Difference In Mean Change Research Articles

Comparative Efficacy of Antipsychotic Medication for Stereotypic Behavior in Autism Spectrum Disorder: A Systematic Review and Meta-analysis

Background: Stereotypic movements in autism form core symptoms under the rubric of repetitive and restricted patterns of behavior. Aim: The systematic review was aimed to find which antipsychotic has better efficacy in treating stereotypic behavior in autism spectrum disorder. Methods: We searched for journal publications in the English from PubMed and Cochrane databases (CENTRAL), January 1992–June 2024, for randomized controlled trials that compared antipsychotics with a placebo of at least 6 weeks’ trial, with the outcome measure being a change in stereotypy score. Quality assessment of the included studies in the meta-analysis was done using Cochrane risk of bias tool version 2. We followed PRISMA guidelines for systematic review. The mean difference in change of stereotypy symptoms score was calculated between antipsychotic and placebo participants along with 95% confidence interval (CI) using the random-effects model. Results: 146 studies were screened, and 25 studies were deemed eligible to retrieve full-length articles for review. A total of nine studies were included in the systematic review that had used aripiprazole, risperidone, or lurasidone as an antipsychotic. Six studies (n = 726) that had all data on mean difference in stereotypy scores on the Aberrant Behavior Checklist (ABC)-Stereotypy subscale and four studies (n = 554) that reported stereotypy scores using Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS)-Compulsions subscale were included in the meta-analysis. Antipsychotics showed a significant reduction in ABC-Stereotypy scores (−1.84 [−2.84, −0.85; 95% CI], Z = 3.83, P < 0.001) with moderate heterogeneity between the studies (I 2 = 53%). Whereas, antipsychotics did not show significant improvement in compulsions as measured on CY-BOCS (−0.87 [−1.89, 0.16; 95% CI], Z = 1.65, P = 0.10). Conclusion: Stereotypy in autism is difficult to measure, and no uniform measure exists. Trials are limited to short duration and limited to few antipsychotics. Among antipsychotics, risperidone has robust efficacy in reducing stereotypic behaviors.

Treatment of prehypertension among adults with HIV: a randomized clinical trial

Objective: Elevated blood pressure (BP), even at prehypertensive levels, increases cardiovascular disease risk among people with HIV (PWH); yet international guidelines in low-income countries recommend treatment initiation at BP at least 140/90 mmHg. We determined the efficacy, feasibility, and acceptability of treating prehypertension in PWH in Haiti. Design: An unblinded randomized clinical trial (enrolled April 2021–March 2022) with 12-month follow-up. Setting: GHESKIO Centres, Port-au-Prince, Haiti. Participants: Two hundred fifty adults with HIV with prehypertension (SBP 120–138 or DBP 80–89) not on medication, aged 18–65 years, virally suppressed, and without pregnancy, diabetes, or kidney disease. Intervention: Participants were randomized to treatment (amlodipine 5 mg) or control (no amlodipine unless two BP ≥140/90 mmHg). Main outcome measure: Primary outcome was mean change in SBP between intervention versus control groups from enrollment to 12 months. Results: Among 250 adults, median age was 49 years, 40.8% were women. Baseline median BP was 129/78 mmHg intervention versus 128/77 mmHg control. After 12 months, the difference in mean change between study groups for SBP was -5.9 mmHg [95% confidence interval (95% CI) -8.8 to -3.0] and for DBP was -5.5 mmHg (95% CI -7.9 to -3.2). At 12 months, 5.6% intervention and 23.0% control participants developed incident hypertension (hazard ratio 0.18; 95% CI 0.07–0.47). There were no differences in viral load suppression at 12 months or drug-related serious adverse events. Intervention acceptability was high among providers and participants in qualitative interviews. Conclusion: In PWH in a resource-poor setting, prehypertension treatment was feasible, acceptable, and effective in reducing mean SBP and incident hypertension. Registration: Clinicaltrials.gov NCT04692467

Abstract 4136334: Treatment Satisfaction With an “Inclisiran First” Implementation Strategy Versus Usual Care in Patients With Atherosclerotic Cardiovascular Disease

Background: Despite the availability of effective lipid-lowering therapies (LLTs), most patients (pts) with ASCVD do not meet guideline-recommended LDL-C goals. In VICTORION-INITIATE (NCT04929249), an “inclisiran first” (IF) strategy of adding inclisiran immediately on failure to achieve LDL-C <70 mg/dL, despite maximally tolerated statin therapy, in pts with ASCVD led to significantly higher LDL-C goal attainment vs usual care (UC) at Day 330. Objective: To evaluate change from baseline to Day 330 in pt-reported treatment satisfaction with an IF implementation strategy vs UC in pts with ASCVD enrolled in VICTORION-INITIATE. Methods: VICTORION-INITIATE, a Phase 3b, open-label, prospective trial, was conducted at 45 representative clinical sites across 20 US states. Pts randomized 1:1 (stratified by insurance status) received inclisiran 284 mg (300 mg inclisiran sodium) at Days 0, 90, and 270 plus UC or UC alone (lipid management directed by treating physicians). We evaluated change from baseline to Day 330 in pt-reported satisfaction with IF vs UC using the validated 11-question Treatment Satisfaction Questionnaire for Medication (TSQM)-II comprising 4 domains (effectiveness, side effects, convenience, and global satisfaction) scored from 0–100. As a post-hoc analysis of a pre-specified exploratory endpoint, we analyzed the difference in least-squares (LS) mean change in TSQM-II domain scores for IF vs UC using ANCOVA with baseline scores as a covariate. Results: We randomized 450 patients: median age 67 years, 30.9% female, 25.8% with a history of statin intolerance. From baseline to Day 330, difference in LS mean change (95% confidence interval) in TSQM-II scores for IF (n=139) vs UC (n=105) was significant (p<0.001) for effectiveness (10.4 [5.4, 15.5]), convenience (10.5 [5.8, 15.2]), and global satisfaction (12.1 [7.2, 16.9]). Statistical comparison was not applicable for the side effects domain at Day 330 due to the small sample size (IF: n=6, UC: n=7). On Day 330, mean scores for IF exceeded UC for each TSQM-II question (Figure). Conclusions: An IF implementation strategy resulted in significantly greater change from baseline to Day 330 across multiple domains of pt-reported treatment satisfaction vs UC.

