Controlled Intervention Trial Research Articles

Health interventions for migrants and refugees in host Southeast Asian countries: a systematic review

Abstract Background Understanding the different types of health interventions that have been conducted for migrants and refugees is crucial for the improvement and implementation of future health interventions for these populations. This systematic review aimed to identify and to look at the scope and outcomes of health interventions focused on migrants and refugees in the main host counties in Southeast Asia which are Thailand, Singapore, and Malaysia. Methods This study was conducted in line with the PRISMA guidelines and its protocol has been submitted to PROSPERO. The following databases were searched until June 2021: PubMed, Web of Science, Science Direct, Cochrane, and Google Scholar. Studies were excluded if: 1) they were conducted outside Thailand, Singapore, and Malaysia; 2) had only had qualitative results; 3) were non-peer reviewed; 4) not written in English. Results The search yielded 8,266 studies, out of which 33 were included in the review. The majority of the studies (79%) were conducted in Thailand of which most were focused on migrants or refugees from Myanmar (85%). Besides two randomized controlled trials (RCTs) of mental health interventions, most Thai studies were observational (81%) and focused on infectious disease-related interventions (33%) or the evaluation of health-related programs (29%). Six studies were conducted in Malaysia (18%) of which 4 assessed mental health interventions in refugees. Three of these studies were RCTs, whereas 1 was an observational study. Only 1 study was situated in Singapore and was an RCT evaluating treatments for COVID-19 in migrant workers. Even in studies with similar interventions, outcomes were too diverse to conduct a meta-analysis. Conclusions The low number of studies highlights the gap in literature on health interventions for migrants and refugees, especially in Malaysia and Singapore. More rigorous and cohesive intervention-related research needs to be conducted in Southeast Asia. Key messages • More intervention-related research for migrant and refugee populations in the main Southeast Asian host countries is needed. • Interventions for migrant and refugee populations in host countries in Southeast Asia often do not follow the gold standard RCT study design, limiting the knowledge on their effectiveness.

Program of Intensive Support in Emergency Departments for Care Partners of Cognitively Impaired Patients: Protocol for a Multisite Randomized Controlled Trial.

Older adults with cognitive impairment have more emergency department visits and 30-day readmissions and are more likely to die after visiting the emergency department than people without cognitive impairment. Emergency department providers frequently do not identify cognitive impairment. Use of cognitive screening tools, along with better understanding of root causes for emergency department visits, could equip health care teams with the knowledge needed to develop individually tailored care management strategies for post-emergency department care. By identifying and directly addressing patients' and informal caregivers' (or care partners') psychosocial and health care needs, such strategies could reduce the need for repeat acute care. We have used the terms "caregiver" and "care partner" interchangeably. We aimed to describe the protocol for a randomized controlled trial of a new care management intervention, the Program of Intensive Support in Emergency Departments for Care Partners of Cognitively Impaired Patients (POISED) trial, compared with usual care. We described the research design, intervention, outcome measures, data collection techniques, and analysis plans. Emergency department patients who were aged ≥75 years and screened positive for cognitive impairment via either the Mini-Cog or the proxy-reported Short Informant Questionnaire on Cognitive Decline in the Elderly, with a planned discharge to home, were recruited to participate with their identified informal (family or friend) caregiver in the 2-site POISED randomized controlled trial at New York University Langone Health and Indiana University. The intervention group received 6 months of care management from the POISED Care Team of registered nurses and specialty-trained paraprofessionals, who perform root cause analyses, administer standardized assessments, provide advice, recommend appropriate referrals, and, when applicable, implement dementia-specific comorbid condition protocols. The control group received care as recommended at emergency department discharge (usual care) and were given information about resources for further cognitive assessment. The primary outcome is repeat emergency department use; secondary outcomes include caregiver activation for patient health care management, caregiver depression, anxiety, and experience of social support as important predisposing and time-varying enabling and need characteristics. Data were collected from questionnaires and patients' electronic health records. Recruitment was conducted between March 2018 and May 2021. Study findings will be published in peer-reviewed journals and presented to peer audiences, decision makers, stakeholders, and other interested persons. The POISED intervention is a promising approach to tailoring care management based on root causes for emergency department admission of patients with cognitive impairment with the aim of reducing readmissions. This trial will provide insights for caregivers and emergency department and primary care providers on appropriate, personalized, and proactive treatment plans for older adults with cognitive impairment. The findings will be relevant to audiences concerned with quality of life for individuals with cognitive impairment and their caregivers. ClinicalTrials.gov NCT03325608; https://clinicaltrials.gov/ct2/show/NCT03325608. DERR1-10.2196/36607.

