The limited availability of randomized controlled trials (RCTs) in nephrology undermines causal inferences in meta-analyses. Systematic reviews of observational studies have grown more common under ...such circumstances. We conducted systematic reviews of all comparative observational studies in nephrology from 2006 to 2016 to assess the trends in the past decade. We then focused on the meta-analyses combining observational studies and RCTs to evaluate the systematic differences in effect estimates between study designs using two statistical methods: by estimating the ratio of odds ratios (ROR) of the pooled OR obtained from observational studies versus those from RCTs and by examining the discrepancies in their statistical significance. The number of systematic reviews of observational studies in nephrology had grown by 11.7-fold in the past decade. Among 56 records combining observational studies and RCTs, ROR suggested that the estimates between study designs agreed well (ROR 1.05, 95% confidence interval 0.90-1.23). However, almost half of the reviews led to discrepant interpretations in terms of statistical significance. In conclusion, the findings based on ROR might encourage researchers to justify the inclusion of observational studies in meta-analyses. However, caution is needed, as the interpretations based on statistical significance were less concordant than those based on ROR.
Major depression is often a relapsing disorder. It is therefore important to start its treatment with therapies that maximize the chance of not only getting the patients well but also keeping them ...well. We examined the associations between initial treatments and sustained response by conducting a network meta‐analysis of randomized controlled trials (RCTs) in which adult patients with major depression were randomized to acute treatment with a psychotherapy (PSY), a protocolized antidepressant pharmacotherapy (PHA), their combination (COM), standard treatment in primary or secondary care (STD), or pill placebo, and were then followed up through a maintenance phase. By design, acute phase treatment could be continued into the maintenance phase, switched to another treatment or followed by discretionary treatment. We included 81 RCTs, with 13,722 participants. Sustained response was defined as responding to the acute treatment and subsequently having no depressive relapse through the maintenance phase (mean duration: 42.2±16.2 weeks, range 24‐104 weeks). We extracted the data reported at the time point closest to 12 months. COM resulted in more sustained response than PHA, both when these treatments were continued into the maintenance phase (OR=2.52, 95% CI: 1.66‐3.85) and when they were followed by discretionary treatment (OR=1.80, 95% CI: 1.21‐2.67). The same applied to COM in comparison with STD (OR=2.90, 95% CI: 1.68‐5.01 when COM was continued into the maintenance phase; OR=1.97, 95% CI: 1.51‐2.58 when COM was followed by discretionary treatment). PSY also kept the patients well more often than PHA, both when these treatments were continued into the maintenance phase (OR=1.53, 95% CI: 1.00‐2.35) and when they were followed by discretionary treatment (OR=1.66, 95% CI: 1.13‐2.44). The same applied to PSY compared with STD (OR=1.76, 95% CI: 0.97‐3.21 when PSY was continued into the maintenance phase; OR=1.83, 95% CI: 1.20‐2.78 when PSY was followed by discretionary treatment). Given the average sustained response rate of 29% on STD, the advantages of PSY or COM over PHA or STD translated into risk differences ranging from 12 to 16 percentage points. We conclude that PSY and COM have more enduring effects than PHA. Clinical guidelines on the initial treatment choice for depression may need to be updated accordingly.
Pharmacotherapy remains the mainstay of treatment for acute bipolar mania, but there are many choices, including mood stabilizers (MSs) and antipsychotics (APs).
To provide an up-to-date and ...comprehensive review of the efficacy, acceptability and adverse effects of MSs and APs as combination or augmentation therapy versus monotherapy with either drug class for the treatment of acute mania.
The Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, Scopus, and clinical trial databases were searched for articles published between the inception of the databases and July 1, 2014. The following keywords were used: bipolar disorder, mania, manic, mixed bipolar, schizoaffective combined with the names of MSs and APs. The reference lists of all the identified randomized controlled trials (RCTs), articles that cited the identified trials, and recent systematic reviews were also checked.
