Showing papers by "Public Health Research Institute published in 2020"

Prediction models for diagnosis and prognosis of covid-19: systematic review and critical appraisal

Abstract: Objective To review and appraise the validity and usefulness of published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (covid-19) in patients with suspected infection, for prognosis of patients with covid-19, and for detecting people in the general population at increased risk of covid-19 infection or being admitted to hospital with the disease. Design Living systematic review and critical appraisal by the COVID-PRECISE (Precise Risk Estimation to optimise covid-19 Care for Infected or Suspected patients in diverse sEttings) group. Data sources PubMed and Embase through Ovid, up to 1 July 2020, supplemented with arXiv, medRxiv, and bioRxiv up to 5 May 2020. Study selection Studies that developed or validated a multivariable covid-19 related prediction model. Data extraction At least two authors independently extracted data using the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist; risk of bias was assessed using PROBAST (prediction model risk of bias assessment tool). Results 37 421 titles were screened, and 169 studies describing 232 prediction models were included. The review identified seven models for identifying people at risk in the general population; 118 diagnostic models for detecting covid-19 (75 were based on medical imaging, 10 to diagnose disease severity); and 107 prognostic models for predicting mortality risk, progression to severe disease, intensive care unit admission, ventilation, intubation, or length of hospital stay. The most frequent types of predictors included in the covid-19 prediction models are vital signs, age, comorbidities, and image features. Flu-like symptoms are frequently predictive in diagnostic models, while sex, C reactive protein, and lymphocyte counts are frequent prognostic factors. Reported C index estimates from the strongest form of validation available per model ranged from 0.71 to 0.99 in prediction models for the general population, from 0.65 to more than 0.99 in diagnostic models, and from 0.54 to 0.99 in prognostic models. All models were rated at high or unclear risk of bias, mostly because of non-representative selection of control patients, exclusion of patients who had not experienced the event of interest by the end of the study, high risk of model overfitting, and unclear reporting. Many models did not include a description of the target population (n=27, 12%) or care setting (n=75, 32%), and only 11 (5%) were externally validated by a calibration plot. The Jehi diagnostic model and the 4C mortality score were identified as promising models. Conclusion Prediction models for covid-19 are quickly entering the academic literature to support medical decision making at a time when they are urgently needed. This review indicates that almost all pubished prediction models are poorly reported, and at high risk of bias such that their reported predictive performance is probably optimistic. However, we have identified two (one diagnostic and one prognostic) promising models that should soon be validated in multiple cohorts, preferably through collaborative efforts and data sharing to also allow an investigation of the stability and heterogeneity in their performance across populations and settings. Details on all reviewed models are publicly available at https://www.covprecise.org/. Methodological guidance as provided in this paper should be followed because unreliable predictions could cause more harm than benefit in guiding clinical decisions. Finally, prediction model authors should adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guideline. Systematic review registration Protocol https://osf.io/ehc47/, registration https://osf.io/wy245. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 3 of the original article published on 7 April 2020 (BMJ 2020;369:m1328). Previous updates can be found as data supplements (https://www.bmj.com/content/369/bmj.m1328/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.

Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome?

Abstract: Background Many patients with COVID-19 did not require hospitalisation, nor underwent COVID-19 testing. There is anecdotal evidence that patients with “mild” COVID-19 may complain about persistent symptoms, even weeks after the infection. This suggests that symptoms during the infection may not resolve spontaneously. The objective of this study was to assess whether multiple relevant symptoms recover following the onset of symptoms in hospitalised and nonhospitalised patients with COVID-19. Methods A total of 2113 members of two Facebook groups for coronavirus patients with persistent complaints in the Netherlands and Belgium, and from a panel of people who registered on a website of the Lung Foundation Netherlands, were assessed for demographics, pre-existing comorbidities, health status, date of symptoms onset, COVID-19 diagnosis, healthcare utilisation, and the presence of 29 symptoms at the time of the onset of symptoms (retrospectively) and at follow-up (mean±sd 79±17 days after symptoms onset). Results Overall, 112 hospitalised patients and 2001 nonhospitalised patients (confirmed COVID-19, n=345; symptom-based COVID-19, n=882; and suspected COVID-19, n=774) were analysed. The median number of symptoms during the infection reduced significantly over time (median (interquartile range) 14 (11–17) versus 6 (4–9); p Conclusion In previously hospitalised and nonhospitalised patients with confirmed or suspected COVID-19, multiple symptoms are present about 3 months after symptoms onset. This suggests the presence of a “post-COVID-19 syndrome” and highlights the unmet healthcare needs in a subgroup of patients with “mild” or “severe” COVID-19.

COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration.

Abstract: Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3–30.2%] in kidney transplant and 25.0% (95% CI 20.2–30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59–1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation <1 year before presentation (HR adjusted for sex, age and frailty 0.20, 95% CI 0.07–0.56, P < 0.01). Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

Sarcopenia Definition: The Position Statements of the Sarcopenia Definition and Outcomes Consortium

Abstract: Objectives To develop an evidence-based definition of sarcopenia that can facilitate identification of older adults at risk for clinically relevant outcomes (eg, self-reported mobility limitation, falls, fractures, and mortality), the Sarcopenia Definition and Outcomes Consortium (SDOC) crafted a set of position statements informed by a literature review and SDOC's analyses of eight epidemiologic studies, six randomized clinical trials, four cohort studies of special populations, and two nationally representative population-based studies. Methods Thirteen position statements related to the putative components of a sarcopenia definition, informed by the SDOC analyses and literature synthesis, were reviewed by an independent international expert panel (panel) iteratively and voted on by the panel during the Sarcopenia Position Statement Conference. Four position statements related to grip strength, three to lean mass derived from dual-energy x-ray absorptiometry (DXA), and four to gait speed; two were summary statements. Results The SDOC analyses identified grip strength, either absolute or scaled to measures of body size, as an important discriminator of slowness. Both low grip strength and low usual gait speed independently predicted falls, self-reported mobility limitation, hip fractures, and mortality in community-dwelling older adults. Lean mass measured by DXA was not associated with incident adverse health-related outcomes in community-dwelling older adults with or without adjustment for body size. Conclusion The panel agreed that both weakness defined by low grip strength and slowness defined by low usual gait speed should be included in the definition of sarcopenia. These position statements offer a rational basis for an evidence-based definition of sarcopenia. The analyses that informed these position statements are summarized in this article and discussed in accompanying articles in this issue of the journal. J Am Geriatr Soc 68:1410-1418, 2020.

A System Dynamics and Participatory Action Research Approach to Promote Healthy Living and a Healthy Weight among 10-14-Year-Old Adolescents in Amsterdam : The LIKE Programme

Abstract: This paper describes the design of the LIKE programme, which aims to tackle the complex problem of childhood overweight and obesity in 10–14-year-old adolescents using a systems dynamics and participatory approach. The LIKE programme focuses on the transition period from 10-years-old to teenager and was implemented in collaboration with the Amsterdam Healthy Weight Programme (AHWP) in Amsterdam-East, the Netherlands. The aim is to develop, implement and evaluate an integrated action programme at the levels of family, school, neighbourhood, health care and city. Following the principles of Participatory Action Research (PAR), we worked with our population and societal stakeholders as co-creators. Applying a system lens, we first obtained a dynamic picture of the pre-existing systems that shape adolescents’ behaviour relating to diet, physical activity, sleep and screen use. The subsequent action programme development was dynamic and adaptive, including quick actions focusing on system elements (quick evaluating, adapting and possibly catalysing further action) and more long-term actions focusing on system goals and/or paradigm change. The programme is supported by a developmental systems evaluation and the Intervention Level Framework, supplemented with routinely collected data on weight status and health behaviour change over a period of five years. In the coming years, we will report how this approach has worked to provide a robust understanding of the programme's effectiveness within a complex dynamic system. In the meantime, we hope our study design serves as a source of inspiration for other public health intervention studies in complex systems.

Anemia and iron metabolism in COVID-19: a systematic review and meta-analysis.