Reliability of the evidence to guide decision-making in foot ulcer prevention in diabetes: an overview of systematic reviews

BackgroundReliable evidence on the effectiveness of interventions to prevent diabetes-related foot ulceration is essential to inform clinical practice. Well-conducted systematic reviews that synthesise evidence from all relevant trials offer the most robust evidence for decision-making. We conducted an overview to assess the comprehensiveness and utility of the available secondary evidence as a reliable source of robust estimates of effect with the aim of informing a cost-effective care pathway using an economic model. Here we report the details of the overview. [PROSPERO Database (CRD42016052324)].MethodsMedline (Ovid), Embase (Ovid), Epistomonikos, Cochrane Database of Systematic Reviews (CDSR), Database of s of Reviews of Effectiveness (DARE), and the Health Technology Assessment Journals Library were searched to 17th May 2021, without restrictions, for systematic reviews of randomised controlled trials (RCTs) of preventive interventions in people with diabetes. The primary outcomes of interest were new primary or recurrent foot ulcers. Two reviewers independently extracted data and assessed the risk of bias in the included reviews.FindingsThe overview identified 30 systematic reviews of patient education, footwear and off-loading, complex and other interventions. Many are poorly reported and have fundamental methodological shortcomings associated with increased risk of bias. Most concerns relate to vague inclusion criteria (60%), weak search or selection strategies (70%) and quality appraisal methods (53%) and inexpert conduct and interpretation of quantitative and narrative evidence syntheses (57%). The 30 reviews have collectively assessed 26 largely poor-quality RCTs with substantial overlap.InterpretationThe majority of these systematic reviews of the effectiveness of interventions to prevent diabetic foot ulceration are at high risk of bias and fail to provide reliable evidence for decision-making. Adherence to the core principles of conducting and reporting systematic reviews is needed to improve the reliability of the evidence generated to inform clinical practice.

Effectiveness of letters to patients with or without Cochrane blogshots on 10-year cardiovascular risk change among women in menopausal transition: 6-month three-arm randomized controlled trial

BackgroundHealth information and patient education on lifestyle changes may have a positive effect on the prevention of many chronic conditions, especially cardiovascular diseases (CVDs). We performed a parallel, three-arm randomized controlled trial (RCT) of 6-month educational intervention in a form of letters containing a reminder of the participant’s CVD risk with or without Cochrane blogshots to reduce CVD risk among women aged 45–65 with one or more known CVD risk factors.MethodsThe control group received a letter about their CVD risk at the beginning of the trial. The intervention groups received the initial letter about their CVD risk and remainder letters about their CVD risk every 2 months, with or without Cochrane blogshots: (1) effect of calcium in the prevention of high blood pressure, (2) effect of reducing saturated fat acids in eating habits, and (3) effects of green and black tea in CVD prevention. The primary outcome was CVD risk reduction calculated as the difference between the baseline and 6-month score for a 10-year risk of fatal CVD according to the ACC/AHA guidelines.ResultsAfter both interventions, CVD risk reduction was significantly higher compared to the control group (P < 0.001, Kruskal-Wallis H test). The number of participants who decreased their CV risk was 29% (20/70) in the control group, 69% (48/70) in the group receiving the reminder letters, and 70% (49/70) in the group receiving the reminder letters and blogshots. The number needed to treat to achieve risk reduction was 2.41 (95% CI = 1.77 to 3.78) for letters with a CVD risk reminder and 2.50 (1.81 to 4.03) for letters with a reminder and a blogshot. The group receiving reminder letters with Cochrane blogshots had a significant change in the category of CVD risk, mainly from high to moderate and from moderate to low CVD risk category.ConclusionsA simple and inexpensive intervention method in a form of letters reminding women about their CVD risk with or without providing additional health information in the form of Cochrane blogshots about interventions for important CVD risk factors may be effective in CVD management and could be considered by primary care providers.Trial registrationClinicalTrials.gov, NCT04601558. Retrospectively registered on October 19, 2020

