Search

Diya Jhuti,1,2 Gohar Zakaryan,1 Hussein El-Kechen,3 Nadia Rehman,3 Mark Youssef,4 Cristian Garcia,4 Vaibhav Arora,1 Babalwa Zani,5 Alvin Leenus,6 Michael Wu,7 Oluwatoni Makanjuola,8 Lawrence Mbuagbaw3,9– 11 1Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada; 2Department of Health, Behavior, and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 3Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 4Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 5Public Health Research Unit, AB Consulting, Cape Town, South Africa; 6Faculty of Law, University of Ottawa, Ottawa, ON, Canada; 7Michael DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada; 8Faculty of Science, McMaster University, Hamilton, ON, Canada; 9Biostatistics Unit, Father Sean O’Sullivan Research Centre, Hamilton, ON, Canada; 10Centre for Development of Best Practices in Health, Yaoundé Central Hospital, Yaoundé, Cameroon; 11Department of Global Health, Stellenbosch University, Cape Town, South AfricaCorrespondence: Lawrence Mbuagbaw, Biostatistics Unit/FSORC, 50 Charlton Avenue East, St Joseph’s Healthcare—Hamilton, 3rd Floor Martha Wing, Room H321, Hamilton, ON, L8N 4A6, Canada, Tel +1-905-522-1155 ext 35929, Fax +1-905-528-7386, Email mbuagblc@mcmaster.caIntroduction: Engagement in the HIV care cascade is required for people living with HIV (PLWH) to achieve an undetectable viral load. However, varying definitions of engagement exist, contributing to heterogeneity in research regarding how many individuals are actively participating and benefitting from care. A standardized definition is needed to enhance comparability and pooling of data from engagement studies.Objectives: The objective of this paper was to describe the various definitions for engagement used in HIV clinical trials.Methods: Articles were retrieved from CASCADE, a database of 298 clinical trials conducted to improve the HIV care cascade (https://hivcarecascade.com/), curated by income level, vulnerable population, who delivered the intervention, the setting in which it was delivered, the intervention type, and the level of pragmatism of the intervention. Studies with engagement listed as an outcome were selected from this database.Results: 13 studies were eligible, of which five did not provide an explicit definition for engagement. The remaining studies used one or more of the following: appointment adherence (n=6), laboratory testing (n=2), adherence to antiretroviral therapy (n=2), time specification (n=5), intervention adherence (n=5), and quality of interaction (n=1).Conclusion: This paper highlights the existing diversity in definitions for engagement in the HIV care cascade and categorize these definitions into appointment adherence, laboratory testing, adherence to antiretroviral therapy, time specification, intervention adherence, and quality of interaction. We recommend consensus on how to describe and measure engagement.Keywords: HIV, engagement, antiretroviral therapy, adherence, retention, cascade

Background: To compare the effectiveness of four surveillance strategies for detecting SARS-CoV-2 within the homeless shelter population in Hamilton, ON and assess participant adherence over time for each surveillance method., Methods: This was an open-label, cluster-randomized controlled trial conducted in eleven homeless shelters in Hamilton, Ontario, from April 2020 to January 2021. All participants who consented to the study and participated in the surveillance were eligible for testing by self-swabbing. SARS-CoV-2 detection rate as the primary outcome, number of outbreaks, adherence, and overall acceptability were assessed. All participants, which included staff and residents, underwent daily symptom surveillance conducted by shelter staff and shelters were allocated to one of three asymptomatic surveillance arms (once weekly, self-collected oral swabs (OS); once-weekly self-collected oral-nasal swab (ONS); or once-weekly nurse collected nasopharyngeal swab (NPS) or a symptomatic only SARS-CoV-2 testing arm., Results: A total of 9747 SARS-CoV-2 tests were performed on 1570 participants. There were 4527 participants allocated to oral swab collection and 4935 participants allocated to oral-nasal swab collection. For nasopharyngeal swab collection, 285 participants were assigned before this arm was discontinued. The OS group identified 5 new cases (1.1 per 1000; 95% CI 0.4-2.3), while the ONS group identified 15 new cases (3.0 per 1000; 95% CI 1.9-4.7), resulting in a Risk Ratio (RR) of 2.76 (95% CI 1.00-7.58; p = 0.040). However, the mixed-effect model did not show a significantly higher positivity rate in the ONS compared to OS (OR 1.64; 95% CI 0.76-9.14; p = 0.129). Both ONS and OS were preferred over NPS, which did not detect any cases due to low adherence. Three outbreaks were identified during the study period within the shelters, two of the outbreaks had 2 positive cases each and the third outbreak had 3 positive cases., Conclusions: The two self-collection strategies were superior and showed the best adherence, with the ONS strategy shown to be superior or non-inferior in all measures. We are now studying the operationalization of a large-scale self-collected ONS surveillance strategy in a prospective cohort study of multiple homeless shelters. Funding was provided by the Hamilton Academic Hospital Organization (HAHSO) and Research St. Joseph's - Hamilton., Trial Registration: The trial was retrospectively registered with ClinicalTrials.gov on June 18, 2020, with the identifier NCT04438070., Competing Interests: Declarations. Ethics approval: The protocol for this trial was approved by the Hamilton Integrated Research Ethics Board (HiREB), and all shelters, residents, and staff provided verbal consent for involvement in the study. The trial was also registered on ClinicalTrials.gov, under identification number NCT04438070 (18/06/2020). This cluster-randomized multi-shelter trial was conducted according to the Consolidated Standards of Reporting Trials (CONSORT). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: There is a high prevalence of depression among refugee youth in low- and middle-income countries, yet depression trajectories are understudied. This study examined depression trajectories, and factors associated with trajectories, among urban refugee youth in Kampala, Uganda., Methods: We conducted a longitudinal cohort study with refugee youth aged 16-24 in Kampala, Uganda. We assessed depression using the Patient Health Questionnaire-9 and conducted latent class growth analysis (LCGA) to identify depression trajectories. Sociodemographic and socioecological factors were examined as predictors of trajectory clusters using multivariable logistic regression., Results: Data were collected from n = 164 participants (n = 89 cisgender women, n = 73 cisgender men, n = 2 transgender persons; mean age: 19.9, standard deviation: 2.5 at seven timepoints; n = 1,116 observations). Two distinct trajectory clusters were identified: "sustained low depression level" (n = 803, 71.9%) and "sustained high depression level" (n = 313, 28.1%). Sociodemographic (older age, gender [cisgender women vs. cisgender men], longer time in Uganda), and socioecological (structural: unemployment, food insecurity; interpersonal: parenthood, recent intimate partner violence) factors were significantly associated with the sustained high trajectory of depression., Conclusions: The chronicity of depression highlights the critical need for early depression screening with urban refugee youth in Kampala. Addressing multilevel depression drivers prompts age and gender-tailored strategies and considering social determinants of health., Competing Interests: The authors affirm that there are no known competing financial interests or personal relationships that could have influenced the work reported in this article., (© The Author(s) 2024.)

