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Door verslag te doen van je eigen zwaktes kun je volgens Gerben ter Riet een bijdrage leveren aan de ‘georganiseerde scepsis’ van de onderzoeksgemeenschap. ‘Voor mij persoonlijk geldt dat ik de gebreken in het onderzoek van anderen veel beter zie dan die in onderzoek waarvan ik de bedenker en projectleider ben.’

BackgroundPrevalence of research misconduct, questionable research practices (QRPs) and their associations with a range of explanatory factors has not been studied sufficiently among academic researchers.Methods The National Survey on Research Integrity was aimed at all disciplinary fields and academic ranks in the Netherlands. The survey enquired about engagement in fabrication, falsification and 11 QRPs over the previous three years, and 12 explanatory factor scales. We ensured strict identity protection and used a randomized response method for questions on research misconduct. Results6,813 respondents completed the survey. Prevalence of fabrication was 4.3% (95% CI: 2.9, 5.7) and falsification 4.2% (95% CI: 2.8, 5.6). Prevalence of QRPs ranged from 0.6% (95% CI: 0.5, 0.9) to 17.5% (95 % CI: 16.4, 18.7) with 51.3% (95% CI: 50.1, 52.5) of respondents engaging frequently in ≥ 1 QRP. Being a PhD candidate or junior researcher increased the odds of frequently engaging in ≥ 1 QRP, as did being male. Scientific norm subscription (odds ratio (OR) 0.79; 95% CI: 0.63, 1.00) and perceived likelihood of detection by reviewers (OR 0.62, 95% CI: 0.44, 0.88) were associated with lower odds of research misconduct. Publication pressure was associated with higher odds of engaging frequently in ≥ 1 QRP (OR 1.22, 95% CI: 1.14, 1.30).ConclusionsWe found higher prevalence of misconduct than earlier surveys. Our results suggest that greater emphasis on scientific norm subscription, strengthening reviewers in their role as gatekeepers of research quality and curbing the “publish or perish” incentive system can promote research integrity.

Background: Traditionally, research integrity studies have focused on research misbehaviors and their explanations. Over time, attention has shifted towards preventing questionable research practices and promoting responsible ones. However, data on the prevalence of responsible research practices, especially open methods, open codes and open data and their underlying associative factors, remains scarce. Methods: We conducted a web-based anonymized questionnaire, targeting all academic researchers working at or affiliated to a university or university medical center in The Netherlands, to investigate the prevalence and potential explanatory factors of 11 responsible research practices. Results: A total of 6,813 academics completed the survey, the results of which show that prevalence of responsible practices differs substantially across disciplines and ranks, with 99 percent avoiding plagiarism in their work but less than 50 percent pre-registering a research protocol. Arts and humanities scholars as well as PhD candidates and junior researchers engaged less often in responsible research practices. Publication pressure negatively affected responsible practices, while mentoring, scientific norms subscription and funding pressure stimulated them. Conclusions: Understanding the prevalence of responsible research practices across disciplines and ranks, as well as their associated explanatory factors, can help to systematically address disciplinary- and academic rank-specific obstacles, and thereby facilitate responsible conduct of research.

Additional file 2. Data collection forms, quality checklists, and summary of findings tables.

Additional file 1. Search strategy.

Only a few efforts have been made to define competencies for epidemiologists working in academic settings. Here we describe a multi-national effort to define competencies for epidemiologists who are increasingly facing emerging and potentially disruptive technological and societal health trends in academic research. During a 1,5 years period, we followed an iterative process that aimed to be inclusive and multi-national to reflect the various perspectives of the diverse group of epidemiologists. Competencies were developed by a consortium in a consensus-oriented process that spanned three main activities: two in-person interactive meetings in Amsterdam and Zurich and an online survey. In total, 93 meeting participants from 16 countries and 173 respondents from 19 countries contributed to the development of 31 competencies. These 31 competencies included 14 on “Developing a scientific question” and “Study planning”, 12 on “Study conduct \amp; analysis”, 3 on “Overarching competencies” and 2 competencies on “Communication and translation”. The process described here provides a consensus-based framework for defining and adapting the field. It should initiate a continuous process of thinking about competencies and the implications for teaching epidemiology to ensure that epidemiologists working in academic settings are well prepared for today’s and tomorrow’s health research.

