[Mental health and climate change: reconceptualizing eco-anxiety]. / Bestaat er zoiets als eco-angst?

Climate change may bring about anxiety, which may be referred to as eco-anxiety. Commonly accepted conceptual or diagnostic criteria for eco-anxiety are currently lacking. Here, we briefly summarize the current literature on climate change and mental illness. We suggest dividing the concept of eco-anxiety into adaptive eco-anxiety and an anxiety disorder where climate change plays a major role. This distinction may be helpful in clinical practice to discern relatively common and potentially healthy eco-anxiety from a disorder causing impairment in daily functioning. Benefits of adaptive eco-anxiety include the development of active coping strategies (increasing resilience) as well as behavioural changes to mitigate climate change. When debilitating anxiety comes with avoidance and centers around climate change, a specific phobia called eco-anxiety disorder may be considered. Importantly, as validated diagnostic criteria for this disorder are currently lacking, further conceptualization is highly needed. Future clinical research may help fill these current knowledge gaps.

Risk of suicidality in mental and neurological disorders in low and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Both fatal and nonfatal suicidal behaviours are important complications of mental, neurological, and substance use disorders (MNSDs) worldwide. We aimed at quantifying the association of suicidal behaviour with MNSDs in Low and Middle Income Countries (LMICs) where varying environmental and socio-cultural factors may impact outcome. METHODS: We conducted a systematic review and meta-analysis to report the associations between MNSDs and suicidality in LMICs and the study-level factors of these associations. We searched the following electronic databases: PUBMED, PsycINFO, MEDLINE, CINAHL, World Cat, and Cochrane library for studies on suicide risk in MNSDs, with a comparison/control group of persons without MNSDs, published from January 1, 1995 to September 3, 2020. Median estimates were calculated for relative risks for suicide behaviour and MNSDs, and when appropriate, these were pooled using random effects metanalytic model. This study was registered with PROSPERO, CRD42020178772. RESULTS: The search identified 73 eligible studies: 28 were used for quantitative synthesis of estimates and 45 for description of risk factors. Studies included came from low and upper middle-income countries with a majority of these from Asia and South America and none from a low-income country. The sample size was 13,759 for MNSD cases and 11,792 hospital or community controls without MNSD. The most common MNSD exposure for suicidal behaviour was depressive disorders (47 studies (64%)), followed by schizophrenia spectrum, and other psychotic disorders (28 studies (38%)). Pooled estimates from the meta-analysis were statistically significant for suicidal behaviour with any MNSDs (odds ratios (OR) = 1∙98 (95%CI = 1∙80-2∙16))) and depressive disorder (OR = 3∙26 (95%CI = 2∙88-3∙63))), with both remaining significant after inclusion of high-quality studies only. Meta-regression identified only hospital-based studies (ratio of OR = 2∙85, CI:1∙24-6∙55) and sample size (OR = 1∙00, CI:0∙99-1∙00) as possible sources of variability in estimates. Risk for suicidal behaviour in MNSDs was increased by demographic factors (e.g., male sex, and unemployment), family history, psychosocial context and physical illness. INTERPRETATION: There is an association between suicidal behaviour and MNSDs in LMICs, the association is greater for depressive disorder in LMICs than what has been reported in High Income Countries (HICs). There is urgent need to improve access for MNSDs care in LMICs. FUNDING: None.

Perspectives on reasons for suicidal behaviour and recommendations for suicide prevention in Kenya: qualitative study.

BACKGROUND: Little is known about the reasons for suicidal behaviour in Africa, and communities' perception of suicide prevention. A contextualised understanding of these reasons is important in guiding the implementation of potential suicide prevention interventions in specific settings. AIMS: To understand ideas, experiences and opinions on reasons contributing to suicidal behaviour in the Coast region of Kenya, and provide recommendations for suicide prevention. METHOD: We conducted a qualitative study with various groups of key informants residing in the Coast region of Kenya, using in-depth interviews. Audio-recorded interviews were transcribed and translated from the local language before thematic inductive content analysis. RESULTS: From the 25 in-depth interviews, we identified four key themes as reasons given for suicidal behaviour: interpersonal and relationship problems, financial and economic difficulties, mental health conditions and religious and cultural influences. These reasons were observed to be interrelated with each other and well-aligned to the suggested recommendations for suicide prevention. We found six key recommendations from our thematic content analysis: (a) increasing access to counselling and social support, (b) improving mental health awareness and skills training, (c) restriction of suicide means, (d) decriminalisation of suicide, (e) economic and education empowerment and (f) encouraging religion and spirituality. CONCLUSIONS: The reasons for suicidal behaviour are comparable with high-income countries, but suggested prevention strategies are more contextualised to our setting. A multifaceted approach in preventing suicide in (coastal) Kenya is warranted based on the varied reasons suggested. Community-based interventions will likely improve and increase access to suicide prevention in this study area.