Introduction: GRADE and other Evidence to Decision (EtD) frameworks are widely used by guideline development groups (GDG) and other decision-makers. When GDGs judge the magnitude of desirable and undesirable health outcomes on EtDs, they typically categorize them as trivial, small, moderate or large. However, generic judgment or decision thresholds (DTs) that could guide the user about such estimates of effect size or serve as references for interpretation of findings are not yet available. The objective of this study was to empirically derive DTs for EtD judgments about the magnitude of dichotomously assessed health benefits and harms., Methods: We conducted a methodological randomised controlled trial to derive empirical DTs across conditions and health outcomes. We invited stakeholders including clinicians, epidemiologists, decision scientists, health research methodologists, experts in Health Technology Assessment (HTA), members of GDGs, patient representatives, and the public to participate in the trial. We employed randomly assigned case scenarios to elicit ranges of absolute risk differences (ARD) judged as small and moderate effects from study participants. We then used the collected data to derive empirical decision thresholds. We also investigated the validity of our DTs by measuring the agreement between judgments that were made by GDGs in the past and the judgments that our DTs approach would suggest if applied to the same guideline data., Results: A total of 445 stakeholders accessed the survey of which 409 were randomised and 288 rated at least one case scenario. Based on these participants, the study findings support our a priori hypothesis of a difference in the DTs for trivial, small, moderate, and large effects and are suggestive of a relation between raters' judgments and the joint measure of absolute effects and outcome values. The results permit the use and calculation of DTs for a variety of scenarios and we present three ways of how to use the results practically., Conclusions: In this trial we confirmed that empirically derived DTs discriminate between judgments on the EtDs. These DTs can be used for judgments about desirable and undesirable health effects in systematic reviews or to initiate and inform a discussion with a GDG. This ensures consistency in judgments across different guideline questions and promotes transparency in judgments., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To compare the effectiveness of interventions for the management of long covid (post-covid condition)., Design: Living systematic review., Data Sources: Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials from inception to December 2023., Eligibility Criteria: Trials that randomised adults (≥18 years) with long covid to drug or non-drug interventions, placebo or sham, or usual care., Results: 24 trials with 3695 patients were eligible. Four trials (n=708 patients) investigated drug interventions, eight (n=985) physical activity or rehabilitation, three (n=314) behavioural, four (n=794) dietary, four (n=309) medical devices and technologies, and one (n=585) a combination of physical exercise and mental health rehabilitation. Moderate certainty evidence suggested that, compared with usual care, an online programme of cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference -8.4, 95% confidence interval (CI) -13.11 to -3.69; Checklist for Individual Strength fatigue subscale; range 8-56, higher scores indicate greater impairment) and probably improves concentration (mean difference -5.2, -7.97 to -2.43; Checklist for Individual Strength concentration problems subscale; range 4-28; higher scores indicate greater impairment). Moderate certainty evidence suggested that, compared with usual care, an online, supervised, combined physical and mental health rehabilitation programme probably leads to improvement in overall health, with an estimated 161 more patients per 1000 (95% CI 61 more to 292 more) experiencing meaningful improvement or recovery, probably reduces symptoms of depression (mean difference -1.50, -2.41 to -0.59; Hospital Anxiety and Depression Scale depression subscale; range 0-21; higher scores indicate greater impairment), and probably improves quality of life (0.04, 95% CI 0.00 to 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; range -0.022-1; higher scores indicate less impairment). Moderate certainty evidence suggested that intermittent aerobic exercise 3-5 times weekly for 4-6 weeks probably improves physical function compared with continuous exercise (mean difference 3.8, 1.12 to 6.48; SF-36 physical component summary score; range 0-100; higher scores indicate less impairment). No compelling evidence was found to support the effectiveness of other interventions, including, among others, vortioxetine, leronlimab, combined probiotics-prebiotics, coenzyme Q10, amygdala and insula retraining, combined L-arginine and vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, a mobile application providing education on long covid., Conclusion: Moderate certainty evidence suggests that CBT and physical and mental health rehabilitation probably improve symptoms of long covid., Systematic Review Registration: Open Science Framework https://osf.io/9h7zm/., Readers' Note: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Long COVID Web and the Canadian Institutes of Health Research for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Self-rated health (SRH) has shown to be a strong predictor of morbidity, functional decline, and mortality outcomes. This paper investigates the association between sociodemographic variables (e.g., employment, education, sex) and SRH among Black Canadians., Methods: We used cross-sectional survey data (n = 1380) from the A/C (African Caribbean) Study of first- and second-generation Black Canadians in Toronto and Ottawa. Participants were invited to complete an electronic survey questionnaire in English or French in 2018-2019. Generalized linear model analyses were used to evaluate the associations among sociodemographic factors and self-rated quality of health., Results: A total of 1380 self-identified Black individuals completed the survey and were included in the analysis. The majority of participants were under the age of 60 (89.7%), female (63.4%), born outside of Canada (75.1%), and residing in Toronto, Ontario (61.9%). The strongest association with poor SRH was found for difficulties accessing health care, sexual orientation, and substance misuse/disorder, while accessing/meeting basic needs was associated with better SRH, following adjustment for other socioeconomic conditions and lifestyle factors., Conclusion: Our findings underscore the importance of improving the social determinants of health as a conduit to improving the general health status and the quality of life of Black Canadians. Results revealed that Black Canadians may be demonstrating high levels of resilience in circumventing their current social circumstances and structural disadvantages to live the best quality of life. Understanding sociodemographic and socio-structural barriers that Black people face is essential to reducing vulnerabilities to poor outcomes and improving their health and well-being., Competing Interests: Declarations. Ethics approval: A/C Study protocols were approved by the research ethics boards (REB) at the University of Toronto, Toronto Public Health, the University of Ottawa, and Ottawa Public Health. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Despite a high burden of Human Papilloma Virus (HPV)-associated diseases, HPV vaccine uptake is disparate globally. The objective of this systematic review is to summarize the existing evidence on knowledge, attitudes, and practices (KAP) regarding HPV and the uptake of the HPV vaccine., Methods and Analysis: We will conduct a systematic review of observational studies that report data on HPV KAP and vaccine uptake among people aged 16 and above. We will search MEDLINE, CINAHL, Embase, Emcare, Web of Science, Cochrane Library, Global Health, and PsycInfo. We will conduct screening, data extraction, and assessment of the methodological quality of the included studies in duplicate. A random-effects model will be used to pool data. Subgroup analysis will be done for age younger adults (≤ 26 years old) and older adults (> 26 years old), sex (men and women), income level (as per World Bank), and WHO region. This systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PROSPERO registration number for the review is CRD42024532230., Ethics and Dissemination: Ethical approval is not necessary as this study will review secondary published data. Our findings will be disseminated as part of a doctoral thesis and through peer-reviewed journal publications and conferences., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Anni et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: As researchers and practitioners in the field of global health continue to acknowledge the ongoing impact of colonialism in their work, the call for decolonized research has increased. This has particular relevance in the field of sexual and reproductive health. Despite this recognized need, there is no singularly agreed upon definition of what it means to conduct decolonized research using decolonized methodologies. The aim of this review is to explore the approaches and methodologies used in contemporary sexual and reproductive health research aligned with decolonized systems of thinking., Methods: This review was developed and conducted in accordance with the JBI and the Extension for Scoping Reviews (PRISMA-ScR) Checklist. In January 2023, Medline (Ovid), Embase, EMCare, Global Health Database, and Web of Science were systematically searched for relevant studies. Relevant grey literature was also scanned. The screening and data extraction were conducted by four independent reviewers using an iterative approach. The findings were analyzed to uncover shared characteristics between the studies., Results: A total of 1775 articles were retrieved through our search strategy, of which 35 were included as discussing sexual health topics, and representing the principles of decolonization. Few of the included articles explicitly self-identified as decolonized literature. Common themes between studies included that most of the data collection was conducted in high-income countries, largely in North America, and the most prevalent sexual health topics were HIV/AIDs, and STIs/STDs. Most studies were qualitative, used community-based methodologies, and included some form of community advisory board., Conclusions: This scoping review identifies shared characteristics of both successes and gaps in decolonized research that may inform the methodological processes of future researchers. It emphasizes the need for more decolonized research originating in low- and middle-income countries, as well as decolonization of quantitative research methodologies. The findings also emphasize the importance of community engagement throughout the research process. A shared definition of decolonization is necessary to codify this body of work. Future researchers should focus on clearly communicating their approach in the methodology so that it can be replicated and become part of a shared definition. International Registered Report Identifier (IRRID): DERR1-10.2196/45771., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Research with urban refugee youth in Uganda has documented co-occurring social (e.g., poverty) and health (e.g., depression) disparities associated with HIV vulnerabilities. Benefits of HIV self-testing (HIVST) in increasing HIV testing uptake among youth are well established, yet limited interventions have examined if combining HIVST with mental health promotion, or with mental health promotion alongside poverty reduction, is associated with greater improvements in HIV prevention and testing outcomes., Methods and Analysis: The aim is to evaluate the effectiveness of: (1) HIVST alone (standard of care); (2) mobile health (mHealth) and graphic medicine (comic) programme for mental health alongside HIVST; and (3) the combination of HIVST, a livelihoods programme, and mHealth mental health programme, in advancing the primary outcome of HIV testing uptake and secondary outcomes (HIV status knowledge, linkage to confirmatory testing and HIV care, HIV knowledge, consistent condom use, condom use self-efficacy, sexual risk) with urban refugee youth in Kampala, Uganda. A three-arm randomised controlled trial will be implemented from 8 April 2024 to 31 October 2024 with youth across five informal settlements in Kampala, grouped into three sites based on proximity, and randomised in a 1:1:1 design. Approximately 330 participants (110 per arm) are