Shortening the Edinburgh postnatal depression scale using optimal test assembly methods: Development of the EPDS-Dep-5.

AIMS: This study used a large database to develop a reliable and valid shortened form of the Edinburgh Postnatal Depression Scale (EPDS), a self-report questionnaire used for depression screening in pregnancy and postpartum, based on objective criteria. METHODS: Item responses from the 10-item EPDS were obtained from 5157 participants (765 major depression cases) from 22 primary screening accuracy studies that compared the EPDS to the Structured Clinical Interview for DSM (SCID). Unidimensionality of the EPDS latent construct was verified using confirmatory factor analysis, and an item response theory model was fit. Optimal test assembly (OTA) methods identified a maximally informative shortened form for each possible scale length between 1 and 9 items. The final shortened form was selected based on pre-specified validity and reliability criteria and non-inferiority of screening accuracy of the EPDS as compared to the SCID. RESULTS: A 5-item short form of the EPDS (EPDS-Dep-5) was selected. The EPDS-Dep-5 had a Cronbach's alpha of 0.82. Sensitivity and specificity of the EPDS-Dep-5 for a cutoff of 4 or greater were 0.83 (95% CI, 0.73, 0.89) and 0.86 (95% CI, 0.80, 0.90) and were statistically non-inferior to the EPDS. The correlation of total scores with the full EPDS was high (r = 0.91). CONCLUSION: The EPDS-Dep-5 is a valid short form with minimal loss of information when compared to the full-length EPDS. The EPDS-Dep-5 was developed with OTA methods using objective, pre-specified criteria, but the approach is data-driven and exploratory. Thus, there is a need to replicate results of this study in different populations.

Potentially Avertable Child Mortality Associated with Surgical Workforce Scale-up in Low- and Middle-Income Countries: A Global Study.

BACKGROUND: Expansion of access to surgical care can improve health outcomes, although the impact that scale-up of the surgical workforce will have on child mortality is poorly defined. In this study, we estimate the number of child deaths potentially avertable by increasing the surgical workforce globally to meet targets proposed by the Lancet Commission on Global Surgery. METHODS: To estimate the number of deaths potentially avertable through increases in the surgical workforce, we used log-linear regression to model the association between surgeon, anesthetist and obstetrician workforce (SAO) density and surgically amenable under-5 mortality rate (U5MR), infant mortality rate (IMR), and neonatal mortality rate (NMR) for 192 countries adjusting for potential confounders of childhood mortality, including the non-surgical workforce (physicians, nurses/midwives, community health workers), gross national income per capita, poverty rate, female literacy rate, health expenditure per capita, percentage of urban population, number of surgical operations, and hospital bed density. Surgically amenable mortality was determined using mortality estimates from the UN Inter-agency Group for Child Mortality Estimation adjusted by the proportion of deaths in each country due to communicable causes unlikely to be amenable to surgical care. Estimates of mortality reduction due to upscaling surgical care to support the Lancet Commission on Global Surgery (LCoGS) minimum target of 20-40 SAO/100,000 were calculated accounting for potential increases in surgical volume associated with surgical workforce expansion. RESULTS: Increasing SAO workforce density was independently associated with lower surgically amenable U5MR as well as NMR (p < 0.01 for each model). When accounting for concomitant increases in surgical volume, scale-up of the surgical workforce to 20-40 SAO/100,000 could potentially prevent between 262,709 (95% CI 229,643-295,434) and 519,629 (465,046-573,919) under 5 deaths annually. The majority (61%) of deaths averted would be neonatal deaths. CONCLUSION: Scale up of surgical workforce may substantially decrease childhood mortality rates around the world. Our analysis suggests that scale-up of surgical delivery through increase in the SAO workforce could prevent over 500,000 children from dying before the age of 5 annually. This would represent significant progress toward meeting global child mortality reduction targets.

Equivalency of the diagnostic accuracy of the PHQ-8 and PHQ-9: a systematic review and individual participant data meta-analysis.