Improving Power and Accuracy in Randomized Controlled Trials of Pain Treatments by Accounting for Concurrent Analgesic Use

The 0 to 10 numeric rating scale of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics, there may be a disparity between “observed” pain intensity (pain intensity with concurrent analgesic use) and pain intensity without concurrent analgesic use (what the numeric rating scale would be had analgesics not been taken). Using a contemporary causal inference framework, we compare analytic methods that can potentially account for concurrent analgesic use, first in statistical simulations, and second in analyses of real (non-simulated) data from an RCT of lumbar epidural steroid injections. The default analytic method was ignoring analgesic use, which is the most common approach in pain RCTs. Compared to ignoring analgesic use and other analytic methods, simulations showed that a quantitative pain and analgesia composite outcome based on adding 1.5 points to pain intensity for those who were taking an analgesic (the QPAC1.5) optimized power and minimized bias. Analyses of real RCT data supported the results of the simulations, showing greater power with analysis of the QPAC1.5 as compared to ignoring analgesic use and most other methods examined. We propose alternative methods that should be considered in the analysis of pain RCTs. PerspectiveThis article presents the conceptual framework behind a new quantitative pain and analgesia composite outcome, the QPAC1.5, and the results of statistical simulations and analyses of trial data supporting improvements in power and bias using the QPAC1.5. Methods of this type should be considered in the analysis of pain RCTs.

Outcomes and outcome measurement instruments reported in randomised controlled trials of anxiety disorder treatments in children and adolescents: a scoping review protocol

IntroductionPaediatric anxiety disorders (AD) are prevalent and persistent mental health conditions worldwide affecting between 10% and 20% of children and adolescents. Despite the high prevalence of paediatric AD, there is...

Perceived influence of alcohol consumption, substance use, and mental health on PrEP adherence and condom use among PrEP-prescribed gay, bisexual, and other men-who-have-sex-with-men: a qualitative investigation

BackgroundGay, bisexual, and other men-who-have-sex-with-men (GBMSM) continue to be disproportionately affected by Human Immunodeficiency Virus (HIV). Although HIV pre-exposure prophylaxis (PrEP) offers an effective means of reducing incident HIV among this population, the HIV-preventive success of oral-based PrEP is contingent upon regimen adherence. Elevated rates of alcohol-, substance use-, and mental health-related issues among GBMSM potentially hinder PrEP-taking efforts, however the evidence for this remains mixed. Accordingly, the present study entailed a comprehensive qualitative investigation to explore PrEP-prescribed GBMSM’s perceptions surrounding the influence of alcohol, substance use, and mental health on PrEP adherence.MethodsPrEP-prescribed GBMSM (age ≥ 18 years; prescribed PrEP for ≥ 3 months) were recruited from two PrEP-delivery clinics in Toronto, Canada for focus groups as part of the formative phase of an alcohol-, substance use-, and mental health-focused randomized controlled intervention trial. Focus group discussions qualitatively explored perceived strengths and barriers associated with adherence to PrEP treatment; with an emphasis on alcohol, substance use, and mental health concerns. Condom use among PrEP-prescribed GBMSM within the context of these concerns was also discussed.ResultsA total of five focus groups involving 35 GBMSM were conducted (4–10/group; mean age = 42.4; white = 71.4%). Although participants themselves generally reported successfully adhering to their PrEP regimens—resulting from a strong, underlying motivation for self-care—they recognized the detrimental impact that alcohol, substance use, and mental health had on adherence among their peers. In this regard, alcohol and substances were perceived as detracting from adherence only when consumption was excessive or temporally linked to PrEP dosing. Pronounced mental health issues (e.g., severe depression) were also seen as hindering adherence, although these effects were nuanced and perceived as person-dependent. Alcohol and substances were linked to condomless sex, regardless of PrEP use, and PrEP was therefore viewed as an HIV-protective ‘safety net.’ConclusionsOverall, findings suggest that PrEP adherence can often be successfully achieved in the presence of alcohol-, substance use-, and mental health-related issues. Augmenting self-care, and addressing pronounced addictions- and mental health-related concerns, may enhance PrEP treatment among GBMSM.