Vadadustat Three Times Weekly in Patients With Anemia Due to Dialysis-Dependent CKD

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) may offer an alternative erythropoiesis-stimulating agents (ESA) for the treatment of anemia in the setting of CKD. To investigate the efficacy and safety of conversion from long-acting erythropoiesis-stimulating agent (ESA) methoxy polyethylene glycol-epoetin beta (MPG-EPO) to the oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) vadadustat 3-times-weekly versus maintenance on MPG-EPO. Phase 3b, open-label, noninferiority trial. Multicenter study in United States; 456 patients adults with anemia and dialysis-dependent chronic kidney disease. Participants were randomized 1:1:1 either to vadadustat (starting dose: 600 mg thrice weekly), vadadustat (starting dose: 900 mg thrice weekly), or MPG-EPO, for up to 52 treatment weeks and 4 safety follow-up weeks after the end of treatment or early termination. Primary and secondary efficacy endpoints were the mean change in hemoglobin from baseline during primary (weeks 20-26) and secondary (weeks 46-52) evaluation periods, respectively. Noninferiority was specified as a lower bound of the 95% CI above -0.75 g/dL for the difference in mean change in hemoglobin from baseline. Other efficacy endpoints were the proportion of participants with hemoglobin levels within the target range and the proportions of participants requiring ESA or red blood cell transfusion rescue for anemia during the evaluation periods. Transfusion rates were low and occurred at similar rates across treatment groups (2.7% and 4.0% in the combined vadadustat and MPG-EPO groups, respectively). Primary safety endpoints were any treatment-emergent and serious adverse events (AEs). After combining the vadadustat groups (600 mg and 900 mg thrice weekly, n=304), vadadustat was noninferior to MPG-EPO (n=152) for both primary (least squares mean treatment difference, -0.33; 95% CI, -0.53 to -0.13) and secondary efficacy endpoints (-0.33; -0.56 to -0.09). Mean hemoglobin concentrations were stable for all groups, except for an initial slight decline in the vadadustat 600 mg group, which stabilized by week 12. ESA rescue for anemia was more frequent in the MPG-EPO group (primary evaluation period, 27.7%; secondary evaluation period, 16.2%) than in the combined vadadustat (14.2%; 7.3%) groups. The incidences of any treatment-emergent and serious treatment-emergent AEs were similar across treatment groups. Potential errors in attribution of AEs as drug related. Three-times-weekly vadadustat was noninferior to MPG-EPO on their effect on hemoglobin levels without detectable differences in AEs.

The effects of a dyadic empowerment-based heart failure management (De-HF) programme on self-care and HRQL : a randomized controlled trial

Abstract Background The ever-growing epidemiology of heart failure (HF) and its detrimental impacts on patients’ quality of life and healthcare cost urge for effective interventions to ameliorate the modifiable prognostic factors. As substantial evidence suggests ineffective self-care as an important candidate especially for the post-discharge outcomes, various care approaches are developed to optimize this behavioral outcome. However, even family carers are heavily involved in the self-care process, dyadic approach to improve the health outcomes of both interactive partners are least applied in the HF transitional care model. Purpose To evaluate the effects of a dyadic empowerment-based heart failure management program (De-HF) on dyadic health and hospital service utilization outcomes. Methods This double-blind RCT randomized 88 HF patient-carer dyads to receive the De-HF program or a dialectic education program, after hospital discharge. Based on the Theory of Dyadic Illness Management, the 16-week De-HF Program, comprising i) a dyadic assessment, ii) five online empowerment modules and iii) follow-up telecare, integrated explicit strategies (scenario-based training, teach-back and goal-setting) to actively engage the care dyads in collaborative disease management. Figure 1 is the graphical presentation of the De-HF Program. The primary outcome is health-related quality of life (HRQL) of the care dyads. Secondary outcomes include patients’ self-care as well as shared care and perceived control of the dyad. Results The mean age of the HF patients was 76.8 (9.4). The patients were in moderate disease severity [NYHA II/II: 56/44%; mean LVEF = 42.5%]. Figure 2 shows the consort flow diagram. After adjusting the socio-demographic characteristic, two-way analysis of covariance showed that patients in the De-HF program showed significantly greater improvement in patients’ self-care domains [Mean difference in change of score (95% CI): Self-care maintenance = 7.15 (1.82-12.46),Cohen’s d = 0.26, p=0.009; Self-care management = 10.04(3.29-16.79), Cohen’s d=0.65, p=0.004; symptom perception = 15.59 (8.20-22.98), Cohen’s d=0.928, p<0.001] and Minnesota Living with Heart Failure score [Mean different in the change of score (95% CI) = -11.45 (-18.24 - -4.66). Cohen’s d = -0.742, p=0.001]. The patient-carer dyads also have significantly greater improvement in perceived control (p=0.001) and collaborative disease management in terms of joint decision-making (p=0.001) and sense of reciprocity (p=0.026). Conclusion Dyadic science has evolved in self-care research for HF. This trial provides the first evidence to inform the positive effects of a theory-based dyadic transitional care program in improving the collaborative self-care management in a family context and patient health outcome. Longer-term evaluation on the effects of De-HF program on health service utilization outcomes and cost-effectiveness will be followed.The De-HF Managment ProgramThe Consort Flow Diagram

