Female participation, and sex-specific reporting practices, in polypill randomised controlled trials in the prevention of atherosclerotic cardiovascular disease: a secondary analysis of a systematic review.

BACKGROUND: The polypill is an emerging strategy for the prevention and management of cardiovascular disease. We assessed the participation of females in randomised controlled trials evaluating polypills for prevention of cardiovascular disease and subsequent sex-specific analyses and reporting. METHODS: Cardiovascular polypill trials were identified through a systematic review. Data were extracted on the use of sex-specific eligibility criteria, female participation, and the conduct, findings, and interpretation of sex-specific analyses. RESULTS: Of 26 trials included, 12 (46%) excluded groups of females, mainly if pregnant or lactating or of childbearing potential. Female participation ranged from 10% to 73% across trials. Overall, 42% of included participants were female. Of 18 trials conducted in a mostly primary prevention population, females represented 49% of trial participants. In mixed or exclusively secondary prevention trials (n=8), females represented 26% of trial participants. Females represented 46% of trial participants in trials that excluded groups of females (n=12). In trials without explicit exclusion criteria (n=13), females represented 32% of trial participants. Nine out of 26 trials reported sex-stratified analyses (35% of trials; 70% of all participants). Of these, two found some evidence for possible sex differences, both reporting larger blood pressure effects in females than males. Four trials provided sex considerations in the discussion section of the report. CONCLUSION: The participation of females in cardiovascular polypill trials is substantially higher in primary prevention trials as compared to trials conducted in mixed or exclusively secondary prevention populations. The use of sex-specific eligibility criteria was not linked to lower female participation. Sex-specific reporting is sparsely conducted, although most frequent in larger trials.

Historically, women have been underrepresented in clinical trials, making it difficult to determine if treatments work differently in males and females. Despite efforts to include more females, their participation in cardiovascular research remains lower than expected. This study investigated the participation of females in clinical trials that evaluate the effectiveness of polypills. Polypills, which combine multiple medications into a single pill, are a promising approach for managing cardiovascular diseases. We conducted a systematic review of 26 trials to assess how many females were included, whether there were sex-specific eligibility criteria, and if the trials analysed and reported results separately for males and females. We found that nearly half of the trials (46%) excluded certain groups of females, often due to pregnancy or the potential to become pregnant. The participation of females in these trials varied 10% to 73%, with an overall average of 42%. Females were better represented in trials in individuals with a history of cardiovascular disease (49% participation) than in those treating existing conditions (26% participation). The explicit exclusion of specific female groups did not result in lower overall female participation. Only 35% of the trials reported results separately for males and females, and just two of these found differences between sexes, specifically in blood pressure outcomes. The study concludes that while females are reasonably well-represented in some polypill trials, there is still a lack of consistent sex-specific analysis and reporting, which is crucial for understanding how treatments may affect males and females differently.

The efficacy of interventions to prevent type 2 diabetes among women with recent gestational diabetes mellitus-A living systematic review and meta-analysis.

BACKGROUND: While previously considered a transient condition, with no lasting adverse impact, gestational diabetes mellitus (GDM) is now a well-established risk factor for developing type 2 diabetes mellitus (T2DM). The risk of developing T2DM appears to be particularly high in the first few years after childbirth, providing a compelling case for early intervention. This review provides an up-to-date systematic review and meta-analysis to assess the effectiveness of interventions to reduce incidence of T2DM in women with a recent history of GDM. METHODS: The search was conducted on October 20, 2023 with an annual surveillance planned for the next 5 years to maintain a living systematic review. The inclusion criteria were randomized controlled trials of any type in women within 5 years of GDM-complicated pregnancy that reported outcomes of T2DM diagnosis or measures of dysglycemia with a follow-up of at least 12 months. RESULTS: Seventeen studies met our inclusion criteria and have been included in this review. There were 3 pharmacological and 14 lifestyle interventions. Intervention was not associated with significant reduction in the primary outcome of T2DM (risk ratio, 0.78; 95% confidence interval [CI]: 0.43-1.41; p = 0.41; I2 = 79%) compared with the control group (placebo or usual care). However, meta-analysis of the four studies reporting hazard ratios suggested a reduction in diabetes incidence (hazard ratio, 0.68; 95% CI: 0.48-0.97; p = 0.03; I2 = 31%). CONCLUSION: This review provides equivocal evidence about the efficacy of interventions to reduce the risk of T2DM in women within 5 years of GDM-complicated pregnancy and highlights the need for further studies, including pharmacotherapy.