Additional file 1. Hypothetical data example to illustrate the noncollapsibility effect.

Deze rapportage omvat de evaluatie van de pilot Open Science Support Desk (OSSD). Het bemensen van de OSSD is een van de activiteiten die erop gericht zijn om de kwaliteit van het onderzoek dat uitgevoerd wordt in de faculteiten Gezondheid (FG), Bewegen, Sport en Voeding (FBSV) en Digitale Media en Creatieve Industrie (FDMCI) te ondersteunen in het kader van de SIA SPRONG subsidie Mensen in Beweging die in 2018 werd toegekend. Bij de OSSD kunnen Urban Vitality onderzoekers terecht voor individueel advies over kwantitatief en kwalitatief onderzoek, open science en over datamanagement. Deze evaluatie bestrijkt de pilotperiode tussen september 2019 en juni 2020. De evaluatie richt zich op: 1. De mening van de gebruikers over de dienstverlening van OSSD; 2. De motivatie van niet-gebruikers om geen gebruik te maken van OSSD; 3. Het inventariseren van wensen van (potentiële) gebruikers voor OSSD diensten; 4. Het geven van aanbevelingen voor de organisatie en toekomst van de OSSD diensten. Gegevensverzameling Gegevens zijn verzameld m.b.v. twee verschillende vragenlijsten: Eén vragenlijst voor gebruikers van OSSD en één vragenlijst voor niet-gebruikers die wel tot de doelgroep horen. Daarnaast zijn gegevens gebruikt die in een excel databestand zijn bijgehouden over de dienstverlening, zoals aan wie waarover advies is gegeven en hoeveel tijd daaraan is besteed. Resultaten OSSD-gebruikers waren zeer tevreden over onze diensten en hoe deze werden geleverd. Iets minder hoog scoort de duidelijkheid van waarmee men bij de OSSD kan aankloppen. De onderzoekers die geen gebruik hadden gemaakt van de diensten van de OSSD wisten niet dat hij bestond, waarvoor ze bij de desk terecht kunnen, of hadden geen vragen. Een kanttekening is hierbij dat slechts een kwart van de niet-gebruikers de vragenlijst hebben ingevuld. Een meerderheid van de gebruikers en niet-gebruikers lijkt geïnteresseerd in deelname aan journal clubs, hulp bij literatuur zoeken en inloopspreekuren. Verder zijn onder OSSD-gebruikers de belangrijkste onderwerpen voor nieuwe dienstverlening journal clubs over statistiek, datavisualisatie, kwalitatieve analyse, kwalitatieve onderzoeksmethoden, kwantitatieve methoden en open science-tools. De belangrijkste taken voor de OSSD zijn volgens zowel gebruikers als niet-gebruikers advies, co-auteurschap en (data-) analytische ondersteuning. Conclusie De OSSD is geraadpleegd door ongeveer de helft van de potentiële gebruikers. De onderzoekers die advies hebben gekregen zijn (zeer) tevreden over de inhoud van de adviezen en over andere aspecten van de dienstverlening, zoals snelheid van reageren op vragen en de sfeer waarin de consultaties werden uitgevoerd. Daarnaast bestaat er een relatief grote groep die geen gebruik heeft gemaakt van de OSSD. De belangrijkste reden voor het niet gebruiken van de desk lijkt onbekendheid. Dit heeft mogelijk te maken met de huidige onduidelijke positie en inbedding van de OSSD. Aanbevelingen 1. Formaliseer de OSSD binnen het Urban Vitality Center of Expertise (UV) of op faculteitsniveau 2. Stroomlijn de rol van de OSSD in de procedures voorafgaand aan en na toekenning van subsidie en stem deze af met IXA 3. Neem de 14 Open Science principes op in het UV-beleid 4. Zorg er (middels beleid) voor dat de OSSD in een vroeg stadium bij nieuwe onderzoeksvoorstellen betrokken wordt 5. Vervul tijdig de vacature die ontstaat voor een kwalitatief methodoloog 6. Formaliseer de posities van privacy officer en informatiespecialist binnen OSSD 7. Maak glashelder welke lectoraten de OSSD bedient 8. Maak bij een promotieproject duidelijk welke verantwoordelijkheden liggen bij de verschillende instellingen die bij de promotie betrokken zijn 9. Maak een toegankelijk content management systeem om inzicht te hebben in en te kunnen leren van lopend onderzoek 10. Bespreek dit rapport en de aanbevelingen in de stuurgroepen van MiB en van UV en in het management van FG, FBSV en FDMCI.

