conducted in multiple electronic databases (from their inception onwards), including the following: PubMed/MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). Two researchers will screen all citations, full-text articles, and abstract data independently. The risk of bias (quality) of individual studies will be appraised using an appropriate tool. If feasible, we will use a two-stage approach to evidence synthesis: (1) Peto's method for meta-analysis of data from randomised trials alone; and (2) Random-effects model for meta-analysis adding data from non-randomised studies. We will calculate odds ratios and their associated 95% confidence intervals. Potential sources of heterogeneity will be explored in additional analyses (e.g. subgroups considering different DMTs individually, mechanism of action, type of control, length of follow-up, mode of treatment). DISCUSSION: This systematic review and meta-analysis of randomised and non-randomised studies will provide an updated synthesis of the risk of cancer associated with DMTs for adult patients with multiple sclerosis. This study will also examine some factors that may explain potential variations across studies. The findings will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework ( https://osf.io/v4sez ).

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.

Prevalence of attention deficit hyperactivity disorder among children and adolescents in Spain: a systematic review and meta-analysis of epidemiological studies.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed neuropsychiatric disorder in childhood, but the frequency of the condition is not well established in many countries. The aim of the present study was to quantify the overall prevalence of ADHD among children and adolescents in Spain by means of a systematic review and meta-analysis. METHODS: PubMed/MEDLINE, IME, IBECS and TESEO were comprehensively searched. Original reports were selected if they provided data on prevalence estimates of ADHD among people under 18 years old in Spain and were cross-sectional, observational epidemiological studies. Information from included studies was systematically extracted and evaluated. Overall pooled-prevalence estimates of ADHD were calculated using random-effects models. Sources of heterogeneity were explored by means sub-groups analyses and univariate meta-regressions. RESULTS: Fourteen epidemiological studies (13,026 subjects) were selected. The overall pooled-prevalence of ADHD was estimated at 6.8% [95% confidence interval (CI) 4.9 - 8.8%] representing 361,580 (95% CI 260,550 - 467,927) children and adolescents in the community. There was significant heterogeneity (P < 0.001), which was incompletely explained by subgroup analyses and meta-regressions. CONCLUSIONS: Our findings suggest that the prevalence of ADHD among children and adolescents in Spain is consistent with previous studies conducted in other countries and regions. This study represents a first step in estimating the national burden of ADHD that will be essential to building evidence-based programs and services.

Timing of surgery for hip fracture and in-hospital mortality: a retrospective population-based cohort study in the Spanish National Health System.

BACKGROUND: While the benefits or otherwise of early hip fracture repair is a long-running controversy with studies showing contradictory results, this practice is being adopted as a quality indicator in several health care organizations. The aim of this study is to analyze the association between early hip fracture repair and in-hospital mortality in elderly people attending public hospitals in the Spanish National Health System and, additionally, to explore factors associated with the decision to perform early hip fracture repair. METHODS: A cohort of 56,500 patients of 60-years-old and over, hospitalized for hip fracture during the period 2002 to 2005 in all the public hospitals in 8 Spanish regions, were followed up using administrative databases to identify the time to surgical repair and in-hospital mortality. We used a multivariate logistic regression model to analyze the relationship between the timing of surgery (< 2 days from admission) and in-hospital mortality, controlling for several confounding factors. RESULTS: Early surgery was performed on 25% of the patients. In the unadjusted analysis early surgery showed an absolute difference in risk of mortality of 0.57 (from 4.42% to 3.85%). However, patients undergoing delayed surgery were older and had higher comorbidity and severity of illness. Timeliness for surgery was not found to be related to in-hospital mortality once confounding factors such as age, sex, chronic comorbidities as well as the severity of illness were controlled for in the multivariate analysis. CONCLUSIONS: Older age, male gender, higher chronic comorbidity and higher severity measured by the Risk Mortality Index were associated with higher mortality, but the time to surgery was not.

Revisiting systematic geographical variations in tonsils surgery in children in the Spanish National Health System: spatiotemporal ecological study on hospital administrative data.