Mental Health Care Support in Rural India: A Cluster Randomized Clinical Trial.

Importance: More than 150 million people in India need mental health care but few have access to affordable care, especially in rural areas. Objective: To determine whether a multifaceted intervention involving a digital health care model along with a community-based antistigma campaign leads to reduced depression risk and lower mental health-related stigma among adults residing in rural India. Design, Setting, and Participants: This parallel, cluster randomized, usual care-controlled trial was conducted from September 2020 to December 2021 with blinded follow-up assessments at 3, 6, and 12 months at 44 rural primary health centers across 3 districts in Haryana and Andhra Pradesh states in India. Adults aged 18 years and older at high risk of depression or self-harm defined by either a Patient Health Questionnaire-9 item (PHQ-9) score of 10 or greater, a Generalized Anxiety Disorder-7 item (GAD-7) score of 10 or greater, or a score of 2 or greater on the self-harm/suicide risk question on the PHQ-9. A second cohort of adults not at high risk were selected randomly from the remaining screened population. Data were cleaned and analyzed from April 2022 to February 2023. Interventions: The 12-month intervention included a community-based antistigma campaign involving all participants and a digital mental health intervention involving only participants at high risk. Primary health care workers were trained to identify and manage participants at high risk using the Mental Health Gap Action Programme guidelines from the World Health Organization. Main Outcomes and Measures: The 2 coprimary outcomes assessed at 12 months were mean PHQ-9 scores in the high-risk cohort and mean behavior scores in the combined high-risk and non-high-risk cohorts using the Mental Health Knowledge, Attitude, and Behavior scale. Results: Altogether, 9928 participants were recruited (3365 at high risk and 6563 not at high risk; 5638 [57%] female and 4290 [43%] male; mean [SD] age, 43 [16] years) with 9057 (91.2%) followed up at 12 months. Mean PHQ-9 scores at 12 months for the high-risk cohort were lower in the intervention vs control groups (2.77 vs 4.48; mean difference, -1.71; 95% CI, -2.53 to -0.89; P < .001). The remission rate in the high-risk cohort (PHQ-9 and GAD-7 scores <5 and no risk of self-harm) was higher in the intervention vs control group (74.7% vs 50.6%; odds ratio [OR], 2.88; 95% CI, 1.53 to 5.42; P = .001). Across both cohorts, there was no difference in 12-month behavior scores in the intervention vs control group (17.39 vs 17.74; mean difference, -0.35; 95% CI, -1.11 to 0.41; P = .36). Conclusions and Relevance: A multifaceted intervention was effective in reducing depression risk but did not improve intended help-seeking behaviors for mental illness. Trial Registration: Clinical Trial Registry India: CTRI/2018/08/015355.

Protocol for a randomized controlled trial of intensive blood pressure control on cardiovascular risk reduction in patients with atrial fibrillation: Rationale and design of the CRAFT trial.

BACKGROUND: Co-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined. METHODS: The Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1,675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months postrandomization, and every 6 months thereafter during the study. CONCLUSIONS: This clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT04347330).

Integrating depression and acute coronary syndrome care in low resource hospitals in China: the I-CARE randomised clinical trial.

