International Standard Randomized Controlled Trial Number Research Articles

Evaluating and Enhancing an Educational Intervention to Reduce Smallholder Farmers' Exposure to Pesticides in Uganda Through a Digital, Systematic Approach to Behavior Change: Protocol for a Cluster-Randomized Controlled Trial.

Smallholder farmers receive educational interventions on safe pesticide handling by governmental agencies, industries, or nongovernmental organizations to reduce exposure risks. However, existing educational interventions have limited effects on changing behaviors. Targeting psychosocial determinants of behavior change in educational interventions through theory- and evidence-based approaches may enhance their effectiveness. We aim at describing the intervention development and study design of a 3-arm cluster-randomized controlled trial to assess the effects in improving safe pesticide handling and reducing pesticide exposure of (1) an existing educational intervention and (2) a newly developed SMS text messaging intervention based on the Risks, Attitudes, Norms, Abilities, and Self-regulation (RANAS) behavior change approach. We enrolled 539 Ugandan smallholder farmers in 12 clusters (subcounties). The clusters, each with 45 farmers, were randomly allocated to one of the three arms: (1) educational intervention, (2) educational intervention+RANAS-based SMS text messages, or (3) control group. The educational intervention comprised a 2-day workshop that targeted multiple aspects of safe pesticide handling, whereas the SMS text messages targeted the use of personal protective equipment (PPE) and were based on the RANAS approach. For intervention development in this study, this approach includes identifying psychosocial determinants of PPE use at baseline and selecting behavior change techniques to target them in SMS text messages. The primary outcomes of the study are (1) pesticide knowledge, attitude, and practice scores indicating performance throughout the educational intervention; and (2) frequency of PPE use. Secondary outcomes are the RANAS-based behavioral determinants of PPE use, the frequency of glove use, algorithm-based pesticide exposure intensity scores, and signs and symptoms of pesticide poisoning. The outcomes were assessed in structured interviews before the intervention (baseline) and at the 12-month follow-up. The effect of the interventions among the arms will be analyzed using the intervention arms and baseline measures as predictors and the follow-up measures as outcomes in linear multivariable mixed models including the clusters as random effects. The mediating psychosocial determinants of the interventions will be assessed in multiple mediation models. The study was conducted from 2020 to 2021-baseline interviews were conducted in October 2020, and the educational intervention was delivered in November 2020. The RANAS-based SMS text messages were developed based on the baseline data for relevant behavioral determinants of PPE use and sent between February 2021 and September 2021. Follow-up interviews were conducted in October 2021. Overall, 539 farmers were enrolled in the study at baseline; 8.3% (45/539) were lost to follow-up by the end of the study. This study will contribute to a better understanding of the effectiveness and behavior change mechanisms of educational interventions by using an experimental, cluster-randomized study design to improve pesticide handling among smallholder farmers. International Standard Randomised Controlled Trial Number (ISRCTN) 18237656; https://doi.org/10.1186/ISRCTN18237656. DERR1-10.2196/55238.

Digital Self-Management Platform for Adult Asthma: Randomized Attention-Placebo Controlled Trial.

Asthma is one of the most common chronic conditions worldwide, with a substantial individual and health care burden. Digital apps hold promise as a highly accessible, low-cost method of enhancing self-management in asthma, which is critical to effective asthma control. We conducted a fully remote randomized controlled trial (RCT) to assess the efficacy of juli, a commercially available smartphone self-management platform for asthma. We conducted a pragmatic single-blind, RCT of juli for asthma management. Our study included participants aged 18 years and older who self-identified as having asthma and had an Asthma Control Test (ACT) score of 19 or lower (indicating uncontrolled asthma) at the beginning of the trial. Participants were randomized (1:1 ratio) to receive juli for 8 weeks or a limited attention-placebo control version of the app. The primary outcome measure was the difference in ACT scores after 8 weeks. Secondary outcomes included remission (ACT score greater than 19), minimal clinically important difference (an improvement of 3 or more points on the ACT), worsening of asthma, and health-related quality of life. The primary analysis included participants using the app for 8 weeks (per-protocol analysis), and the secondary analysis used a modified intention-to-treat (ITT) analysis. We randomized 411 participants between May 2021 and April 2023: a total of 152 (37%) participants engaged with the app for 8 weeks and were included in the per-protocol analysis, and 262 (63.7%) participants completed the week-2 outcome assessment and were included in the modified ITT analysis. Total attrition between baseline and week 8 was 259 (63%) individuals. In the per-protocol analysis, the intervention group had a higher mean ACT score (17.93, SD 4.72) than the control group (16.24, SD 5.78) by week 8 (baseline adjusted coefficient 1.91, 95% CI 0.31-3.51; P=.02). Participants using juli had greater odds of achieving or exceeding the minimal clinically important difference at 8 weeks (adjusted odds ratio 2.38, 95% CI 1.20-4.70; P=.01). There were no between group differences in the other secondary outcomes at 8 weeks. The results from the modified ITT analyses were similar. Users of juli had improved asthma symptom control over 8 weeks compared with users of a version of the app with limited functionality. These findings suggest that juli is an effective digital self-management platform that could augment existing care pathways for asthma. The retention of patients in RCTs and real-world use of digital health care apps is a major challenge. International Standard Randomised Controlled Trial Number (ISRCTN) registry ISRCTN87679686; https://www.isrctn.com/ISRCTN87679686.