Indicators of questionable research practices were identified in 163,129 randomized controlled trials.

OBJECTIVES: To explore indicators of the following questionable research practices (QRPs) in randomized controlled trials (RCTs): (1) risk of bias in four domains (random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment); (2) modifications in primary outcomes that were registered in trial registration records (proxy for selective reporting bias); (3) ratio of the achieved to planned sample sizes; and (4) statistical discrepancy. STUDY DESIGN AND SETTING: Full texts of all human RCTs published in PubMed in 1996-2017 were automatically identified and information was collected automatically. Potential indicators of QRPs included author-specific, publication-specific, and journal-specific characteristics. Beta, logistic, and linear regression models were used to identify associations between these potential indicators and QRPs. RESULTS: We included 163,129 RCT publications. The median probability of bias assessed using Robot Reviewer software ranged between 43% and 63% for the four risk of bias domains. A more recent publication year, trial registration, mentioning of CONsolidated Standards Of Reporting Trials-checklist, and a higher journal impact factor were consistently associated with a lower risk of QRPs. CONCLUSION: This comprehensive analysis provides an insight into indicators of QRPs. Researchers should be aware that certain characteristics of the author team and publication are associated with a higher risk of QRPs.

Research funders should be more transparent: a plea for open applications.

Transparency is increasingly becoming the new norm and modus operandi of the global research enterprise. In this mini-review, we summarize ongoing initiatives to increase transparency in science and funding in particular. Based on this, we make a plea for the next step in funders' compliance with the principles of Open Science, suggesting the adoption of open applications. Our proposed model includes a plea for the publication of all submitted grant applications; open sharing of review reports, argumentations for funding decisions and project evaluation reports; and the disclosure of reviewers' and decision committee members' identities. In line with previous calls for transparency and the available evidence about these measures' effectiveness, we argue that open applications could lead to more diverse collaboration, recognition of research ideas, fairer procedures for grant allocation, more research on funding practices and increased trust in the funding allocation process.

Designing and implementing a research integrity promotion plan: Recommendations for research funders.

Various stakeholders in science have put research integrity high on their agenda. Among them, research funders are prominently placed to foster research integrity by requiring that the organizations and individual researchers they support make an explicit commitment to research integrity. Moreover, funders need to adopt appropriate research integrity practices themselves. To facilitate this, we recommend that funders develop and implement a Research Integrity Promotion Plan (RIPP). This Consensus View offers a range of examples of how funders are already promoting research integrity, distills 6 core topics that funders should cover in a RIPP, and provides guidelines on how to develop and implement a RIPP. We believe that the 6 core topics we put forward will guide funders towards strengthening research integrity policy in their organization and guide the researchers and research organizations they fund.

Analysis of 567,758 randomized controlled trials published over 30 years reveals trends in phrases used to discuss results that do not reach statistical significance.