Background: Acute coronary syndrome (ACS) often co-occurs with depression, which adversely affects prognosis and increases medical costs, but effective treatment models are lacking, particularly in low-resource settings. This study aims to determine the effectiveness of an ACS and depression integrative care (IC) model compared to usual care (UC) in improving depression symptoms and other health outcomes among patients discharged for ACS in Chinese rural hospitals. Methods: A multicentre, randomised controlled trial was conducted in sixteen rural county hospitals in China, from October 2014 to March 2017, to recruit consecutively all ACS patients aged 21 years and older after the disease stablised and before discharge. Patients were randomly assigned in a 1:1 ratio to receive either the IC or UC, stratified by hospital and depression severity. Patients allocated to IC received an ACS secondary prevention program and depression care including case screening, group counselling, and individual problem-solving therapy. Patients allocated to UC received usual care. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) from baseline to 6 and 12 months. Main secondary outcomes included major adverse events (MAEs) composed of all-cause death, non-fatal myocardial infarction and stroke, and all-cause re-hospitalisation. Participants were followed up till March 2018. All data were collected in person by trained assessors blinded to treatment group and MAEs were adjudicated centrally. This trial is registered with ClinicalTrials.gov, NCT02195193. Findings: Among 4041 eligible patients (IC: 2051; UC: 1990), the mean age was 61 ± 10 years and 63% were men. The mean PHQ-9 score lowered at both 6 and 12 months in both groups but was not lower in IC compared to UC at 6 months (mean difference (MD): -0.04, 95% confidence interval (CI): -0.20, 0.11) or 12 months (MD: -0.06, 95% CI: -0.21, 0.09). There were no treatment group differences for MAEs or other secondary outcomes except for secondary prevention medications at 12 months (45.2% in IC vs 40.8% in UC; relative risk: 1.21, 95% CI: 1.05-1.40). Pre-specified subgroup analyses showed that IC, compared to UC, may be more effective in lowering PHQ-9 scores in women, older patients, and patients with low social support, but less effective in moderately and severely depressed patients (all p for interaction <0.05). Interpretation: The study found that the cardiology nurse-led ACS- and depression-integrated care, compared to usual care, did not improve depression symptoms in all patients discharged with ACS. Greater benefits in certain subgroups warrants further studies. Funding: R01MH100332 National Institute of Mental Health.

Improving the management of type 2 diabetes in China using a multifaceted digital health intervention in primary health care: the SMARTDiabetes cluster randomised controlled trial.

Background: There is limited evidence, mainly from high-income countries, that digital health interventions improve type 2 diabetes (T2DM) care. Large-scale implementation studies are lacking. Methods: A multifaceted digital health intervention comprising: (1) a self-management application ('app') for patients and lay 'family health promotors' (FHPs); and (2) clinical decision support for primary care doctors was evaluated in an open-label, parallel, cluster randomized controlled trial in 80 communities (serviced by a primary care facility for >1000 residents) in Hebei Province, China. People >40 years with T2DM and a glycated haemoglobin (HbA1c) ≥7% were recruited (∼25/community). After baseline assessment, community clusters were randomly assigned to intervention or control groups (1:1) via a web-based system, stratified by locality (rural/urban). Control arm clusters received usual care without access to the digital health application or family health promoters. The primary outcome was at the participant level defined as the proportion with ≥2 "ABC" risk factor targets achieved (HbA1c < 7.0%, blood pressure < 140/80 mmHg and LDL-cholesterol < 2.6 mmol/L) at 24 months. Findings: A total of 2072 people were recruited from the 80 community clusters (40 urban and 40 rural), with 1872 (90.3%) assessed at 24 months. In the intervention arm, patients used FHPs for support more in rural than urban communities (252 (48.6%) rural vs 92 (21.5%) urban, p < 0.0001). The mean monthly proportion of active app users was 46.4% (SD 7.8%) with no significant difference between urban and rural usage rates. The intervention was associated with improved ABC control rates (339 [35.9%] intervention vs 276 [29.9%] usual care; RR 1.20, 95% CI 1.02-1.40; p = 0.025), with significant heterogeneity by geography (rural 220 [42.6%] vs 158 [31.0%]; urban 119 [27.9%] vs 118 [28.6%]; p = 0.022 for interaction). Risk factor reductions were mainly driven by improved glycaemic control (mean HbA1C difference -0.33%, 95% CI -0.48 to -0.17; p = 0.00025 and mean fasting plasma glucose difference -0.58 mmol, 95% CI -0.89 to -0.27; p = 0.00013). There were no changes in blood pressure and LDL-cholesterol levels. Interpretation: A multifaceted digital health intervention improved T2DM risk factor control rates, particularly in rural communities where there may be stronger relationships between patients and doctors and greater family member support. Funding: National Health and Medical Research CouncilGlobal Alliance for Chronic Diseases (ID 1094712).