The FraiLTI (Frailty in chronic Limb-Threatening Ischaemia) Protocol

Background: Frailty, sarcopenia and multimorbidity are conditions commonly associated with the ageing process, and they are frequently observed in patients with chronic limb-threatening ischaemia (CLTI). Nevertheless, the extent to which these conditions are prevalent within the CLTI patient population has not been adequately examined in the UK. This proposed multicentre observational study aims to investigate the prevalence of these conditions in patients with CLTI and to assess their potential impact on important clinical outcomes including mortality, amputation and quality of life. Methods: FraiLTI (Frailty in chronic Limb-Threatening Ischaemia) is a multicentre prospective observational study in the UK that that aims to investigate the prevalence of frailty, sarcopenia and multimorbidity associated with CLTI. The secondary objective is to investigate potential correlations between frailty, sarcopenia and multimorbidity, with clinical outcomes such as amputation, mortality, major adverse cardiovascular events and readmission rates within a 90-day period. FraiLTI is led by Newcastle University, supported by the Vascular and Endovascular Research Network (VERN) and funded by the National Institute for Health Research (NIHR) and the Newcastle Hospital Charities. REDCap will be used to collect anonymised patient data. All hospitals with a dedicated vascular centre are eligible to participate. Full ethical approval (21/PR/0750) was granted on 13 July 2021. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. Anticipated impact of the study: This study has the potential to address critical questions identified by the James–Lind Alliance (JLA) Priority Setting Partnership (PSP) in peripheral arterial disease. It is expected to make a substantial contribution to the creation of a prospective CLTI database, integrating essential data on frailty, sarcopenia and multimorbidity that are not currently captured by other registries, despite their profound impact on patient outcomes. This research could provide pivotal insights into the prevalence of frailty, sarcopenia and multimorbidity among the UK’s CLTI population and their corresponding effects on clinical outcomes. Findings from the study will be shared at global scientific conferences and submitted to be published in peer-reviewed journals.

Serum vitamin B12 concentration is associated with improved memory in older individuals with higher adherence to the Mediterranean diet

Vitamin B12 plays a crucial role in cognition, but its effect might be regulated by the presence of other micronutrients, such as folate. The aim was to evaluate the effects of vitamin B12 on cognitive performance according to adherence to the Mediterranean diet, and whether the Mediterranean dietalso results in increased folate or vitamin B12 levels. This is a cohort study nested in a randomized controlled clinical trial performed in Hospital Clinic in Barcelona, Spain. A total of 170 participants of the PREDIMED trial (Barcelona - Hospital Clinic site) aged 55-80 years at high cardiovascular risk were included. Adherence to the Mediterranean diet was assessed using a validated 14-item questionnaire, memory function was evaluated with a battery of neuropsychological tests and serum vitamin B12 and folate were determined using an automated electrochemiluminiscence immunoassay system. In the multivariable adjusted linear regression model, serum vitamin B12 concentration presented a significant correlation with memory function (r2=0.57; P=0.028) in participants with high adherence to the Mediterranean diet whereas the correlation was weak and inverse for those who presented a low adherence to the Mediterranean diet (r2=0.37, P=0.731). Mediterranean diet adherence showed a positive association with serum folate, but not with serum vitamin B12. In an older Mediterranean population at high cardiovascular risk, changes in serum vitamin B12 correlate with better memory function only in the context of a high adherence to the Mediterranean pattern, suggesting that the effects of vitamin B12 goes further than a mere nutritional requirement. The study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board of the 11 participating centres. The study was registered with the International Standard Randomized Controlled Trial Number (ISRCTN) 35739639 (https://www.isrctn.com/ISRCTN35739639).

Effectiveness of Facebook Groups and Pages on Participant Recruitment Into a Randomized Controlled Trial During the COVID-19 Pandemic: Descriptive Study.

In response to the unprecedented challenges posed by the COVID-19 pandemic, conventional recruitment approaches were halted, causing the suspension of numerous clinical trials. Previously, Facebook (Meta Platforms, Inc) has emerged as a promising tool for augmenting participant recruitment. While previous research has explored the use of Facebook for surveys and qualitative studies, its potential for recruiting participants into randomized controlled trials (RCTs) remains underexplored. This study aimed to comprehensively examine the effectiveness of using Facebook groups and pages to facilitate participant recruitment during the COVID-19 pandemic for an RCT on the effectiveness of a remote parenting program, 1-2-3 Magic, in families who have children with attention-deficit/hyperactivity disorder (ADHD) in the United Kingdom. We disseminated 5 Facebook posts with an attached digital flyer across 4 prominent ADHD UK support groups and pages run by the National Attention Deficit Disorder Information and Support Services, reaching an audience of around 16,000 individuals over 2 months (January 7 to March 4, 2022). Eligibility criteria mandated participants to be parents or caregivers of a child with diagnosed ADHD aged 12 years or younger, be residing in the United Kingdom, have access to stable internet, and have a device with the Zoom (Zoom Video Communications) app. Participants were required to have never attended 1-2-3 Magic training previously. Prospective participants expressed their interest through Microsoft Forms (Microsoft Corporation). The trial aimed to recruit 84 parents. It is important to note that the term "parent" or "caregiver" in the RCT and in this study within a trial refers to anybody who has legal responsibility for the child. Overall, 478 individuals registered their interest through Microsoft Forms within the stipulated 2-month window. After the eligibility check, 135 participants were contacted for a baseline meeting through Zoom. The first 84 participants who attended a baseline meeting and returned a completed consent form were enrolled. Subsequently, another 16 participants were added, resulting in a final sample of 100 participants. This recruitment strategy incurred negligible expenses and demanded minimal human resources. The approach yielded favorable outcomes by efficiently attracting eligible participants in a condensed time frame, transcending geographical barriers throughout the United Kingdom, which would have been tedious to achieve through traditional recruitment methods. Our experience demonstrated that digital flyers posted in the targeted Facebook groups were a cost-effective and quick method for recruiting for an RCT, which opened during the COVID-19 pandemic when lockdown restrictions were in place in the United Kingdom. Trialists should consider this low-cost recruitment intervention for trials going forward, and in the case of a global pandemic, this novel recruitment method enabled the trial to continue where many have failed. International Standard Randomized Controlled Trial Number (ISRCTN) 15281572; https://www.isrctn.com/ISRCTN15281572.