Effect of acupuncture for non-motor symptoms in patients with Parkinson's disease: A systematic review and meta-analysis.

BackgroundAlthough non-motor symptoms of Parkinson’s disease (PD) are serious, effective treatments are still lacking. Acupuncture may have clinical benefits for non-motor symptoms of PD patients, but high-quality evidence supporting this possibility is still limited. Hence, we conducted this meta-analysis to evaluate the effect of acupuncture treatment on non-motor symptoms in patients with PD.MethodsRandomized controlled trials (RCTs) of acupuncture treatment for PD were retrieved from the following electronic databases: Medline (OVID), Embase (OVID), Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, Chonqing VIP (CQVIP), and Wangfang database. Studies evaluating non-motor symptoms of PD were retrieved. Methodological quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions.ResultsA total of 27 RCTs were included, among which 8 outcomes related to non-motor symptoms were evaluated. The results showed that acupuncture combined with medication had benefits for PD-related insomnia relative to medication alone or sham acupuncture [standardized mean difference (SMD) = 0.517; 95% confidence interval (CI) = 0.242–0.793; p = 0.000], and acupuncture treatment had benefits at 8 weeks (SMD = 0.519; 95% CI = 0.181–0.857; p = 0.003). Regarding depression, acupuncture treatment was more effective (SMD = −0.353; 95% CI = −0.669 to −0.037; p = 0.029) within 2 months (SMD = −0.671; 95% CI = −1.332 to −0.011; p = 0.046). Regarding cognition, quality of life, and Unified Parkinson’s Disease Rating Scale (UPDRS) I and II scores, acupuncture treatment was effective [SMD = 0.878, 95% CI = 0.046–1.711, p = 0.039; SMD = −0.690, 95% CI = −1.226 to −0.155, p = 0.011; weighted mean difference (WMD) = −1.536, 95% CI = −2.201 to −0.871, p = 0.000; WMD = −2.071, 95% CI = −3.792 to −0.351, p = 0.018; respectively]. A significant difference was not found in terms of PD-related constipation. Only one study evaluated PD-related fatigue.ConclusionThe results of the analysis suggested that acupuncture treatment could ameliorate the symptoms of depression, quality of life, cognition, total mentation, behavior and mood, and activities of daily living in PD patients. Nevertheless, more prospective, well-designed RCTs with larger sample sizes are required to confirm our findings.

The value of compassionate support to address smoking: A qualitative study with people who experience severe mental illness.

IntroductionPeople experiencing severe mental illness (SMI) smoke at much higher rates than the general population and require additional support. Engagement with existing evidence-based interventions such as quitlines and nicotine replacement therapy (NRT) may be improved by mental health peer worker involvement and tailored support. This paper reports on a qualitative study nested within a peer researcher-facilitated tobacco treatment trial that included brief advice plus, for those in the intervention group, tailored quitline callback counseling and combination NRT. It contextualizes participant life experience and reflection on trial participation and offers insights for future interventions.MethodsQualitative semi-structured interviews were conducted with 29 participants in a randomized controlled trial (intervention group n = 15, control group n = 14) following their 2-month (post-recruitment) follow-up assessments, which marked the end of the “Quitlink” intervention for those in the intervention group. Interviews explored the experience of getting help to address smoking (before and during the trial), perceptions of main trial components including assistance from peer researchers and tailored quitline counseling, the role of NRT, and other support received. A general inductive approach to analysis was applied.ResultsWe identified four main themes: (1) the long and complex journey of quitting smoking in the context of disrupted lives; (2) factors affecting quitting (desire to quit, psychological and social barriers, and facilitators and reasons for quitting); (3) the perceived benefits of a tailored approach for people with mental ill-health including the invitation to quit and practical resources; and (4) the importance of compassionate delivery of support, beginning with the peer researchers and extended by quitline counselors for intervention participants. Subthemes were identified within each of these overarching main themes.DiscussionThe findings underscore the enormity of the challenges that our targeted population face and the considerations needed for providing tobacco treatment to people who experience SMI. The data suggest that a tailored tobacco treatment intervention has the potential to assist people on a journey to quitting, and that compassionate support encapsulating a recovery-oriented approach is highly valued.Clinical trial registrationThe Quitlink trial was registered with ANZCTR (www.anzctr.org.au): ACTRN12619000244101 prior to the accrual of the first participant and updated regularly as per registry guidelines.