Quality of life in patients with heart failure and improved ejection fraction: one-year follow-up with ARNI and SGLT2i

Abstract Introduction A baseline Heart Failure (HF) with reduced Ejection fraction (HFrEF) <=40% that improved for >=10 points and a second measured left ventricle ejection fraction (LVEF) >40%, can be considered as HF with improved ejection fraction (HFimpEF). The novel therapy for HFrEF and HFimpEF are sacubitril/valsartan (ARNI- angiotensin receptor/neprilysin inhibitor) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i). Purpose Our study aimed to evaluate ARNI and SGLT2i therapy on the health status of HFrEF patients, as well as the prognostic impact of HFimpEF in terms of quality of life and outcomes (mortality and rehospitalization due to HF) during a one-year follow-up. Methods In this prospective study, we included 376 hospitalized HFrEF patients, in whom ARNI and SGLT2i were initiated into regular therapy. A 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) was performed at discharge and after one year. The primary prognostic endpoints were all-cause mortality and HF rehospitalization. Results Initially, about two-thirds of the study population were men (71%), mean age of 61.0±11.5 years, mean LVEF 27.5±5.2 % and mean KCCQ overall summary (KCCQ-OS) score of 48.5±12.5, while quality of life KCCQ-QoL 37.4±10.2. After one year LVEF was increased by 35.6±7.1 %. The total number of 143 patients (38%) met the criteria for HFimpEF, with the improvement of mean LVEF (45.2±8.6 %., p<0.001). Overall, HFimpEF patients experienced an average 5.3 ± 18.6-point improvement in the KCCQ-OS compared with 2.5 ± 17.4 points for non-HFimpEF group (differences in mean changes of 2.9 [95% CI: 1.4 to 4.7). This is largely due to improvements in the domain of KCCQ-QoL (5.8 ± 29.7 points vs. 2.9 ± 22.2 points, respectively). During one year of follow-up, combined SGLT2i + ARNI therapy was represented statistically significantly more in HFimpEF compared to the non-HFimpEF group (86% vs. 34%, p<0.0005), where 45% took only one medicine and 21% none. The HFimpEF group had a significantly better outcome in terms of all-cause mortality (2.8% vs. 18.9%, p<0.005) and HF rehospitalization (3.5% vs. 40%, p<0.0001). The one-year KCCQ-12 was independently associated with outcomes; the hazard ratio for the integrated endpoints (mortality and HF rehospitalization) was 1.08 (95% CI: 1.05–1.11, p = 0.005). Conclusions In routine clinical practice, initiation of the ARNI and SGLT2i therapy was associated with significant improvements in the health status of HFrEF patients, but also change to HFimpEF. The one-year quality of life in patients with heart failure and improved ejection fraction was superior to baseline and compared to the non-HFimpEF group. HFimpEF was associated with a better outcome. All HF patients should undergo KCCQ-12 because it is an independent predictor of outcome.

Waist circumference as a parameter in school-based interventions to prevent overweight and obesity - a systematic review and meta-analysis