BACKGROUND: Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9. METHODS: We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy. RESULTS: 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01). CONCLUSIONS: PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

The Accuracy of the Patient Health Questionnaire-9 Algorithm for Screening to Detect Major Depression: An Individual Participant Data Meta-Analysis.

BACKGROUND: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results. OBJECTIVE: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10. METHODS: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview. RESULTS: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88). CONCLUSIONS: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.

Shortening self-report mental health symptom measures through optimal test assembly methods: Development and validation of the Patient Health Questionnaire-Depression-4.

BACKGROUND: The objective of this study was to develop and validate a short form of the Patient Health Questionnaire-9 (PHQ-9), a self-report questionnaire for assessing depressive symptomatology, using objective criteria. METHODS: Responses on the PHQ-9 were obtained from 7,850 English-speaking participants enrolled in 20 primary diagnostic test accuracy studies. PHQ unidimensionality was verified using confirmatory factor analysis, and an item response theory model was fit. Optimal test assembly (OTA) methods identified a maximally precise short form for each possible length between one and eight items, including and excluding the ninth item. The final short form was selected based on prespecified validity, reliability, and diagnostic accuracy criteria. RESULTS: A four-item short form of the PHQ (PHQ-Dep-4) was selected. The PHQ-Dep-4 had a Cronbach's alpha of 0.805. Sensitivity and specificity of the PHQ-Dep-4 were 0.788 and 0.837, respectively, and were statistically equivalent to the PHQ-9 (sensitivity = 0.761, specificity = 0.866). The correlation of total scores with the full PHQ-9 was high (r = 0.919). CONCLUSION: The PHQ-Dep-4 is a valid short form with minimal loss of information of scores when compared to the full-length PHQ-9. Although OTA methods have been used to shorten patient-reported outcome measures based on objective, prespecified criteria, further studies are required to validate this general procedure for broader use in health research. Furthermore, due to unexamined heterogeneity, there is a need to replicate the results of this study in different patient populations.

Probability of major depression diagnostic classification using semi-structured versus fully structured diagnostic interviews.

BACKGROUND: Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.AimsTo evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics. METHOD: Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit. RESULTS: A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15-3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98-10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7-15) (OR = 0.96; 95% CI = 0.56-1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26-0.97). CONCLUSIONS: The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.Declaration of interestDrs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

Selective Cutoff Reporting in Studies of Diagnostic Test Accuracy: A Comparison of Conventional and Individual-Patient-Data Meta-Analyses of the Patient Health Questionnaire-9 Depression Screening Tool.

In studies of diagnostic test accuracy, authors sometimes report results only for a range of cutoff points around data-driven "optimal" cutoffs. We assessed selective cutoff reporting in studies of the diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) depression screening tool. We compared conventional meta-analysis of published results only with individual-patient-data meta-analysis of results derived from all cutoff points, using data from 13 of 16 studies published during 2004-2009 that were included in a published conventional meta-analysis. For the "standard" PHQ-9 cutoff of 10, accuracy results had been published by 11 of the studies. For all other relevant cutoffs, 3-6 studies published accuracy results. For all cutoffs examined, specificity estimates in conventional and individual-patient-data meta-analyses were within 1% of each other. Sensitivity estimates were similar for the cutoff of 10 but differed by 5%-15% for other cutoffs. In samples where the PHQ-9 was poorly sensitive at the standard cutoff, authors tended to report results for lower cutoffs that yielded optimal results. When the PHQ-9 was highly sensitive, authors more often reported results for higher cutoffs. Consequently, in the conventional meta-analysis, sensitivity increased as cutoff severity increased across part of the cutoff range-an impossibility if all data are analyzed. In sum, selective reporting by primary study authors of only results from cutoffs that perform well in their study can bias accuracy estimates in meta-analyses of published results.

Nonparametric causal inference for optogenetics: sequential excursion effects for dynamic regimes.

