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There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries.
Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function.
Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care.
Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.
Framing is a crucial skill for connecting problem and solution spaces in the creative design process, both for individuals and teams. Frames are implicit in individuals’ cognitive thinking, but the creation of shared frames plays a vital role in collaborative design. Many studies have attempted to describe the framing process, but little is still known about how to support designers in framing, specifically in teams. This paper addresses this gap, by exploring the connection between sketching and framing within interdisciplinary teams. Following a qualitative and explorative approach, we have investigated the process and outcome of five interdisciplinary teams. We identified that sketching assists in the creation and elaboration of frames. Furthermore, in tandem with discussion and reflection, sketching helps increase the chance of a frame to survive within the design process. Our findings have practical and educational implications for improving the creative design process in interdisciplinary teams.
This chapter addresses a special category of cases in which an asserted patent is, or has been declared to be, essential to the implementation of a collaboratively developed voluntary consensus standard, and the holder of that patent has agreed to license it to implementers of the standard on terms that are fair, reasonable, and nondiscriminatory (FRAND).This chapter explores how the existence of such a FRAND commitment may affect a patent holder’s entitlement to monetary damages and injunctive relief. In addition to issues of patent law, remedies law, and contracts law, we consider the effect of competition law on this issue.
As depression has a recurrent course, relapse and recurrence prevention is essential.
In our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/−AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact.
Data were analysed (n = 289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model.
Mean total costs over 24 months were €6814, €10 264 and €13 282 for AD+PCT, antidepressants only and PCT/−AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/−AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/−AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/−AD.
Adding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/−AD will become cost-effective.
Declaration of interest
C.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.
Previous studies on reporting bias generally examined whether trials were published in stand-alone publications. In this study, we investigated whether pooled-trials publications constitute a specific form of reporting bias. We assessed whether negative trials were more likely to be exclusively published in pooled-trials publications than positive trials and examined the research questions, individual trial results, and conclusions presented in these articles.
Data from a cohort of 105 randomized controlled trials of 16 antidepressants were extracted from earlier publications and the corresponding Food and Drug Administration (FDA) reviews. A systematic literature search was conducted to identify pooled-trials publications.
We found 107 pooled-trials publications that reported results of 23 (72%) of 32 trials not published in stand-alone publications. Only two (3.8%) of 54 positive trials were published exclusively in pooled-trials publications, compared with 21 (41.1%) of 51 negative trials (p < 0.001). Thirteen (12%) of 107 publications had as primary aim to present data on the trial's primary research question (drug efficacy compared with placebo). Only four of these publications, reporting on five (22%) trials, presented individual efficacy data for the primary research question. Additionally, only five (5%) of 107 pooled-trials publications had a negative conclusion.
Compared with positive trials, negative trials of antidepressants for depression were much more likely to be reported exclusively in pooled-trials publications. Pooled-trials publications flood the evidence base with often-redundant articles that, instead of addressing the original primary research question, present (positive) results on secondary questions. Therefore, pooled-trials publications distort the apparent risk–benefit profile of antidepressants.
Improvement in depression within the first 2 weeks of antidepressant treatment predicts good outcomes, but non-improvers can still respond or remit, whereas improvers often do not.
We aimed to investigate whether early improvement of individual depressive symptoms better predicts response or remission.
We obtained individual patient data of 30 trials comprising 2184 placebo-treated and 6058 antidepressant-treated participants. Primary outcome was week 6 response; secondary outcomes were week 6 remission and week 12 response and remission. We compared models that only included improvement in total score by week 2 (total improvement model) with models that also included improvement in individual symptoms.
For week 6 response, the area under the receiver operating characteristic curve and negative and positive predictive values of the total improvement model were 0.73, 0.67 and 0.74 compared with 0.77, 0.70 and 0.71 for the item improvement model. Model performance decreased for week 12 outcomes. Of predicted non-responders, 29% actually did respond by week 6 and 43% by week 12, which was decreased from the baseline (overall) probabilities of 51% by week 6 and 69% by week 12. In post hoc analyses with continuous rather than dichotomous early improvement, including individual items did not enhance model performance.
Examining individual symptoms adds little to the predictive ability of early improvement. Additionally, early non-improvement does not rule out response or remission, particularly after 12 rather than 6 weeks. Therefore, our findings suggest that routinely adapting pharmacological treatment because of limited early improvement would often be premature.
Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders.
In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments.
After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1–1.5] to 1.9 (95% CI 1.4–2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2–1.9) to 1.7 (95% CI 1.2–2.4).
PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research.