BackgroundPreventing childhood obesity remains an important public health issue worldwide. Since visceral fat in particular is understood as an important risk factor for many chronic diseases, waist circumference is recommended as a measurement parameter for global obesity surveillance. This systematic review and meta-analysis focused on waist circumference as an outcome parameter for studies of school-based interventions to prevent overweight and obesity.MethodsA systematic literature search was conducted at the end of 2019 in nine data bases, including Medline and Embase, in order to identify relevant studies evaluating interventions in schools aimed at preventing obesity. Eligibility criteria admitted randomised and non-randomised controlled trials. After screening titles, abstracts and full texts, the data of the identified studies were systematically extracted. Risk of bias was assessed according to study type with the appropriate Cochrane Risk of Bias Tool. The review gives a qualitative overview over all included studies structured by extracted data. Separate meta-analyses were done for the outcome mean difference in change in waist circumference, measured in cm or reported as z-score value, using an inverse variance random-effects model due to study design.ResultsA total of 2421 publications were screened based on titles, abstracts and full texts. Complemented by results of a former systematic literature search 44 studies were identified for inclusion, comprising a total of 39.837 participants (age range: 6 to 18 years). Nearly half of the studies were conducted in Europe, two-thirds combined diet and exercise-based interventions. Likewise two thirds of the studies were conducted as cluster-randomised trials. Most of the reported effects favoured the experimental groups, indicating the basic effectiveness of school-based measures. Based on reported data, only one third of the studies could be included in the meta-analyses. For the difference in mean change of the outcome parameter waist circumference measured in cm (95% CI), we found a pooled effect estimate of -0.95 (-1.87; -0.46). For the difference in mean change of the outcome parameter waist circumference reported as z-score value (95% CI), the pooled effect estimate was -0.10 (-0.15; -0.05). Both effect estimates were in favour of the experimental group. The overall effect sizes were small with a p-value < 0.05.ConclusionsPooled effect estimates were small but in favour of the experimental groups. The same applies to the majority of the effects reported in the included studies. The included cluster of randomised controlled trials demonstrated an especially sound methodological standard. The possibility of achieving larger effects in studies of preventive interventions and health promotion is limited. Schools can only realise their full potential in preventing overweight and obesity in children and adolescents if they are accompanied by measures in other areas of the obesogenic environment.

Do Personalized Nutrition Interventions Improve Dietary Intake and Risk Factors in Adults With Elevated Cardiovascular Disease Risk Factors? A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Dietary modifications can improve cardiovascular disease (CVD) risk factors. Personalized nutrition (PN) refers to individualized nutrition care based on genetic, phenotypic, medical, behavioral, and/or lifestyle characteristics. PN may be beneficial in improving CVD risk factors, including diet. However, this has not been reviewed previously. The aim was to evaluate the effectiveness of PN interventions on CVD risk factors and diet in adults at elevated CVD risk. Six databases were searched for randomized controlled trials published between 2000 and 2023 that tested the impact of PN interventions on CVD risk factors in people at elevated risk. Risk of bias was assessed using the Academy of Nutrition and Dietetics Quality Criteria checklist. Data synthesis of eligible articles included participant characteristics, intervention details, and change in primary CVD risk factor outcomes, including blood pressure (BP), plasma lipids, and CVD risk score, and secondary risk factors, including anthropometric outcomes and diet quality. Random-effects meta-analyses were conducted to explore weighted mean differences (WMDs) in change or final mean values for studies with comparable data (studies with dietary counseling interventions) for outcomes including BP, blood lipids, and anthropometric measurements. Of 7676 identified articles, 16 articles representing 15 studies met the inclusion criteria. Studies included between 40 and 563 participants and reported outcomes for CVD risk factors, including hyperlipidemia (n = 5), elevated BP (n = 3), overweight/obesity (n = 1), and multiple risk factors (n = 6). Risk of bias was low. Results suggested potential benefit of PN on systolic BP (WMD: -1.91; 95% CI: -3.51, -0.31 mmHg) and diastolic BP (WMD: -1.49; 95% CI: -2.39, -0.58 mmHg) and dietary intake in individuals at high CVD risk. Results were inconsistent for plasma lipid and anthropometric outcomes. Results were promising for PN interventions that used dietary counseling on CVD risk factors in at-risk individuals. However, further evidence for other personalization methods is required, including improving methodological quality and longer study duration in future PN interventions. OpenScience Framework (https://doi.org/10.17605/OSF.IO/SHVWP).

Home blood pressure-lowering effect of esaxerenone versus trichlormethiazide for uncontrolled hypertension: a predefined subanalysis of the EXCITE-HT randomized controlled trial by basal calcium channel blocker versus angiotensin receptor blocker.

This prespecified subanalysis of the multicenter, randomized, open-label, parallel-group EXCITE-HT study aimed to examine the non-inferiority of esaxerenone to trichlormethiazide as a second-line antihypertensive agent according to the basal antihypertensive agent used (angiotensin receptor blocker [ARB] or calcium channel blocker [CCB]). The primary endpoint, change in morning home systolic/diastolic blood pressure (SBP/DBP) from baseline to end of treatment was similar between the two groups (intergroup difference in least squares mean change [95% confidence interval]: -1.3 [-3.8, 1.3]/-0.2 [-1.6, 1.3] mmHg for ARB; -2.7 [-4.2, -1.2]/-0.8 [-1.7, 0.1] mmHg for CCB). The respective incidences of serum potassium levels <3.5 mEq/L and ≥5.5 mEq/L in the ARB subgroup were 3.4% and 4.2% for esaxerenone and 7.9% and 0% for trichlormethiazide; in the CCB subgroup, they were 2.8% and 0.6% for esaxerenone and 13.9% and 1.2% for trichlormethiazide, respectively. The incidence of uric acid level ≥7.0 mg/dL was numerically higher in the trichlormethiazide group than the esaxerenone group in both the ARB and CCB subgroups. The non-inferiority of esaxerenone to trichlormethiazide in lowering morning home BP was demonstrated regardless of whether the basal antihypertensive agent was an ARB or CCB. Esaxerenone with a CCB showed superiority to trichlormethiazide in lowering SBP, without any new safety concerns. Serum potassium levels tended to be higher when esaxerenone was combined with an ARB than with a CCB, but this can be mitigated if administered according to the package insert. A subgroup analysis of the EXCITE-HT study according to basal antihypertensive agent demonstrated the non-inferiority of esaxerenone to trichlormethiazide in lowering morning home BP regardless irrespective of the basal antihypertensive agent. Esaxerenone with a CCB showed superiority to trichlormethiazide in lowering SBP, without any new safety concerns.