enrolled and data collection will occur at three time points (baseline enrolment, 3-month follow-up and 6-month follow-up)., Ethics and Dissemination: The study received ethical approval from the University of Toronto (#37496), Mildmay Uganda Research Ethics Committee (#MUREC-2021-41) and Uganda National Council for Science & Technology (#SS1021ES). The trial is registered at ClinicalTrials.gov (NCT06270160). Study findings will produce new knowledge of the impacts of a mental health programme, and a combined mental health and livelihoods programme, on improving HIV prevention outcomes among urban refugee youth in Kampala. Findings will be shared in peer-reviewed publications, conference presentations and in community dissemination., Trial Registration Number: NCT06270160 (date of registration: 13 February 2024)., Trial Sponsor: Dr. Carmen Logie, carmen.logie@utoronto.ca., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Missing outcome data can pose a serious threat to the validity of randomised clinical trial results. We aimed to study the extent of missing outcome data in randomised clinical trials of psychological interventions., Methods: We performed a retrospective study of randomised clinical trial reports of psychological interventions published in World Psychiatry, JAMA Psychiatry, Lancet Psychiatry, American Journal of Psychiatry, British Journal of Psychiatry, or Psychotherapy and Psychosomatics from 2017 to 2022. We assessed the proportion of missing outcome data, whether missing data patterns differed between types of outcomes, participants, intervention lengths, and psychological intervention types, how missing outcome data were handled in the statistical analyses, and whether trialists discussed missing outcome data in the discussion section of the manuscript., Results: We identified 182 randomised clinical trials (233 primary outcomes), of which 206 outcomes (88.4%) were assessed at high risk of bias due to missing data. The overall mean percentage of missing outcome data was 18.3% (95% confidence interval (CI): 16.7-20%) for all outcomes. The percentages of missing data were 18.9% (95% CI: 17.1-20.6%; 180 outcomes) for symptom severity scales and 1.8% (95% CI: 2.3-3.3%; 6 outcomes) for 'hard' binary outcomes. Trials including participants with borderline personality disorder had the highest percentage of missing outcome data (33.1%; 95% CI: 22.3-43.9%) compared with other psychiatric disorders. Fisher's exact test showed that intervention lengths and psychological intervention types were associated with the proportion of missing outcome data (p < 0.001), but there were no clear patterns., Conclusion: Missing outcome data is a considerable problem in randomised clinical trials of psychological interventions, and trialists should consider the corresponding methodological limitations in the design and analysis to reduce the risk of bias due to missing outcome data., Clinical Trial Registration Number: Not applicable., Competing Interests: Declarations Ethics approval and consent to participate The analyses in this study were performed on publicly available, published trial data that have already been approved by the respective ethical committees that originally assessed the included trials. Hence, it was not applicable to obtain ethical approval nor participation consent, e.g. in accordance with the Declaration of Helsinki, for this study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In Jamaica, stigma experiences of sex workers (SW), gay men and other men who have sex with men (MSM), and transgender women living with HIV remain understudied. To address this gap, we explored experiences of stigma and linkages with the HIV care cascade among key populations living with HIV in Jamaica, including cisgender women SW, MSM, and transgender women. This qualitative study involved n = 9 focus groups (FG), n = 1 FG per population living with HIV (SW, MSM, transgender women) in each of three sites (Kingston, St. Ann, Montego Bay). We also conducted key informant (KI) interviews. We applied thematic analysis informed by the Health Stigma and Discrimination (HSD) Framework. FG participants (n = 67) included SW (n = 18), MSM (n = 28), and trans women (n = 21); we interviewed n = 10 KI (n = 5 cisgender women, n = 5 cisgender men). Participant discussions revealed that stigma drivers included low HIV treatment literacy, notably misinformation about antiretroviral therapy (ART) benefits and HIV acquisition risks, and a lack of legal protection from discrimination. Stigma targets health (HIV) and intersecting social identities (sex work, LGBTQ identities, gender non-conformity, low socio-economic status). Stigma manifestations included enacted stigma in communities and families, and internalized stigma-including lateral violence. HIV care cascade impacts included reduced and/or delayed HIV care engagement and ART adherence challenges/disruptions. Participants discussed strategies to live positively with HIV, including ART adherence as stigma resistance; social support and solidarity; and accessing affirming institutional support. In addition to addressing intersecting stigma, future research and programing should bolster multi-level stigma-resistance strategies to live positively with HIV., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Pilot or feasibility trials examine the feasibility, viability and recruitment potential of larger, main trials. Specifically, a pilot trial can be instrumental in identifying methodological issues essential to the development of an effective research protocol. However, numerous studies published as pilot or feasibility studies have demonstrated notable inconsistencies in the nature of information reported, resulting in poor-quality and incomplete reporting. It is unclear whether such low quality or incompleteness of reporting is also prevalent in arthroplasty pilot trials., Methods and Analysis: This protocol outlines a methodological survey examining the completeness of reporting among hip and knee arthroplasty pilot trials in accordance with the Consolidated Standards of Reporting Trials (CONSORT) 2010 extension to pilot trials. Secondary objectives include: (1) determining the prevalence of 'spin' practices, defined as: (a) placing a focus on statistical significance rather than feasibility, (b) presenting results that show the trial to be non-feasible as feasible or (c) emphasising the effectiveness or potential intervention benefits rather than feasibility; (2) determining factors associated with incomplete reporting, and 'spin'. A search of PubMed will be conducted for pilot trials in hip or knee arthroplasty published between 01 January 2017 and 31 December 2023. Following screening, appropriate data will be extracted from eligible publications and reported as descriptive statistics, encompassing elements of the CONSORT checklist associated with completeness of reporting. Logistic regression analysis and Poisson regression will be used to analyse factors associated with completeness of reporting and spin., Ethics and Dissemination: This methodological review does not require formal ethical approval, as it will solely involve the use of published and publicly reported literature. The results of this study will be disseminated through submission to peer-reviewed journals and academic conference presentations. Study details will be sent to McMaster University's media coordinators to be shared through the institution's research-focused platforms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This scoping review aims to summarize the existing literature on how machine learning can be used to impact systemic sclerosis diagnosis, management, and treatment. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) reporting guidelines, Embase, Web of Science, Medline (PubMed), IEEE Xplore, and ACM Digital Library were searched from inception to 3 March 2024, for primary literature reporting on machine learning models in any capacity regarding scleroderma. Following robust triaging, 11 retrospective studies were included in this scoping review. Three studies focused on the diagnosis of scleroderma to influence preferred management and nine studies on treatment and predicting treatment response to scleroderma. Nine studies used supervision in their machine learning model training; two used supervised and unsupervised training and one used solely unsupervised training. A total of 817 patients were included in the data sets. Seven of the included articles used patients from the United States, one from Belgium, two from Japan, and two from China. Although currently limited to retrospective studies, the results indicate that machine learning modeling may have a role in early diagnosis, management, therapeutic decision-making, and in the development of future therapies for systemic sclerosis. Prospective studies examining the use of machine learning in clinical practice are recommended to confirm the utility of machine learning in patients with systemic sclerosis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Posthemorrhagic ventricular dilatation (PHVD) is a major complication of intraventricular hemorrhage (IVH); it is associated with high risks of cerebral palsy and cognitive deficits compared with infants without PHVD. This study aims to explore the early perinatal risk factors-associated with the risk of progressive PHVD., Methods: Neonates ≤29 weeks gestational age (GA) with Grade II-III IVH and periventricular hemorrhagic infarct (PVHI) between 2015 and 2021 were retrospectively reviewed. All cranial ultrasounds done within 14 days postnatal age (PNA) were assessed for grade of IVH, anterior horn width (AHW), ventricular index (VI), and thalamo-occipital index (TOD). The outcome was defined as death of any cause or VI and/or AHW and/or TOD ≥ moderate-risk zone based on an ultrasound done beyond two weeks PNA., Results: A total of 146 infants with a mean GA of 26 ± 1.8 weeks, birth weight 900 ± 234 g were included, 46% were females. The primary outcome occurred in 56 (39%) infants; among them 17 (30%) and 11 (20%) needed ventricular reservoir and shunt insertion, respectively. The risk factors present within 14 days PNA that significantly increased the odds of developing PHVD were hemodynamically significant patent ductus arteriosus (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.9 to 22), culture-proven sepsis (OR 5.4, 95% CI 1.8 to 18), Grade III IVH (OR 4.6, 95% CI 1.1 to 22), PVHI (OR 3.0, 95% CI 0.9 to 10), and VI (OR 2.1, 95% CI 1.6 to 2.9)., Conclusions: Clinical predictors such as significant ductus arteriosus and bacterial septicemia, along with risk levels of AHW and VI measured with early cranial ultrasounds, are potential predictors of subsequent onset of PHVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Enteral nutrition (EN) is the recommended nutritional support in most critically ill populations. When given by feeding tube, EN may be administered either continuously or intermittently. It is unclear which approach is superior in reducing gastrointestinal complications-such as diarrhea-and meeting nutritional targets. The main objectives of this systematic review and meta-analysis are to (1) determine whether continuous or intermittent enteral nutrition is associated with higher incidence of adverse gastrointestinal outcomes, including diarrhea, and (2) determine which feeding modality is associated with reaching nutritional goals. METHODS AND ANALYSIS: This systematic review protocol is reported in accordance with guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. We will search MEDLINE, Embase, the Cochrane Library, and the World Health Organization (WHO) International Clinical Trials Registry (ICTRP) search portal for studies comparing continuous EN and intermittent EN in critically ill patients with no date or language restrictions. Studies will be screened, selected, and extracted independently and in duplicate. We will assess the risk-of-bias assessment using the Cochrane Collaboration's Risk of Bias (RoB) 2 tool. The primary outcome will include the incidence of diarrhea; secondary outcomes include other adverse GI outcomes (nausea, vomiting, abdominal pain, and constipation), as well as reaching nutritional goals, and length of ICU and hospital stay and mortality. We will pool data using a random-effects model and assess the certainty of the evidence for each outcome using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology., Ethics and Dissemination: Ethics approval is not required for this study as no original data will be collected. We will disseminate results through peer-reviewed publication and conference presentations., Systematic Review Registration: PROSPERO CRD42022330118., (© 2024. The Author(s).)