Double-blind RCTs comparing MS and AP as combination or augmentation therapy with either monotherapy during the acute phase treatment of mania were included in the present study. The electronic search yielded 6,445 potential articles in September 2013 and 264 new references in an updated search performed in July 2014. Finally, 19 RCTs were considered eligible for our meta-analyses: MS plus AP combination or augmentation therapy was compared with MS monotherapy in 14 trials (n = 3,651) and with AP monotherapy in 6 trials (n = 606) one study compared combination therapy versus both MS monotherapy and AP monotherapy.
The primary outcomes were the mean change scores on validated rating scales for mania and all-cause discontinuation at 3 weeks. The secondary outcomes included response, remission, the mean change scores for depression, dropouts due to adverse events and to inefficacy, and adverse events at 3 weeks and mean change scores on validated rating scales at 1 week. Using random-effects models, standardized mean difference (SMD), risk ratio (RR) and numbers needed to treat with their 95 % confidence intervals (CIs) were calculated.
Most patients included in trials comparing combination/augmentation therapy versus MS monotherapy had prior treatment with an MS, while more than 70 % of participants in trials comparing combination/augmentation therapy versus AP monotherapy had not been on medications or were washed out from their previous medication before randomization. MS plus AP combination/augmentation therapy was more effective than MS monotherapy in terms of change in scores on mania rating scales at 3 weeks (SMD -0.26; 95 % CI -0.36 to -0.15) and at 1 week (SMD -0.17, -0.29 to -0.04). MS plus AP combination/augmentation therapy was more effective than AP monotherapy at 3 weeks (SMD -0.31, -0.50 to -0.12), but not at 1 week (SMD -0.22, -0.84 to 0.40). No significant differences were seen between the combination/augmentation therapy and either monotherapy group in study withdrawal for any reason (MS + AP vs. MS monotherapy: RR 0.99, 0.88-1.12; MS + AP vs. AP monotherapy: RR 0.70, 0.47-1.04) or adverse events (MS + AP vs. MS monotherapy: RR 1.39, 0.97-1.99; MS + AP vs. AP monotherapy: RR 0.62, 0.27-1.40). The combination/augmentation therapy was associated with more side effects, especially with somnolence, while it did not increase treatment-emergent depression.
Combining MS and AP is more efficacious and more burdensome than, but overall as acceptable as, the continuation of MS or AP monotherapy, when either monotherapy has not been successful. There is currently no robust evidence to judge whether MS and AP combination therapy is more efficacious than MS monotherapy as the initial therapy for acutely manic patients without prior medication.
Computer-assisted treatment may reduce therapist contact and costs and promote client participation. This meta-analysis examined the efficacy and acceptability of an unguided computer-assisted ...therapy in patients with obsessive-compulsive disorder (OCD) compared with a waiting list or attention placebo.
This study aimed to evaluate the effectiveness and adherence of computer-assisted self-help treatment without human contact in patients with OCD using a systematic review and meta-analysis approach.
Randomized controlled trials with participants primarily diagnosed with OCD by health professionals with clinically significant OCD symptoms as measured with validated scales were included. The interventions included self-help treatment through the internet, computers, and smartphones. We excluded interventions that used human contact. We conducted a search on PubMed, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov, as well as the reference lists of the included studies. The risk of bias was evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials. We calculated the standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes. The primary outcomes were short-term improvement of OCD symptoms measured by validated scales and dropout for any reason.
We included 11 randomized controlled trials with a total of 983 participants. The results indicated that unguided computer-assisted self-help therapy was significantly more effective than a waiting list or psychological placebo (standard mean difference -0.47, 95% CI -0.73 to -0.22). Unguided computer-assisted self-help therapy had more dropouts for any reason than waiting list or psychological placebo (risk ratio 1.98, 95% CI 1.21 to 3.23). However, the quality of evidence was very low because of the risk of bias and inconsistent results among the included studies. The subgroup analysis showed that exposure response and prevention and an intervention duration of more than 4 weeks strengthen the efficacy without worsening acceptability. Only a few studies have examined the interaction between participants and systems, and no study has used gamification. Most researchers only used text-based interventions, and no study has used a mobile device. The overall risk of bias of the included studies was high and the heterogeneity of results was moderate to considerable.
Unguided computer-assisted self-help therapy for OCD is effective compared with waiting lists or psychological placebo. An exposure response and prevention component and intervention duration of more than 4 weeks may strengthen the efficacy without worsening the acceptability of the therapy.