Abstract: Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19) We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value Six bibliographic databases were searched up to August 3rd 2020 We included 189 unique studies, with data from 57,563 COVID-19 patients Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 1297 g/L (95% Confidence Interval (CI), 12851; 13088) and 77733 ng/mL (95% CI, 70133; 85277), respectively Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), - 408 g/L (95% CI - 512; - 305)] and red blood cell count [WMD, - 016 × 1012 /L (95% CI - 031; - 0014)], and higher ferritin [WMD, - 47325 ng/mL (95% CI 38252; 56398)] and red cell distribution width [WMD, 182% (95% CI 010; 355)] A significant difference in mean ferritin levels of 60637 ng/mL (95% CI 46186; 75088) was found between survivors and non-survivors, but not in hemoglobin levels Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19

Low physical functioning and impaired performance of activities of daily life in COVID-19 patients who survived hospitalisation.

Abstract: About half of the post-COVID-19 patients had severe impairments in physical functioning and during the ADLs at discharge home.This current results provide a clear rationale to study the safety and efficacy of rehabilitative interventions in these patients.

Prospective biomarkers of major depressive disorder: a systematic review and meta-analysis.

Abstract: Leading biological hypotheses propose that biological changes may underlie major depressive disorder onset and relapse/recurrence. Here, we investigate if there is prospective evidence for biomarkers derived from leading theories. We focus on neuroimaging, gastrointestinal factors, immunology, neurotrophic factors, neurotransmitters, hormones, and oxidative stress. Searches were performed in Pubmed, Embase and PsychInfo for articles published up to 06/2019. References and citations of included articles were screened to identify additional articles. Inclusion criteria were having an MDD diagnosis as outcome, a biomarker as predictor, and prospective design search terms were formulated accordingly. PRISMA guidelines were applied. Meta-analyses were performed using a random effect model when three or more comparable studies were identified, using a random effect model. Our search resulted in 67,464 articles, of which 75 prospective articles were identified on: Neuroimaging (N = 24), Gastrointestinal factors (N = 1), Immunology (N = 8), Neurotrophic (N = 2), Neurotransmitters (N = 1), Hormones (N = 39), Oxidative stress (N = 1). Meta-analyses on brain volumes and immunology markers were not significant. Only cortisol (N = 19, OR = 1.294, p = 0.024) showed a predictive effect on onset/relapse/recurrence of MDD, but not on time until MDD onset/relapse/recurrence. However, this effect disappeared when studies including participants with a baseline clinical diagnosis were removed from the analyses. Other studies were too heterogeneous to compare. Thus, there is a lack of evidence for leading biological theories for onset and maintenance of depression. Only cortisol was identified as potential predictor for MDD, but results are influenced by the disease state. High-quality (prospective) studies on MDD are needed to disentangle the etiology and maintenance of MDD.

Which conditions should be considered as disorders in the International Classification of Diseases (ICD-11) designation of “other specified disorders due to addictive behaviors”?

Abstract: © 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes – if any – are indicated.

Lessons on the COVID-19 pandemic, for and by primary care professionals worldwide.

Abstract: The COVID-19 pandemic has modified organisation and processes of primary care. In this paper, we aim to summarise experiences of international primary care systems. We explored personal accounts and findings in reporting on the early experiences from primary care during the pandemic, through the online Global Forum on Universal Health Coverage and Primary Health Care. During the early stage of the pandemic, primary care continued as the first point of contact to the health system but was poorly informed by policy makers on how to fulfil its role and ill equipped to provide care while protecting staff and patients against further spread of the infection. In many countries, the creativity and initiatives of local health professionals led to the introduction or extension of the use of telephone, e-mail and virtual consulting, and introduced triaging to separate 'suspected' COVID-19 from non-COVID-19 care. There were substantial concerns of collateral damage to the health of the population due to abandoned or postponed routine care. The pandemic presents important lessons to strengthen health systems through better connection between public health, primary care, and secondary care to cope better with future waves of this and other pandemics.

The Trans-Ancestral Genomic Architecture of Glycaemic Traits

Abstract: Glycaemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycaemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated haemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P

Equivalency of the diagnostic accuracy of the PHQ-8 and PHQ-9: A systematic review and individual participant data meta-analysis

Abstract: BACKGROUND: Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9. METHODS: We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy. RESULTS: 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01). CONCLUSIONS: PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

COSMIN Risk of Bias tool to assess the quality of studies on reliability or measurement error of outcome measurement instruments: a Delphi study.