Functional outcome and histologic analysis of late onset total type brachial plexus injury treated with intercostal nerve transfer to median nerve with local umbilical cord-derived mesenchymal stem cells or secretome injection: a double-blinded, randomized control study.

Intercostal nerve transfer is a surgical technique used to restore function in patients with total brachial plexus injury. Stem cell and secretome therapy has been explored as a potential treatment for brachial plexus injuries. This study aimed to compare the functional and histologic outcome of intercostal nerve transfer to median nerve with local stem cells or secretome injection in total type brachial plexus injuries. This was a double-blinded, randomized controlled study (RCT). We included patients with neglected total type brachial plexus injury (BPI) who underwent nerve transfer and local injection of either umbilical cord-derivedmesenchymal stem cells (UC-MSC) or secretome into median nerve-flexor digitorum superficialis (FDS) neuromuscular junction (NMJ). We measured preoperative and 8-month postoperative FDS muscle strength, SF-36, DASH score, and histologic assessment. We then analyzed the difference outcome between those two groups. A total of 15 patients were included in this study. Our study found that after nerve transfer and implantation with either UC-MSC or secretome, significant postoperative improvements were observed in physical functioning, role limitations, energy/fatigue, emotional well-being, social functioning, pain, general health, and DASH scores, particularly in the overall cohort and the secretome group. When we compared the mean difference of clinical outcome from preoperative to postoperative between UC-MSC and secretome groups, the UC-MSC group showed better improvement of health change in SF-36 subgroup compared to secretome group. From the analysis, there was no significant difference in the histologic outcomes (inflammation, regeneration, and fibrosis) in overall cohort between preoperative and postoperative cohort. There was also no significant difference in mean change of the histologic outcomes (inflammation, regeneration, and fibrosis) preoperative and postoperatively between UC-MSC and secretome groups. Implantation of either UC-MSC or secretome along with nerve transfer may provide clinical improvement, while to achieve histologic improvement, further conditioning should be performed.

Impact of primary care and public health integration of chronic conditions in China: a protocol for a prospective multicentre cohort study

IntroductionThe prevalence of chronic conditions is increasing. Given that the majority of chronic patients are managed by primary healthcare providers, there is a need to integrate primary care with public...

Model of integrated mental health video consultations for people with depression or anxiety in primary care (PROVIDE-C): assessor masked, multicentre, randomised controlled trial

ObjectiveTo evaluate whether an integrated mental health video consultation approach (PROVIDE model) can improve symptoms compared with usual care in adults with depression and anxiety disorders attending primary care.DesignAssessor masked,...

Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema

Biosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME). To compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME. This was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021. Formulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52. The primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of -3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs). A total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, -1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was -112 (7) μm vs -124 (7) μm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 μm; 90% CI, -3 to 26 μm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms. MYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept. ClinicalTrials.gov Identifier: NCT03610646.

Avoiding Treatment in Hospital With Subcutaneous Furosemide for Worsening Heart Failure: A Pilot Study (AT HOME-HF)

BackgroundTherapies are needed to address worsening congestion, without hospitalization, in patients with chronic heart failure (HF). ObjectivesThis pilot study assessed outcomes of a novel subcutaneous (SC) furosemide formulation compared to usual care in outpatients with worsening congestion. MethodsParticipants with chronic HF and worsening congestion were randomized open-label 2:1 to SC furosemide compared to usual care (UC). Decongestion was estimated by tracking body weight. The primary endpoint was a win ratio of a 30-day hierarchical composite of cardiovascular death, HF events, and change in N-terminal pro–B-type natriuretic peptide. Secondary endpoints included dyspnea severity, functional capacity, and quality of life. ResultsThirty-four participants were randomized to SC furosemide and 17 to UC. SC furosemide caused greater reduction in body weight: between-group difference in least square mean change was −2.02 kg at day 3 (95% CI: −3.9 to −0.14; P = 0.035). SC furosemide-to-UC win ratio was 1.11 (95% CI: 0.48-2.50; P = 0.806). Significant between-group least square mean differences favoring SC furosemide occurred in 7-point dyspnea score (P = 0.017) and 6-minute walk test (P = 0.032), with trend in Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 Overall Summary Score of 9.15 (95% CI: 1.95-20.3; P = 0.106). The most common related adverse event with SC furosemide was mild infusion site pain (11.8%). ConclusionsSC furosemide augmented weight loss in patients with HF and worsening congestion. The composite primary endpoint was not statistically significant in this pilot investigation. However, findings of improved dyspnea scores and functional capacity, with favorable trend in KCCQ-12 score, warrant additional investigation to further document the clinical value of SC furosemide as an alternative to hospitalization (AT HOME-HF [Avoiding Treatment in the Hospital With Furoscix for the Management of Congestion in Heart Failure—A Pilot Study]; NCT04593823)