Optogenetics is a powerful neuroscience technique for studying how neural circuit manipulation affects behavior. Standard analysis conventions discard information and severely limit the scope of the causal questions that can be probed. To address this gap, we 1) draw connections to the causal inference literature on sequentially randomized experiments, 2) propose a non-parametric framework for analyzing "open-loop" (static regime) optogenetics behavioral experiments, 3) derive extensions of history-restricted marginal structural models for dynamic treatment regimes with positivity violations for "closed-loop" designs, and 4) propose a taxonomy of identifiable causal effects that encompass a far richer collection of scientific questions compared to standard methods. From another view, our work extends "excursion effect" methods, popularized recently in the mobile health literature, to enable estimation of causal contrasts for treatment sequences in the presence of positivity violations. We describe sufficient conditions for identifiability of the proposed causal estimands, and provide asymptotic statistical guarantees for a proposed inverse probability-weighted estimator, a multiply-robust estimator (for two intervention timepoints), a framework for hypothesis testing, and a computationally scalable implementation. Finally, we apply our framework to data from a recent neuroscience study and show how it provides insight into causal effects of optogenetics on behavior that are obscured by standard analyses.

Multi-Source Conformal Inference Under Distribution Shift.

Recent years have experienced increasing utilization of complex machine learning models across multiple sources of data to inform more generalizable decision-making. However, distribution shifts across data sources and privacy concerns related to sharing individual-level data, coupled with a lack of uncertainty quantification from machine learning predictions, make it challenging to achieve valid inferences in multi-source environments. In this paper, we consider the problem of obtaining distribution-free prediction intervals for a target population, leveraging multiple potentially biased data sources. We derive the efficient influence functions for the quantiles of unobserved outcomes in the target and source populations, and show that one can incorporate machine learning prediction algorithms in the estimation of nuisance functions while still achieving parametric rates of convergence to nominal coverage probabilities. Moreover, when conditional outcome invariance is violated, we propose a data-adaptive strategy to upweight informative data sources for efficiency gain and downweight non-informative data sources for bias reduction. We highlight the robustness and efficiency of our proposals for a variety of conformal scores and data-generating mechanisms via extensive synthetic experiments. Hospital length of stay prediction intervals for pediatric patients undergoing a high-risk cardiac surgical procedure between 2016-2022 in the U.S. illustrate the utility of our methodology.

Evaluation of Intensive Telephonic Nutritional and Lifestyle Counseling to Enhance Outcomes of Bariatric Surgery.

BACKGROUND: To determine the impact of an intensive perioperative nutritional and lifestyle support protocol on long-term outcomes of bariatric surgery. METHODS: A retrospective observational study was conducted of 955 patients who underwent gastric bypass surgery between 2005 and 2015. Patients were divided into two cohorts: (1) 2005 through August 2013: these 767 patients were required to participate in the intensive telephone-based nutritional support program from 8 weeks preoperative through 44 weeks postoperative; (2) after August 2013, the program was discontinued and 188 patients did not have intensive telephonic nutritional support. Inverse probability weighting was used to obtain weight loss estimates at 1 and 3 years postoperative. Time-to-event analyses were used to investigate hospitalization rates postoperative. Poisson models were used to investigate healthcare utilization. RESULTS: Patients who participated in the program exhibited 1.97% (95% CI 0.7, 3.3) greater %TWL at 1 year and 2.2% (95% CI -0.3, 4.1) greater %TWL at 3 years postoperative than patients who did not participate. Secondary analyses indicated participation in the program was associated with 44% shorter time to first hospitalization postoperative (p < 0.001). CONCLUSIONS: In this health system, intensive nutritional support was associated with greater weight loss at 1 and 3 years postoperative and higher hospitalization rates.

Randomized controlled trial of an internet-based self-guided hand exercise program to improve hand function in people with systemic sclerosis: the Scleroderma Patient-centered Intervention Network Hand Exercise Program (SPIN-HAND) trial.