Comparative efficacy and acceptability of non-pharmacological interventions in fibromyalgia: Protocol for a network meta-analysis.

IntroductionAlthough several non-pharmacological interventions have been tested in the management of Fibromyalgia (FM), there is little consensus regarding the best options for the treatment of this health condition. The purpose of this network meta-analysis (NMA) is to investigate the comparative efficacy and acceptability of non-pharmacological interventions for FM, in order to assist clinical decision making through a ranking of interventions in relation to the most important clinical outcomes in these patients.Methods and analysisWe will perform a systematic search to identify randomised controlled trials of non-pharmacological interventions endorsed in guidelines and systematic reviews. Information sources searched will include major bibliographic databases without language or date restrictions (MEDLINE, Cochrane Library, EMBASE, AMED, PsycINFO and PEDro). Our primary outcomes will be pain intensity, patient-reported quality of life (QoL), and acceptability of treatment will be our secondary outcome. Risk of bias of the included trials will be assessed using the Cochrane risk of bias tool (RoB2). For each pairwise comparison between the different interventions, we will present mean differences (MDs) for pain intensity and QoL outcomes and Relative Risks (RRs) for acceptability, both with respective 95% confidence intervals (CIs). Initially, standard pairwise meta-analyses will be performed using a DerSimonian-Laird random effects model for all comparisons with at least two trials and then we will perform a frequentist NMA using the methodology of multivariate meta-analysis assuming a common heterogeneity parameter, using the mvmeta command and network suite in STATA. In the NMA, two different types of control group, such as placebo/sham and no intervention/waiting list will be combined as one node called “Control”. The competing interventions will be ranked using the P-score, which is the frequentist analogue of surface under the cumulative ranking curve (SUCRA) for the outcomes of interest at immediate- (intervention duration of up to 2 weeks), short- (over 2 weeks up to 12 weeks) and long-terms (over 12 weeks). The confidence in the results from NMA will be assessed using the Confidence in Network Meta‐analysis (CINeMA) framework.Ethics and disseminationThis work synthesises evidence from previously published studies and does not require ethics review or approval. A manuscript describing the findings will be submitted for publication in a peer-reviewed scientific journal.RegistrationOSF (DOI: 10.17605/OSF.IO/7MS25) and registered in the PROSPERO database (CRD42020216374).

Effectiveness of nutrition and dietary interventions for people with serious mental illness: systematic review and meta-analysis.

To review recent published trials of nutrition and dietary interventions for people with serious mental illness; to assess their effectiveness in improving metabolic syndrome risk factors. Systematic review and meta-analysis of randomised and non-randomised controlled trials of interventions with a nutrition/diet-related component delivered to people with serious mental illness, published 1 January 2010 - 6 September 2021. Primary outcomes were weight, body mass index (BMI), and waist circumference. Secondary outcomes were total serum cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglyceride, and blood glucose levels. MEDLINE, EMBASE, PsycINFO, CINAHL, and CENTRAL databases. In addition, reference lists of relevant publications were examined for further additional studies. Twenty-five studies encompassing 26 intervention arms were included in our analysis. Eight studies were at low or some risk of bias, seventeen were deemed to be at high risk. Eight of seventeen intervention arms found statistically significant intervention effects on weight, ten of 24 on BMI, and seven of seventeen on waist circumference. The pooled effects of nutrition interventions on metabolic syndrome risk factors were statistically non-significant. However, we identified small size effects on weight for interventions delivered by dietitians (five studies; 262 intervention, 258 control participants; standardised mean difference [SMD], -0.28; 95% CI, -0.51 to -0.04) and interventions consisting of individual sessions only (three studies; 141 intervention, 134 control participants; SMD, -0.30; 95% CI, -0.54 to -0.06). We found only limited evidence for nutrition interventions improving metabolic syndrome risk factors in people with serious mental illness. However, they may be more effective when delivered on an individual basis or by dietitians. CRD42021235979 (prospective).