Treatment of Recurrent Low-grade Serous Ovarian Cancer With MEK Inhibitors: A Systematic Review.

Low-grade serous ovarian cancer (LGSC) represents 5% of all epithelial ovarian cancers. They are characterized by indolent growth and KRAS and BRAF mutations, differing from high-grade serous ovarian cancer both clinically and molecularly. LGSC has low response rates to traditional systemic therapies, including chemotherapy and hormonal therapy. The objective of this systematic review was to appraise the literature describing the efficacy of MEK inhibitors in the treatment of LGSC. A comprehensive search was conducted of the following databases: Medline ALL, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Sciences, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICFRP), and International Standard Randomized Controlled Trials Number (ISRCTN) Registry. All studies investigating MEKi in the treatment of LGSC in the adjuvant or recurrent setting for patients 18 years of age or older were included. All titles/abstracts were then screened by 2 independent reviewers (A.K. and C.C.). The full-text articles were then screened. All disagreements were resolved by a third independent reviewer (T.Z.). Two independent reviewers (A.K. and C.C.) extracted data from the studies deemed eligible for final review. A total of 2108 studies were identified in the initial search. Of these, a total of 4 studies met the eligibility criteria for systematic review. In these studies, 416 patients were treated with an MEKi alone. All patients included in the studies were being treated for LGSC in the recurrent setting. Varied results and efficacy of the MEKi were reported in each study. The results highlighted in this systematic review demonstrate varied responses to MEKi for recurrent LGSC. Further research is needed in this field comparing the efficacy to current therapies, as well as to further evaluate the safety and toxicity profile with long-term use of MEKi.

Development and Implementation of DIALOG+S in the School Setting as a Tool for Promoting Adolescent Mental Well-Being and Resilience in a Post-Armed Conflict Area in Colombia: Exploratory Cluster Randomized Controlled Trial.

Educational settings are ideal for promoting mental well-being and resilience in children. The challenges of the COVID-19 pandemic made evident the important role that teachers and school counselors play in the mental health of their students. Therefore, it is imperative to develop and implement cost-effective interventions that allow them to identify and address mental health problems early, especially in post-armed conflict areas, to reduce the burden of mental disorders in this population. This study aimed to adapt an existing patient-focused digital intervention called DIALOG+ from an adult clinical setting to an adolescent educational setting and to assess the feasibility, acceptability, and estimated effect of implementing this intervention as a tool for promoting quality of life, mental well-being, and resilience. We conducted an exploratory mixed methods study in 2 public schools in postconflict areas in Tolima, Colombia. This study was conducted in 3 phases. In the adaptation phase, focus groups were conducted with students and teachers to identify changes required in DIALOG+ for it to be used in the school setting. The exploration phase consisted of an exploratory cluster randomized controlled trial. A total of 14 clusters, each with 1 teacher and 5 students, were randomly allocated to either the experimental (DIALOG+S) group or to an active control group (counseling as usual). Teachers in both groups delivered the intervention once a month for 6 months. Through screening scales, information was collected on mental health symptoms, quality of life, self-esteem, resilience, and family functionality before and after the intervention. Finally, the consolidation phase explored the experiences of teachers and students with DIALOG+S using focus group discussions. The changes suggested by participants in the adaptation phase highlighted the central importance of the school setting in the mental health of adolescents. In the exploratory phase, 70 participants with a mean age of 14.69 (SD 2.13) years were included. Changes observed in the screening scale scores of the intervention group suggest that the DIALOG+S intervention has the potential to improve aspects of mental health, especially quality of life, resilience, and emotional symptoms. The consolidation phase showed that stakeholders felt that using this intervention in the school setting was feasible, acceptable, and an enriching experience that generated changes in the perceived mental health and behavior of participants. Our results are encouraging and show that the DIALOG+S intervention is feasible and acceptable as a promising opportunity to promote well-being and prevent and identify mental health problems in the school context in a postconflict area in Colombia. Larger, fully powered studies are warranted to properly assess the efficacy and potential impact of the intervention and to refine implementation plans. International Standard Randomised Controlled Trial Number (ISRCTN) registry ISRCTN14396374; https://www.isrctn.com/ISRCTN14396374. RR2-10.2196/40286.

Representation of ethnic and racial minority groups in European vaccine trials: a quantitative analysis of clinical trials registries

ObjectivesThe representation of ethnic minority groups in European vaccine trials is an important and hitherto unaddressed gap in the literature. The objectives of this study were to determine the proportion...

Evaluating the Effectiveness of the Housing First for Youth Intervention for Youth Experiencing Homelessness in Canada: Protocol for a Multisite, Mixed Methods Randomized Controlled Trial.