Culturally Adapted Lifestyle Intervention for South Asian Adults With Cardiovascular Risk Factors

South Asian adults in the US experience excess cardiovascular disease (CVD) compared with other racial and ethnic groups. The effectiveness and reach of guideline-recommended lifestyle interventions have not been evaluated in this population. To evaluate whether a culturally adapted, group lifestyle intervention will improve CVD risk factors more effectively than written health education materials among US South Asian adults. This single-blind randomized clinical trial was conducted from March 6, 2018, to February 11, 2023 at community sites in the Chicago, Illinois, metropolitan area. South Asian adults aged 18 to 65 years who were overweight or obese, had no history of CVD events, and had at least 1 additional CVD risk factor (hypertension, dyslipidemia, prediabetes, or diabetes) were eligible for inclusion. A 16-week, culturally adapted, group-based lifestyle intervention led by community health coaches. Lifestyle modification counseling was delivered in English, Gujarati, Hindi, and Urdu. Participants tracked their diet and physical activity (PA) and received 4 optional group maintenance sessions between months 5 and 11 of follow-up. The intervention was delivered in person prior to the onset of the COVID-19 pandemic and via videoconference starting in March 2020. The control group received written health education materials, delivered monthly. Primary outcomes were the between-group differences in CVD risk factor changes from baseline to 12 months, including weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), and total cholesterol, estimated using multivariate mixed-effects regression models. Secondary outcomes were self-reported diet quality, PA, and self-efficacy, estimated using univariate mixed-effects regression models. Among 549 randomized participants, 318 (57.9%) were women, and mean (SD) participant age was 49.2 (9.5) years. Mean differences in CVD risk factor changes from baseline to 12 months in the intervention vs control group were calculated for weight (mean difference, -0.07 kg; 95% CI, -0.55 to 0.42), SBP (mean difference, 0.47 mm Hg; 95% CI, -1.85 to 2.79), DBP (mean difference, 0.44 mm Hg; 95% CI, -1.06 to 1.95), cholesterol (mean difference, -2.47 mg/dL; 95% CI, -8.51 to 3.57), and HbA1c (mean difference, -0.07%; 95% CI -0.20% to 0.07%). Intervention participation was associated with greater improvements in dietary quality, PA, and self-efficacy than control. In the SAHELI randomized clinical trial, a culturally adapted, group lifestyle intervention was not more effective than written health education materials for CVD risk factor reduction among US South Asian adults, but the intervention was associated with small improvements in self-reported health behaviors. Effective CVD prevention interventions for this elevated-risk population require further investigation. ClinicalTrials.gov Identifier: NCT03336255.

Efficacy and safety of dapagliflozin add-on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled study.

To evaluate the efficacy and safety of dapagliflozin versus placebo as an add-on in patients with type 2 diabetes who did not achieve adequate glycaemic control with evogliptin and metformin combination. In this multicentre, randomized, double-blind, placebo-controlled Phase 3 trial, patients with glycated haemoglobin (HbA1c) levels ≥7.0% (≥53 mmol/mol) and ≤10.5% (≤91 mmol/mol) who had received stable-dose metformin (≥1000 mg) and evogliptin (5 mg) for at least 8 weeks were randomized to receive dapagliflozin 10 mg or placebo once daily for 24 weeks. Participants continued treatment with metformin and evogliptin. The primary endpoint was change in HbA1c level after 24 weeks of treatment from baseline level. In total, 198 patients were randomized, and 195 patients were included in the efficacy analyses (dapagliflozin: 96, placebo: 99). At Week 24, dapagliflozin significantly reduced HbA1c levels. The least squares mean difference in HbA1c level change from baseline after 24 weeks of treatment was -0.70% (-7.7 mmol/mol)(p < 0.0001). The proportion of participants achieving HbA1c <7.0% (≥53 mmol/mol)was higher in the dapagliflozin group than in the placebo group. Compared to placebo, dapagliflozin significantly reduced fasting plasma glucose, mean daily glucose, 2-h postprandial plasma glucose, fasting insulin, uric acid and gamma-glutamyl transferase levels, homeostatic model assessment for insulin resistance index, body weight, hepatic steatosis index, and albuminuria. Adiponectin level significantly increased from baseline level after 24 weeks of dapagliflozin treatment. Adverse event rates were similar in the two groups. Dapagliflozin add-on to evogliptin plus metformin improved glycaemic control and was well tolerated by the target patients.

Health-related quality of life with rivaroxaban plus aspirin vs. aspirin alone in chronic stable cardiovascular disease: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial.