BACKGROUND: Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. Functional impairment of hands is common. The Scleroderma Patient-centered Intervention Network (SPIN)-HAND trial compared effects of offering access to an online self-guided hand exercise program to usual care on hand function (primary) and functional health outcomes (secondary) in people with SSc with at least mild hand function limitations. METHODS: The pragmatic, two-arm, parallel-group cohort multiple randomized controlled trial was embedded in the SPIN Cohort. Cohort participants with Cochin Hand Function Scale (CHFS) scores ≥ 3 and who indicated interest in using the SPIN-HAND Program were randomized (3:2 ratio) to an offer of program access or to usual care (targeted N = 586). The SPIN-HAND program consists of 4 modules that address (1) thumb flexibility and strength; (2) finger bending; (3) finger extension; and (4) wrist flexibility and strength. The primary outcome analysis compared CHFS scores 3 months post-randomization between participants offered versus not offered the program. Secondary outcomes were CHFS scores 6 months post-randomization and functional health outcomes (Patient-Reported Outcomes Measurement Information System profile version 2.0 domain scores) 3 and 6 months post-randomization. RESULTS: In total, 466 participants were randomized to intervention offer (N = 280) or usual care (N = 186). Of 280 participants offered the intervention, 170 (61%) consented to access the program. Of these, 117 (69%) viewed at least one hand exercise instruction video and 77 (45%) logged into the program website at least 3 times. In intent-to-treat analyses, CHFS scores were 1.2 points lower (95% CI - 2.8 to 0.3) for intervention compared to usual care 3 months post-randomization and 0.1 points lower (95% CI - 1.8 to 1.6 points) 6 months post-randomization. There were no statistically significant differences in other outcomes. CONCLUSION: The offer to use the SPIN-HAND Program did not improve hand function. Low offer uptake, program access, and minimal usage among those who accessed the program limited our ability to determine if using the program would improve function. To improve engagement, the program could be tested in a group format or as a resource to support care provided by a physical or occupational therapist. TRIAL REGISTRATION: NCT03419208 . Registered on February 1, 2018.

Effects of a support group leader education program jointly developed by health professionals and patients on peer leader self-efficacy among leaders of scleroderma support groups: a two-arm parallel partially nested randomised controlled trial.

BACKGROUND: More people with rare diseases likely receive disease education and emotional and practical support from peer-led support groups than any other way. Most rare-disease support groups are delivered outside of the health care system by untrained leaders. Potential benefits may not be achieved and harms, such as dissemination of inaccurate information, may occur. Our primary objective was to evaluate the effects of a rare-disease support group leader education program, which was developed collaboratively by researchers, peer support group leaders, and patient organization leaders, compared to waitlist control, on peer leader self-efficacy among scleroderma support group leaders. METHODS: The trial was a pragmatic, two-arm partially nested randomised controlled trial with 1:1 allocation into intervention or waitlist control. Eligible participants were existing or candidate peer support group leaders affiliated with a scleroderma patient organization. Leader training was delivered in groups of 5-6 participants weekly for 13 weeks in 60-90 min sessions via the GoToMeeting® videoconferencing platform. The program included 12 general leader training modules and one module specific to scleroderma. Primary outcome was leader self-efficacy, measured by the Support Group Leader Self-efficacy Scale (SGLSS) immediately post-intervention. Secondary outcomes were leader self-efficacy 3 months post-intervention; emotional distress, leader burnout, and volunteer satisfaction post-intervention and 3 months post-intervention; and program satisfaction among intervention participants post-intervention. RESULTS: One hundred forty-eight participants were randomised to intervention (N = 74) or waitlist (N = 74). Primary outcome data were provided by 146 (99%) participants. Mean number of sessions attended was 11.4 (standard deviation = 2.6). Mean program satisfaction score (CSQ-8) was 30.3 (standard deviation = 3.0; possible range 8-32). Compared to waitlist control, leader self-efficacy was higher post-intervention [SGLSS; 16.7 points, 95% CI 11.0-22.3; standardized mean difference (SMD) 0.84] and 3 months later (15.6 points, 95% CI 10.2-21.0; SMD 0.73); leader volunteer satisfaction was significantly higher at both assessments, emotional distress was lower post-intervention but not 3 months later, and leader burnout was not significantly different at either assessment. CONCLUSIONS: Peer support group leader education improved leader self-efficacy substantially. The program could be easily adapted for support group leaders in other rare diseases. TRIAL REGISTRATION: NCT03965780 ; registered on May 29, 2019.