Emerging evidence at the international level suggests that the Housing First approach could improve the housing stability of young people experiencing homelessness. However, there is a dearth of literature in Canada on whether the Housing First intervention for young people experiencing homelessness can improve outcomes including housing stability, health and well-being, and access to complementary supports. Adapted from the original Housing First model, Housing First for Youth (HF4Y) was developed in Canada as a rights-based approach tailored specifically for young people aged 16 to 24 years who are experiencing or are at risk of homelessness. The Making the Shift Youth Homelessness Social Innovation Lab is testing the effectiveness of the HF4Y intervention in Canada. The objective of this study is to determine whether the HF4Y model results in better participant-level outcomes than treatment-as-usual services for young people experiencing homelessness in 2 urban settings: Ottawa and Toronto, Ontario. Primary outcomes include housing stability, health and well-being, and complementary supports, and secondary outcomes include employment and educational attainment and social inclusion. The HF4Y study used a multisite, mixed methods, randomized controlled trial research approach for data collection and analysis. Eligible participants included young people aged 16 to 24 years who were experiencing homelessness or housing precarity. The participants were randomly assigned to either the treatment-as-usual group or the housing first intervention group. Survey and interview data in Ottawa and Toronto, Ontario are being collected at multiple time points (3-6 months) over 4 years to capture a range of outcomes. Analytic strategies for quantitative data will include mixed-effects modeling for repeated measures and logistic models. A thematic analysis will be used to analyze qualitative data based on participants' narratives and life journeys through homelessness. Furthermore, program fidelity evaluations are conducted within each HF4Y program. These evaluations assess how well the intervention aligns with the HF4Y model and identify any areas that may require adjustments or additional support. The HF4Y study has received human participant research ethics approval from the Office of Research Ethics at York University. Recruitment was conducted between February 2018 and March 2020. Data collection is expected to be completed at both sites by March 2024. A preliminary analysis of the quantitative and qualitative data collected between baseline and 24 months is underway. This pilot randomized controlled trial is the first to test the effectiveness of the HF4Y intervention in Canada. The findings of this study will enhance our understanding of how to effectively deliver and scale up the HF4Y intervention, with the aim of continually improving the HF4Y model to promote better outcomes for youth. International Standard Randomized Controlled Trial Number (ISRCTN) ISRCTN10505930; https://www.isrctn.com/ISRCTN10505930. DERR1-10.2196/46690.

From research to daily clinical practice: implementation of orthogeriatric co-management in the trauma ward.

Evidence strongly suggests that orthogeriatric co-management improves patient outcomes in frail older patients with a fracture, but evidence regarding how to implement this model of care in daily clinical practice is scarce. In this paper, we first describe the implementation process and selection of implementation strategies for an orthogeriatric co-management program in the traumatology ward of the University Hospitals Leuven in Belgium. Second, we report the results of a multi-method feasibility study. This study (1) measures the fidelity towards the program's core components, (2) quantifies the perceived feasibility and acceptability by the healthcare professionals, and (3) defines implementation determinants. Implementation strategies were operationalized based on the Expert Recommendations for Implementing Change (ERIC) guidelines. In the feasibility study, fidelity towards the core components of the program was measured in a group of 15 patients aged 75 years and over by using electronic health records. Feasibility and acceptability as perceived by the involved healthcare professionals was measured using a 15-question survey with a 5-point Likert scale. Implementation determinants were mapped thematically based on seven focus group discussions and two semi-structured interviews by focusing on the healthcare professionals' experiences. We observed low fidelity towards completion of a screening questionnaire to map the premorbid situation (13%), but high fidelity towards the other program core components: multidimensional evaluation (100%), development of an individual care plan (100%), and systematic follow-up (80%). Of the 50 survey respondents, 94% accepted the program and 62% perceived it as feasible. Important implementation determinants were feasibility, awareness and familiarity, and improved communication between healthcare professionals that positively influenced program adherence. Fidelity, acceptability, and feasibility of an orthogeriatric co-management program were high as a result of an iterative process of selecting implementation strategies with intensive stakeholder involvement from the beginning. [https://www.isrctn.com/ISRCTN20491828], International Standard Randomised Controlled Trial Number (ISRCTN) Registry: [ISRCTN20491828]. Registered on October 11, 2021.

Left Head Rotation as Alternative to Difficult Tracheal Intubation: Randomized Open Label Clinical Trial.