Abstract: Scores on an outcome measurement instrument depend on the type and settings of the instrument used, how instructions are given to patients, how professionals administer and score the instrument, etc. The impact of all these sources of variation on scores can be assessed in studies on reliability and measurement error, if properly designed and analyzed. The aim of this study was to develop standards to assess the quality of studies on reliability and measurement error of clinician-reported outcome measurement instruments, performance-based outcome measurement instrument, and laboratory values. We conducted a 3-round Delphi study involving 52 panelists. Consensus was reached on how a comprehensive research question can be deduced from the design of a reliability study to determine how the results of a study inform us about the quality of the outcome measurement instrument at issue. Consensus was reached on components of outcome measurement instruments, i.e. the potential sources of variation. Next, we reached consensus on standards on design requirements (n = 5), standards on preferred statistical methods for reliability (n = 3) and measurement error (n = 2), and their ratings on a four-point scale. There was one term for a component and one rating of one standard on which no consensus was reached, and therefore required a decision by the steering committee. We developed a tool that enables researchers with and without thorough knowledge on measurement properties to assess the quality of a study on reliability and measurement error of outcome measurement instruments.

Effects of Internet-Based Cognitive Behavioral Therapy in Routine Care for Adults in Treatment for Depression and Anxiety : Systematic Review and Meta-Analysis

Abstract: Background: Although there is evidence for the efficacy of internet-based cognitive behavioral therapy (iCBT), the generalizability of results to routine care is limited. Objective: This study systematically reviews effectiveness studies of guided iCBT interventions for the treatment of depression or anxiety. Methods: The acceptability (uptake, participants’ characteristics, adherence, and satisfaction), effectiveness, and negative effects (deterioration) of nonrandomized pre-post designs conducted under routine care conditions were synthesized using systematic review and meta-analytic approaches. Results: A total of 19 studies including 30 groups were included in the analysis. Despite high heterogeneity, individual effect sizes of investigated studies indicate clinically relevant changes, with effect sizes ranging from Hedges’ g=0.42-1.88, with a pooled effect of 1.78 for depression and 0.94 for anxiety studies. Uptake, participants’ characteristics, adherence, and satisfaction indicate a moderate to high acceptability of the interventions. The average deterioration across studies was 2.9%. Conclusions: This study provides evidence supporting the acceptability and effectiveness of guided iCBT for the treatment of depression and anxiety in routine care. Given the high heterogeneity between interventions and contexts, health care providers should select interventions that have been proven in randomized controlled clinical trials. The successful application of iCBT may be an effective way of increasing health care in multiple contexts.

Commentary: COVID in care homes-challenges and dilemmas in healthcare delivery.

Abstract: The COVID-19 pandemic has disproportionately affected care home residents internationally, with 19-72% of COVID-19 deaths occurring in care homes. COVID-19 presents atypically in care home residents and up to 56% of residents may test positive whilst pre-symptomatic. In this article, we provide a commentary on challenges and dilemmas identified in the response to COVID-19 for care homes and their residents. We highlight the low sensitivity of polymerase chain reaction testing and the difficulties this poses for blanket screening and isolation of residents. We discuss quarantine of residents and the potential harms associated with this. Personal protective equipment supply for care homes during the pandemic has been suboptimal and we suggest that better integration of procurement and supply is required. Advance care planning has been challenged by the pandemic and there is a need to for healthcare staff to provide support to care homes with this. Finally, we discuss measures to implement augmented care in care homes, including treatment with oxygen and subcutaneous fluids, and the frameworks which will be required if these are to be sustainable. All of these challenges must be met by healthcare, social care and government agencies if care home residents and staff are to be physically and psychologically supported during this time of crisis for care homes.