This study aimed to compare the effects of the combination of rivaroxaban and aspirin with aspirin alone on health-related quality of life in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial. Health-related quality of life assessed using the EQ-5D-3L. The treatment effects on health utility and EQ visual analogue scale (EQ VAS) scores were compared between rivaroxaban plus aspirin and aspirin alone in terms of adjusted mean difference in change from baseline and odds ratio of having deterioration events. Nine thousand forty-nine (98.9%) and 6916 (75.5%) completed the EQ-5D-3L at baseline and at final visit, respectively. Nine thousand twenty-eight (98.9%) and 6887 (76.3%) completed the EQ-5D-3L at baseline and final visit, respectively. Mean (standard deviation) health utility and EQ VAS scores at baseline were 0.871 (0.141) and 76.0 (15.3), respectively, for the rivaroxaban plus aspirin group, compared with 0.873 (0.139) and 75.8 (15.1) for the aspirin group. Adjusted mean difference in change from baseline utility was -0.002 [95% confidence interval (CI), -0.006, 0.002, P = 0.30] between the combination therapy group and the aspirin group. The odds ratio (95% CI) of experiencing deterioration in health utility was 1.01 (95% CI, 0.93, 1.10, P = 0.81) between the two groups. Adjusted mean difference in change from baseline EQ VAS was 0.02 (95% CI, -0.43, 0.47, P = 0.93) between the two groups. This analysis of the COMPASS trial demonstrated that the quality of life of patients was similar between the rivaroxaban plus aspirin group and the aspirin alone group. Trial registration number: ClinicalTrials.gov number (NCT01776424). Trial protocol and statistical analysis plan: https://www.nejm.org/doi/full/10.1056/NEJMoa1709118#APPNEJMoa1709118PRO.

Capivasertib and fulvestrant for patients with hormone receptor-positive, HER2-negative advanced breast cancer (CAPItello-291): patient-reported outcomes from a phase 3, randomised, double-blind, placebo-controlled trial

CAPItello-291 is an ongoing phase 3 trial in which capivasertib-fulvestrant significantly improved progression-free survival versus placebo-fulvestrant in patients with hormone receptor-positive, HER2-negative advanced breast cancer who had relapse or disease progression during or after aromatase inhibitor treatment, in both the overall population and in patients with PIK3CA, AKT1, or PTEN-altered tumours. This study further explored patient-reported health-related quality of life (HRQOL), functioning, symptoms, and symptom tolerability in CAPItello-291. This phase 3, randomised, double-blind, placebo-controlled trial, which was conducted across 193 hospitals and cancer centres in 19 countries, enrolled women with any menopausal status or men, aged ≥18 years (≥20 years in Japan), with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer who had relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase (CDK) 4 or 6 inhibitor therapy. Patients had an Eastern Cooperative Oncology Group/WHO performance score of 0 or 1 and could have received up to two previous lines of endocrine therapy and up to one previous line of chemotherapy for advanced disease. Patients were randomly assigned (1:1) using block randomisation (stratified according to the presence or absence of liver metastases, previous use of a CDK4/6 inhibitor [yes vs no], and geographical region) to receive oral capivasertib 400 mg (twice daily for 4 days, followed by 3 days off) plus intramuscular fulvestrant 500 mg (every 14 days for the first three injections, then every 28 days) or placebo with matching fulvestrant dosing. The dual primary endpoint of the trial was investigator-assessed progression-free survival assessed both in the overall population and among patients with PIK3CA, AKT1, or PTEN-altered tumours. The EORTC Quality of Life Questionnaire 30-item core module (QLQ-C30) and breast module (QLQ-BR23), Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and Patient Global Impression of Treatment Tolerability (PGI-TT) questionnaires were used to assess patient-reported outcomes. Evaluation of EORTC QLQ-C30 and EORTC QLQ-BR23 were secondary endpoints and evaluation of PRO-CTCAE and PGI-TT were pre-defined exploratory endpoints, and these endpoints are the subject of analysis in this Article. Data were collected at baseline and prespecified timepoints. Patient-reported outcomes were analysed in all randomly assigned patients with an evaluable baseline assessment and at least one evaluable post-baseline assessment. Change from baseline was assessed using mixed model with repeated measures for EORTC QLQ-C30 and summarised for QLQ-BR23. Time to deterioration was described using the Kaplan-Meier method. PGI-TT and PRO-CTCAE responses were summarised at each treatment cycle. Patient-reported outcomes were not prospectively powered for statistical comparison. The trial is registered with ClinicalTrials.gov, NCT04305496. Between June 2, 2020, and Oct 13, 2021, 901 patients were enrolled, of whom 708 patients were randomly assigned to receive capivasertib-fulvestrant (n=355) or placebo-fulvestrant (n=353). The median age of the patients was 59 years (IQR 51-67) in the capivasertib-fulvestrant group and 58 years (IQR 49-66) in the placebo-fulvestrant group. At data cutoff (Aug 15, 2022), the median duration of follow-up for progression-free survival in censored patients was 13·0 months (IQR 9·1-16·7) for capivasertib-fulvestrant and 12·7 months (IQR 2·0-16·4) for placebo-fulvestrant in the overall population. EORTC QLQ-C30 global health status/quality of life (GHS/QOL) scores were maintained from baseline and were similar between treatment groups throughout the study period (difference in mean change from baseline of -2·5 [95% CI -4·5 to -0·6] with capivasertib-fulvestrant vs -5·6 [-7·9 to -3·4] with placebo-fulvestrant; treatment difference 3·1 [95% CI 0·2 to 6·0]). Median time to deterioration in EORTC QLQ-C30 GHS/QOL was 24·9 months (95% CI 13·8 to not reached) in the capivasertib-fulvestrant group and 12·0 months (10·2 to 15·7) in the placebo-fulvestrant group (hazard ratio [HR] 0·70, 95% CI 0·53 to 0·92). Time to deterioration HRs for all EORTC QLQ-C30 and QLQ-BR23 subscale scores showed little difference between the treatment groups, except for diarrhoea, which was worse in the capivasertib-fulvestrant group than in the placebo-fulvestrant group (HR 2·75, 95% CI 2·01-3·81). In PRO-CTCAE symptom assessment, the proportion of patients reporting loose and watery stools "frequently" or "almost constantly" was 29% higher at cycle 1, day 15 in the capivasertib-fulvestrant group than in the placebo-fulvestrant group, decreasing at subsequent cycles. Other PRO-CTCAE-reported symptoms (rash, mouth or throat sores, itchy skin, and numbness or tingling in hands or feet) were absent or mild in most patients in both groups throughout treatment. According to the PGI-TT, most patients in both groups reported "not at all" or "a little bit" of bother from treatment side-effects. Patient-reported outcomes from CAPItello-291 demonstrated that capivasertib-fulvestrant delayed time to deterioration of GHS/QOL and maintained other dimensions of HRQOL (except symptoms of diarrhoea) similarly to fulvestrant. With the clinical efficacy and manageable safety profile, these exploratory results further support the positive benefit-risk profile of capivasertib-fulvestrant in this population. AstraZeneca.