Introduction: The Road to Recovery (R2R) Initiative is an innovative model of substance use care that seeks to increase treatment capacity by creating approximately 100 new addiction treatment beds to provide on-demand addiction care in Vancouver, British Columbia, for patients with substance use disorders. The new model also coordinates the region's existing clinical substance use services to support patients across a care continuum that includes traditional office-based addiction treatment and harm reduction services, early withdrawal management and more intensive abstinence-based treatment programming. To understand the impact of offering on-demand and coordinated substance use care, an observational cohort of individuals who access any R2R clinical service will be created to examine health and social outcomes over time., Methods and Analysis: This prospective mixed-methods study will invite individuals from Vancouver, Canada, who access substance use treatment through the R2R model of care to (1) complete a baseline and 12-month follow-up quantitative questionnaire that solicits sociodemographic, substance use and previous addiction treatment data and (2) provide consent to the use of participants' personal identifiers to access health records for chart review and for annual linkage to select health and administrative databases to allow for ongoing (virtual) community follow-up over 5 years. Additionally, a purposive sample of cohort participants will be invited to participate in baseline and 12-month follow-up qualitative interviews to share their experiences accessing R2R and identify challenges and opportunities associated with the implementation of R2R., Ethics and Dissemination: The study was approved by the University of British Columbia Providence Health Care Research Ethics Board in September 2023. Results from the proposed study will be published in peer-reviewed journals, presented at national and international scientific conferences and disseminated through regular meetings with policymakers, individuals with lived and living experience, and other high-level stakeholders, academic presentations and lay media., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Cluster randomised trials (CRTs) are used for evaluating health-related interventions in low-income and middle-income countries (LMICs) but raise complex ethical issues. To inform the development of future ethics guidance, we aim to characterise CRTs conducted exclusively in LMICs by examining the types of clusters, settings, author affiliations and primary clinical focus and to evaluate adherence to trial registration and ethics reporting requirements over time., Design: A systematic scoping review using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews., Data Sources: We searched MEDLINE between 1 January 2017 and 17 August 2022., Eligibility Criteria for Selecting Studies: We included primary reports of CRTs evaluating health-related interventions, conducted exclusively in LMICs and published in English between 2017 and 2022., Data Extraction and Synthesis: Data were extracted by one reviewer; a second reviewer verified accuracy by extracting data from 10% of the reports. Results were summarised overall and categorised by country's economic level or publication year., Results: Among 800 identified CRTs, 400 (50.0%) randomised geographical areas and 373 (46.6%) were conducted in Africa. 30 (3.7%) had no authors with an LMIC affiliation, and 246 (30.8%) had neither first nor last author with an LMIC affiliation. The relative frequency of first or last authors holding an LMIC affiliation increases as a country's economic level increases. Most CRTs focused on reducing maternal and neonatal disorders (106, 13.3%). 670 (83.8%) CRTs reported trial registration, 786 (98.2%) reported research ethics committee review and 757 (94.6%) reported consent statements. Among the 757 CRTs, 46 (6.1%) reported a waiver or no consent and, among these, 10 (21.7%) did not provide a rationale. Gatekeepers were identified in 403 (50.4%) CRTs. No meaningful trends were observed in adherence to trial registration or ethics reporting requirements over time., Conclusion: Our findings suggest existing inequity in authorship practices. There is high adherence to trial registration and ethics reporting requirements, although greater attention to reporting a justification for using a waiver of consent is needed., Competing Interests: Competing interests: CW receives consulting income from Cardialen and Eli Lilly & Company. Other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Men's participation is imperative for improving antenatal care (ANC) access and mother and child health outcomes in sub-Saharan Africa (SSA). Research looking at improving men's participation in ANC often focuses on their instrumental and psychosocial roles and on biomedical ANC systems. There is limited understanding of how context-specific cultural experiences of fatherhood influence men's participation in ANC within broader communal support networks and across different ANC systems in SSA. Against this background, and to understand how local communities in SSA conceive men's participation in ANC, a scoping review will be undertaken to synthesise existing literature around local cultural experiences of fatherhood and men's participation in ANC in rural settings in SSA., Methods and Analysis: The classical scoping review methodology developed by Arksey and O'Malley will be used to conduct the scoping review described above. Empirical studies published between 1 January 2000 and 31 August 2024 will be systematically searched for in key online databases (eg, PubMed/MEDLINE, CINAHL, EMBASE, PsycINFO, Cochrane Library, African Index Medicus, African Journals Online) and grey literature (eg, reports from key organisations like UNICEF and the WHO). Literature reviews, personal opinion articles and theoretical or conceptual articles that do not systematically analyse data, and non-English texts, will be excluded. Data will be extracted from the included texts in the form of study characteristics, which will be analysed using descriptive statistics, and key issues to be analysed thematically., Ethics and Dissemination: No ethical approvals are needed for this scoping review since data will be abstracted from already-published literature and no additional data will be collected. The findings will be shared with policymakers, practitioners, researchers, students and local communities through peer-reviewed journal publication(s), conference presentations, public lectures and policy-focused stakeholder and community meetings in and outside SSA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Surgical site infections continue to be a significant challenge following colorectal surgery. These can result in extended hospital stays, hospital readmissions, increased treatment costs, and negative effects on patients' quality of life. Antibiotic prophylaxis plays a crucial role in preventing infection during surgery, specifically in preventing surgical site infections after colorectal surgery in adult patients. However, the optimal antibiotic regimen is still unclear based on current evidence. Considering the limitations of existing reviews, our goal is to conduct a comprehensive systematic review and network meta-analysis of randomized controlled trials to evaluate the comparative benefits and harms of available antibiotic prophylaxis regimens for preventing surgical site infections following colorectal surgery in adult patients., Methods: We will search the Medline, EMBASE, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials databases to identify relevant randomized controlled trials. We will include trials that (1) enrolled adults who underwent colorectal surgeries and (2) randomized them to any systemic administration of antibiotic (single or combined) prophylaxis before surgery compared to an alternative systemic antibiotic (single or combined antibiotic), placebo, control, or no prophylactic treatment. Pairs of reviewers will independently assess the risk of bias among eligible trials using a modified Cochrane risk of bias instrument for randomized trials. Our outcomes of interest include the rate of surgical site infection within 30 days of surgery, hospital length of stay, 30-day mortality, and treatment-related adverse effects. We will perform a contrast-based network meta-analysis using a frequentist random-effects model assuming a common heterogeneity parameter. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be utilized to assess the certainty of evidence for treatment effects., Discussion: By synthesizing evidence from available RCTs, this study will provide valuable insight for clinicians, patients, and health policymakers on the most effective antibiotics for preventing surgical site infection., Systematic Review Registration: PROSPERO CRD42023434544., (© 2024. The Author(s).)