Salivary Areca and tobacco alkaloids for bioverification in the Betel Nut Intervention Trial.

The Betel Nut Intervention Trial (BENIT) is the first known randomized controlled intervention trial designed to help minority Pacific Islanders in Guam and Saipan quit chewing the carcinogenic Areca catechu nut (AN). We report the BENIT's saliva bioverification results against the self-reported chewing status ("quitter" or "chewer") at day 22 follow-up. AN-specific (arecoline, arecaidine, guvacoline, and guvacine) and tobacco-specific (nicotine, cotinine, and hydroxycotinine) alkaloids were analyzed in saliva from 176 BENIT participants by an established and sensitive liquid chromatography mass spectrometry-based assay. The combined four AN alkaloid levels decreased from baseline in quitters (n = 50) and chewers (n = 108) by 32% and 9%, respectively. In quitters, decreases were significant for arecoline (p = 0.044)-the most prominent AN alkaloid, along with arecaidine (p = 0.042) and nicotine (p = 0.011). In chewers, decreases were significant only for hydroxycotinine (p = 0.004). Similar results were obtained when quitters and chewers were stratified by treatment arm. Salivary AN alkaloid levels generally agreed with self-reported chewing status, which suggests the former can be used to verify the latter. Our results can help to objectively evaluate compliance and program effectiveness in AN cessation programs.

Protocol of a cluster randomised controlled trial evaluating the effectiveness of an online parenting intervention for promoting oral health of 2–6 years old Australian children

IntroductionDental decay is a major problem among Australian children. It can be prevented through good self-care and limiting sugar intake, but many parents/caregivers lack the skills and confidence to help...

A pilot randomized controlled trial of smartphone-assisted mindfulness-based intervention with contingency management for smokers with mood disorders.

Adult smokers receiving outpatient psychiatric treatment for mood disorders were randomized to receive a smartphone-assisted mindfulness-based smoking cessation intervention with contingency management (SMI-CM, n = 25) or enhanced standard treatment (EST, n = 24) with noncontingent rewards. Participants in SMI-CM were prompted to practice audio-guided mindfulness five times per day for 38 days (vs. no comparison intervention in EST), and received monetary incentives for carbon monoxide (CO) ≤ 6 ppm. The primary outcome was biochemically verified 7-day point prevalence abstinence rates 2, 4, and 13 weeks after a target quit day. Of the 49 participants, 63.3% were Latinx and 30.6% Black; 75.5% reported household incomes < $25,000. Abstinence rates for SMI-CM were 40.0%, 36.0%, and 16.0% versus 4.2%, 8.3%, and 4.2% in EST at weeks 2, 4, and 13. A generalized estimating equations (GEE) model showed significant overall differences in abstinence rates in SMI-CM versus EST (adjusted odds ratio [AOR] = 8.12, 95% CI = 1.42-46.6, p = .019). Those who received SMI-CM reported significantly greater reduction in smoking-specific experiential avoidance from baseline to 3 days prior to quit date (β = -7.21, 95% CI = -12.1-2.33, p = .006). SMI-CM may increase cessation rates among smokers with mood disorders, potentially through reduced smoking-specific experiential avoidance. SMI-CM is a promising intervention, and warrants investigation in a fully powered randomized controlled trial (RCT). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

SIOG2022-0015 - Managing Anxiety from Cancer (MAC): A pilot randomized controlled trial of a dyadic intervention for older adults with cancer and their caregivers

SIOG2022-0015 - Managing Anxiety from Cancer (MAC): A pilot randomized controlled trial of a dyadic intervention for older adults with cancer and their caregivers

NAVKIDS2 trial: a multi-centre, waitlisted randomised controlled trial of a patient navigator intervention in children with chronic kidney disease — statistical analysis plan and update to the protocol

