Single-arm studies, particularly single-arm trials (SATs), are increasingly being used in submissions for marketing authorization and health technology assessment. As reviewers of evidence, we sought to better understand the validity of SATs, compared with observational single-arm studies (case series), and how to assess them in our reviews.

We conducted a highly pragmatic literature review to create a convenience sample of recent systematic reviews published from January to July 2023 to establish the following: (i) what single-arm study designs are included; (ii) what quality assessment tools are used; and (iii) whether there is a difference in effect size and variability among different study designs. A single reviewer identified reviews of interventions that included single-arm studies and extracted information on the numbers of included SATs and case series, and the quality assessment tools used. Any misclassifications by review authors were identified. For meta-analyses, outcome data were extracted and a subgroup analysis comparing SATs and case series was conducted.

Work is still underway to complete this investigation. So far, it appears that a large proportion of systematic reviews misclassify SATs and case series studies and few use appropriate quality assessment tools. There is not yet any evidence of a systematic difference between SATs and case series in terms of effect size.

Findings suggest that there is poor understanding of SATs in the review community. There are limited specific quality assessment tools for SATs and review authors frequently use inappropriate tools to assess them. More research is likely to be needed to investigate the relative validity of SATs and single-arm observational studies.

As the most internally rigorous design, randomized controlled trials (RCTs) are the gold standard for assessing the efficacy and safety profile of interventions. Increasingly, health technology assessment (HTA) considers evidence from non-randomized studies. Guidance recommends synthesizing different study designs separately due to their different inherent biases/limitations. But when authors or reviewers misclassify studies, this could affect which studies are included and therefore have an impact on review results.

We are conducting a methods project to (i) identify a clear study design classification system, (ii) explore whether its use produces consistent study design categorizations among reviewers, and (iii) iteratively improve the classification system. We performed a pragmatic web-based search for study design categorization tools and used the resulting schemas to develop a clear algorithm for use by reviewers of all levels of experience, specifically in reviews of treatment interventions. Next, we tested tool consistency and user experience by web-based survey in a small internal sample of reviewers, each independently using the system to categorize 18 published studies.

A median of seven reviewers (range four to eight) categorized each study. Rater agreement using the chart varied widely, with 100 percent agreement on the designs of three studies (17%), and at least 75 percent of reviewers agreeing on one design for nine studies (50%). The most common agreement was reached on RCTs and non-randomized controlled trials. The most common sources of disagreement were between different types of cohort studies and between case series and controlled cohort studies, largely due to inconsistent reporting. We also identified several improvements: the wording of prompt questions, the ordering of designs, and the addition of new elements.

The classification system as initially designed led to too much variation in study design categorization to be useful. Consequently, we present a revised version that we now aim to evaluate in a larger sample of reviewers. Further research will also investigate whether using the tool would change the results of systematic reviews, using a small sample of published reviews.

Childhood bullying is a public health priority. We evaluated the effectiveness and costs of KiVa, a whole-school anti-bullying program that targets the peer context.

A two-arm pragmatic multicenter cluster randomized controlled trial with embedded economic evaluation. Schools were randomized to KiVa-intervention or usual practice (UP), stratified on school size and Free School Meals eligibility. KiVa was delivered by trained teachers across one school year. Follow-up was at 12 months post randomization. Primary outcome: student-reported bullying-victimization; secondary outcomes: self-reported bullying-perpetration, participant roles in bullying, empathy and teacher-reported Strengths and Difficulties Questionnaire. Outcomes were analyzed using multilevel linear and logistic regression models.

Between 8/11/2019–12/02/2021, 118 primary schools were recruited in four trial sites, 11 111 students in primary analysis (KiVa-intervention: n = 5944; 49.6% female; UP: n = 5167, 49.0% female). At baseline, 21.6% of students reported being bullied in the UP group and 20.3% in the KiVa-intervention group, reducing to 20.7% in the UP group and 17.7% in the KiVa-intervention group at follow-up (odds ratio 0.87; 95% confidence interval 0.78 to 0.97, p value = 0.009). Students in the KiVa group had significantly higher empathy and reduced peer problems. We found no differences in bullying perpetration, school wellbeing, emotional or behavioral problems. A priori subgroup analyses revealed no differences in effectiveness by socioeconomic gradient, or by gender. KiVa costs £20.78 more per pupil than usual practice in the first year, and £1.65 more per pupil in subsequent years.