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).

Development of a risk prediction model for postpartum onset of type 2 diabetes mellitus, following gestational diabetes; the lifestyle InterVention in gestational diabetes (LIVING) study.

AIMS: This study aimed to develop a prediction model for identifying a woman with gestational diabetes mellitus (GDM) at high risk of type 2 diabetes (T2DM) post-birth. METHODS: Utilising data from 1299 women in the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, two models were developed: one for pregnancy and another for postpartum. Key predictors included glucose test results, medical history, and biometric indicators. RESULTS: Of the initial cohort, 124 women developed T2DM within three years. The study identified seven predictors for the antenatal T2DM risk prediction model and four for the postnatal one. The models demonstrated good to excellent predictive ability, with Area under the ROC Curve (AUC) values of 0.76 (95% CI: 0.72 to 0.80) and 0.85 (95% CI: 0.81 to 0.88) for the antenatal and postnatal models, respectively. Both models underwent rigorous validation, showing minimal optimism in predictive capability. Antenatal model, considering the Youden index optimal cut-off point of 0.096, sensitivity, specificity, and accuracy were measured as 70.97%, 70.81%, and 70.82%, respectively. For the postnatal model, considering the cut-off point 0.086, sensitivity, specificity, and accuracy were measured as 81.40%, 75.60%, and 76.10%, respectively. CONCLUSIONS: These models are effective for predicting T2DM risk in women with GDM, although external validation is recommended before widespread application.

Explaining Suicide Among Indian Women: Applying the Cultural Theory of Suicide to Indian Survivors of Gender-Based Violence Reporting Suicidal Ideation.

Indian women account for 36.6% of suicide-related deaths worldwide and gender-based violence (GBV) is a key social determinant. The cultural theory of suicide (CTS), which synthesizes risk factors and explanations of suicide among racial/ethnic minorities, posits four tenets: idioms of distress, cultural sanctions, and social discord. Our study applied the CTS to Indian women from slums reporting GBV to explore (1) culturally relevant risk pathways towards suicidal ideation using qualitative analyses, and test (2) the association between idioms of distress and suicidal ideation. 112 women from urban slums were recruited and 99 completed surveys. A subset were administered qualitative interviews. Aim 1 explored the CTS framework among participants describing suicidal ideation in qualitative interviews [n = 18]; Aim 2 explored if idioms of distress severity was associated with suicidal ideation through an ANCOVA [N = 99]. Idioms of distress such as 'tension' indicated suicidal ideation. Communities did not sanction suicidal ideation, leading to secrecy regarding disclosure. Women in 'love marriages' (versus arranged marriages) reported minority stress. Social discord heightened suicidal thoughts. Results of the ANCOVA confirmed that women reporting suicidal ideation had higher idioms of distress severity (M = 28.56, SD = 6.37), compared to women who did not (M = 21.77, SD = 6.07), F(1, 96) = 28.58, p < .001 (ηp2 = .23). Our study empirically validates the CTS among Indian GBV survivors. Culturally responsive suicide prevention can include assessing idioms of distress, improving family support, and educating to reduce stigma and enhance help-seeking.

Antenatal oral glucose tolerance test abnormalities in the prediction of future risk of postpartum diabetes in women with gestational diabetes: Results from the LIVING study.