PROSPERO (International Prospective Register of Systematic Reviews) CRD42021264644; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=264644.
•It is important to avoid false-negatives in diagnosis of recurrent depression.•Daily hours of sitting idly increased the chances of recurrent depression two or four weeks later.•Change in exposure ...to daily ultraviolet light from non-exposure reduced recurrent depression.•Daily hours of sitting idly can contribute to accurate measurement of recurrent depression.
When studying recurrence of depression, researchers should pay attention to cases where physicians' assessment corresponds to the patients' perception. However, they should also focus on potential signs of recurrence when the recurrence is suspected by the physicians but not the patients (false-negative zeros). Because false negatives can delay diagnosis and treatment, we aimed to investigate “sitting idly” as a predictor influencing no alert sign of recurrence and estimated the counts of recurrence of depression. A smartphone application and a wearable device were used to collect lifelog data from 89 remitted depressive patients over one year. Recurrent depression was defined using the Japanese version of the Kessler Psychological Distress Scale and Patient Health Questionnaire-9 scores. Estimates of the population-averaged parameters indicated that daily hours of sitting idly increased the chances of recurrent depression occurring two to four weeks later. Exposure to daily ultraviolet light reduced depression relapse. Although long sleep was a determinant of zero outcome of the recurrence of depression after two to four weeks, daily hours of sitting idly can negate it. Thus, daily hours of sitting idly could reduce overdispersion of the recurrence of depression, and we could measure recurrent depression accurately by considering changes in sitting idly.
For patients starting treatment for depression, current guidelines recommend titrating the antidepressant dosage to the maximum of the licenced range if tolerated. When patients do not achieve ...remission within several weeks, recommendations include adding or switching to another antidepressant. However, the relative merits of these guideline strategies remain unestablished.
This multi-centre, open-label, assessor-blinded, pragmatic trial involved two steps. Step 1 used open-cluster randomisation, allocating clinics into those titrating sertraline up to 50 mg/day or 100 mg/day by week 3. Step 2 used central randomisation to allocate patients who did not remit after 3 weeks of treatment to continue sertraline, to add mirtazapine or to switch to mirtazapine. The primary outcome was depression severity measured with the Patient Health Questionnaire-9 (PHQ-9) (scores between 0 and 27; higher scores, greater depression) at week 9. We applied mixed-model repeated-measures analysis adjusted for key baseline covariates.
Between December 2010 and March 2015, we recruited 2011 participants with hitherto untreated major depression at 48 clinics in Japan. In step 1, 970 participants were allocated to the 50 mg/day and 1041 to the 100 mg/day arms; 1927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 point, 95% confidence interval (CI), - 0.58 to 1.07, P = 0.55). Other outcomes proved similar in the two groups. In step 2, 1646 participants not remitted by week 3 were randomised to continue sertraline (n = 551), to add mirtazapine (n = 537) or to switch to mirtazapine (n = 558): 1613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 point (0.43 to 1.55, P = 0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P = 0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1 to 19.0%) and switching by 8.4% (2.5 to 14.8%). There were no differences in adverse effects.
In patients with new onset depression, we found no advantage of titrating sertraline to 100 mg vs 50 mg. Patients unremitted by week 3 gained a small benefit in reduction of depressive symptoms at week 9 by switching sertraline to mirtazapine or by adding mirtazapine.
ClinicalTrials.gov, NCT01109693 . Registered on 23 April 2010.
Aim
While evidence‐based antidepressant treatment is available for major depressive disorder, standard approaches for discontinuation of antidepressants after remission have not yet been established. ...Decision aids are structured clinical tools that facilitate shared decision‐making between patients and healthcare providers. This study aimed to describe the development process and acceptability of decision aids for major depressive disorder following discontinuation of antidepressant treatment after remission.
Methods
We systematically developed a decision aids according to the International Patient Decision Aid Standards. First, a decision aids prototype was created using the results of a systematic review and meta‐analysis previously conducted to identify the consequences of continuing and discontinuing antidepressant treatment. Second, a mixed‐methods questionnaire (alpha acceptability testing) was administered to patients and healthcare providers to improve the decision aids prototype and develop it into a final version acceptable for clinical settings.
