Interventions for the management of post COVID-19 condition (long COVID): Protocol for a living systematic review & network meta-analysis (preprint)

Background: Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia, and impaired cognitive function, termed post COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice. Objective To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID. Methods Eligible trials will randomize adults with long COVID, to pharmacologic or non-pharmacologic interventions, placebo, sham, or usual care. We will identify eligible studies by searches of MEDLINE, EMBASE, CINAHL, PsycInfo, AMED, and CENTRAL, from inception, without language restrictions. Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest, and assess risk of bias. Our outcomes of interest will include fatigue, pain, post-exertional malaise, changes in education or employment status, cognitive function, mental health, dyspnea, quality of life, patient-reported physical function, recovery, and serious adverse events. For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The GRADE approach will guide our assessment of the certainty of evidence. We will update our living review biannually, upon the publication of a seminal trial, or when new evidence emerges that may change clinical practice. Conclusion This living systematic review and network meta-analysis will provide comprehensive, trustworthy, and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline producing organizations to inform their recommendations.

The Feasibility of a Randomized Controlled Trial to evaluate interactive weekly mobile phone text messaging plus motivational interviewing to promote breastfeeding among women living with HIV (preprint)

Background In 2011, South Africa changed infant feeding guidelines for women with HIV from government-supplied formula feeding to exclusive breastfeeding for six months and continued breastfeeding for two years or longer. With only 8% of infants under 6 months of age being breastfed, interventions are required to improve breastfeeding rates. We assessed whether an appropriately powered randomized trial was feasible regarding i) recruitment and retention, and ii) protocol adherence. We explored the potential effects of the intervention on sustaining exclusive breastfeeding at 24 weeks postpartum. Methods We conducted a randomized parallel, two arm feasibility trial. Women were included if they initiated breastfeeding within 24 hours of giving birth at the Worcester midwife obstetric unit, on antiretroviral treatment, and aged ≥18 years. We randomly assigned mother-infant pairs to receive weekly text messaging encouraging exclusive breastfeeding plus in-person individual motivational interviews postpartum at weeks 2, 6, and 10 at Family Clinical Research with Ubuntu or standard infant feeding counselling during routine postnatal clinic visits. Results Of 123 mothers consented for screening, 52 eligible participants consented for study participation. We recruited an average of five participants per month over 11 months. Most participants were unemployed (75%), had some high school education (84%), and disclosed their HIV status to someone close (88%). About 65% participants completed outcome evaluation at week 10, decreasing to 35% at week 24. Twenty participants had the week 24 visit planned between 20 March and August 2020, during COVID-19 lockdown. Of these, four completed the visit telephonically, 16 were lost to follow up. Exclusive breastfeeding rate remained relatively high across both groups through week 24. Although the intervention group had higher rates of exclusive breastfeeding at week 24 than the control group this difference was minimal; rate difference 22.2% [95% confidence interval (CI) -20.1% to 64.5%]. Conclusions With a large enough eligible target population recruitment targets could be achieved for the large randomized trial. Strategies to retain participants, such as remote monitoring in addition to in-person follow-up visits, will be essential. Trial registration: The trial was registered on ClinicalTrials.gov on 31/10/2016; NCT02949713 and on Pan African Clinical Trial Registry on 08/11/2016; PACTR201611001855404.

Knowledge mobilization activities to support decision-making by youth, parents, and adults using a systematic and living map of evidence and recommendations on COVID-19: protocol for a randomized controlled trial (preprint)

IntroductionThe COVID-19 pandemic underlined that guidelines and recommendations must be made more accessible and more understandable to the general public, including adults, parents, and youth, to improve health outcomes. The objective of this study is to evaluate, quantify, and compare the publics (youth, parents, and adult populations) understanding, usability, satisfaction, intention to implement, and preference for different ways of presenting COVID-19 health recommendations derived from the COVID-19 Living Map of Recommendations and Gateway to Contextualization (herein referred to as the RecMap). Methods and AnalysisThis is a protocol for a multi-method study. We will conduct pragmatic allocation-concealed, blinded superiority randomized controlled trials (RCT) in three populations to test alternative formats of presenting health recommendations: adults (21 years of age or older), parents (18 years or above and are a parent or legal guardian of a child under 18 years old), and youth (15 to 24 years old), with at least 240 participants in each population. The research will consist of a randomized online survey and an optional one-on-one interview. Prior to initiating the RCT, our interventions will have been refined with relevant stakeholder input. In each population group, the intervention arm will receive a plain language recommendation (PLR) format while the control arm will receive the corresponding original recommendation format as originally published by the guideline organizations (herein referred to as Standard Language Version). Our primary outcome is understanding, and our secondary outcomes are accessibility and usability, satisfaction, intended behavior, and preference for the two recommendation formats. Each populations results will be analyzed separately. However, we are planning a meta-analysis of the results across populations, and will also explore potential interaction and subgroup effects within each population. At the end of each survey, participants will be invited to participate in a one-on-one, virtual semi-structured interview to explore their user experience and their learning preferences and future research. All interviews will be transcribed and analyzed using the principles of thematic analysis and a hybrid inductive and deductive approach. Iterative member checking, triangulation, interpretation, and saturation of themes will be sought to enhance reliability. Ethics and DisseminationThrough Clinical Trials Ontario (CTO), the Hamilton Integrated Research Ethics Board has reviewed and approved this protocol (Project ID: 3856). The University of Alberta has approved the parent portion of the trial (Project ID:00114894). All potential participants will be required to provide informed consent. The findings from this study will be disseminated through open-access publications in peer-reviewed journals and using social media. Strengths and limitations of this studyO_LIWe are following a multi-method approach: randomized controlled trials and qualitative interviews. The qualitative results will supplement and help explain our quantitative findings. C_LIO_LIThis protocol is reported in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT), which enhances transparency and completeness. The trials use previously validated outcomes from similar trials. This will strengthen the credibility of our results. C_LIO_LIOur study is testing an optimized plain language recommendation format, which makes our intervention relevant to our stakeholder groups, and is recruiting internationally, which ensures the inclusion of a diverse population. Recruitment will take place online using social media, and data will be collected using an online survey. This allows for self-selection and limits accessibility to those who have no or limited digital access, which in turn limits generalizability. C_LIO_LIWhile the recommendations are offered in multiple languages through the RecMap, the study is only testing English plain language recommendation summaries. C_LI