OBJECTIVES: To explore associations between type and number of abnormal glucose values on antenatal oral glucose tolerance test (OGTT) with postpartum diabetes in South Asian women diagnosed with gestational diabetes (GDM) using International Association of the Diabetes and Pregnancy Study Groups criteria. METHODS: This post-hoc evaluation of the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, a randomized controlled trial, was conducted among women with GDM in the index pregnancy, across 19 centers in Bangladesh, India, and Sri Lanka. Postpartum diabetes (outcome) was defined on OGTT, using American Diabetes Association (ADA) criteria. RESULTS: We report data on 1468 women with GDM, aged 30.9 (5.0) years, and with median (interquartile range) follow-up period of 1.8 (1.4-2.4) years after childbirth following the index pregnancy. We found diabetes in 213 (14.5%) women with an incidence of 8.7 (7.6-10.0)/100 women-years. The lowest incidence rate was 3.8/100 women years, in those with an isolated fasting plasma glucose (FPG) abnormality, and highest was 19.0/100 women years in participants with three abnormal values. The adjusted hazard ratios for two and three abnormal values compared to one abnormal value were 1.73 (95% confidence interval [CI], 1.18-2.54; p = .005) and 3.56 (95% CI, 2.46-5.16; p < .001) respectively. The adjusted hazard ratio for the combined (combination of fasting and postglucose load) abnormalities was 2.61 (95% CI, 1.70-4.00; p < .001), compared to isolated abnormal FPG. CONCLUSIONS: Risk of diabetes varied significantly depending upon the type and number of abnormal values on antenatal OGTT. These data may inform future precision medicine approaches such as risk prediction models in identifying women at higher risk and may guide future targeted interventions.

Unpacking the 'black box' of suicide: A latent class analysis predicting profiles of suicidal ideation in a longitudinal cohort of adolescent girls from India.

INTRODUCTION: Indian women account for 37% of global suicide-related deaths. As suicide is a growing concern among adolescent girls, identifying the social determinants of suicide with this group targeted prevention. We selected social determinants that include intersectional identities and broader syndemics; we then used longitudinal data from a prospective cohort of adolescent girls from Northern India to classify them into unique profiles across multiple socioecological levels. METHODS: Girls aged 10-19 (N = 11,864) completed self-report questionnaires measuring socio-demographic and trauma exposure variables. At three-year follow-up, they were asked to indicate current suicidal ideation (SI). We conducted latent class analysis (LCA) to classify profiles and then predicted risk of current SI at three-year follow-up. RESULTS: LCA supported a four-class solution: a 'privileged' class (Class 1; n = 1,470), a 'modal' class (Class 2; n = 7,449), an 'intergenerational violence' class (Class 3; n = 2,113), and a 'psychological distress' class (Class 4; n = 732). Classes significantly predicted odds ratios (OR) for SI at follow up; women in Class 4 were associated with the greatest likelihood of SI (OR 1.84, 95% CI 1.38, 2.47), suggesting that psychological distress factors confer greatest risk. CONCLUSION: Results of the distinct classes of risk and protective factors indicate targets for policy-level interventions. Disrupting cycles of psychological distress and substance use, increasing access to behavioral interventions, and intervening to mitigate intergenerational violence may be particularly impactful with this population.

Implementation of mobile-health technology is associated with five-year survival among individuals in rural areas of Indonesia.

There is an urgent need to focus on implementing cost-effective health interventions and policies to reduce the burden of cardiovascular disease in Indonesia. This study aims to evaluate whether a mobile technology-supported primary health care intervention, compared with usual care, would reduce the risk of all-cause mortality among people in rural Indonesia. Data were collected from 11,098 participants in four intervention villages and 10,981 participants in four control villages in Malang district, Indonesia. The baseline data were collected in 2016. All the participants were followed for five years, and the mortality data were recorded. Cox proportional hazard model was used to examine the association between the intervention and the risk of all-cause mortality, adjusted for the covariates, including age, gender, educational attainment, employment and marital status, obesity and the presence of diabetes mellitus. During the five-year follow-up, 275 participants died in intervention villages, compared with 362 in control villages. Participants residing in intervention villages were at 18% (95%CI = 4 to 30) lower risk of all-cause mortality. Higher education attainment and being married are associated with lower risks of all-cause mortality among respondents who lived in the control villages, but not among those living in the intervention villages. A mobile technology-supported primary health care intervention had the potential to improve the five-year survival among people living in villages in an upper-middle income country.

Improving access to evidence-based interventions for trauma-exposed adults in low- and middle-income countries.