Tracheal intubation is a life-saving intervention not only for physicians but also for allied health workers. Optimizing the patient's head and neck position for the best glottic view is a crucial step that accelerates tracheal intubation. The left head rotation maneuver has been recently described as an innovative approach to tracheal intubation with marked improvement in glottic visualization and can be an alternative before proceeding to a surgical airway. This study compared the glottic view and intubating conditions in the sniffing position versus left head rotation during direct laryngoscopy. This randomized, open-label clinical trial enrolled fifty-two adult patients admitted to the Baguio General Hospital & Medical Center from September 2020 to January 2021 for an elective surgical procedure requiring tracheal intubation under general anesthesia. Intubation was done using a 45-degree left head rotation in the experimental group (n=26), while the control group (n=26) was intubated using the conventional sniffing position. Glottic visualization and intubation difficulty with left head rotation and sniffing position were assessed using Cormack-Lehane Grade and Intubation Difficulty Scale, respectively. Successful intubation is measured by observing a capnographic waveform in the end-tidal CO2 monitor after placement of the endotracheal tube. There was no significant statistical difference in the clinicodemographic characteristics between the left head rotation and sniffing position groups. There was no statistically significant difference in the Cormack-Lehane Grade, with 85% of patients classified under Grades 1 and 2 in both groups. Also, there were no statistically significant differences in the Intubation Difficulty Scale scores of patients intubated with left head rotation or sniffing position; 30.7% of patients in both groups were easily intubated, while 53.8% in left head rotation and 57.6% in sniffing position groups were intubated with slight difficulty. Similarly, there were no significant differences between the two techniques in any of the seven parameters of the Intubation Difficulty Scale, although numerically fewer patients required the application of additional lifting force [7 (26.9%) vs. 11 (42.3%)] or laryngeal pressure [3 (11.5%) vs. 7 (26.9%)] when intubated with left head rotation. The intubation success rate with left head rotation was 92.3% vs. 100% in the sniffing position, but this difference was not statistically significant. Left head rotation produces comparable laryngeal exposure and intubation ease to the conventional sniffing position. Therefore, left head rotation may be an alternative for patients who cannot be intubated in the sniffing position, especially in hospitals where advanced techniques such as video laryngoscopes and flexible bronchoscopes are unavailable, as is the case in this study. However, since our sample size was small, studies with a larger study population are warranted to establish the generalizability of our findings. In addition, we observed inadequate familiarity among anesthesiologists with the left head rotation technique, and the intubation success rate may improve as practitioners attain greater technical familiarization. This trial was registered in the International Traditional Medicine Clinical Trial Registry (ISRCTN23442026).

Study protocol: biomechanical testing, finite element analysis and prospective, randomized, clinical study of single screw cephalomedullary nailing versus integrated dual interlocking screw fixation for unstable (31A21–3) intertrochanteric fractures in patients > 70 years old

BackgroundHip fractures are an increasingly common consequence of falls in older people that are associated with a high risk of death and reduced function. The vast majority of intertrochanteric fractures require surgical treatment to withstand early mobilization and weight bearing, which prevents complications due to prolonged bed rest and aids in fracture healing.MethodsThis study is compromised by two parts, the experimental study and the clinical part. In the first part, a standard 130° nail will be used with the appropriate lag screw(s) and dynamic distal locking in synthetic osteoporotic femurs and the transmission of forces in the proximal femur, measured by a cortical surface-strain distribution, will be evaluated using digital image correlation. Finite element parametric models of the bone, the nails and their interface will be also developed. Finite element computations of surface strains in implanted femurs, after being validated against biomechanical testing measurements, will be used to assist the comparison of the nails by deriving important data on the developed stress and strain fields, which cannot be measured through biomechanical testing. In the other part, will set up a prospective, randomized, comparative clinical study among the Gamma3 and IT cephalomedullary nailing, in order to investigate if there are any statistical important differences in the main radiological measurements and functional status in closed unstable intertrochanteric fractures (A21-3) in patients aged over 70 years old at the 24-week follow-up evaluation using patient reported disease-specific outcomes.DiscussionThis study will be the first to compare clinical, radiological and biomechanical measurements of the two different cephalomedullary nails. Our main hypothesis is that the IT nail would provide better radiological outcome and probably better clinical results than the Gama3 nail.Clinical trial registration International Standard Randomized Controlled Trial Number (ISRCTN): https://doi.org/10.1186/ISRCTN15588442, registered on 19/4/2022.

Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial

Aims/hypothesisIn sub-Saharan Africa (SSA), 5% of adults are living with type 2 diabetes and this is rising sharply, with a greater increase among people with HIV. Evidence on the efficacy of prevention strategies in this cohort is scarce. We conducted a Phase II double-blind placebo-controlled trial that aimed to determine the impact of metformin on blood glucose levels among people with prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) and HIV in SSA.MethodsAdults (≥18 years old) who were stable in HIV care and found to have prediabetes (IFG and/or IGT) and who were attending hospitals in Dar es Salaam, Tanzania, were randomised to receive sustained-release metformin, 2000 mg daily, or matching placebo between 4 November 2019 and 21 July 2020. Randomisation used permuted blocks. Allocation was concealed in the trial database and made visible only to the Chief Pharmacist after consent was taken. All participants, research and clinical staff remained blinded to the allocation. Participants were provided with information on diet and lifestyle and had access to various health information following the start of the coronavirus disease 2019 (COVID-19) pandemic. Participants were followed up for 12 months. The primary outcome measure was capillary blood glucose measured 2 h following a 75 g glucose load. Analyses were by intention-to-treat.ResultsIn total, 364 participants (182 in each arm) were randomised to the metformin or placebo group. At enrolment, in the metformin and placebo arms, mean fasting glucose was 6.37 mmol/l (95% CI 6.23, 6.50) and 6.26 mmol/l (95% CI 6.15, 6.36), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 8.39 mmol/l (95% CI 8.22, 8.56) and 8.24 mmol/l (95% CI 8.07, 8.41), respectively. At the final assessment at 12 months, 145/182 (79.7%) individuals randomised to metformin compared with 158/182 (86.8%) randomised to placebo indicated that they had taken >95% of their medicines in the previous 28 days (p=0.068). At this visit, in the metformin and placebo arms, mean fasting glucose levels were 6.17 mmol/l (95% CI 6.03, 6.30) and 6.30 mmol/l (95% CI 6.18, 6.42), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 7.88 mmol/l (95% CI 7.65, 8.12) and 7.71 mmol/l (95% CI 7.49, 7.94), respectively. Using a linear mixed model controlling for respective baseline values, the mean difference between the metformin and placebo group (metformin–placebo) was −0.08 mmol/l (95% CI −0.37, 0.20) for fasting glucose and 0.20 mmol/l (95% CI −0.17, 0.58) for glucose levels 2 h post a 75 g glucose load. Weight was significantly lower in the metformin arm than in the placebo arm: using the linear mixed model adjusting for baseline values, the mean difference in weight was −1.47 kg (95% CI −2.58, −0.35). In total, 16/182 (8.8%) individuals had a serious adverse event (Grade 3 or Grade 4 in the Division of Acquired Immunodeficiency Syndrome [DAIDS] adverse event grading table) or died in the metformin arm compared with 18/182 (9.9%) in the placebo arm; these events were either unrelated to or unlikely to be related to the study drugs.Conclusions/interpretationBlood glucose decreased over time in both the metformin and placebo arms during the trial but did not differ significantly between the arms at 12 months of follow up. Metformin therapy was found to be safe for use in individuals with HIV and prediabetes. A larger trial with longer follow up is needed to establish if metformin can be safely used for the prevention of diabetes in people who have HIV.Trial registrationThe trial is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry (www.isrctn.com/), registration number: ISCRTN76157257.FundingThis research was funded by the National Institute for Health Research using UK aid from the UK Government to support global health research.Graphical