Background: Traditionally, research integrity studies have focused on research misbehaviors and their explanations. Over time, attention has shifted towards preventing questionable research practices and promoting responsible ones. However, data on the prevalence of responsible research practices, especially open methods, open codes and open data and their underlying associative factors, remains scarce. Methods: We conducted a web-based anonymized questionnaire, targeting all academic researchers working at or affiliated to a university or university medical center in The Netherlands, to investigate the prevalence and potential explanatory factors of 11 responsible research practices. Results: A total of 6,813 academics completed the survey, the results of which show that prevalence of responsible practices differs substantially across disciplines and ranks, with 99 percent avoiding plagiarism in their work but less than 50 percent pre-registering a research protocol. Arts and humanities scholars as well as PhD candidates and junior researchers engaged less often in responsible research practices. Publication pressure negatively affected responsible practices, while mentoring, scientific norms subscription and funding pressure stimulated them. Conclusions: Understanding the prevalence of responsible research practices across disciplines and ranks, as well as their associated explanatory factors, can help to systematically address disciplinary- and academic rank-specific obstacles, and thereby facilitate responsible conduct of research.

Reporting of research findings is often selective. This threatens the validity of the published body of knowledge if the decision to report depends on the nature of the results. The evidence derived from studies on causes and mechanisms underlying selective reporting may help to avoid or reduce reporting bias. Such research should be guided by a theoretical framework of possible causal pathways that lead to reporting bias. We build upon a classification of determinants of selective reporting that we recently developed in a systematic review of the topic. The resulting theoretical framework features four clusters of causes. There are two clusters of necessary causes: (A) motivations (e.g. a preference for particular findings) and (B) means (e.g. a flexible study design). These two combined represent a sufficient cause for reporting bias to occur. The framework also features two clusters of component causes: (C) conflicts and balancing of interests referring to the individual or the team, and (D) pressures from science and society. The component causes may modify the effect of the necessary causes or may lead to reporting bias mediated through the necessary causes. Our theoretical framework is meant to inspire further research and to create awareness among researchers and end-users of research about reporting bias and its causes.

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide novel insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function. Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations. Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD., Editorial summary Genome-wide analysis of chronic obstructive pulmonary disease identifies 82 loci, 35 of which are new. Integration of gene expression and genomic annotation data shows enrichment of signals in lung tissue, smooth muscle and several lung cell types.

Prediction models in health care use predictors to estimate for an individual the probability that a condition or disease is already present (diagnostic model) or will occur in the future (prognostic model). Publications on prediction models have become more common in recent years, and competing prediction models frequently exist for the same outcome or target population. Health care providers, guideline developers, and policymakers are often unsure which model to use or recommend, and in which persons or settings. Hence, systematic reviews of these studies are increasingly demanded, required, and performed. A key part of a systematic review of prediction models is examination of risk of bias and applicability to the intended population and setting. To help reviewers with this process, the authors developed PROBAST (Prediction model Risk Of Bias ASsessment Tool) for studies developing, validating, or updating (for example, extending) prediction models, both diagnostic and prognostic. PROBAST was developed through a consensus process involving a group of experts in the field. It includes 20 signaling questions across 4 domains (participants, predictors, outcome, and analysis). This explanation and elaboration document describes the rationale for including each domain and signaling question and guides researchers, reviewers, readers, and guideline developers in how to use them to assess risk of bias and applicability concerns. All concepts are illustrated with published examples across different topics. The latest version of the PROBAST checklist, accompanying documents, and filled-in examples can be downloaded from www.probast.org.