The power of language to modify the reader's perception of interpreting biomedical results cannot be underestimated. Misreporting and misinterpretation are pressing problems in randomized controlled trials (RCT) output. This may be partially related to the statistical significance paradigm used in clinical trials centered around a P value below 0.05 cutoff. Strict use of this P value may lead to strategies of clinical researchers to describe their clinical results with P values approaching but not reaching the threshold to be "almost significant." The question is how phrases expressing nonsignificant results have been reported in RCTs over the past 30 years. To this end, we conducted a quantitative analysis of English full texts containing 567,758 RCTs recorded in PubMed between 1990 and 2020 (81.5% of all published RCTs in PubMed). We determined the exact presence of 505 predefined phrases denoting results that approach but do not cross the line of formal statistical significance (P < 0.05). We modeled temporal trends in phrase data with Bayesian linear regression. Evidence for temporal change was obtained through Bayes factor (BF) analysis. In a randomly sampled subset, the associated P values were manually extracted. We identified 61,741 phrases in 49,134 RCTs indicating almost significant results (8.65%; 95% confidence interval (CI): 8.58% to 8.73%). The overall prevalence of these phrases remained stable over time, with the most prevalent phrases being "marginally significant" (in 7,735 RCTs), "all but significant" (7,015), "a nonsignificant trend" (3,442), "failed to reach statistical significance" (2,578), and "a strong trend" (1,700). The strongest evidence for an increased temporal prevalence was found for "a numerical trend," "a positive trend," "an increasing trend," and "nominally significant." In contrast, the phrases "all but significant," "approaches statistical significance," "did not quite reach statistical significance," "difference was apparent," "failed to reach statistical significance," and "not quite significant" decreased over time. In a random sampled subset of 29,000 phrases, the manually identified and corresponding 11,926 P values, 68,1% ranged between 0.05 and 0.15 (CI: 67. to 69.0; median 0.06). Our results show that RCT reports regularly contain specific phrases describing marginally nonsignificant results to report P values close to but above the dominant 0.05 cutoff. The fact that the prevalence of the phrases remained stable over time indicates that this practice of broadly interpreting P values close to a predefined threshold remains prevalent. To enhance responsible and transparent interpretation of RCT results, researchers, clinicians, reviewers, and editors may reduce the focus on formal statistical significance thresholds and stimulate reporting of P values with corresponding effect sizes and CIs and focus on the clinical relevance of the statistical difference found in RCTs.

Selective outcome reporting across psychopharmacotherapy randomized controlled trials.

OBJECTIVE: Selective reporting impairs the valid interpretation of trials and leads to bias with regards to the clinical evidence. We aimed to examine factors associated with selective reporting in psychopharmacotherapy trials and thus enable solutions to prevent such selective reporting in the future. METHODS: We retrieved all registry records of trials investigating medication for depressive, bipolar and psychotic disorders. Multivariate logistic regression was performed with selective reporting as outcome, and funding source, psychiatric disorder, year of study start date, participating centers, and anticipated sample size as explanatory variables, after testing for multicollinearity. Adjusted odds ratios (AOR) were calculated. Two-sided Fisher exact test was used to compare the proportions of newly added positive primary outcomes with the proportions of positive results in the overall group of primary outcomes. RESULTS: Of 151 included trials (N = 94,303 participants), 21 (14%) showed irregularities between registered and published primary outcomes. Higher odds of such irregularities were associated with non-industry-funded RCTs (AOR 5.3; p = 0.014) and trials investigating major depressive disorder (AOR 12.7; p = 0.024) or schizophrenia (AOR 14.5; p = 0.016; Table 1). CONCLUSION: We demonstrate discrepancies between trial registrations and publications across RCTs investigating debilitating psychiatric disorders, especially in non-industry funded RCTs.

Suicidal attempts and ideations in Kenyan adults with psychotic disorders: An observational study of frequency and associated risk factors.

Background: Psychotic disorders increase the risk for premature mortality with up to 40% of this mortality attributable to suicide. Although suicidal ideation (SI) and suicidal behavior (SB) are high in persons with psychotic disorders in sub-Saharan Africa, there is limited data on the risk of suicide and associated factors among persons with psychotic disorders. Methods: We assessed SI and SB in persons with psychotic disorders, drawn from a large case-control study examining the genetics of psychotic disorders in a Kenyan population. Participants with psychotic disorders were identified using a clinical review of records, and the diagnosis was confirmed with the Mini-International Neuropsychiatric Interview (MINI). We conducted bivariate and multivariate logistic (for binary suicide outcomes) or linear regression (for suicide risk score) analysis for each of the suicide variables, with demographic and clinical variables as determinants. Results: Out of 619 participants, any current SI or lifetime suicidal attempts was reported by 203 (32.8%) with psychotic disorders, of which 181 (29.2%) had a lifetime suicidal attempt, 60 (9.7%) had SI in the past month, and 38 (20.9%) had both. Family history of suicidality was significantly associated with an increased risk of suicidality across all the following four outcomes: SI [OR = 2.56 (95% CI: 1.34-4.88)], suicidal attempts [OR = 2.01 (95% CI: 1.31-3.06)], SI and SB [OR = 2.00 (95% CI: 1.31-3.04)], and suicide risk score [beta coefficient = 7.04 (2.72; 11.36), p = 0.001]. Compared to persons aged <25 years, there were reduced odds for SI for persons aged ≥ 25 years [OR = 0.30 (95% CI: 0.14-0.62)] and ≥ 45 years [OR = 0.32 (95% CI: 0.12-0.89)]. The number of negative life events experienced increased the risk of SI and SB [OR = 2.91 (95% CI: 1.43-5.94)] for 4 or more life events. Higher negative symptoms were associated with more suicidal attempts [OR = 2.02 (95%CI: 1.15-3.54)]. Unemployment was also associated with an increased risk for suicidal attempts [OR = 1.58 (95%CI: 1.08-2.33)] and SI and SB [OR = 1.68 (95% CI: 1.15-2.46)]. Conclusion: Suicidal ideation and SB are common in persons with psychotic disorders in this African setting and are associated with sociodemographic factors, such as young age and unemployment, and clinical factors, such as family history of suicidality. Interventions targeted at the community (e.g., economic empowerment) or at increasing access to care and treatment for persons with psychotic disorders may reduce the risk of suicide in this vulnerable population group.