In low- and middle-income countries (LMICs), the mental health consequences of trauma exposure pose a substantial personal, societal, and economic burden. Yet, the significant need for evidence-based mental health treatment remains largely unmet. To unlock the potential for mental health care for trauma survivors in lower-resource contexts, it is critical to map treatment barriers and identify strategies to improve access to evidence-based, culturally appropriate, and scalable interventions. This review, based on an International Society for Traumatic Stress (ISTSS) briefing paper, describes the treatment gap facing adults with traumatic stress in LMICs and identifies the barriers that contribute to this gap. We then highlight strategies for enhancing access to effective treatments for these populations, including task-sharing, the use of culturally adapted and multiproblem interventions, and digital tools to scale access to appropriate care. Finally, we offer recommendations for policymakers, researchers, and service providers to guide an agenda for action to close the treatment gap for trauma survivors in LMICs.

The association between influenza vaccination, cardiovascular mortality and hospitalization: A living systematic review and prospective meta-analysis.

BACKGROUND: The effects of seasonal influenza vaccination on cardiovascular disease (CVD) outcomes, including among individuals with established CVD, are uncertain. METHODS: To evaluate the efficacy and safety of influenza vaccines compared to no vaccines or placebo for preventing all-cause/CVD mortality or all-cause/CVD hospitalization in the general population and in populations with pre-existing CVD, we conducted a living systematic review (LSR) and prospective meta-analysis (PMA). Published randomized controlled trials (RCT) and observational studies between 1994 and 2023 were searched. PRISMA guidelines were followed in the extraction of study details, and risk of bias was assessed using the Cochrane tools. Analyses were stratified by study design and CVD history. Study quality was evaluated using GRADE system. Meta analyses based on random-effects models were performed between July and October 2022. Pooled risk ratios (RRs) for all-cause/CVD mortality and all-cause/CVD hospitalization were main outcomes. RESULTS: Six published RCTs comprising 12,662 participants (mean age, 62 years; 45 % women; 8,797 with pre-existing CVD) and 37 observational studies comprising 6,311,703 participants (mean age, 49 years; 50 % women; 1,189,955 with pre-existing CVD) were included. Only those RCTs judged to be low risk were included in the analyses, and observational studies at anything greater than moderate risk of bias were excluded. In RCTs, influenza vaccine was not significantly associated with lower all-cause mortality (RR, 0.85; 95 %CI, 0.61-1.17), cardiovascular death (RR, 0.80; 95 %CI, 0.60-1.07), or CVD hospitalization (RR, 0.69; 95 %CI, 0.47-1.02). A statistically significant reduction in all-cause hospitalization (RR, 0.86; 95 %CI, 0.76-0.97) was observed. The evidence level was assessed as moderate for all-cause hospitalization, and low for other outcomes. Overall, observational studies suggested a stronger protective association between influenza vaccination and outcomes, except for CVD hospitalization. Based on RCTs, there was no difference in the effects of influenza vaccination on all-cause mortality among the general population compared to those with pre-existing CVD, although the summary point estimate favored benefits only in those with pre-existing CVD. CONCLUSIONS: While observational studies suggest that influenza vaccination may be associated with lower all-cause and CVD mortality and all-cause hospitalization, RCTs reported to date suggest a reduction in the risk of all-cause hospitalization but do not provide clear evidence to support preventive effects on mortality (all-cause or CVD) or CVD hospitalization.

Psychotherapies for Generalized Anxiety Disorder in Adults: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials.