The debate on reproducibility in biomedicine will gain precision only if we agree what reproducibility means. Importantly, reproducibility should be distinguished from validity (“truth”). We propose the application of an equivalence trials framework to clarify the concept of reproducibility by changing the (narrow) equivalence zone around a zero difference by a zone of reproducibility around (a) previous finding(s).

Lisa SM Eurelings,1,* Jan Willem van Dalen,1,* Gerben ter Riet,2 Eric P Moll van Charante,2 Edo Richard,1,3 Willem A van Gool1 On behalf of the ICARA Study Group 1Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 2Department of General Practice, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 3Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Centre, Nijmegen, the Netherlands *These authors contributed equally to this work Background: Previous findings suggest that apathy symptoms independently of depressive symptoms measured using the Geriatric Depression Scale (GDS) are associated with cardiovascular disease (CVD) in older individuals.Aims: To study whether apathy and depressive symptoms in older people are associated with future CVD, stroke, and mortality using individual patient-data meta-analysis.Methods: Medline, Embase, and PsycInfo databases up to September 3, 2013, were systematically searched without language restrictions. We sought prospective studies with older (mean age ≥65 years) community-dwelling populations in which the GDS was employed and subsequent stroke and/or CVD were recorded to provide individual participant data. Apathy symptoms were defined as the three apathy-related subitems of the GDS, with depressive symptoms the remaining items. We used myocardial infarction (MI), stroke, and all-cause mortality as main outcomes. Analyses were adjusted for age, sex, and MI/stroke history. An adaptation of the Newcastle–Ottawa scale was used to evaluate bias. Hazard ratios were calculated using one-stage random-effect Cox regression models.Results: Of the 52 eligible studies, 21 (40.4%) were included, comprising 47,625 older people (mean age [standard deviation] 74 [7.4] years), over a median follow-up of 8.8 years. Participants with apathy symptoms had a 21% higher risk of MI (95% confidence interval [CI] 1.08–1.36), a 37% higher risk of stroke (95% CI 1.18–1.59), and a 47% higher risk of all-cause mortality (95% CI 1.38–1.56). Participants with depressive symptoms had a comparably higher risk of stroke (HR 1.36, 95% CI 1.18–1.56) and all-cause mortality (HR 1.44, 95% CI 1.35–1.53), but not of MI (HR 1.08, 95% CI 0.91–1.29). Associations for isolated apathy and isolated depressive symptoms were comparable. Sensitivity analyses according to risk of bias yielded similar results.Conclusion: Our findings stress the clinical importance of recognizing apathy independently of depressive symptoms, and could help physicians identify persons at increased risk of vascular disease. Keywords: apathy, older people, depression, cardiovascular disease, meta-analysis, stroke, myocardial infarction