The KiVa anti-bullying program is effective at reducing bullying victimization with small-moderate effects of public health importance.

The study was funded by the UK National Institute for Health and Care Research (NIHR) Public Health Research program (17-92-11). Intervention costs were funded by the Rayne Foundation, GwE North Wales Regional School Improvement Service, Children's Services, Devon County Council and HSBC Global Services (UK) Ltd.

Personalised management of recurrent depression, considering individual patient characteristics, is crucial.

This study evaluates the potentially different mediating role of mindfulness skills in managing recurrent depression using mindfulness-based cognitive therapy (MBCT) among people with varying depression severity.

Data from the Prevention of Depressive Relapse or Recurrence (PREVENT) trial, comparing MBCT (with antidepressant medication (ADM) tapering support, MBCT-tapering support) versus maintenance-ADM, were used. The study included pre, post, 9-, 12-, 18- and 24-month follow-ups. Adults with ≥3 previous major depressive episodes, in full/partial remission (below threshold for a current episode), on ADM, were assessed for eligibility in primary care practices in the UK. People were randomised (1:1) to MBCT-tapering support or maintenance-ADM. We used the Beck Depression Inventory-II to evaluate depressive symptom changes over the six time points. Pre-post treatment, we employed the Five Facets of Mindfulness Questionnaire to gauge mindfulness skills. Baseline symptom and history variables were used to identify individuals with varying severity profiles. We conducted Latent Profile Moderated-Mediation Growth Mixture Models.

A total of 424 people (mean (s.d.) age = 49.44 (12.31) years; with 325 (76.7%) self-identified as female) were included. A mediating effect of mindfulness skills, between trial arm allocation and the linear rate of depressive symptoms change over 24 months, moderated by depression severity, was observed (moderated-mediation index = −0.27, 95% CI = −0.66, −0.03). Conditional indirect effects were −0.42 (95% CI = −0.78, −0.18) for higher severity (expected mean BDI-II reduction = 10 points), and −0.15 (95% CI = −0.35, −0.02) for lower severity (expected mean BDI-II reduction = 3.5 points).

Mindfulness skills constitute a unique mechanism driving change in MBCT (versus maintenance-ADM). Individuals with higher depression severity may benefit most from MBCT-tapering support for residual symptoms. It is unclear if these effects apply to those with a current depressive episode. Future research should investigate individuals who are not on medication. This study provides preliminary evidence for personalised management of recurrent depression.

ISRCTN26666654.

Systematic reviews are important for informing decision-making and primary research, but they can be time consuming and costly. With the advent of machine learning, there is an opportunity to accelerate the review process in study screening. We aimed to understand the literature to make decisions about the use of machine learning for screening in our review workflow.

A pragmatic literature review of PubMed to obtain studies evaluating the accuracy of publicly available machine learning screening tools. A single reviewer used ‘snowballing’ searches to identify studies reporting accuracy data and extracted the sensitivity (ability to correctly identify included studies for a review) and specificity, or workload saved (ability to correctly exclude irrelevant studies).

Ten tools (AbstractR, ASReview Lab, Cochrane RCT classifier, Concept encoder, Dpedia, DistillerAI, Rayyan, Research Screener, Robot Analyst, SWIFT-active screener) were evaluated in a total of 16 studies. Fourteen studies were single arm where, although compared with a reference standard (predominantly single reviewer screening), there was no other comparator. Two studies were comparative, where tools were compared with other tools as well as a reference standard. All tools ranked records by probability of inclusion and either (i) applied a cut-point to exclude records or (ii) were used to rank and re-rank records during screening iterations, with screening continuing until most relevant records were obtained. The accuracy of tools varied widely between different studies and review projects. When used in method (ii), at 95 percent to 100 percent sensitivity, tools achieved workload savings of between 7 percent and 99 percent. It was unclear whether evaluations were conducted independent of tool developers.