We found that rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and reverse transcriptase (RT)-PCR-confirmed infection were approximately 50% higher in a population-based cohort of people with HIV compared with a matched cohort of people without HIV during the Omicron era (2 January 2022 to 31 March 2023) in Ontario, Canada, after controlling for age, sex, residential census tract, and country of birth. Rates of coronavirus disease 2019 (COVID-19)-related hospitalization and/or death were more than double. Differences persisted independent of vaccination, healthcare access, and COVID-19 diagnosis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background Stigma towards sexually active young people presents profound barriers to uptake of sexual and reproductive health (SRH) services, including HIV testing and contraception. Yet, few studies have examined adolescent SRH stigma trajectories over time. To address this knowledge gap, we examined associations between social-ecological factors and trajectories of adolescent SRH stigma among urban refugee youth in Kampala, Uganda. Methods This longitudinal cohort study with refugee youth in Kampala collected data on adolescent SRH stigma at four time-points between 2022 and 2024. We used latent class growth analyses to examine distinct trajectories of adolescent SRH stigma, and examined baseline social-ecological and socio-demographic factors associated with class membership using multivariable logistic regression. Results Among the participants (n =164 with n =668 observations; mean age 19.9 years, standard deviation2.5 years; 52.8% cisgender women), we categorised two distinct adolescent SRH stigma trajectories: consistently high (n =496; 74.2%) and sustained low (n =172; 25.8%). In multivariable analyses, living in Uganda ≥1year at baseline assessment (1-5years: adjusted odds ratio [aOR]5.28, confidence interval [CI]2.29-12.19, P P 10years: aOR3.89, CI1.56-9.68, P P P P P Conclusions Social-ecological and socio-demographic factors were associated with consistently high levels of adolescent SRH stigma over 2years. Multi-level strategies can meaningfully engage youth in developing stigma reduction strategies for SRH service delivery.

For people at risk of HIV infection, pre-exposure prophylaxis (PrEP) can reduce the risk of infection in anticipation of exposure to HIV. The effectiveness of PrEP relies upon a user's adherence to their PrEP regimen. We sought to assess the effect of PrEP adherence interventions compared to usual care or another intervention for people at risk of HIV. We searched electronic databases from 2010 onwards for randomized controlled trials (RCTs) involving persons at risk of HIV randomized to an adherence promoting intervention vs usual care or another intervention. We used network meta-analyses to compare PrEP adherence for all participant populations. Certainty of evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). 21 trials (N = 4917) were included in qualitative analysis (19 in network meta-analyses (N = 4101)). HIV self-testing interventions with adherence feedback elements improved adherence compared to usual care (risk ratio (RR): 1.83, 95%CI 1.19, 2.82). In contrast, HIV self-testing alone was inferior to HIV self-testing with adherence feedback (RR: 0.58, 95%CI 0.37-0.92). Reminders alone also were inferior to HIV self-testing with adherence feedback on adherence (RR: 0.53, 95%CI 0.34-0.84) and had similar effects on adherence as usual care (RR: 0.98, 95%CI: 0.86-1.11). Interventions with only one component were inferior for adherence than those with two components (RR: 0.74, 95%CI 0.62-0.88) and those with three components (RR: 0.78, 95%CI 0.65-0.93). The certainty of evidence was moderate for HIV self-testing plus adherence feedback and interventions with two or three components. When designing future PrEP adherence interventions, we recommend strategies with more than one but no more than three components., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The ordering of routine blood test panels in advance is common in intensive care units (ICUs), with limited consideration of the pretest probability of finding abnormalities. This practice contributes to anemia, false positive results, and health care costs. We sought to understand practices and attitudes of Canadian adult intensivists regarding ordering of blood tests in critically ill patients., Methods: We conducted a nationwide Canadian cross-sectional survey consisting of 15 questions assessing three domains (global perceptions, test ordering, daily practice), plus 11 demographic questions. The target sample was one intensivist per adult ICU in Canada. We summarized responses using descriptive statistics and present data as mean with standard deviation (SD) or count with percentage as appropriate., Results: Over seven months, 80/131 (61%) physicians responded from 77 ICUs, 50% of which were from Ontario. Respondents had a mean (SD) clinical experience of 12 (9) years, and 61% worked in academic centres. When asked about their perceptions of how frequently unnecessary blood tests are ordered, 61% responded "sometimes" and 23% responded "almost always." Fifty-seven percent favoured ordering complete blood counts one day in advance. Only 24% of respondents believed that advanced blood test ordering frequently led to changes in management. The most common factors perceived to influence blood test ordering in the ICU were physician preferences, institutional patterns, and order sets., Conclusion: Most respondents to this survey perceived that unnecessary blood testing occurs in the ICU. The survey identified possible strategies to decrease the number of blood tests., (© 2024. Canadian Anesthesiologists' Society.)

Background: Cholinesterase inhibitors (ChEIs) are regularly used in Alzheimer's disease. Of the three ChEIs approved for dementia, donepezil is among the most prescribed drugs in the United States with nearly 6 million prescriptions in 2020; however, it is classified as a "known risk" QT interval-prolonging medication (QTPmed). Given this claim is derived from observational data including single case reports, we aimed to evaluate high-quality literature on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) associated with donepezil., Methods: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onwards for randomized controlled trials (RCTs) involving patients age ≥18 years comparing donepezil to placebo. The MACE composite included mortality, sudden cardiac death, non-fatal cardiac arrest, Torsades de pointes, ventricular tachyarrhythmia, seizure or syncope. Random-effects meta-analyses were performed with a treatment-arm continuity correction for single and double zero event studies., Results: Sixty RCTs (n = 12,463) were included. Twenty-five of 60 trials (n = 5886) investigated participants with Alzheimer's disease and 33 trials monitored electrocardiogram data. The mean follow-up duration was 31 weeks (SD = 36). Mortality was the most commonly reported MACE (252/331, 75.8% events), the remainder were syncope or seizures, with no arrhythmia events. There was no increased risk of MACE with exposure to donepezil compared to placebo (risk ratio [RR] 1.08, 95% CI 0.88-1.33, I 2  = 0%) and this was consistent in the subgroup analysis of trials including participants with cardiovascular morbidities (RR 1.14, 95% CI 0.88-1.47). Subgroup analysis suggested a trend toward more events with donepezil with follow-up ≥52 weeks (RR: 1.32, 0.98-1.79)., Conclusions: This systematic review with meta-analysis found donepezil may not be arrhythmogenic. Donepezil was not associated with mortality, ventricular arrhythmias, seizure or syncope, although longer durations of therapy need more study. Further research to clarify actual clinical outcomes related to QTPmed is important to inform prescribing practices., (© 2024 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Introduction: The commonly used frequentist paradigm of null hypothesis statistics testing with its reliance on the p-value and the corresponding notion of 'statistical significance' has been under ongoing criticism. Misinterpretation and misuse of the p-value have contributed to publication bias, unreliable studies, frequent false positives, fraud and mistrust in results of scientific studies. While p-values themselves are still useful, part of the problem may be the confusion between statistical and clinical significance. In randomised controlled trials of health interventions, this confusion could lead to erroneous conclusions about treatment efficacy, research waste and compromised patient outcomes. The extent to which clinical and statistical significance of published randomised clinical trials do not match is not known. This is a protocol for a methodological study to understand the extent of the problem of disparities between statistical and clinical significance in published clinical trials, and to identify and assess the factors associated with discrepant results in these studies., Methods and Analysis: A methodological survey of published randomised controlled trials is planned. Trials published between 2018 and 2022 and their protocols will be searched and screened for inclusion, with a planned sample size of 500 studies. The reported minimum clinically important difference, the study effect size and confidence intervals will be used to assess clinical importance of trial results. Comparison of statistical significance and clinical importance of the trial results will be used to determine disparity. Data will be analysed to estimate the outcomes, and factors associated with disparate study results will be assessed using logistic regression analysis., Ethics and Dissemination: Ethical approval for the study has been granted by Stellenbosch University's Health Research Ethics Committee. This is part of a larger study towards a PhD in Biostatistics and will be disseminated as a thesis, conference abstract and peer-reviewed manuscript., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: JM and MAH are collaborating investigators on the NHMRC- and MRFF-funded RELEASE and RELEASE + trials in Australia investigating hyperbolic tapering of antidepressants. MAH is a co-founder of Outro Health, a digital clinic which aims to help people who wish to stop no longer needed antidepressant medication in the US. MAH has received honoraria for lectures on deprescribing from NHS Trusts, Washington University and the University of Arizona. JM is a co-investigator on a National Institute of Health Research (NIHR) funded study exploring methods of antidepressant discontinuation (REDUCE) and the Chief Investigator on the RADAR trial of antipsychotic reduction and discontinuation funded by the NIHR. She collects royalties from three books on psychiatric drugs. ZS is a board member of the Canadian mood and anxiety disorders treatment guidelines. LM receives consulting fees from Astra Zeneca, Bayer, and WHO. All other authors declare that they have no competing interests.