OBJECTIVE: To provide new evidence on how tonsils surgery in children has geographically varied over time in the context of the Spanish National Health System. DESIGN: Observational ecological spatiotemporal study on geographical variations in medical practice, using linked administrative datasets, including virtually all surgeries performed from 2003 to 2015. SETTING: The Spanish National Health System, a quasi-federal structure with 17 autonomous communities (ACs), and 203 healthcare areas (HCAs). PARTICIPANTS: Patients aged 19 and younger residing in the HCAs and ACs. INTERVENTIONS: Tonsillectomy with adenoidectomy (T&A); and tonsillectomies alone (T). MAIN ENDPOINTS: (1) Evolution of T&A and T rates; (2) spatiotemporal variation in the risk of receiving T&A or T surgery at regional level (ACs) and HCAs; and (3) the fraction of the variation (FV) attributed to each of the components of variation-ACs, HCAs, year and interaction ACs year. RESULTS: T&A age-sex standardised rates increased over the period of analysis from 15.2 to 20.9 (5.7 points per 10 000 inhabitants). T alone remained relatively lower than T&A rates, evolving from 3.6 in 2003 to 3.9 in 2015 (0.3 points per 10 000 inhabitants). Most of the risk variation was captured at the HCAs level in both procedures (FV: 55.3% in T&A and 72.5% in T). The ACs level explained 27.6% of the FV in the risk in T&A versus 8% in T. The interaction ACs year was similar in both procedures (FV: 15.5% in T&A and 17.5% in T). The average trend hardly explained 1.46% and 1.83% of the variation, respectively. CONCLUSION: Our study showed wide persistent variations with a steady increase in rates and risk of T&A and a stagnation of T alone, where most of the variation risk was explained at HCA level.

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.

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.

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.

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

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.

Prevalence and comorbidity of attention deficit hyperactivity disorder in Spain: study protocol for extending a systematic review with updated meta-analysis of observational studies.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder characterized by a persistent pattern of symptoms of developmentally inappropriate and impaired inattention and/or hyperactivity/impulsivity, with difficulties often continuing into adulthood. ADHD can come with other comorbid conditions. The aim of this study will be to quantify the prevalence and comorbidity of ADHD among children, adolescent, and adult population in Spain. METHODS/DESIGN: We designed and registered a study protocol for an update and expansion of a systematic review and meta-analysis of pooled prevalence data. We will include cross-sectional observational studies reporting prevalence of ADHD in Spain and conducted in the general population, outpatient, and/or school settings. The primary outcome will be the prevalence of ADHD. Secondary outcomes will be the prevalence of any physical or mental comorbidity in association with ADHD. No limitations will be imposed on publication status, study conduct period, and language of dissemination. Comprehensive literature searches will be conducted in multiple electronic databases, including PubMed/MEDLINE, EMBASE, Scopus, Web of Science, PsycINFO, IME - Spanish Medical Index, and IBECS - Spanish Bibliographic Index of Health Sciences. We will also search Google Scholar, dissertation databases, 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 methodological quality (or risk of bias) of individual studies will be appraised using an appropriate tool. If feasible, we will conduct random effects meta-analysis. 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 provide an updated synthesis of the prevalence and comorbidity of ADHD in Spain. This study will also examine factors that may explain potential variations in prevalence data. The findings of this study will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018106082 .

Reporting guidelines for health research: protocol for a cross-sectional analysis of the EQUATOR Network Library.

INTRODUCTION: Transparency and completeness of health research is highly variable, with important deficiencies in the reporting of methods and results of studies. Reporting guidelines aim to improve transparency and quality of research reports, and are often developed by consortia of journal editors, peer reviewers, authors, consumers and other key stakeholders. The objective of this study will be to investigate the characteristics of scientific collaboration among developers and the citation metrics of reporting guidelines of health research. METHODS AND ANALYSIS: This is the study protocol for a cross-sectional analysis of completed reporting guidelines indexed in the Enhancing the QUAlity and Transparency Of health Research Network Library. We will search PubMed/MEDLINE and the Web of Science. Screening, selection and data abstraction will be conducted by one researcher and verified by a second researcher. Potential discrepancies will be resolved via discussion. We will include published papers of reporting guidelines written in English. Published papers will have to meet the definition of a reporting guideline related to health research (eg, a checklist, flow diagram or explicit text), with no restrictions by study design, medical specialty, disease or condition. Raw data from each included paper (including title, publication year, journal, subject category, keywords, citations, and the authors' names, author's affiliated institution and country) will be exported from the Web of Science. Descriptive analyses will be conducted (including the number of papers, citations, authors, countries, journals, keywords and main collaboration metrics). We will identify the most prolific authors, institutions, countries, journals and the most cited papers. Network analyses will be carried out to study the structure of collaborations. ETHICS AND DISSEMINATION: No ethical approval will be required. Findings from this study will be published in peer-reviewed journals. 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.

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.

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.

The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents. METHODS AND FINDINGS: We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution. CONCLUSIONS: Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD. Uncertainties about therapies and the balance between benefits, costs and potential harms should be considered before starting treatment. There is an urgent need for high-quality randomised trials of the multiple treatments for ADHD in children and adolescents. PROSPERO, number CRD42014015008.