Introduction In the preface of the first issue of Philosophical Transactions in 1665, Henry Oldenburg wrote: “Whereas there is nothing more necessary for promoting the improvement of Philosophical Matters, than the communicating to such things as are discovered or put in practise by others ; …to the end, that such Productions being clearly and truly communicated…”1 In the centuries to come, the fields of inquiry grew to such a degree that today they are published in more than 36 000 scientific journals. 2 In the last few decades most of scientific publishing switched from print based to electronic formats, different financial and peer review models were being explored, and the emphasis on “clear and true” reporting had been reinstated with publishing of multiple reporting guidelines and increasing calls for replications of studies.3, 4 Yet published science is not flawless. Corrections such as errata are published for approximately 4% of all published papers today, with a quarter of the corrections drastically changing the conclusions of the studies.5 Another peculiarity is the fact that the quality of a study is perceived to be reflected by the journal in which it is published.6 Additionally, many journals mandate the number of words, formats, and even the number of authors the papers may have, with the submission of the paper to a journal often being perceived as needlessly complicated and long.7 Instructions to authors (ItA), the documents that are supposed to help authors prepare their manuscripts for submission and inform the authors of journals’ policies, today cover topics, that the editors in the past did not perceive as part of scientific publishing (e.g. a 1966 study reported most medical journal editors did not see as being part of their responsibility to check or monitor that the researchers followed ethical guidelines regarding human experimentation).8 It was therefore our goal to explore the changes that have occurred in journals’ instructions to authors through time, especially regarding peer review. Methods The systematic review included all studies that have analysed ItAs of more than one journal, irrespective of the topic(s) or parts within the ItAs that were analysed. Information sources The search was conducted on 1st of May 2017 in MEDLINE (through Ovid), Scopus and WoS. There were no language or time restrictions. The full search strategy is available from the authors and will be publish with the study. Study selection The search results were exported in Rayyan software, where manual deduplication done by MMal led to a total of 783 articles for screening.9 Abstracts were screened independently by MMal and AJ, leading to a 167 possible studies for inclusion (15 studies were later excluded for not being analysis of ItAs, while 12 studies were found using Google Scholar and through the references of screened studies). Data collection process and data items The following variables were extracted: 1) year when the ItAs were accessed, 2) number of journals whose ItAs were analysed, 3) journal selection method, 4) journals scientific area, 5) journal country of publication, 6) the method used for analysis of ItA, 7) the number of topics that were analysed in ItAs, 8) the number and percentage of journals which mentioned the analysed topics. All raw data will be published with the study. Preliminary results In total 141 studies were included for analysis. The studies were published from 1987 till 2017 (Figure 2), while the analysed ItA dated from 1967 till 2017. Median number of journals instructions to authors analysed per study was 56 (IQR 20 to 56). The median number of studies which analysed appearance of a same topic within instruction to authors of journals was 3 (IQR 1 to 12). Forty topics were analysed only in one study, and 26 were analysed in more than 10 studies (Figure 1). Percentages of ItAs mentioning peer review show large variation (Figure 2). Studies that have followed the same journals over time show an increase in mentioning of peer review (Figure 2). Additionally, while older studies have most often looked at peer review in instructions to authors of journals published in different countries, newer studies usually focus on country specific journals (Figure 3). Discussion Our preliminary results indicate that mentioning of peer review in journals’ instruction to authors has increased with time, but still shows a great variation between countries and scientific fields. As improvement of reporting of studies has been shown to be influenced by the endorsement or mentioning of reporting guidelines within the journals’ instructions to authors, 10, 11 it is also possible that a more detailed description of the peer review process, with detailed description on what the studies will be judge upon, may lead to an increase in the quality of manuscripts submitted to journals.

BACKGROUND: Several cross-sectional and short-term studies suggest that patient-reported outcomes (PROs) may be useful to help predict COPD exacerbations, but evidence from long-term prospective cohort studies is lacking. Our aim was to assess if PROs add to the prediction of exacerbations. METHODS: Four hundred eight primary care patients with COPD participated in the multi-center prospective International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts (ICE COLD ERIC) study. PROs included the Chronic Respiratory Disease Questionnaire, the Hospital Anxiety and Depression Scale, the Feeling Thermometer, and the LASA Physical Activity Questionnaire (LAPAQ). Exacerbations during 41/2 years were adjudicated by experts. We used negative binomial regression to assess the association between PROs and exacerbations while considering age, sex, airflow obstruction, previous exacerbations, and smoking status. We then assessed if adding PROs improved the predictive properties of widely used indices. RESULTS: Lower levels of dyspnea, fatigue, and anxiety and higher levels of physical activity were associated with a lower risk of exacerbations (adjusted incidence rate ratio [IRR], 0.90; 95% CI, 0.84-0.97; P = .01; IRR, 0.93; 95% CI, 0.86-1.00; P = .04; IRR, 1.03; 95% CI, 1.00-1.06; P = .03; IRR, 0.93; 95% CI, 0.87-0.99; P = .04, respectively). The best prediction was when LAPAQ was added to the BMI, airflow obstruction, dyspnea, and previous exacerbations (BODEx) index (area under the curve Delta+0.02, from 0.72-0.74). However, this increase was not clinically relevant (net reclassification improvement, 0.03; 95% CI, -0.03 to 0.08). CONCLUSIONS: Some domains of PROs are independently associated with exacerbations but do not lead to clearly improved prediction when added to established indices to predict exacerbations. There is still much room for improvement in the prediction of exacerbations