Introduction: The results of the phase 3 ALSYMPCA trial showed that Radium-223 (Ra-223) improves overall survival (OS) and delays onset of first symptomatic skeletal event vs. placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of the REACTIVATE study was to inform the optimal placement of Ra-233 in the treatment sequence by evaluating clinical outcomes and healthcare resource utilization using real-world data from multiple Canadian provinces., Methods: This retrospective cohort study analyzed patient outcomes according to Ra-223 placement using administrative databases of four Canadian provinces, encompassing 4301 patients with mCRPC who received at least two lines of life-prolonging therapy (LPT) for mCRPC. Outcomes included OS, event-free survival (EFS), and healthcare resource utilization. Each province was analyzed separately., Results: OS, measured from the start of second-line LPT, differed between provinces: those in Ontario receiving second-line Ra-223 had a longer OS vs. those receiving it in third-line or later (hazard ratio [HR ] 0.79, 95% confidence interval [CI] 0.66-0.95). There was no difference between lines of therapy in patients in British Columbia (HR 1.165, 95% CI, 0.894-1.518, p=0.2576), and OS was numerically worse but not statistically significant in patients receiving Ra-223 in second-line in Quebec (HR 1.44, 95% CI, 0.93-2.24). Other outcomes also varied across provinces, with second-line use of Ra-223 being associated with longer EFS and reduced healthcare utilization vs. third-line use in Ontario but not in Quebec., Conclusions: Significant heterogeneity exists in the management and outcomes of mCRPC between provinces, particularly regarding the placement of Ra-223 in the treatment sequence.

Objectives: We aimed to evaluate the high-quality literature on the frequency and nature of major adverse cardiac events (MACE) associated with either hydroxychloroquine (HCQ) or chloroquine (CQ)., Data Sources: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onward using search strategies created in collaboration with medical science librarians., Study Selection and Data Extraction: Randomized controlled trials (RCTs) published in English language from January 1996 to September 2022, involving adult patients at least 18 years of age, were selected. Outcomes of interest were death, arrhythmias, syncope, and seizures. Random-effects meta-analyses were performed with a Treatment Arm Continuity Correction for single and double zero event studies., Data Synthesis: By study drug, there were 31 HCQ RCTs (n = 6677), 9 CQ RCTs (n = 622), and 1 combined HCQ-CQ trial (n = 105). Mortality was the most commonly reported MACE at 220 of 255 events (86.3%), with no reports of torsades de pointes or sudden cardiac death. There was no increased risk of MACE with exposure to HCQ-CQ compared with control (risk ratio [RR] = 0.90, 95% CI = 0.69-1.17, I 2 = 0%)., Relevance to Patient Care and Clinical Practice: These findings have important implications with respect to patient reassurance and updated guidance for prescribing practices of these medications., Conclusions: Despite listing as QT-prolonging meds, HCQ-CQ did not increase the risk of MACE., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The SQUEEZE trial is a multicentred randomized controlled trial which seeks to determine the optimal approach to fluid resuscitation in paediatric septic shock. SQUEEZE also includes a nested translational study, SQUEEZE-D, investigating the value of plasma cell-free DNA for prediction of clinical outcomes., Objective: To present a pre-specified statistical analysis plan (SAP) for the SQUEEZE trial prior to finalizing the trial data set and prior to commencing data analysis., Design: SQUEEZE is a pragmatic, two-arm, open-label, prospective multicentre randomized controlled trial., Setting: Canadian paediatric tertiary care centres., Participants: Paediatric patients with suspected sepsis and persistent signs of shock in need of ongoing resuscitation. Sample size target: 400 participants., Interventions: The trial is designed to compare a fluid-sparing resuscitation strategy to usual care., Main Outcome Measures: The primary outcome for the SQUEEZE trial is the time to shock reversal (in hours). The primary outcome analysis will assess the difference in time to shock reversal between the intervention and control groups, reported as point estimate with 95% confidence intervals. The statistical test for the primary analysis will be a two-sided t-test. Secondary outcome measures include clinical outcomes and adverse events including measures of organ dysfunction and mortality outcomes., Results: The SAP presented here is reflective of and where necessary clarifies in detail the analysis plan as presented in the trial protocol. The SAP includes a mock CONSORT diagram, figures and tables. Data collection methods are summarized, primary and secondary outcomes are defined, and outcome analyses are described., Conclusions: We have developed a statistical analysis plan for the SQUEEZE Trial for transparency and to align with best practices. Analysis of SQUEEZE Trial data will adhere to the SAP to reduce the risk of bias., Registration: ClinicalTrials.gov identifiers: Definitive trial NCT03080038; Registered Feb 28, 2017. Pilot Trial NCT01973907; Registered Oct 27, 2013., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: High-income countries offer social assistance (welfare) programs to help alleviate poverty for people with little or no income. These programs have become increasingly conditional and stringent in recent decades based on the premise that transitioning people from government support to paid work will improve their circumstances. However, many people end up with low-paying and precarious jobs that may cause more poverty because they lose benefits such as housing subsidies and health and dental insurance, while incurring job-related expenses. Conditional assistance programs are also expensive to administer and cause stigma. A guaranteed basic income (GBI) has been proposed as a more effective approach for alleviating poverty, and several experiments have been conducted in high-income countries to investigate whether GBI leads to improved outcomes compared to existing social programs., Objectives: The aim of this review was to conduct a synthesis of quantitative evidence on GBI interventions in high-income countries, to compare the effectiveness of various types of GBI versus "usual care" (including existing social assistance programs) in improving poverty-related outcomes., Search Methods: Searches of 16 academic databases were conducted in May 2022, using both keywords and database-specific controlled vocabulary, without limits or restrictions on language or date. Sources of gray literature (conference, governmental, and institutional websites) were searched in September 2022. We also searched reference lists of review articles, citations of included articles, and tables of contents of relevant journals in September 2022. Hand searching for recent publications was conducted until December 2022., Selection Criteria: We included all quantitative study designs except cross-sectional (at one timepoint), with or without control groups. We included studies in high income countries with any population and with interventions meeting our criteria for GBI: unconditional, with regular payments in cash (not in-kind) that were fixed or predictable in amount. Although two primary outcomes of interest were selected a priori (food insecurity, and poverty level assessed using official, national, or international measures), we did not screen studies on the basis of reported outcomes because it was not possible to define all potentially relevant poverty-related outcomes in advance., Data Collection and Analysis: We followed the Campbell Collaboration conduct and reporting guidelines to ensure a rigorous methodology. The risk of bias was assessed across seven domains: confounding, selection, attrition, motivation, implementation, measurement, and analysis/reporting. We conducted meta-analyses where results could be combined; otherwise, we presented the results in tables. We reported effect estimates as standard mean differences (SMDs) if the included studies reported them or provided sufficient data for us to calculate them. To compare the effects of different types of interventions, we developed a GBI typology based on the characteristics of experimental interventions as well as theoretical conceptualizations of GBI. Eligible poverty-related outcomes were classified into categories and sub-categories, to facilitate the synthesis of the individual findings. Because most of the included studies analyzed experiments conducted by other researchers, it was necessary to divide our analysis according to the "experiment" stage (i.e., design, recruitment, intervention, data collection) and the "study" stage (data analysis and reporting of results)., Main Results: Our searches yielded 24,476 records from databases and 80 from other sources. After screening by title and abstract, the full texts of 294 potentially eligible articles were retrieved and screened, resulting in 27 included studies on 10 experiments. Eight of the experiments were RCTs, one included both an RCT site and a "saturation" site, and one used a repeated cross-sectional design. The duration ranged from one to 5 years. The control groups in all 10 experiments received "usual care" (i.e., no GBI intervention). The total number of participants was unknown because some of the studies did not report exact sample sizes. Of the studies that did, the smallest had 138 participants and the largest had 8019. The risk of bias assessments found "some concerns" for at least one domain in all 27 studies and "high risk" for at least one domain in 25 studies. The risk of bias was assessed as high in 21 studies due to attrition and in 22 studies due to analysis and reporting bias. To compare the interventions, we developed a classification framework of five GBI types, four of which were implemented in the experiments, and one that is used in new experiments now underway. The included studies reported 176 poverty-related outcomes, including one pre-defined primary outcome: food insecurity. The second primary outcome (poverty level assessed using official, national, or international measures) was not reported in any of the included studies. We classified the reported outcomes into seven categories: food insecurity (as a category), economic/material, physical health, psychological/mental health, social, educational, and individual choice/agency. Food insecurity was reported in two studies, both showing improvements (SMD = -0.57, 95% CI: -0.65 to -0.49, and SMD = -0.41, 95% CI: -0.57 to -0.26) which were not pooled because of different study designs. We conducted meta-analyses on four secondary outcomes that were reported in more than one study: subjective financial well-being, self-rated overall physical health, self-rated life satisfaction, and self-rated mental distress. Improvements were reported, except for overall physical health or if the intervention was similar to existing social assistance. The results for the remaining 170 outcomes, each reported in only one study, were summarized in tables by category and subcategory. Adverse effects were reported in some studies, but only for specific subgroups of participants, and not consistently, so these results may have been due to chance., Authors' Conclusions: The results of the included studies were difficult to synthesize because of the heterogeneity in the reported outcomes. This was due in part to poverty being multidimensional, so outcomes covered various aspects of life (economic, social, psychological, educational, agency, mental and physical health). Evidence from future studies would be easier to assess if outcomes were measured using more common, validated instruments. Based on our analysis of the included studies, a supplemental type of GBI (provided along with existing programs) may be effective in alleviating poverty-related outcomes. This approach may also be safer than a wholesale reform of existing social assistance approaches, which could have unintended consequences., (© 2024 The Author(s). Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Canadian Institutes of Health Research for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Objective: Smoking cessation interventions are underutilized in the surgical setting. We aimed to systematically identify the barriers and facilitators to smoking cessation in the surgical setting., Methods: Following the Joanna Briggs Institute (JBI) framework for scoping reviews, we searched 5 databases (MEDLINE, Embase, Cochrane CENTRAL, CINAHL, and PsycINFO) for quantitative or qualitative studies published in English (since 2000) evaluating barriers and facilitators to perioperative smoking cessation interventions. Data were analyzed using thematic analysis and mapped to the theoretical domains framework (TDF)., Results: From 31 studies, we identified 23 unique barriers and 13 facilitators mapped to 11 of the 14 TDF domains. The barriers were within the domains of knowledge (e.g., inadequate knowledge of smoking cessation interventions) in 23 (74.2%) studies; environmental context and resources (e.g., lack of time to deliver smoking cessation interventions) in 19 (61.3%) studies; beliefs about capabilities (e.g., belief that patients are nervous about surgery/diagnosis) in 14 (45.2%) studies; and social/professional role and identity (e.g., surgeons do not believe it is their role to provide smoking cessation interventions) in 8 (25.8%) studies. Facilitators were mainly within the domains of environmental context and resources (e.g., provision of quit smoking advice as routine surgical care) in 15 (48.4%) studies, reinforcement (e.g., surgery itself as a motivator to kickstart quit attempts) in 8 (25.8%) studies, and skills (e.g., smoking cessation training and awareness of guidelines) in 5 (16.2%) studies., Conclusion: The identified barriers and facilitators are actionable targets for future studies aimed at translating evidence informed smoking cessation interventions into practice in perioperative settings. More research is needed to evaluate how targeting these barriers and facilitators will impact smoking outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ofori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Globally, a shift is occurring to recognize the importance of young peoples' health and well-being, their unique health challenges, and the potential they hold as key drivers of change in their communities. In Haiti, one of the four leading causes of death for those 20-24 years old is pregnancy, childbirth, and the weeks after birth or at the end of a pregnancy. Important gaps remain in existing knowledge about youth perspectives of maternal health and well-being within their communities. Youth with lived experiences of maternal near-misses are well-positioned to contribute to the understanding of maternal health in their communities and their potential role in bringing about change., Objectives: To explore and understand youth perspectives of maternal near-miss experiences that occurred in a local healthcare facility or at home in rural Haiti., Methods: We will conduct a qualitative, community-based participatory research study regarding maternal near-miss experiences to understand current challenges and identify solutions to improve community maternal health, specifically focused on youth maternal health. We will use Photovoice to seek an understanding of the lived experiences of youth maternal near-miss survivors. Participants will be from La Pointe, a Haitian community served by their local healthcare facility. We will undertake purposeful sampling to recruit approximately 20 female youth, aged 15-24 years. Data will be generated through photos, individual interviews and small group discussions (grouped by setting of near-miss experience). Data generation and analysis are expected to occur over a three-month period., Ethics and Dissemination: Ethics approval will be sought from Centre Médical Béraca in La Pointe, Haiti, and from the Hamilton Integrated Research Ethics Board in Hamilton ON, Canada. We will involve community stakeholders, especially youth, in developing dissemination and knowledge mobilisation strategies. Our findings will be disseminated as an open access publication, be presented publicly, at conferences, and defended as part of a doctoral thesis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 MacDonald et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: An emerging body of randomized controlled trials (RCTs) on COVID-19 vaccines has served as the evidence base for public health decision-making. While it is recommended that RCTs report results by health equity stratifiers to reduce bias in health care and gaps in research, it is unknown whether this was done in COVID-19 vaccine trials. To critically examine the use of health equity stratifiers in COVID-19 vaccine trials., Study Design and Setting: We conducted a methodological review of published COVID-19 vaccine trials available in the COVID-19 living Network Meta-Analysis systematic review database through February 8, 2023. Based on the PROGRESS-Plus framework, we examined the following health equity stratifiers: place of residence, race/ethnicity, occupation, gender/sex, religion, education, socio-economic status, social capital, age, disability, features of relationships, and temporary situations. We assessed each study in duplicate according to three criteria for comprehensive health-equity reporting: 1) describing participants, 2) reporting equity-relevant results, and 3) discussing equity-relevant implications of trial findings., Results: We reviewed 144 trial manuscripts. The most frequently used PROGRESS-Plus stratifiers to describe participants were age (100%), place of residence (100%), gender/sex (99%), and race/ethnicity (64%). Age was most often used to disaggregate or adjust results (67%), followed by gender or sex (35%). Discussions of equity-relevant implications often indicated limited generalizability of results concerning age (40% of studies). Half (47%) of the studies considered at least one health equity stratifier for all three criteria. No trials included stratifiers related to religion, socioeconomic status, sexual orientation, or features of relationships., Conclusion: COVID-19 vaccine trials provided a limited description of health equity stratifiers as defined by PROGRESS-Plus and infrequently disaggregated results or discussed the study implications as they related to health equity. Considering the health disparities exacerbated during the pandemic, increased uptake of PROGRESS-Plus in RCTs would support a more nuanced understanding of health disparities and better inform actions to improve health equity., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare. This study receieved no funding., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: People living with HIV (PLHIV) have a higher risk of developing pulmonary hypertension (PH) with subsequent poorer prognosis. This review aimed to determine the (1) survival outcomes and (2) proportion of emergency department (ED) visits and hospitalisations of PLHIV and PH., Methods: We conducted a systematic review and meta-analysis of observational studies reporting survival outcomes for PLHIV and PH. Electronic databases (Medline, EMBASE, PubMed, Web of Science, Global Index Medicus and Cochrane Library), trial registries and conference proceedings were searched until 22 July 2023. We pooled similar measures of effect, assessed apriori subgroups and used meta-regression to determine mortality and associated variables., Results: 5248 studies were identified; 28 studies were included with a total of 5459 PLHIV and PH. The mean survival (95% CI) of PLHIV and PH was 37.4 months (29.9 to 44.8). Participants alive at 1, 2 and 3 years were 85.8% (74.1% to 95.0%), 75.2% (61.9% to 86.7%) and 61.9% (51.8% to 71.6%), respectively. ED visits and hospitalisation rates were 73.3% (32.5% to 99.9%) and 71.2% (42.4% to 94.2%), respectively. More severe disease, measured by echocardiogram, was associated with poorer prognosis (β -0.01, 95% CI -0.02 to 0.00, p=0.009). Survival was higher in high-income countries compared with lower-income countries (β 0.50, 95% CI 0.28 to 0.73, p<0.001) and in Europe compared with the America (β 0.56, 95% CI 0.37 to 0.75, p<0.001)., Conclusion: Our study confirms poor prognosis and high healthcare utilisation for PLHIV and PH. Prognosis is associated with country income level, geographic region and PH severity. This highlights the importance of screening in this population., Prospero Registration Number: CRD42023395023., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Seniors with recurrent hospitalizations who are taking multiple medications including high-risk medications are at particular risk for serious adverse medication events. We will assess whether an expert Clinical Pharmacology and Toxicology (CPT) medication management intervention during hospitalization with follow-up post-discharge and communication with circle of care is feasible and can decrease drug therapy problems amongst this group., Methods: The design is a pragmatic pilot randomized trial with 1:1 patient-level concealed randomization with blinded outcome assessment and data analysis. Participants will be adults 65 years and older admitted to internal medicine services for more than 2 days, who have had at least one other hospitalization in the prior year, taking five or more chronic medications including at least one high-risk medication. The CPT intervention identifies medication targets; completes consult, including priorities for improving prescribing negotiated with the patient; starts the care plan; ensures a detailed discharge medication reconciliation and circle-of-care communication; and sees the patient at least twice after hospital discharge via virtual visits to consolidate the care plan in the community. Control group receives usual care. Primary outcomes are feasibility - recruitment, retention, costs, and clinical - number of drug therapy problems improved, with secondary outcomes examining coordination of transitions in care, quality of life, and healthcare utilization and costs. Follow-up is to 3-month posthospital discharge., Discussion: If results support feasibility of ramp-up and promising clinical outcomes, a follow-up definitive trial will be organized using a developing national platform and medication appropriateness network. Since the intervention allows a very scarce medical specialty expertise to be offered via virtual care, there is potential to improve the safety, outcomes, and cost of care widely., Trial Registration Number: ClinicalTrials.gov identifier: NCT04077281., (© 2024. The Author(s).)