Investigating Bias from Missing Data in an Electronic Health Records-Based Study of Weight Loss After Bariatric Surgery.

PURPOSE: Missing data is common in electronic health records (EHR)-based obesity research. To avoid bias, it is critical to understand mechanisms that underpin missingness. We conducted a survey among bariatric surgery patients in three integrated health systems to (i) investigate predictors of disenrollment and (ii) examine differences in weight between disenrollees and enrollees at 5 years. MATERIALS AND METHODS: We identified 2883 patients who had bariatric surgery between 11/2013 and 08/2014. Patients who disenrolled before their 5-year anniversary were invited to participate in a survey to ascertain reasons for disenrollment and current weight. Logistic regression was used to investigate predictors of disenrollment. Five-year percent weight change distributions were estimated using inverse-probability weighting to adjust for (un)availability of EHR weight data at 5 years among enrollees and survey (non-)response among disenrollees. RESULTS: Among 536 disenrolled patients, 104 (19%) completed the survey. Among 2347 patients who maintained enrollment, 384 (16%) had no weight measurement in the EHR near 5 years. Insurance, age, Hispanic ethnicity, and site predicted disenrollment. Disenrollees had slightly greater weight loss than enrollees. CONCLUSION: We found little evidence of weight loss differences by enrollment status. Collecting information through surveys can be an effective tool to investigate and adjust for missingness in EHR-based studies.

Effects of a multi-faceted education and support programme on anxiety symptoms among people with systemic sclerosis and anxiety during COVID-19 (SPIN-CHAT): a two-arm parallel, partially nested, randomised, controlled trial.

BACKGROUND: No trials have tested multifaceted mental health interventions recommended by public health organisations during COVID-19. The objective of this trial was to evaluate the effect of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Program on anxiety symptoms and other mental health outcomes among people vulnerable during COVID-19 owing to a pre-existing medical condition. METHODS: The SPIN-CHAT Trial was a pragmatic, two-arm, parallel, partially nested, randomised, controlled trial (1:1 allocation to intervention or waitlist). Eligible participants with systemic sclerosis were recruited from the international SPIN COVID-19 Cohort. SPIN COVID-19 Cohort participants were eligible for the trial if they completed baseline measures and had at least mild anxiety symptoms, had not tested positive for COVID-19, and were not currently receiving mental health counselling. SPIN-CHAT is a 4-week (3 sessions per week) videoconference-based group intervention that provided education and practice with mental health coping strategies, and provided social support to reduce isolation. Groups included 6-10 participants. The primary outcome analysed in the intention-to-treat population was anxiety symptoms (PROMIS Anxiety 4a version 1.0) immediately post-intervention. This trial is registered with ClinicalTrials.gov, NCT04335279 and is complete. FINDINGS: Of participants who completed baseline measures between April 9, 2020, and April 27, 2020, 560 participants were eligible and 172 participants were randomly assigned to intervention (n=86) or waitlist (n=86). Mean age was 55·0 years (SD 11·4 years), 162 (94%) were women, and 136 (79%) identified as White. In intention-to-treat analyses, the intervention did not significantly reduce anxiety symptoms post-intervention (-1·57 points, 95% CI -3·59 to 0·45; standardised mean difference [SMD] -0·22 points) but reduced symptoms 6 weeks later (-2·36 points, 95% CI -4·56 to -0·16; SMD -0·31). Depression symptoms were significantly lower 6 weeks post-intervention (-1·64 points, 95% CI -2·91 to -0·37; SMD -0·31); no other secondary outcomes were significant. No adverse events were reported. INTERPRETATION: The intervention did not significantly improve anxiety symptoms or other mental health outcomes post-intervention. However, anxiety and depression symptoms were significantly lower 6 weeks later, potentially capturing the time it took for new skills and social support between intervention participants to affect mental health. Multi-faceted interventions such as SPIN-CHAT have potential to address mental health needs in vulnerable groups during COVID-19, yet uncertainty remains about effectiveness. FUNDING: Canadian Institutes of Health Research (CIHR; VR4-172745, MS1-173066); McGill Interdisciplinary Initiative in Infection and Immunity Emergency COVID-19 Research Fund; Scleroderma Canada, made possible by an educational grant for patient support programming from Boehringer Ingelheim; the Scleroderma Society of Ontario; Scleroderma Manitoba; Scleroderma Atlantic; Scleroderma Australia; Scleroderma New South Wales; Scleroderma Victoria; Scleroderma Queensland; Scleroderma SASK; the Scleroderma Association of BC; and Sclérodermie Québec.