BackgroundThis update summarises key changes made to the protocol since the publication of the original protocol for the NAVKIDS2 trial of patient navigators for children with chronic kidney disease (CKD) experiencing social disadvantage and provides the statistical analysis plan (SAP) which has not previously been published.Methods/designThe original protocol was published in BMC Nephrology (https://doi.org/10.1186/s12882-019-1325-y) prior to the commencement of trial recruitment. During the course of the trial, some key methodological changes needed to be made including changes to eligibility criteria (addition of patients with CKD stages 1–2, broadening of financial status eligibility criterion, addition of patients living in rural/remote areas, modification of age eligibility to 0–16 years, addition of limits related to the language spoken by family, guidance regarding families with multiple eligible children), changes to sites, reduction of sample size, addition of virtual options for consent and study procedures in response to the COVID-19 pandemic, removal of staggered recruitment across sites, addition of outcomes, and changes to the timing and number of assessments. This update summarises the changes made and their rationale and provides the detailed plan for statistical analysis of the trial. These changes have been finalised prior to the completion of study follow-up and the commencement of data analysis.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001152213. Prospectively registered on 12 July 2018

Effect of Yearly Exercise on Medication Expense and Benefit-Cost Ratio in Individuals with Metabolic Syndrome: A Randomized Clinical Trial.

Lifestyle modification through incorporation of exercise training could improve metabolic syndrome (MetS) clinical components (hypertension, dyslipidemia, hyperglycemia, and visceral abdominal obesity). We aimed to assess if long-term exercise training could restrain the increased pharmacological cost of the clinical management of the MetS. Medicine cost during a 5-yr-long randomized controlled exercise intervention trial was analyzed. After a per-protocol analysis, a group of 64 individuals 53 ± 2 yr old, with overweight (body mass index, 33.4 ± 0.9 kg·m -2 ) and MetS (3.6 ± 0.2 factors) were randomized to a training (4 months·yr -1 for 5 yr; EXERCISE, n = 25) or to a control group (CONTROL, n = 26). Subjects were studied on three occasions during the 5-yr follow-up. Participants continued their routine medication managed by their general practitioner. The main outcome is the 5-yr evolution of medication cost to treat MetS (hyperglycemia, hypertension, and hyperlipidemia). A secondary outcome is the benefit-cost ratio of the exercise intervention. In CONTROL, medicine cost increased 160% from baseline ( P < 0.001), whereas in EXERCISE, it remained unchanged (33%; P = 0.25). After the 5-yr follow-up, medicine use was 60% and medicine cost 74% higher in CONTROL than EXERCISE ( P < 0.05 in both cases). However, MetS z score was similarly reduced over time in both groups ( P = 0.244 for group-time interaction). The number of prescribed medications increased after 5 yr in CONTROL (89%; P < 0.001), whereas it remained stable with yearly training (17%; P = 0.72 in EXERCISE). Ten-year atherosclerotic cardiovascular disease risk estimation increased only in CONTROL (15%; P = 0.05 for group-time interaction). The benefit in medicine savings (€153 per year and patient) triplicated the estimated cost (€50.8 per year and patient) of the exercise intervention. A 5-yr-long supervised exercise training program in middle-age individuals with MetS prevents the need for increasing medicine use. The savings in pharmacological therapy outweighs the estimated costs of implementing the exercise program.

A protocol for a type 1 effectiveness-implementation randomized controlled trial of the WHO digital mental health intervention Step-by-Step to address depression among Chinese young adults in Macao (SAR), China