Development of an online intervention for the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) trial.

Up to half of people hospitalised with COVID-19 report diverse and persistent symptoms affecting quality of life for months and sometimes years after discharge (long-COVID). We describe the development of an online group exercise and behavioural support intervention for people who continue to experience such physical and/or emotional health problems more than three months after hospital discharge. Intervention development was informed by the Medical Research Council framework for complex interventions. Our multidisciplinary team of academics, clinicians, and people with long-COVID, had collective expertise in the development and testing of complex interventions. We integrated a bio-psycho-social model of care drawing on rehabilitation literature for long-term health conditions and experiences from our pre-pilot study. Multiple stakeholder meetings were held to refine the intervention which was designed to be deliverable within the UK National Health Service. We adhere to TIDieR guidance for transparent and explicit reporting of telehealth interventions. The final REGAIN online exercise and behavioural support intervention consisted of an initial 1:1 consultation with a trained practitioner, followed by eight online group exercise, and six group support, sessions delivered over eight weeks. Participants could also access an online library of on-demand exercise and support videos. The final REGAIN intervention, combining exercise and behavioural support, is fully manualised with clear pathways to delivery and implementation. It is currently being tested in a randomised controlled trial. The intervention, developed with extensive patient and stakeholder engagement, could be incorporated into existing NHS rehabilitation programmes, should it prove to be clinically and cost-effective for people with long-COVID. International Standard Randomised Controlled Trial Number (ISRCTN) 11466448: Rehabilitation exercise and psychological support after COVID-19 infection: REGAIN.

Evaluation of Diabetes Care Performance in Cambodia Through the Cascade-of-Care Framework: Cross-Sectional Study.

Cambodia has seen an increase in the prevalence of type 2 diabetes (T2D) over the last 10 years. Three main care initiatives for T2D are being scaled up in the public health care system across the country: hospital-based care, health center-based care, and community-based care. To date, no empirical study has systematically assessed the performance of these care initiatives across the T2D care continuum in Cambodia. This study aimed to assess the performance of the 3 care initiatives-individually or in coexistence-and determine the factors associated with the failure to diagnose T2D in Cambodia. We used a cascade-of-care framework to assess the T2D care continuum. The cascades were generated using primary data from a cross-sectional population-based survey conducted in 2020 with 5072 individuals aged ≥40 years. The survey was conducted in 5 operational districts (ODs) selected based on the availability of the care initiatives. Multiple logistic regression analysis was used to identify the factors associated with the failure to diagnose T2D. The significance level of P<.05 was used as a cutoff point. Of the 5072 individuals, 560 (11.04%) met the definition of a T2D diagnosis (fasting blood glucose level ≥126 mg/dL and glycated hemoglobin level ≥6.5%). Using the 560 individuals as the fixed denominator, the cascade displayed substantial drops at the testing and control stages. Only 63% (353/560) of the participants had ever tested their blood glucose level in the last 3 years, and only 10.7% (60/560) achieved blood glucose level control with the cutoff point of glycated hemoglobin level <8%. The OD hosting the coexistence of care displayed the worst cascade across all bars, whereas the OD with hospital-based care had the best cascade among the 5 ODs. Being aged 40 to 49 years, male, and in the poorest category of the wealth quintile were factors associated with the undiagnosed status. The unmet needs for T2D care in Cambodia were large, particularly in the testing and control stages, indicating the need to substantially improve early detection and management of T2D in the country. Rapid scale-up of T2D care components at public health facilities to increase the chances of the population with T2D of being tested, diagnosed, retained in care, and treated, as well as of achieving blood glucose level control, is vital in the health system. Specific population groups susceptible to being undiagnosed should be especially targeted for screening through active community outreach activities. Future research should incorporate digital health interventions to evaluate the effectiveness of the T2D care initiatives longitudinally with more diverse population groups from various settings based on routine data vital for integrated care. International Standard Randomized Controlled Trials Number (ISRCTN) ISRCTN41932064; https://www.isrctn.com/ISRCTN41932064. RR2-10.2196/36747.

Feasibility and Preliminary Efficacy of Digital Interventions for Depressive Symptoms in Working Adults: Multiarm Randomized Controlled Trial.