Importance: Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatments for GAD, but which should be considered as first-line treatment needs to be clarified. Objective: To use a network meta-analysis to examine the short- and long-term associations of different psychotherapies with outcomes of effectiveness and acceptability in adults with GAD. Data Sources: MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials were searched from database inception to January 1, 2023, to identify randomized clinical trials (RCTs) of psychotherapies for adults with GAD. Study Selection: RCTs comparing any type of psychotherapy against another or with a control condition for the treatment of adults (≥18 years, both sexes) with a primary diagnosis of GAD were eligible for inclusion. Data Extraction and Synthesis: This study followed Cochrane standards for extracting data and assessing data quality and used the PRISMA guideline for reporting. Risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis was used to rate the certainty of evidence for meta-analytical results. Main Outcomes and Measures: Eight psychotherapies were compared against one another and with 2 control conditions. Primary outcomes were severity of GAD symptoms and acceptability of the psychotherapies. Random-effects model pairwise and network meta-analyses were conducted. For effectiveness, standardized mean differences (SMDs) were pooled, and for acceptability, relative risks with 95% CIs were calculated. Results: Data from 65 RCTs were included. Effect size estimates on data from 5048 participants (mean [SD], 70.9% [11.9%] women; mean [SD] age, 42.2 [12.5] years) suggested that third-wave cognitive behavior therapies (CBTs) (SMD, -0.76 [95% CI, -1.15 to -0.36]; certainty, moderate), CBT (SMD, -0.74 [95% CI, -1.09 to -0.38]; certainty, moderate), and relaxation therapy (SMD, -0.59 [95% CI, -1.07 to -0.11]; certainty, low) were associated with reduced GAD symptoms vs treatment as usual. Relative risks for all-cause discontinuation (indication of acceptability) signaled no differences compared with treatment as usual for all psychotherapies (eg, relative risk, 1.04 [95% CI, 0.64-1.67] for CBT vs treatment as usual). When excluding studies at high risk of bias, relaxation therapy lost its superiority over treatment as usual (SMD, -0.47; 95% CI, -1.18 to 0.23). When considering anxiety severity at 3 to 12 months after completion of the intervention, only CBT remained significantly associated with greater effectiveness than treatment as usual (SMD, -0.60; 95% CI, -0.99 to -0.21). Conclusions and Relevance: Given the evidence in this systematic review and network meta-analysis for its associations with both acute and long-term effectiveness, CBT may represent the first-line therapy of GAD. Third-wave CBTs and relaxation therapy were associated with short-term effectiveness and may also be offered.

The incidence and risk factors of postpartum diabetes in women from Bangladesh, India and Sri Lanka (South Asia) with prior gestational diabetes mellitus: Results from the LIVING study.

AIM: To study, the incidence and risk factors for postpartum diabetes (DM), in women with gestational diabetes mellitus (GDM) from South Asia (Bangladesh, India and Sri Lanka), followed for nearly two years after delivery. METHODS: Women with prior GDM diagnosed using IADPSG criteria were invited at 19 centres across Bangladesh, India and Sri Lanka for an oral glucose tolerance test (OGTT) following childbirth, and were enrolled in a randomized controlled trial. The glycaemic category (outcome) was defined from an OGTT based on American Diabetes Association criteria. RESULTS: Participants (n = 1808) recruited had a mean ± SD age of 31.0 ± 5.0 years. Incident DM was identified, between childbirth and the last follow-up, in 310 (17.1 %) women [incidence 10.75/100 person years], with a median follow-up duration of 1.82 years after childbirth. Higher age, lower education status, higher prior pregnancy count, prior history of GDM, family history of DM, and postpartum overweight/obese status were significantly associated with incident DM. Women in Bangladesh had a higher cumulative incidence of DM [16.49/100 person years] than in Sri Lanka [12.74/100 person years] and India [7.21/100 person years]. CONCLUSIONS: A high incidence of DM was found in women with prior GDM in South Asia, with significant variation between countries. Women from Bangladesh had a significantly higher pregnancy count, family history of DM and overweight/obese status, despite having significantly lower age, which could be responsible for their higher rates of DM. Registration of this study: The study was registered with the Clinical Trials Registry of India (CTRI/2017/06/008744), Sri Lanka Clinical Trials Registry (SLCTR/2017/001), and ClinicalTrials.gov (NCT03305939).

A community-based intervention to improve screening, referral and follow-up of non-communicable diseases and anaemia amongst pregnant and postpartum women in rural India: study protocol for a cluster randomised trial.