BackgroundAmong Chinese college students, the burden of depression is considerably high, affecting up to 30 % of the population. Despite this burden, few Chinese students seek mental health treatment. In addition, depression is highly comorbid with other mental health disorders, such as anxiety. Scalable, transdiagnostic, evidence-based interventions are needed for this population. ObjectiveThe study will evaluate the effectiveness of a World Health Organization transdiagnostic digital mental health intervention, Step-by-Step, to reduce depressive and anxiety symptoms and improve well-being compared with enhanced care as usual and its implementation in a Chinese university community. MethodsA type 1 effectiveness-implementation two-arm, parallel, randomized controlled trial will be conducted. The two conditions are 1) the 5-session Step-by-Step program with minimal guidance by trained peer-helpers and 2) psychoeducational information on depression and anxiety and referrals to local community services. A total of 334 Chinese university students will be randomized with a 1:1 ratio to either of the two groups. Depression, anxiety, wellbeing, and client defined problems will be assessed at pre-intervention, post-intervention, and 3-month follow-up. Endline qualitative interviews and focus group discussions will be conducted to explore SbS implementation among service users, university staff, and stakeholders. Data will be analysed based on the intent-to-treat principle. DiscussionStep-by-Step is an innovative approach to address common mental health problems in populations with sufficient digital literacy. It is a promising intervention that can be embedded to scale mental health services within a university setting. It is anticipated that after successful evaluation of the program and its implementation in the type 1 hybrid design RCT study, Step-by-Step can be scaled and maintained as a low-intensity treatment in universities, and potentially extended to other populations within the Chinese community. Trial registrationChiCTR2100050214.

A Systematic Review and Meta-Analysis of the Efficacy of Uterine Artery Embolization in the Treatment of Endometriosis.

Objective To compare the efficacy of uterine artery embolization (UAE) with traditional methods for treating endometriosis. Methods The randomized controlled trials of uterine artery embolization and other medical treatments for endometriosis in PubMed, Embase, Web of Science, Cochrane Library, China Journal Full-Text Database, Wanfang Database, VIP Database, and China Biomedical Literature Database were retrieved by computer. The search time was up to June 2022. The quality of articles was evaluated by Cochrane ROB 2.0, and meta-analysis was performed by Stata15.1 software. Results 7 studies were finally included. Meta-analysis showed that the serum CA125 level after uterine artery embolization was significantly lower than that in the control group (SMD = −0.85, 95%CI (−1.12, −0.59)], and the postoperative visual analogue scale (VAS) of dysmenorrhea was significantly lower than that in the control group (SMD = −1.86, 95%CI (−2.21, −1.50)) There was no significant difference in the effective rate, FSH level, E2 level, and LH level between the two groups. Conclusion UAE can effectively reduce the VAS score of dysmenorrhea and serum CA125 level for treating endometriosis. However, due to the limitation of the quality of included articles, more large sample size and high quality RCTs are needed to provide stronger evidence-based medicine evidence for clinical practice.

Maternal Glycaemic and Insulinemic Status and Newborn DNA Methylation: Findings in Women With Overweight and Obesity.

Maternal dysglycaemia and prepregnancy obesity are associated with adverse offspring outcomes. Epigenetic mechanisms such as DNA methylation (DNAm) could contribute. To examine relationships between maternal glycaemia, insulinemic status, and dietary glycemic indices during pregnancy and an antenatal behavioral-lifestyle intervention with newborn DNAm. We investigated 172 women from a randomized controlled trial of a lifestyle intervention in pregnant women who were overweight or obese. Fasting glucose and insulin concentrations and derived indices of insulin resistance (HOMA-IR), β-cell function (HOMA-%B), and insulin sensitivity were determined at baseline (15) and 28 weeks' gestation. Dietary glycemic load (GL) and index (GI) were calculated from 3-day food diaries. Newborn cord blood DNAm levels of 850K CpG sites were measured using the Illumina Infinium HumanMethylationEPIC array. Associations of each biomarker, dietary index and intervention with DNAm were examined. Early pregnancy HOMA-IR and HOMA-%B were associated with lower DNAm at CpG sites cg03158092 and cg05985988, respectively. Early pregnancy insulin sensitivity was associated with higher DNAm at cg04976151. Higher late pregnancy insulin concentrations and GL scores were positively associated with DNAm at CpGs cg12082129 and cg11955198 and changes in maternal GI with lower DNAm at CpG cg03403995 (Bonferroni corrected P < 5.99 × 10-8). These later associations were located at genes previously implicated in growth or regulation of insulin processes. No effects of the intervention on cord blood DNAm were observed. None of our findings were replicated in previous studies. Among women who were overweight or obese, maternal pregnancy dietary glycemic indices, glucose, and insulin homeostasis were associated with modest changes in their newborn methylome. ISRCTN29316280.