Depressive symptoms are highly prevalent and have broad-ranging negative implications. Digital interventions are increasingly available in the workplace context, but supporting evidence is limited. This study aimed to evaluate the feasibility, acceptability, and preliminary efficacy of 3 digital interventions for depressive symptoms in a sample of UK-based working adults experiencing mild to moderate symptoms. This was a parallel, multiarm, pilot randomized controlled trial. Participants were allocated to 1 of 3 digital interventions or a waitlist control group and had 3 weeks to complete 6 to 8 short self-guided sessions. The 3 interventions are available on the Unmind mental health app for working adults and draw on behavioral activation, cognitive behavioral therapy, and acceptance and commitment therapy. Web-based assessments were conducted at baseline, postintervention (week 3), and at 1-month follow-up (week 7). Participants were recruited via Prolific, a web-based recruitment platform, and the study was conducted entirely on the web. Feasibility and acceptability were assessed using objective engagement data and self-reported feedback. Efficacy outcomes were assessed using validated self-report measures of mental health and functioning and linear mixed models with intention-to-treat principles. In total, 2003 individuals were screened for participation, of which 20.22% (405/2003) were randomized. A total of 92% (373/405) of the participants were retained in the study, 97.4% (295/303) initiated their allocated intervention, and 66.3% (201/303) completed all sessions. Moreover, 80.6% (229/284) of the participants rated the quality of their allocated intervention as excellent or good, and 79.6% (226/284) of the participants were satisfied or very satisfied with their intervention. All active groups showed improvements in well-being, functioning, and depressive and anxiety symptoms compared with the control group, which were maintained at 4 weeks. Hedges g effect sizes for depressive symptoms ranged from -0.53 (95% CI -0.25 to -0.81) to -0.74 (95% CI -0.45 to -1.03). All interventions were feasible and acceptable, and the preliminary efficacy findings indicated that their use may improve depressive symptoms, well-being, and functioning. The predefined criteria for a definitive trial were met. International Standard Randomised Controlled Trial Number (ISRCTN) ISRCTN13067492; https://www.isrctn.com/ISRCTN13067492.

Effectiveness of Virtual Reality on the Caregiving Competence and Empathy of Caregivers for Elderly with Chronic Diseases: A Systematic Review and Meta-Analysis

Aims. To synthesize evidence on the effectiveness of virtual reality-based training of caregivers for the elderly with chronic diseases. Background. With a growing number of elderly suffering from chronic diseases, caregivers who lack the necessary caregiving skills and competence need practical training. Nowadays, virtual reality in training is a promising approach due to technological advancements. Evaluation. We did a comprehensive search in the following six electronic databases (Web of Science, EMBASE, PubMed, SCOPUS, MEDLINE, and CINAHL) from their inception to April 2022 for original studies. We searched clinical trial registries of Clinical Trials.gov, International Standard Randomized Controlled Trial Number (ISRCTN) Registry, and the International Clinical Trials Registry Platform (ICTRP), for clinical trials. Key Issues. 7610 searched records were yielded, of which nine studies (four randomized controlled trials and five nonrandomized controlled trials) met the eligibility criteria and were included with 1090 caregivers. There was a small but significant overall effect of virtual reality-based interventions on caregivers’ caregiving competence (effect size = 0.362, 95% CI 0.181–0.543, p &lt; 0.001 , I2 = 25.636). The subgroup analysis results showed significant improvement in caregiving competence in caregivers trained by the Dementia LiveTM program (effect size = 0.322, 95% CI 0.046–0.597, p = 0.022 ). Regarding empathy, we did not find a statistically significant overall effect. The subgroup analysis results indicated that caregivers showed improvement in empathy after exposure to the Into D’mentia program (effect size = 0.265, 95% CI 0.015–0.515, p = 0.037 ). Conclusions. Findings of our meta-analysis demonstrated that virtual reality could have merits for improving the caregiving competence of caregivers taking care of the elderly with chronic diseases. Implications for Nursing Management. Virtual reality may be a training alternative for caregivers to improve their caregiving competence. However, empowering the embodiment of virtual reality programs remains a technological challenge that needs to be addressed in the future.

Maternal weight latent trajectories and associations with adverse pregnancy outcomes using a smoothing mixture model

Class membership is a critical issue in health data sciences. Different types of statistical models have been widely applied to identify participants within a population with heterogeneous longitudinal trajectories. This study aims to identify latent longitudinal trajectories of maternal weight associated with adverse pregnancy outcomes using smoothing mixture model (SMM). Data were collected from the Khuzestan Vitamin D Deficiency Screening Program in Pregnancy. We applied the data of 877 pregnant women living in Shooshtar city, whose weights during the nine months of pregnancy were available. In the first step, maternal weight was classified and participants were assigned to only one group for which the estimated trajectory is the most similar to the observed one using SMM; then, we examined the associations of identified trajectories with risk of adverse pregnancy endpoints by applying logistic regression. Three latent trajectories for maternal weight during pregnancy were identified and named as low, medium and high weight trajectories. Crude estimated odds ratio (OR) for icterus, preterm delivery, NICU admission and composite neonatal events shows significantly higher risks in trajectory 1 (low weight) compared to trajectory 2 (medium weight) by 69% (OR = 1.69, 95%CI 1.20, 2.39), 82% (OR = 1.82, 95%CI 1.14, 2.87), 77% (OR = 1.77, 95%CI 1.17, 2.43), and 85% (OR = 1.85, 95%CI 1.38, 2.76), respectively. Latent class trajectories of maternal weights can be accurately estimated using SMM. It is a powerful means for researchers to appropriately assign individuals to their class. The U-shaped curve of association between maternal weight gain and risk of maternal complications reveals that the optimum place for pregnant women could be in the middle of the growth curve to minimize the risks. Low maternal weight trajectory compared to high had even a significantly higher hazard for some neonatal adverse events. Therefore, appropriate weight gain is critical for pregnant women.Trial registration International Standard Randomized Controlled Trial Number (ISRCTN): 2014102519660N1; http://www.irct.ir/searchresult.php?keyword=&id=19660&number=1&prt=7805&total=10&m=1 (Archived by WebCite at http://www.webcitation.org/6p3lkqFdV).