BACKGROUND: Medical complications during pregnancy, including anaemia, gestational diabetes mellitus and hypertensive disorders of pregnancy place women are at higher risk of long-term complications. Scalable and low-cost strategies to integrate non-communicable disease screening into pregnancy care are needed. We aim to determine the effectiveness and implementation components of a community-based, digitally enabled approach, "SMARThealth Pregnancy," to improve health during pregnancy and the first year after birth. METHODS: A pragmatic, parallel-group, cluster randomised, type 2 hybrid effectiveness-implementation trial of a community-based, complex intervention in rural India to decrease anaemia (primary outcome, defined as haemoglobin < 12g/dL) and increase testing for haemoglobin, glucose and blood pressure (secondary outcomes) in the first year after birth. Primary Health Centres (PHCs) are the unit of randomisation. PHCs are eligible with (1) > 1 medical officer and > 2 community health workers; and (2) capability to administer intravenous iron sucrose. Thirty PHCs in Telangana and Haryana will be randomised 1:1 using a matched-pair design accounting for cluster size and distance from the regional centre. The intervention comprises (i) an education programme for community health workers and PHC doctors; (ii) the SMARThealth Pregnancy app for health workers to support community-based screening, referral and follow-up of high-risk cases; (iii) a dashboard for PHC doctors to monitor high-risk women in the community; (iv) supply chain monitoring for consumables and medications and (v) stakeholder engagement to co-develop implementation and sustainability pathways. The comparator is usual care with additional health worker education. Secondary outcomes include implementation outcomes assessed by the RE-AIM framework (reach, effectiveness, adoption, implementation, maintenance), clinical endpoints (anaemia, diabetes, hypertension), clinical service delivery indicators (quality of care score), mental health and lactation practice (PHQ9, GAD7, EuroQoL-5D, WHO IYCF questionnaire). DISCUSSION: Engaging women with screening after a high-risk pregnancy is a challenge and has been highlighted as a missed opportunity for the prevention of non-communicable diseases. The SMARThealth Pregnancy trial is powered for the primary outcome and will address gaps in the evidence around how pregnancy can be used as an opportunity to improve women's lifelong health. If successful, this approach could improve the health of women living in resource-limited settings around the world. TRIAL REGISTRATION: ClinicalTrials.gov NCT05752955. Date of registration 3 March 2023.

Transforming blood pressure control in primary care through a novel remote decision support strategy based on wearable blood pressure monitoring: The NEXTGEN-BP randomized trial protocol.

BACKGROUND: Despite high blood pressure being the leading preventable risk factor for death, only 1 in 3 patients achieve target blood pressure control. Key contributors to this problem are clinical inertia and uncertainties in relying on clinic blood pressure measurements to make treatment decisions. METHODS: The NEXTGEN-BP open-label, multicenter, randomized controlled trial will investigate the efficacy, safety, acceptability and cost-effectiveness of a wearable blood pressure monitor-based care strategy for the treatment of hypertension, compared to usual care, in lowering clinic blood pressure over 12 months. NEXTGEN-BP will enroll 600 adults with high blood pressure, treated with 0 to 2 antihypertensive medications. Participants attending primary care practices in Australia will be randomized 1:1 to the intervention of a wearable-based remote care strategy or to usual care. Participants in the intervention arm will undergo continuous blood pressure monitoring using a wrist-wearable cuffless device (Aktiia, Switzerland) and participate in 2 telehealth consultations with their primary care practitioner (general practitioner [GP]) at months 1 and 2. Antihypertensive medication will be up-titrated by the primary care practitioner at the time of telehealth consults should the percentage of daytime blood pressure at target over the past week be <90%, if clinically tolerated. Participants in the usual care arm will have primary care consultations according to usual practice. The primary outcome is the difference between intervention and control in change in clinic systolic blood pressure from baseline to 12 months. Secondary outcomes will be assessed at month 3 and month 12, and include acceptability to patients and practitioners, cost-effectiveness, safety, medication adherence and patient engagement. CONCLUSIONS: NEXTGEN-BP will provide evidence for the effectiveness and safety of a new paradigm of wearable cuffless monitoring in the management of high blood pressure in primary care. TRIAL REGISTRATION: ACTRN12622001583730.