The Scleroderma Patient-centered Intervention Network Self-Management (SPIN-SELF) Program: protocol for a two-arm parallel partially nested randomized controlled feasibility trial with progression to full-scale trial.

BACKGROUND: Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. We completed an initial feasibility trial of an online self-administered version of the Scleroderma Patient-centered Intervention Network Self-Management (SPIN-SELF) Program using the cohort multiple randomized controlled trial (RCT) design. Due to low intervention offer uptake, we will conduct a new feasibility trial with progression to full-scale trial, using a two-arm parallel, partially nested RCT design. The SPIN-SELF Program has also been revised to include facilitator-led videoconference group sessions in addition to online material. We will test the group-based intervention delivery format, then evaluate the effect of the SPIN-SELF Program on disease management self-efficacy (primary) and patient activation, social appearance anxiety, and functional health outcomes (secondary). METHODS: This study is a feasibility trial with progression to full-scale RCT, pending meeting pre-defined criteria, of the SPIN-SELF Program. Participants will be recruited from the ongoing SPIN Cohort ( http://www.spinsclero.com/en/cohort ) and via social media and partner patient organizations. Eligible participants must have SSc and low to moderate disease management self-efficacy (Self-Efficacy for Managing Chronic Disease (SEMCD) Scale score ≤ 7.0). Participants will be randomized (1:1 allocation) to the group-based SPIN-SELF Program or usual care for 3 months. The primary outcome in the full-scale trial will be disease management self-efficacy based on SEMCD Scale scores at 3 months post-randomization. Secondary outcomes include SEMCD scores 6 months post-randomization plus patient activation, social appearance anxiety, and functional health outcomes at 3 and 6 months post-randomization. We will include 40 participants to assess feasibility. At the end of the feasibility portion, stoppage criteria will be used to determine if the trial procedures or SPIN-SELF Program need important modifications, thereby requiring a re-set for the full-scale trial. Otherwise, the full-scale RCT will proceed, and outcome data from the feasibility portion will be utilized in the full-scale trial. In the full-scale RCT, 524 participants will be recruited. DISCUSSION: The SPIN-SELF Program may improve disease management self-efficacy, patient activation, social appearance anxiety, and functional health outcomes in people with SSc. SPIN works with partner patient organizations around the world to disseminate its programs free-of-charge. TRIAL REGISTRATION: ClinicalTrials.gov NCT04246528 . Registered on 27 January 2020.

Balance of group sizes in randomized controlled trials published in American Psychological Association journals.