[Elderly people with a death wish? Don't forget to take a psychiatrist's point of view]. / Een doodswens bij ouderen?

The debate on a completed life is far from complete. It is a difficult, complex and challenging endeavor to determine what a completed life is given the fact that this is influenced by a wide array of complicating factors, especially in older persons. One of these most challenging factors is to differentiate between a 'normal' death wish and suicidal behavior that may be present in patients with a psychiatric condition, even at higher age. In this commentary, we reflect on this difficult differentiation and emphasize the importance of rigorous psychiatric classification of people with a death wish, and we encourage the use of valid psychiatric screening instruments. Finally we do a plea for more and rigorous research to disentangle the differences between a 'normal' death wish and a death wish that can be partially predisposed by psychiatric symptomatology. We are convinced that more and rigorous research is needed to answer the complex nature of a death wish as a phenomenon. Moreover, these results should first be debated within the scientific community before the results may be wrongly interpreted by media and politicians with the undesirable effect that incorrect interpretation may sway the public opinion and political decisions.

Towards a Research Agenda for Promoting Responsible Research Practices.

This opinion piece aims to inform future research funding programs on responsible research practices (RRP) based on three specific objectives: (1) to give a sketch of the current international discussion on responsible research practices (RRPs); (2) to give an overview of current initiatives and already obtained results regarding RRP; and (3) to give an overview of potential future needs for research on RRP. In this opinion piece, we have used seven iterative methodological steps (including literature review, ranking, and sorting exercises) to create the proposed research agenda. We identified six main themes that we believe need attention in future research: (1) responsible evaluation of research and researchers, (2) the influence of open science and transparency on RRP, (3) research on responsible mentoring, supervision, and role modeling, (4) the effect of education and training on RRP, (5) checking for reproducibility, and (6) responsible and fair peer review. These themes have in common that they address aspects of research that are mostly on the level of the scientific system, more than on the level of the individual researcher. Some current initiatives are already gathering substantial empirical evidence to start filling these gaps. We believe that with sufficient support from all relevant stakeholders, more progress can be made.

The methodological quality of 176,620 randomized controlled trials published between 1966 and 2018 reveals a positive trend but also an urgent need for improvement.