Results
Our decision aids consisted of a description of major depressive disorder, the option to continue or discontinue antidepressant treatment, the advantages and disadvantages of each option, the consequences of each option, and value clarification exercises for each option. The patients (n = 22) reported that the decision aids had acceptable language (91%), adequate information (91%), and a well‐balanced presentation (95%). Healthcare providers (n = 20) provided favorable feedback. The final decision aids fulfilled all six International Patient Decision Aid Standards qualifying criteria.
Conclusion
We successfully developed a decision aids for discontinuation of antidepressant treatment after remission, which could be used during the shared decision‐making process. Further studies are needed to verify the effects of using the decision aids during the shared decision‐making process.
The Japanese Big Five Scale Short Form (JBFS-SF), a 29-item self-report scale, has recently been used to measure the Big Five personality traits. However, the scale lacks psychometric validation. ...This study examined the validity and reliability of the JBFS-SF with data collected from 1,626 Japanese university students participating in a randomized controlled clinical trial. Structural validity was tested with exploratory and confirmatory factor analysis and measurement invariance tests were conducted across sex. Internal consistency was evaluated with McDonald’s omega. Additionally, construct validity was estimated across factors using the PHQ-9, GAD-7, AQ-J-10, and SSQ. EFA results showed that the JBFS-SF can be classified according to the expected five-factor structure, while three items had small loadings. Therefore, we dropped these three items and tested the reliability and validity of the 26-item version. CFA results found that a 26-item JBFS-FS has adequate structural validity (GFI = 0.907, AGFI = 0.886, CFI = 0.907, and RMSEA = 0.057). The omega of each factor was 0.74–0.85. Each JBFS-SF factor was specifically correlated with the PHQ-9, GAD-7, and SSQ. This research has shown that the JBFS-SF can be a clinically useful measure for assessing personality characteristics.
IntroductionThe health burden due to depression is ever increasing in the world. Prevention is a key to reducing this burden. Guided internet cognitive–behavioural therapies (iCBT) appear promising ...but there is room for improvement because we do not yet know which of various iCBT skills are more efficacious than others, and for whom. In addition, there has been no platform for iCBT that can accommodate ongoing evolution of internet technologies.Methods and analysisBased on our decade-long experiences in developing smartphone CBT apps and examining them in randomised controlled trials, we have developed the Resilience Training App Version 2. This app now covers five CBT skills: cognitive restructuring, behavioural activation, problem-solving, assertion training and behaviour therapy for insomnia. The current study is designed as a master protocol including four 2×2 factorial trials using this app (1) to elucidate specific efficacies of each CBT skill, (2) to identify participants’ characteristics that enable matching between skills and individuals, and (3) to allow future inclusion of new skills. We will recruit 3520 participants with subthreshold depression and ca 1700 participants without subthreshold depression, to examine the short-term efficacies of CBT skills to reduce depressive symptoms in the former and to explore the long-term efficacies in preventing depression in the total sample. The primary outcome for the short-term efficacies is the change in depressive symptoms as measured with the Patient Health Questionnaire-9 at week 6, and that for the long-term efficacies is the incidence of major depressive episodes as assessed by the computerised Composite International Diagnostic Interview by week 50.Ethics and disseminationThe trial has been approved by the Ethics Committee of Kyoto University Graduate School of Medicine (C1556).Trial registration numberUMIN000047124.
News value theory rates geographical proximity as an important factor in the process of issue selection by journalists. But does this apply to science journalism? Previous observational studies ...investigating whether newspapers preferentially cover scientific studies involving national scientists have generated conflicting answers. Here we used a database of 123 biomedical studies, 113 of them involving at least one research team working in eight countries (Australia, Canada, France, Ireland, Japan, New Zealand, the United Kingdom, and the United States). We compiled all the newspaper articles covering these 123 studies and published in English, French, and Japanese languages. In all eight countries, we found that newspapers preferentially covered studies involving a national team. Moreover, these “national” studies on average gave rise to a larger number of newspaper articles than “foreign” studies. Finally, our study resolves the conflict with previous conclusions by providing an alternative interpretation of published observations.
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