Locally Prepared Therapeutic Food for Treatment of Severely Underweight Children in Rural India: An Interventional Prospective Controlled Community-Based Study with Long Follow-Up:-'SAMMAN' Trial.

Severely underweight (SUW) children contribute significantly to under-five mortality and morbidity. There are WHO guidelines for the management of severe acute malnutrition but no specific guidelines for SUW management. The objectives were to achieve a recovery rate of 30% at 90 days of treatment for severe underweight (SUW) children aged 6-60 months, compare changes in weight-for-age Z (WAZ) scores, growth patterns, and case fatality rates between intervention and reference arms (RA), and reduce the prevalence of SUW in the intervention arm (IA). The target of a 30% recovery rate was achievable and significant based on our past research conducted in similar settings. Design: A prospective controlled community-based, longitudinal, two arms (IA, RA), intervention study with long follow-up was conducted between January 2011 and October 2023. Primary care for participants from 14 villages in rural Melghat, India. The study participants included SUW children aged 6-60 months and age-matched (±2 weeks) normal controls. The SAMMAN (Acronym for SAM-Management) intervention was comprised of local therapeutic food-micronutrient (LTF-MN) therapy for 90 days, intensive behavior change communication, infection treatment, and quarterly anthropometric records. SUW recovery, growth patterns, case fatality rate, prevalence at 90 days of therapy and at 60 months of age, and survival until early adolescence were assessed. ANCOVA analysis was used to obtain changes in Z-scores. In the IA, the recovery rate was 36.8% at 90 days and 78.2% at 60 months of age. The mean difference in change in WAZ scores between the intervention arm and the reference arm was statistically significant (p < 0.0001). Growth patterns were similar between the two arms up to early adolescence. The SUW case fatality rate was significantly lower in the IA (0.9%) as compared to 4.62% in the RA at 60 months (p = 0.022). The reduction in SUW prevalence in intervention villages was higher than in the control villages (p < 0.001). The cost of management per SUW child was 3888 INR (47 USD) less than RUTF. The SAMMAN intervention is safe and cost-effective for significantly improving WAZ scores, sustainable, and hence replicable in resource-limited areas.

Efficacy and Safety of Valbenazine in Elderly and Nonelderly Japanese Patients With Tardive Dyskinesia: A Post Hoc Analysis of the J-KINECT Study.

The efficacy and safety of valbenazine, a selective vesicular monoamine transporter 2 inhibitor, has been confirmed for treatment of tardive dyskinesia (TD) in patients aged ≥65 years in non-Asian clinical trials; however, data are lacking in elderly Asian patients. This post hoc analysis of J-KINECT aimed to evaluate the efficacy and safety of valbenazine in elderly Japanese patients with TD. J-KINECT was a randomized, double-blind, placebo-controlled study with a 6-week double-blind, placebo-controlled period; 42-week double-blind, valbenazine extension period; and 4-week posttreatment observation period. Outcomes were summarized by age (≥65 years [elderly] and <65 [nonelderly]) and treatment group. The safety analysis set included 100 and 153 patients aged ≥65 and <65 years, respectively (intention-to-treat set: 98 and 151 patients, respectively). In the elderly group, the difference versus placebo in least-squares mean change from baseline in the Abnormal Involuntary Movement Scale total score at week 6 was -3.1 (95% confidence interval: -4.5, -1.7) and -5.5 (-7.0, -3.9) with valbenazine 40 and 80 mg, respectively; in the nonelderly group, respective differences were -1.5 (-2.6, -0.4) and -2.5 (-3.6, -1.3). Both age groups showed improvement in Clinical Global Impression of Change-Tardive Dyskinesia scores with valbenazine. The incidence of treatment-emergent adverse events (TEAEs) leading to treatment discontinuation was higher in the elderly versus nonelderly group. There was no trend toward higher incidences of TEAEs or related TEAEs in the elderly group. The findings suggest that valbenazine may be used effectively and safely as a treatment for TD, even in elderly patients.