Anemia and iron metabolism in COVID-19: A systematic review and meta-analysis

Abstract: Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). If confirmed, this has important implications for the more than 1.62 billion people estimated to have anemia globally. We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and prevalence of anemia) in patients diagnosed with COVID-19, and explore their prognostic value. Six bibliographic databases were searched up to May 5th 2020. We included 56 unique studies, with data from 14,044 COVID-19 patients (59 years median age). Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 130.41 g/L (95% Confidence Interval (CI), 128.42; 132.39) and 673.91 ng/mL (95% CI, 420.98; 926.84), respectively. Hemoglobin levels decreased with advancing age and increasing percentage of comorbid and critically ill patients, while levels of ferritin increased with increasing male proportion and mean hemoglobin levels. Compared to moderate cases, severe cases had lower pooled mean hemoglobin [weighted mean difference (WMD), –4.21 (95% CI –6.63; –1.78)] and higher ferritin [WMD, –730.55 ng/mL (95% CI 413.24; 1047.85)]. A significant difference in mean ferritin level of 1027.23 ng/mL (95% CI 819.53; 1234.94) was found between survivors and non-survivors, but not in hemoglobin levels. No studies provided information on anemia or other biomarkers of interest. Future studies should explore the impact of iron metabolism and anemia and in the pathophysiology, prognosis, and treatment of COVID-19.

Psychotherapy for Depression Across Different Age Groups: A Systematic Review and Meta-analysis.

Abstract: Importance It is not clear whether psychotherapies for depression have comparable effects across the life span. Finding out is important from a clinical and scientific perspective. Objective To compare the effects of psychotherapies for depression between different age groups. Data Sources Four major bibliographic databases (PubMed, PsychINFO, Embase, and Cochrane) were searched for trials comparing psychotherapy with control conditions up to January 2019. Study Selection Randomized trials comparing psychotherapies for depression with control conditions in all age groups were included. Data Extraction and Synthesis Effect sizes (Hedgesg) were calculated for all comparisons and pooled with random-effects models. Differences in effects between age groups were examined with mixed-effects subgroup analyses and in meta-regression analyses. Main Outcomes and Measures Depressive symptoms were the primary outcome. Results After removing duplicates, 16 756 records were screened and 2608 full-text articles were screened. Of these, 366 trials (36 702 patients) with 453 comparisons between a therapy and a control condition were included in the qualitative analysis, including 13 (3.6%) in children (13 years and younger), 24 (6.6%) in adolescents (≥13 to 18 years), 19 (5.2%) in young adults (≥18 to 24 years), 242 (66.1%) in middle-aged adults (≥24 to 55 years), 58 (15.8%) in older adults (≥55 to 75 years), and 10 (2.7%) in older old adults (75 years and older). The overall effect size of all comparisons across all age groups wasg= 0.75 (95% CI, 0.67-0.82), with very high heterogeneity (I2= 80%; 95% CI: 78-82). Mean effect sizes for depressive symptoms in children (g = 0.35; 95% CI, 0.15-0.55) and adolescents (g = 0.55; 95% CI, 0.34-0.75) were significantly lower than those in middle-aged adults (g = 0.77; 95% CI, 0.67-0.87). The effect sizes in young adults (g = 0.98; 95% CI, 0.79-1.16) were significantly larger than those in middle-aged adults. No significant difference was found between older adults (g = 0.66; 95% CI, 0.51-0.82) and those in older old adults (g = 0.97; 95% CI, 0.42-1.52). The outcomes should be considered with caution because of the suboptimal quality of most of the studies and the high levels of heterogeneity. However, most primary findings proved robust across sensitivity analyses, addressing risk of bias, target populations included, type of therapy, diagnosis of mood disorder, and method of data analysis. Conclusions and Relevance Trials included in this meta-analysis reported effect sizes of psychotherapies that were smaller in children than in adults, probably also smaller in adolescents, that the effects may be somewhat larger in young adults, and without meaningful differences between middle-aged adults, older adults, and older old adults.

Reflection on modern methods: Revisiting the area under the ROC Curve.