BACKGROUND: Among patients with coronary artery disease (CAD), improvement of lifestyle-related risk factors (LRFs) reduces cardiovascular morbidity and mortality. However, modification of LRFs is highly challenging. OBJECTIVES: This study sought to evaluate the impact of combining community-based lifestyle programs with regular hospital-based secondary prevention. METHODS: The authors performed a randomized controlled trial of nurse-coordinated referral of patients and their partners to 3 widely available community-based lifestyle programs, in 15 hospitals in the Netherlands. Patients admitted for acute coronary syndrome and/or revascularization, with ≥1 LRF (body mass index >27 kg/m(2), self-reported physical inactivity, and/or smoking) were included. All patients received guideline-based usual care. The intervention was based on 3 lifestyle programs for weight reduction, increasing physical activity, and smoking cessation. The primary outcome was the proportion of success at 12 months, defined as improvement in ≥1 qualifying LRF using weight (≥5% reduction), 6-min-walking distance (≥10% improvement), and urinary cotinine (200 ng/ml detection limit) without deterioration in the other 2. RESULTS: The authors randomized 824 patients. Complete data on the primary outcome were available in 711 patients. The proportion of successful patients in the intervention group was 37% (133 of 360) compared with 26% (91 of 351) in the control group (p = 0.002; risk ratio: 1.43; 95% confidence interval: 1.14 to 1.78). In the intervention group, partner participation was associated with a significantly greater success rate (46% vs. 34%; p = 0.03). CONCLUSIONS: Among patients with coronary artery disease, nurse-coordinated referral to a comprehensive set of community-based, widely available lifestyle interventions, with optional partner participation, leads to significant improvements in LRFs. (RESPONSE-2: Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists 2; NTR3937).

Objective: To identify and synthesize studies that have analysed instructions to authors (ItA) of scientific journals irrespective of the topic(s) within the ItAs that were analysed. Design: Systematic review of studies indexed in MEDLINE (search through Ovid), Web of Science (WoS) and Scopus. Literature search was performed on 1 May 2017 with no language or time limitations. After deduplication 784 records remained. Additionally, Google Scholar (allintitle: instructions authors), and the references of included studies were searched for possible additional sources. Initial screening of titles and abstracts was conducted by two independent reviewers using Rayyan software. Results: Presented here is the preliminary analysis of 150 studies included so far. The studies were published from 1987 till 2017, while the analysed ItA were from 1967 till 2017. Majority of the studies looked into the ItA of Health Sciences (n=111, 74%), followed by ItAs of journals from two or more fields (n=23, 15%), Social Sciences (n=10, 7%), and Physical and Life sciences (n=3, 2% for each of the two fields). Median number of journals analysed per study was 60 (range 3 to 1396). Among the included studies 9 included follow-up of ItAs over time. We identified 114 different topics analysed within the ItA, of which the following were analysed in more than 20 different studies: ICMJE Uniform requirements for manuscripts, conflict of interest, CONSORT guidelines, ethics approval for the study, trial registration, authorship, Declaration of Helsinki, informed consent, and guidelines for research on animals). Mentioning of the majority of topics increased over time. Conclusions: Our preliminary findings indicate that instructions to authors of scientific journals are becoming much longer, and cover an increasing number of topics and regulations regarding conduct of research and scientists.

