Centre for Chronic Disease Control

BackgroundLumacaftor/ivacaftor (LUM/IVA) is a CFTR modulator approved for the treatment of cystic fibrosis (CF) caused by the F508del mutation. While clinical trials have demonstrated its efficacy, the long-term safety profile remains inadequately characterized. This study aims to assess the real-world safety of LUM/IVA through a comprehensive analysis of adverse drug events (ADEs) reported in the U. S. FDA Adverse Event Reporting System (FAERS) from the third quarter of 2015 to 2024.MethodsDisproportionality analysis including the reporting odds ratio (ROR) and Bayesian confidence Propagation Neural Network (BCPNN) was employed to identify potential safety signals associated with LUM/IVA. Furthermore, sensitivity analyses were conducted to eliminate potential confounding arising from concomitant medication use and underlying indications. Potential risk factors for LUM/IVA-associated depression were identified through logistic regression analysis. Finally, time-to-onset (TTO) analysis was conducted to evaluate the temporal patterns of ADEs.ResultsA total of 7,843 LUM/IVA-related ADE reports were extracted, spanning 27 system organ classes (SOCs). We identified 221 positive signals, with 37 signals consistent with the drug label, 61 signals might be associated with disease progression, and 123 signals not listed in the drug label. Positive signals with most reported cases included infective pulmonary exacerbations (n = 1,394, ROR 1201.58, IC025 9.50), hospitalization (n = 841, ROR 20.07, IC025 4.13) and, dyspnoea (n = 517, ROR 4.00, IC025 1.83). Unexpected signals such as depression (n = 81, ROR 1.71, IC025 0.45), suicidal ideation (n = 31, ROR 1.63, IC025 0.20), and hypoglycemia (n = 20, ROR 2.02, IC025 0.39) were detected, highlighting previously unreported risks. Stratified analysis identified risk signals in different subgroups, such as chest discomfort in 50–100 kg subgroup. The TTO analysis revealed that the median onset of ADEs was 256 days, with most ADEs reports occurring after 360 days of treatment LUM/IVA (39.2%), Moreover, cumulative incidence varied significantly among subgroups stratified by age, dosage, and frequency of administration.ConclusionThis study provides a detailed real-world safety profile of LUM/IVA, identifying both known and unexpected adverse events. Our findings underscore the importance of continuous post-marketing surveillance and the need for updated drug label to reflect associated risks, particularly those related to psychiatric symptoms and long-term adverse effects. Personalized treatment strategies based on patient characteristics, including sex, are recommended to optimize safety during LUM/IVA therapy.

Systemic hypertension is a major contributor to global cardiovascular morbidity and mortality. Effective management combines pharmacological and lifestyle interventions. Pranayama, a yogic breathing technique, may modulate cardiovascular function, but its impact on hypertension remains uncertain. A systematic review and meta-analysis following PRISMA guidelines (PROSPERO: CRD42024597502) included RCTs from PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov up to April 2025. We assessed Risk of bias using Cochrane RoB 2, and pooled effects were reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Seven RCTs (683 participants) showed a significant reduction in the primary outcome, heart rate (SMD=-0.43; 95% CI: -0.52 to -0.34; I2=0%). Systolic BP decreased significantly under fixed-effects (SMD=-0.72), while diastolic BP and HRV improvements were modest. Pranayama lowers heart rate and may modestly reduce blood pressure, supporting its role as a safe, adjunctive therapy pending larger standardized trials.

IntroductionHeart failure (HF) remains a major global health challenge, particularly in low-resource settings where access to comprehensive cardiac rehabilitation (CR) is limited. Yoga, a culturally contextualised mind-body intervention, holds promise as an adjunctive therapy in CR. The Yoga-EndOmics study aims to evaluate the effects of Yoga-based cardiac rehabilitation (Yoga-CaRe) on gene expression, endothelial function, vascular biomarkers and clinical outcomes in systolic HF, providing mechanistic insights into its potential integration into conventional cardiac rehabilitation.Methods and analysisThis is a prospective, randomised, open-label, blinded-endpoint (PROBE) mechanistic trial enrolling 78 patients with HF with reduced ejection fraction (HFrEF). Participants will be randomised in a 1:1 ratio to receive either a structured Yoga-CaRe intervention or enhanced standard care for 3 months. The Yoga-CaRe group will attend 20 supervised sessions with guided home practice involving tailored asanas, pranayama and meditation. Primary outcomes are changes in endothelial-dependent flow-mediated dilation (FMD) and functional exercise capacity at 3 months. Secondary outcomes include changes in arterial compliance and stiffness, circulating biomarkers of endothelial dysfunction, oxidative stress and inflammation, and immediate changes in global gene expression profiles in peripheral blood mononuclear cells following the Yoga-CaRe intervention. Data will be analysed using analysis of covariance (ANCOVA) for between-group comparisons and significant analysis of microarray (SAM) for global gene expression profiles.Ethics and disseminationThe study has received ethical clearance from the Institutional Ethics Committee of the SDM College of Medical Sciences and Hospital, India (SDMIEC/2025/1072) and is registered with the Clinical Trials Registry of India. Findings will be disseminated through peer-reviewed journals, scientific conferences and stakeholder engagement platforms to inform future integrative strategies in HF management.Trial registration numberCTRI/2023/12/060758

No abstract available.