Evaluations suggest the potential for tools to correctly classify studies in screening. However, conclusions are limited since (i) tool accuracy is generally not compared with dual reviewer screening and (ii) the literature lacks comparative studies and, because of between-study heterogeneity, it is not possible to robustly determine the accuracy of tools compared with each other. Independent evaluations are needed.

This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care.

We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted.

Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions.

When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.

Although cognitive-behavioural therapy (CBT) is an effective treatment for depression, less than half of patients achieve satisfactory symptom reduction during treatment. Targeting known psychopathological processes such as rumination may increase treatment efficacy. The aim of this study was to test whether adding group rumination-focused CBT (RFCBT) that explicitly targets rumination to routine medical management is superior to adding group CBT to routine medical management in treating major depression.

A total of 131 outpatients with major depression were randomly allocated to 12 sessions group RFCBT v. group CBT, each in addition to routine medical management. The primary outcome was observer-rated symptoms of depression at the end of treatment measured on the Hamilton Rating Scale for Depression. Secondary outcomes were rumination at post-treatment and depressive symptoms at 6 months follow-up (Trial registered: NCT02278224).

RFCBT significantly improved observer-rated depressive symptoms (Cohen's d 0.38; 95% CI 0.03–0.73) relative to group CBT at post-treatment on the primary outcome. No post-treatment differences were found in rumination or in depressive symptoms at 6 months follow-up, although these secondary analyses may have been underpowered.

This is the first randomized controlled trial providing evidence of benefits of RFCBT in major depression compared with CBT. Group RFCBT may be a beneficial alternative to group CBT for major depression.

To define the scope of an outbreak of Legionnaires’ disease (LD), to identify the source, and to stop transmission.

Epidemiologic investigation of an LD outbreak among patients and a visitor exposed to a newly constructed hematology-oncology unit.

An LD case was defined as radiographically confirmed pneumonia in a person with positive urinary antigen testing and/or respiratory culture for Legionella and exposure to the hematology-oncology unit after February 20, 2014. Cases were classified as definitely or probably healthcare-associated based on whether they were exposed to the unit for all or part of the incubation period (2–10 days). We conducted an environmental assessment and collected water samples for culture. Clinical and environmental isolates were compared by monoclonal antibody (MAb) and sequence-based typing.

Over a 12-week period, 10 cases were identified, including 6 definite and 4 probable cases. Environmental sampling revealed Legionella pneumophila serogroup 1 (Lp1) in the potable water at 9 of 10 unit sites (90%), including all patient rooms tested. The 3 clinical isolates were identical to environmental isolates from the unit (MAb2-positive, sequence type ST36). No cases occurred with exposure after the implementation of water restrictions followed by point-of-use filters.

Contamination of the unit’s potable water system with Lp1 strain ST36 was the likely source of this outbreak. Healthcare providers should routinely test patients who develop pneumonia at least 2 days after hospital admission for LD. A single case of LD that is definitely healthcare associated should prompt a full investigation.

Infect Control Hosp Epidemiol 2017;38:306–313

About 20% of major depressive episodes become chronic and medication-refractory and also appear to be less responsive to standard cognitive–behavioural therapy (CBT).

To test whether CBT developed from behavioural activation principles that explicitly and exclusively targets depressive rumination enhances treatment as usual (TAU) in reducing residual depression.

Forty-two consecutively recruited participants meeting criteria for medication-refractory residual depression were randomly allocated to TAU v. TAU plus up to 12 sessions of individual rumination-focused CBT. The trial has been registered (ISRCTN22782150).

Adding rumination-focused CBT to TAU significantly improved residual symptoms and remission rates. Treatment effects were mediated by change in rumination.

This is the first randomised controlled trial providing evidence of benefits of rumination-focused CBT in persistent depression. Although suggesting the internal validity of rumination-focused CBT for residual depression, the trial lacked an attentional control group so cannot test whether the effects were as a result of the specific content of rumination-focused CBT v. non-specific therapy effects.