COPD exacerbation incidence rates are often ascertained retrospectively through patient recall and self-reports. We compared exacerbation ascertainment through patient self-reports and single-physician chart review to central adjudication by a committee and explored determinants and consequences of misclassification. Self-reported exacerbations (event-based definition) in 409 primary care patients with COPD participating in the International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts (ICE COLD ERIC) cohort were ascertained every 6 months over 3 years. Exacerbations were adjudicated by single experienced physicians and an adjudication committee who had information from patient charts. We assessed the accuracy (sensitivities and specificities) of self-reports and single-physician chart review against a central adjudication committee (AC) (reference standard). We used multinomial logistic regression and bootstrap stability analyses to explore determinants of misclassifications. The AC identified 648 exacerbations, corresponding to an incidence rate of 0.60 ± 0.83 exacerbations/patient-year and a cumulative incidence proportion of 58.9%. Patients self-reported 841 exacerbations (incidence rate, 0.75 ± 1.01; incidence proportion, 59.7%). The sensitivity and specificity of self-reports were 84% and 76%, respectively, those of single-physician chart review were between 89% and 96% and 87% and 99%, respectively. The multinomial regression model and bootstrap selection showed that having experienced more exacerbations was the only factor consistently associated with underreporting and overreporting of exacerbations (underreporters: relative risk ratio [RRR], 2.16; 95% CI, 1.76-2.65 and overreporters: RRR, 1.67; 95% CI, 1.39-2.00). Patient 6-month recall of exacerbation events are inaccurate. This may lead to inaccurate estimates of incidence measures and underestimation of treatment effects. The use of multiple data sources combined with event adjudication could substantially reduce sample size requirements and possibly cost of studies. www.ClinicalTrials.gov, NCT00706602

Background: Although a large body of literature assessed the determinants of physical activity in patients with COPD, most of the studies were cross-sectional and focused on one or few determinants. We aimed to examine the determinants of physical activity using longitudinal models. Methods: In a prospective cohort study, 409 patients with COPD managed by general practitioners in the Netherlands or Switzerland were recruited and followed for 5 years. Patients completed a validated questionnaire (Longitudinal Aging Study Amsterdam Physical Activity Questionnaire) at baseline and every 6 months about their physical activity. We fitted linear mixed models to study the associations between predictors at baseline and physical activity (an adapted score on a 0-23 scale) across all study follow-up visits. Results: Unadjusted analysis suggested that there was a decrease in physical activity over time (coefficient = -0.22 per visit, 95% CI = -0.28, -0.17, p Conclusion: We identified in a cohort study several statistically significant determinants of physical activity in patients with COPD. It allows to identify patients who remain having low physical activity and who may benefit particularly from pulmonary rehabilitation that addresses the determinants of physical activity.

Observationeel onderzoek. Methode Er werd gebruikgemaakt van huisartsregistratiebestanden en declaratiegegevens van een zorgverzekeraar. Gepseudonimiseerde gegevens uit de dossiers van 16.531 patiënten (39 huisartsen) werden gekoppeld aan eerste- en tweedelijns kosten vergoed door een zorgverzekeraar in de periode 2007-2009. Huisartskenmerken werden verzameld via administratieve gegevens en een vragenlijst. Via multilevel lineaire regressieanalyse schatten we het effect van de duur van het frequente bezoek op de zorgkosten, na correctie voor aandoeningen van de patiënt en huisartskenmerken

Some authors claimed that if current trends prevail, 1.32 million people will have been diagnosed with diabetes mellitus in the Netherlands by 2025. In this commentary, the author sheds doubt on some of the underlying assumptions. First, the author argues that advanced age in itself cannot be an immutable cause of diabetes since there must be underlying mechanisms, which may be modifiable. Second, improved early detection of diabetes, which is a cause for a higher prevalence, also creates possibilities for action. Finally, the author does not believe that the current rates of overweight will be sustained over the next 16 years through to 2025. The author also discusses the debate surrounding the use of the Diabetes Prevention Program in the U.S. and the application of the Archimedes mathematical model to calculate cost-effectiveness of rapid adoption of the Diabetes Prevention Program versus delayed adoption or drug treatment with metformin, as well as the heated debate with the Markov modellers of the Diabetes Prevention Program research group about model details and validations