I ntroduction: Arterial stiffness and central arterial pressure are independent predictors of cardiovascular morbidity and mortality, with central pressure offering prognostic value beyond peripheral blood pressure (BP). While current guidelines recommend initiating treatment with single-pill combinations (SPCs), but the comparative effects of these combinations on arterial stiffness and central BP remain unclear, and no randomized evidence exists demonstrating their superiority, particularly in South Asian populations. This sub-study of the TOPSIN Trial aimed to evaluate the impact of three SPCs on aortic stiffness and central BP in Indian hypertensive patients. Methods: This is a triple-blind, randomized, three-arm trial involving 210 hypertensive patients aged 30–79 years. Participants were randomized in a 1:1:1 ratio to receive one of the following SPCs: amlodipine + perindopril (AM+PE), perindopril + indapamide (PE+ID), or amlodipine + indapamide (AM+ID). Eligible patients had clinic SBP≥140 and <160 mmHg on one antihypertensive or SBP ≥150 and <180 mmHg with no prior treatment. The study assessed central arterial stiffness- carotid-femoral pulse wave velocity (cf-PWV), carotid β-stiffness index (SI beta); carotid systolic (cSBP), diastolic (cDBP), and pulse pressure (cPP) using validated vascular analyzer (ArtSens-Plus, India). Secondary measures included 24-hour ambulatory BP (24ABPM), plasma nitric oxide concentration (NOx), and oxidative stress markers. SPCs were initiated at standard doses with forced up-titration at 2 months, and efficacy was assessed at 6 months. Results: Of the 210 randomized participants, 184 (38.0% women) aged 51±9.89 years were included in the final analysis. The mean 24h ambulatory SBP was 137.5±15.4 mmHg, and DBP was 85.3±9.1 mmHg. 53.3% had a history of hypertension, and 16.3% had diabetes. All three SPCs significantly reduced central and peripheral BP (p<0.001), but no significant between-group differences were observed. There were no significant changes in arterial stiffness. However, AM+PE and PE+ID combinations significantly improved NOx levels (p<0.01), while oxidative stress and antioxidant capacity remained unchanged across groups. Conclusion: All three single-pill combinations effectively reduced central and peripheral BP in Indian hypertensive patients, with no significant differences in arterial stiffness. Combinations containing perindopril improved nitric oxide levels, suggesting additional vascular benefits.

ABSTRACT Background Chronic conditions cause notable health and economic burdens. While health insurance enables access to healthcare, its effects on chronic care outcomes remain under-explored. Objective To examine the association between health insurance coverage and cardiometabolic risk factors among people with chronic conditions in India. Methods Data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) and Solan studies, including 2,926 adults with chronic conditions were analyzed using propensity score weighting to evaluate the associations between health insurance and cardiometabolic risk factors (HbA1c, low-density lipoprotein cholesterol [LDLc], and blood pressure [BP]) and self-reported health status (measured using European Quality of Life Visual Analogue Scale [EQ-VAS]). Mediation analysis evaluated healthcare visits as a potential mediator. Results Among 2,926 respondents meeting criteria, mean (SD) age was 54.6 years (11.8), and 1630 (55.7%) were women. Health insurance coverage was low (6.5%) and more prevalent among men, higher-income groups, and rural vs urban residents. Insured participants had lower mean diastolic BP (84.8 vs 86.0 mmHg), mean LDLc (113.3 vs 117.2 mg/dl), mean HbA1c (6.9% vs 7.5%), and higher health status (EQ-VAS: 74.6 vs 69.1) than uninsured participants, respectively (p < 0.05). Mediation analysis showed healthcare visits strongly mediated the relationship between insurance and BP and partially mediated effects on LDLc, HbA1c, and self-rated health. Conclusion Health insurance coverage was associated with better cardiometabolic risk profiles and health status, largely mediated by increased healthcare utilization. Expanding insurance coverage to include outpatient chronic care services should be prioritized to improve health outcomes in low- and middle-income countries.