Objectives: Evidence-based research (EBR) is the systematic and transparent use of prior research to inform a new study so that it answers questions that matter in a valid, efficient, and accessible manner. This study surveyed experts about existing (e.g., citation analysis) and new methods for monitoring EBR and collected ideas about implementing these methods., Study Design and Setting: We conducted a cross-sectional study via an online survey between November 2022 and March 2023. Participants were experts from the fields of evidence synthesis and research methodology in health research. Open-ended questions were coded by recurring themes; descriptive statistics were used for quantitative questions., Results: Twenty-eight expert participants suggested that citation analysis should be supplemented with content evaluation (not just what is cited but also in which context), content expert involvement, and assessment of the quality of cited systematic reviews. They also suggested that citation analysis could be facilitated with automation tools. They emphasized that EBR monitoring should be conducted by ethics committees and funding bodies before the research starts. Challenges identified for EBR implementation monitoring were resource constraints and clarity on responsibility for EBR monitoring., Conclusion: Ideas proposed in this study for monitoring the implementation of EBR can be used to refine methods and define responsibility but should be further explored in terms of feasibility and acceptability. Different methods may be needed to determine if the use of EBR is improving over time., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Reporting bias refers to the phenomenon in which the reporting of research findings is influenced by the nature of the results. Without the totality of evidence, clinical practice may be misguided. The objective of this work was to examine the extent of reporting bias in clinical trials of breast reconstruction surgery., Methods: We searched and extracted data from all completed breast reconstruction clinical trials published in ClinicalTrials.gov from database inception to August 2020. Investigators sought to identify published full manuscripts of the registered trials. The primary outcome was classified as positive or nonpositive and trials were classified as industry or nonindustry funded. Time to publication in a peer-reviewed journal was computed and compared using time-to-event analysis. Trial characteristics associated with publication were evaluated using logistic regression., Results: A total of 156 clinical trials were identified, of which, 53 trials were published. The median time to publication was 22 months (IQR, 13-35 months). Industry-funded studies were associated with a longer time to publication (HR = 2.4, p = 0.023) and publication in lower-impact journals (OR = 3.7, p = 0.048). Randomized clinical trials were associated with faster times to publication than nonrandomized studies (aHR = 3.2, p = 0.030). Statistical significance and the effect size were not associated with time to publication., Conclusions: We found no evidence that industry-funded trials were more likely to report a positive primary outcome. However, industry-funded trials were associated with a longer time to publication and publication in lower-impact journals., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: To enhance equity in clinical and epidemiological research, it is crucial to understand researcher motivations for conducting equity-relevant studies. Therefore, we evaluated author motivations in a randomly selected sample of equity-relevant observational studies published during the COVID-19 pandemic., Study Design and Setting: We searched MEDLINE for studies from 2020 to 2022, resulting in 16,828 references. We randomly selected 320 studies purposefully sampled across income setting (high vs low-middle-income), COVID-19 topic (vs non-COVID-19), and focus on populations experiencing inequities. Of those, 206 explicitly mentioned motivations which we analyzed thematically. We used discourse analysis to investigate the reasons behind emerging motivations., Results: We identified the following motivations: (1) examining health disparities, (2) tackling social determinants to improve access, and (3) addressing knowledge gaps in health equity. Discourse analysis showed motivations stem from commitments to social justice and recognizing the importance of highlighting it in research. Other discourses included aspiring to improve health-care efficiency, wanting to understand cause-effect relationships, and seeking to contribute to an equitable evidence base., Conclusion: Understanding researchers' motivations for assessing health equity can aid in developing guidance that tailors to their needs. We will consider these motivations in developing and sharing equity guidance to better meet researchers' needs., Competing Interests: Declaration of competing interest L.G.C. is employed by the Pan American Health Organization (PAHO/WHO). The ideas expressed in this manuscript are the authors' own and do not necessarily reflect the decisions and policies of PAHO/WHO. There are no competing interests for any other author., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Adequate surveillance of HIV drug resistance prevalence is challenged by heterogenous and inadequate data reporting. To address this issue, we recently published reporting guidance documentation for studies of HIV drug resistance prevalence and incidence., Objectives: In this study, we describe the methods used to develop this reporting guidance., Design: We used a mixed-methods sequential explanatory design involving authors and users of studies of HIV drug resistance prevalence. In the quantitative phase, we conducted a cross-sectional electronic survey (n=51). Survey participants rated various reporting items on whether they are essential to report. Validity ratios were computed to determine the items to discuss in the qualitative phase. In the qualitative phase, two focus group discussions (n=9 in total) discussed this draft item checklist, providing a justification and examples for each item. We conducted a descriptive qualitative analysis of the group discussions to identify emergent themes regarding the qualities of an essential reporting item., Results: We identified 38 potential reporting items that better characterise the study participants, improve the interpretability of study results and clarify the methods used for HIV resistance testing. These items were synthesised to create the reporting item checklist. Qualitative insights formed the basis of the explanation, elaboration, and rationale components of the guidance document., Conclusions: We generated a list of reporting items for studies on the incidence or prevalence of HIV drug resistance along with an explanation of why researchers believe these items are important. Mixed methods allowed for the simultaneous generation and integration of the item list and qualitative insights. The integrated findings were then further developed to become the subsequently published reporting guidance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Missing outcome data in clinical trials may jeopardize the validity of the trial results and inferences for clinical practice. Although sick and preterm newborns are treated as a captive patient population during their stay in the NICUs, their long-term outcomes are often ascertained after discharge. This greatly increases the risk of attrition. We surveyed recently published perinatal and neonatal randomized trials in 7 high-impact general medical and pediatric journals to review the handling of missing primary outcome data and any choice of imputation methods. Of 87 eligible trials in this survey, 77 (89%) had incomplete primary outcome data. The missing outcome data were not discussed at all in 9 reports (12%). Most study teams restricted their main analysis to participants with complete information for the primary outcome (61 trials; 79%). Only 38 of the 77 teams (49%) performed sensitivity analyses using a variety of imputation methods. We conclude that the handling of missing primary outcome data was frequently inadequate in recent randomized perinatal and neonatal trials. To improve future approaches to missing outcome data, we discuss the strengths and limitations of different imputation methods, the appropriate estimation of sample size, and how to deal with data withdrawal. However, the best strategy to reduce bias from missing outcome data in perinatal and neonatal trials remains prevention. Investigators should anticipate and preempt missing data through careful study design, and closely monitor all incoming primary outcome data for completeness during the conduct of the trial., (Copyright © 2024 by the American Academy of Pediatrics.)