Abstract: The area under the receiver operating characteristic (ROC) curve (AUC) is commonly used for assessing the discriminative ability of prediction models even though the measure is criticized for being clinically irrelevant and lacking an intuitive interpretation. Every tutorial explains how the coordinates of the ROC curve are obtained from the risk distributions of diseased and non-diseased individuals, but it has not become common sense that therewith the ROC plot is just another way of presenting these risk distributions. We show how the ROC curve is an alternative way to present risk distributions of diseased and non-diseased individuals and how the shape of the ROC curve informs about the overlap of the risk distributions. For example, ROC curves are rounded when the prediction model included variables with similar effect on disease risk and have an angle when, for example, one binary risk factor has a stronger effect; and ROC curves are stepped rather than smooth when the sample size or incidence is low, when the prediction model is based on a relatively small set of categorical predictors. This alternative perspective on the ROC plot invalidates most purported limitations of the AUC and attributes others to the underlying risk distributions. AUC is a measure of the discriminative ability of prediction models. The assessment of prediction models should be supplemented with other metrics to assess their clinical utility.

Genomic and phenomic insights from an atlas of genetic effects on DNA methylation

Abstract: Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait loci (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTL of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We reveal that the genetic architecture of DNAm levels is highly polygenic and DNAm exhibits signatures of negative and positive natural selection. Using shared genetic control between distal DNAm sites we construct networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic factors are associated with both blood DNAm levels and complex diseases but in most cases these associations do not reflect causal relationships from DNAm to trait or vice versa indicating a more complex genotype-phenotype map than has previously been hypothesised.

Advancing the global physical activity agenda: recommendations for future research by the 2020 WHO physical activity and sedentary behavior guidelines development group

Abstract: In July, 2019, the World Health Organization (WHO) commenced work to update the 2010 Global Recommendations on Physical Activity for Health and established a Guideline Development Group (GDG) comprising expert public health scientists and practitioners to inform the drafting of the 2020 Guidelines on Physical Activity and Sedentary Behavior. The overall task of the GDG was to review the scientific evidence and provide expert advice to the WHO on the amount of physical activity and sedentary behavior associated with optimal health in children and adolescents, adults, older adults (> 64 years), and also specifically in pregnant and postpartum women and people living with chronic conditions or disabilities. The GDG reviewed the available evidence specific to each sub-population using systematic protocols and in doing so, identified a number of gaps in the existing literature. These proposed research gaps were discussed and verified by expert consensus among the entire GDG. Evidence gaps across population sub-groups included a lack of information on: 1) the precise shape of the dose-response curve between physical activity and/or sedentary behavior and several of the health outcomes studied; 2) the health benefits of light-intensity physical activity and of breaking up sedentary time with light-intensity activity; 3) differences in the health effects of different types and domains of physical activity (leisure-time; occupational; transportation; household; education) and of sedentary behavior (occupational; screen time; television viewing); and 4) the joint association between physical activity and sedentary time with health outcomes across the life course. In addition, we acknowledge the need to conduct more population-based studies in low- and middle-income countries and in people living with disabilities and/or chronic disease, and to identify how various sociodemographic factors (age, sex, race/ethnicity, socioeconomic status) modify the health effects of physical activity, in order to address global health disparities. Although the 2020 WHO Guidelines for Physical Activity and Sedentary Behavior were informed by the most up-to-date research on the health effects of physical activity and sedentary time, there is still substantial work to be done in advancing the global physical activity agenda.

Preregistering Qualitative Research: A Delphi Study

Abstract: Preregistrations—records made a priori about study designs and analysis plans and placed in open repositories—are thought to strengthen the credibility and transparency of research. Different authors have put forth arguments in favor of introducing this practice in qualitative research and made suggestions for what to include in a qualitative preregistration form. The goal of this study was to gauge and understand what parts of preregistration templates qualitative researchers would find helpful and informative. We used an online Delphi study design consisting of two rounds with feedback reports in between. In total, 48 researchers participated (response rate: 16%). In round 1, panelists considered 14 proposed items relevant to include in the preregistration form, but two items had relevance scores just below our predefined criterion (68%) with mixed argument and were put forth again. We combined items where possible, leading to 11 revised items. In round 2, panelists agreed on including the two remaining items. Panelists also converged on suggested terminology and elaborations, except for two terms for which they provided clear arguments. The result is an agreement-based form for the preregistration of qualitative studies that consists of 13 items. The form will be made available as a registration option on Open Science Framework (osf.io). We believe it is important to assure that the strength of qualitative research, which is its flexibility to adapt, adjust and respond, is not lost in preregistration. The preregistration should provide a systematic starting point.