OBJECTIVE: We evaluated whether sample size differences between arms of two-arm parallel group randomized controlled trials (RCTs) published in American Psychological Association (APA)-affiliated journals were consistently smaller than expected by chance with simple randomization. METHOD: We searched PsycINFO for two-arm parallel group RCTs in APA-affiliated journals published January 2007 to September 2017 that used individual randomization (1:1 allocation ratio), reported the number of participants randomized, and did not describe employing restrictive randomization (e.g., blocking). We queried authors because randomization processes were often not described in articles, and we conducted a post hoc logistic regression analysis to attempt to identify factors associated with overly balanced groups. RESULTS: We identified 203 eligible trials, but after the author query, it was determined that only 115 used simple randomization. Among those 115 trials, there was a significantly greater number of trials with smaller sample size differences between trial arms than would be expected by chance (p < .001); 89 of 115 (77%) had differences in trial arm sample sizes smaller than the 50% prediction interval threshold for these differences. Greater proportionate imbalance may be associated with larger trial size (odds ratio of 0.27, 95% CI [0.08, 0.94] for N > 200 vs. N ≤ 100); greater balance may be more common in higher impact journals, though this was not statistically significant. CONCLUSIONS: Education is needed to ensure that randomization procedures are implemented as intended and fully and accurately reported and that balanced group sample sizes are not understood as an indicator of trial quality. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Perceived Benefits and Facilitators and Barriers to Providing Psychosocial Interventions for Informal Caregivers of People with Rare Diseases: A Scoping Review.

BACKGROUND: Little is known about the benefits, and barriers and facilitators to providing psychosocial support to caregivers to a loved one with a rare disease. OBJECTIVE: The aim of our scoping review was to map evidence on (1) perceived benefits and (2) barriers and facilitators of establishing and maintaining services. METHODS: The CINAHL and PubMed databases were searched in December 2018. Qualitative and quantitative studies in any language that described perceived or tested benefits of participating in psychosocial interventions for caregivers, or the barriers and facilitators of providing these interventions, were eligible. RESULTS: Thirty-four studies were included. Interventions were behavioural or psychological, supportive, educational, or multicomponent. All included studies reported on the benefits of participating in psychosocial interventions; 14 (41%) studies also reported on facilitators and 19 (56%) reported on barriers. Benefits that were most commonly found included statistically significant improvements in emotional states (e.g. stress) and caregiver burden and narrative reports of intervention helpfulness. Statistically significant improvements in mental health outcomes (e.g. depression symptoms) were rarely detected. Four themes for facilitators were identified, including intervention characteristics, intervention delivery characteristics, provision of necessary resources, and support provided outside of the intervention. Four barrier themes were also identified: misalignment of intervention to caregiver needs, inability to make time for intervention, practical barriers, emotional barriers. CONCLUSIONS: Psychosocial interventions for caregivers to a loved one with a rare disease may be helpful in reducing stress, burden, and feelings of isolation among caregivers. Future research should design interventions for caregivers that take into account facilitators and barriers to establishing and maintaining such interventions.

Group sample sizes in nonregulated health care intervention trials described as randomized controlled trials were overly similar.

OBJECTIVES: We evaluated whether sample sizes in different arms of two-arm parallel group randomized controlled trials of nonregulated interventions were systematically closer in size than would plausibly occur by chance if simple randomization had been applied. STUDY DESIGN AND SETTING: We searched PubMed for trials of nonregulated health care interventions that did not report using restricted randomization from journals in behavioral sciences and psychology, nursing, nutrition and dietetics, rehabilitation, and surgery. We emailed trial authors to clarify randomization procedures. RESULTS: We identified 148 nonregulated intervention trials that indicated they used simple randomization. Difference in trial arm sizes was smaller than would be predicted by chance if simple randomization had occurred in all trials (P < 0.001). Rather than approximately half of the trials being within a 50% prediction interval for the difference, 96% had differences within this interval. Results were similar and statistically significant (P < 0.001) for trials that were published in journals with impact factors ≥ 4 and when stratified by type of nonregulated intervention. CONCLUSION: There is a need for education and better understanding of clinical trial methods to ensure that randomization procedures are implemented as intended and reported fully and accurately.