A Virtual Reality-Assisted Cognitive Behavioral Therapy for and With Inuit in Québec: Protocol for a Proof-of-Concept Randomized Controlled Trial.

Emotion regulation is an ability related to psychological well-being; when dysregulated, individuals may have psychiatric symptoms and maladapted physiological responses. Virtual reality-assisted cognitive behavioral therapy (VR-CBT) is an effective psychotherapy to target and strengthen emotion regulation; however, it currently lacks cultural sensitivity and can be improved by adapting it to the cultural context of service users. During previous participatory research, we co-designed a culturally adapted cognitive behavioral therapy (CBT) manual and 2 virtual reality (VR) environments to function as a complement to therapy (VR-CBT) for Inuit who would like to access psychotherapy. Emotion regulation skill building will occur in virtual environments that have interactive components such as heart rate biofeedback. We describe a protocol for a proof-of-concept 2-arm randomized controlled trial (RCT) with Inuit (n=40) in Québec. The primary aims of this research are to investigate the feasibility, benefits, and challenges of the culturally adapted VR-CBT intervention versus an established VR self-management that is available commercially. We will also investigate self-rated mental well-being and objective psychophysiological measures. Finally, we will use proof-of-concept data to identify suitable primary outcome measures, conduct power calculations in a larger trial for efficacy, and collect information about preferences for on-site or at-home treatment. Trial participants will be randomly assigned to an active condition or active control condition in a 1:1 ratio. Inuit aged 14 to 60 years will receive a culturally adapted and therapist-guided VR-CBT with biofeedback or a VR relaxation program with nonpersonalized guided components over a 10-week period. We will collect pre- and posttreatment measures of emotion regulation and biweekly assessments over the treatment and at 3-month follow-up. The primary outcome will be measured by the Difficulties in Emotion Regulation Scale (DERS-16) and a novel psychophysiological reactivity paradigm. Secondary measures include psychological symptoms and well-being via rating scales (eg, anxiety or depressive symptoms). As this is the prospective registration of an RCT protocol, we do not yet report any results from the trial. Funding was confirmed in January 2020, and recruitment is expected to start in March 2023 and is set to finish in August 2025. The expected results are to be published in spring 2026. The proposed study responds to the community's desire for accessible and appropriate resources for psychological well-being, as it was developed in active collaboration with the Inuit community in Québec. We will test feasibility and acceptance by comparing a culturally adapted, on-site psychotherapy with a commercial self-management program while incorporating novel technology and measurement in the area of Indigenous health. We also aim to fulfill the needs for RCT evidence of culturally adapted psychotherapies that are lacking in Canada. International Standard Randomized Controlled Trial Number (ISRCTN) 21831510; https://www.isrctn.com/ISRCTN21831510. PRR1-10.2196/40236.

Orthogeriatric co-management for older patients with a major osteoporotic fracture: Protocol of an observational pre-post study.

Osteoporotic fractures are associated with postoperative complications, increased mortality, reduced quality of life, and excessive costs. The care for older patients with a fracture is often complex due to multimorbidity, polypharmacy, and presence of geriatric syndromes requiring a holistic multidisciplinary approach based on a comprehensive geriatric assessment. Nurse-led geriatric co-management has proven to prevent functional decline and complications, and improve quality of life. The aim of this study is to prove that nurse-led orthogeriatric co-management in patients with a major osteoporotic fracture is more effective than inpatient geriatric consultation to prevent in-hospital complications and several secondary outcomes in at least a cost-neutral manner. An observational pre-post study will be performed on the traumatology ward of the University Hospitals Leuven in Belgium including 108 patients aged 75 years and older hospitalized with a major osteoporotic fracture in each cohort. A feasibility study was conducted after the usual care cohort and prior to the intervention cohort to measure fidelity to the intervention components. The intervention includes proactive geriatric care based on automated protocols for the prevention of common geriatric syndromes, a comprehensive geriatric evaluation followed by multidisciplinary interventions, and systematic follow-up. The primary outcome is the proportion of patients having one or more in-hospital complications. Secondary outcomes include functional status, instrumental activities of daily living status, mobility status, nutritional status, in-hospital cognitive decline, quality of life, return to pre-fracture living situation, unplanned hospital readmissions, incidence of new falls, and mortality. A process evaluation and cost-benefit analysis will also be conducted. This study wants to prove the beneficial impact of orthogeriatric co-management in improving patient outcomes and costs in a heterogenous population in daily clinical practice with the ambition of long-term sustainability of the intervention. International Standard Randomised Controlled Trial Number (ISRCTN) Registry: ISRCTN20491828. Registered on October 11, 2021, https://www.isrctn.com/ISRCTN20491828.