Many randomized controlled trials (RCTs) are biased and difficult to reproduce due to methodological flaws and poor reporting. There is increasing attention for responsible research practices and implementation of reporting guidelines, but whether these efforts have improved the methodological quality of RCTs (e.g., lower risk of bias) is unknown. We, therefore, mapped risk-of-bias trends over time in RCT publications in relation to journal and author characteristics. Meta-information of 176,620 RCTs published between 1966 and 2018 was extracted. The risk-of-bias probability (random sequence generation, allocation concealment, blinding of patients/personnel, and blinding of outcome assessment) was assessed using a risk-of-bias machine learning tool. This tool was simultaneously validated using 63,327 human risk-of-bias assessments obtained from 17,394 RCTs evaluated in the Cochrane Database of Systematic Reviews (CDSR). Moreover, RCT registration and CONSORT Statement reporting were assessed using automated searches. Publication characteristics included the number of authors, journal impact factor (JIF), and medical discipline. The annual number of published RCTs substantially increased over 4 decades, accompanied by increases in authors (5.2 to 7.8) and institutions (2.9 to 4.8). The risk of bias remained present in most RCTs but decreased over time for allocation concealment (63% to 51%), random sequence generation (57% to 36%), and blinding of outcome assessment (58% to 52%). Trial registration (37% to 47%) and the use of the CONSORT Statement (1% to 20%) also rapidly increased. In journals with a higher impact factor (>10), the risk of bias was consistently lower with higher levels of RCT registration and the use of the CONSORT Statement. Automated risk-of-bias predictions had accuracies above 70% for allocation concealment (70.7%), random sequence generation (72.1%), and blinding of patients/personnel (79.8%), but not for blinding of outcome assessment (62.7%). In conclusion, the likelihood of bias in RCTs has generally decreased over the last decades. This optimistic trend may be driven by increased knowledge augmented by mandatory trial registration and more stringent reporting guidelines and journal requirements. Nevertheless, relatively high probabilities of bias remain, particularly in journals with lower impact factors. This emphasizes that further improvement of RCT registration, conduct, and reporting is still urgently needed.

[The Dutch PhD-factory: pivotal or research waste]. / Promoties in de geneeskunde.

This commentary discusses the increase of the number of finished PhD-theses in the Netherlands among young medical doctors. I discuss their motivation, engagement, the lack of mentoring and the mental health symptoms that are highly prevalent among Dutch PhD students in university medical centers. As a consequence, the abovementioned factors may have a detrimental impact on the validity and integrity of research results. Furthermore, I discuss how the current academic hierarchy is shaping academic careers and dictating publication practices. PhD students are pivotal in fulfilling academic dreams of seniors by writing a considerable number of publications that help senior researchers increase their scientific output, advance their careers and help them to get tenured. I suggest that we should invest in sufficient, effective and responsible supervision and mentoring and should train our supervisors to become a responsible role model for their PhD students. For this we need different performance indicators, and more time and skills for seniors to invest in PhD students. As a result, supervisors will become more equipped and engaged in responsible supervision.

Associations between psychiatric disorders, COVID-19 testing probability and COVID-19 testing results: findings from a population-based study.

BACKGROUND: Many psychiatrists are worried their patients, at increased risk for COVID-19 complications, are precluded from receiving appropriate testing. There is a lack of epidemiological data on the associations between psychiatric disorders and COVID-19 testing rates and testing outcomes. AIMS: To compare COVID-19 testing probability and results among individuals with psychiatric disorders with those without such diagnoses, and to examine the associations between testing probability and results and psychiatric diagnoses. METHOD: This is a population-based study to perform association analyses of psychiatric disorder diagnoses with COVID-19 testing probability and such test results, by using two-sided Fisher exact tests and logistic regression. The population were UK Biobank participants who had undergone COVID-19 testing. The main outcomes were COVID-19 testing probability and COVID-19 test results. RESULTS: Individuals with psychiatric disorders were overrepresented among the 1474 UK Biobank participants with test data: 23% of the COVID-19 test sample had a psychiatric diagnosis compared with 10% in the full cohort (P < 0.0001). This overrepresentation persisted for each of the specific psychiatric disorders tested. Furthermore, individuals with a psychiatric disorder (P = 0.01), particularly substance use disorder (P < 0.005), had negative test results significantly more often than individuals without psychiatric disorders. Sensitivity analyses confirmed our results. CONCLUSIONS: In contrast with our hypotheses, UK Biobank participants with psychiatric disorders have been tested for COVID-19 more frequently than individuals without a psychiatric history. Among those tested, test outcomes were more frequently negative for registry participants with psychiatric disorders than in others, countering arguments that people with psychiatric disorders are particularly prone to contract the virus.

Safe and informed prescribing of psychotropic medication during the COVID-19 pandemic.

Treatment with psychotropic medication may sometimes be jeopardised because of the COVID-19 pandemic. One underlying reason is the lack of COVID-19-specific psychopharmacology guidelines. Here, we discuss five considerations arising from our clinical experience and pharmacological background knowledge to enable safe and well-informed psychopharmacotherapy during the COVID-19 pandemic.