BACKGROUND: For the diagnosis of asthma in young children, GPs have to rely on history taking and physical examination, as spirometry is not possible. The additional diagnostic value of specific immunoglobulin E (IgE) to inhalent allergens remains unclear. AIM: To assess the predictive accuracy of specific IgE to cat, dog, and/or house dust mites in young children for the subsequent development of asthma at the age of 6 years. DESIGN OF STUDY: Prospective follow-up study. SETTING: Seventy-two general practices. METHOD: A total of 654 children, aged 1-4 years, visiting their GPs for persistent coughing (>/= 5 days), were tested for IgE antibodies by radio allergosorbent testing (RAST). Parents completed a questionnaire on potential risk indicators. Those children who showed an IgE-positive status (12.7%) and a random sample of those with an IgE-negative status (

BACKGROUND: Acute infectious conjunctivitis is a common disorder in primary care. Despite a lack of evidence regarding the effectiveness of topical antibiotics for the treatment of acute infectious conjunctivitis, most patients presenting in primary care with the condition receive topical antibiotics. In The Netherlands, fusidic acid is most frequently prescribed. AIM: To assess the effectiveness of fusidic acid gel compared to placebo for acute infectious conjunctivitis. DESIGN: Double-blind randomised placebo-controlled trial. SETTING: Twenty-five Dutch primary care centres. METHOD: Adults presenting with a red eye and either (muco)purulent discharge or glued eyelid(s) were allocated to either one drop of fusidic acid gel 1% or placebo, four times daily during one week. The main outcome measure was the difference in recovery rates at 7 days. Secondary outcome measures were difference in bacterial eradication rates, a survival time analysis of the duration of symptoms, and the difference in recovery rates in culture-positive and culture-negative patients. RESULTS: One hundred and eighty-one patients were randomised and 163 patients were analysed. Forty-five of the 73 patients in the treatment and 53 of the 90 patients in the placebo group recovered (adjusted risk difference = 5.3% [95% confidence interval {CI} = -11 to 18]). There was no difference between the median duration of symptoms in the two groups. At baseline, the prevalence of a positive bacterial culture was 32% (58/181). The bacterial eradication rate was 76% in the treatment and 41% in the placebo group (risk difference = 35% [95% CI = 9.3 to 60.4]). In culture positive patients, the treatment effect tended to be strong (adjusted risk difference = 23% [95% CI = -6 to 42]). CONCLUSION: At 7 days, cure rates in the fusidic acid gel and placebo group were similar, but the confidence interval was too wide to clearly demonstrate their equivalence. These findings do not support the current prescription practices of fusidic acid by GPs

Objective. To develop an analytical approach to estimate the probability of endometrial hyperplasia and cancer in women with postmenopausal bleeding, using a combination of patient history and tests. Methods. A prospectively collected database of 428 postmenopausal women investigated for abnormal uterine bleeding in an outpatient rapid access clinic was used. The probability of disease was estimated using multivariable logistic regression models considering a combination of age and the use of hormone replacement therapy (HRT) and tests (ultrasound and hysteroscopy) in keeping with the actual clinical process. Results. The prevalence or prior probability of endometrial cancer in the sample studied was 4.4%. Hysteroscopy alone performed better than ultrasound alone. In all patients, a negative hysteroscopy reduced the probability of cancer to 1.3%. In women less than 60 years of age who use HRT, a negative hysteroscopy further reduced this probability to 0.1%. Overall, a positive hysteroscopy raised the probability of cancer to 38.9%. However, in women over 60 years of age not using HRT, a positive hysteroscopy increased this probability to 59.4%. Combining ultrasound results with hysteroscopy did not meaningfully alter the diagnostic probability. Conclusion. The combination of information obtained from patient history and tests allows generation of specific disease probabilities in postmenopausal bleeding. This type of multivariable analysis puts diagnostic information gained from history and other tests into a perspective that reflects actual clinical practice

This is thorough bibliography of studies on vitamin C and the common cold prior to 1989. This bibliography was used for example in the search for studies included in Cochrane review on vitamin C and the common cold (pmc8078152). These references are from a paper published in Dutch (https://www.ntvg.nl/artikelen/vitamine-c-en-verkoudheid-overzicht-van-een-megadosis-literatuur), which was translated to English in Jos Kleinen's thesis (https://www.mv.helsinki.fi/home/hemila/CC/Kleijnen_1989.pdf).