Browsing by Author "De Silva, H.A."

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Alirocumab and cardiovascular outcomes according to sex and lipoprotein(a) after aute coronary syndrome: Odyssey outcomes.
(Elsevier, 2024) Bittner, V.A.; Schwartz, G.G.; Bhatt, D.L.; Chua, T.; De Silva, H.A.; Diaz, R.; Goodman, S.G.; Harrington, R.A.; Jukema, J.W.; Mcginniss, J.; Pordy, R.; Garon, G.; Scemama, M.; White, H.D.; Steg, G.; Szarek, M.
BACKGROUND The Odyssey outcomes trial (NCT01663402) compared the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS).OBJECTIVE We assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level.METHODS This prespecified analysis compared the effects of alirocumab versus placebo on lipoproteins, MACE (coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischemic stroke, unstable angina requiring hospitalization), death, total cardiovascular events, and adverse events in 4762 women and 14,162 men followed for a median of 2.8 years. In post-hoc analysis, we evaluated total cardiovascular events according to sex, baseline lipoprotein(a), and treatment.RESULTS Women were older, had higher baseline LDL-C levels (89.6 vs 85.3 mg/dL) and lipoprotein(a) (28.0 vs 19.3 mg/dL) and had more co-morbidities than men. At 4 months, alirocumab lowered LDL-C by 49.4 mg/dL in women and 54.0 mg/dL in men and lipoprotein(a) by 9.7 and 8.1 mg/dL, respectively (both p < 0.0001). Alirocumab reduced MACE, death, and total cardiovascular events similarly in both sexes. In the placebo group, lipoprotein(a) was a risk factor for total cardiovascular events in women and men. In both sexes, reduction of total cardiovascular events was greater at higher baseline lipoprotein(a), but this effect was more evident in women than men (pinteraction=0.08). Medication adherence and adverse event rates were similar in both sexes.CONCLUSIONS Alirocumab improves cardiovascular outcomes after ACS irrespective of sex. Reduction of total cardiovascular events was greater at higher baseline lipoprotein(a).
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
(Blackwell Publishing Asia, 2024) Gupta, Y.; Kapoor, D.; Lakshmi, J.K.; Praveen, D.; Santos, J.A.; Billot, L.; Naheed, A.; De Silva, H.A.; Gupta, I.; Farzana, N.; John, R.; Ajanthan, S.; Bhatla, N.; Desai, A.; Pathmeswaran, A.; Prabhakaran, D.; Teede, H.; Zoungas, S.; Patel, A.; Tandon, N.
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.
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
(Elsevier, 2024) Belsti, Y.; Moran, L.J.; Goldstein, R.; Mousa, A.; Cooray, S.D.; Baker, S.; Gupta, Y.; Patel, A.; Tandon, N.; Ajanthan, S.; John, R.; Naheed, A.; Chakma, N.; Lakshmi, J.K.; Zoungas, S.; Billot, L.; Desai, A.; Bhatla, N.; Prabhakaran, D.; Gupta, I.; De Silva, H.A.; Kapoor, D.; Praveen, D.; Farzana, N.; Enticott, J.; Teede, H.
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.
Efficacy and safety of a novel low-dose triple single-pill combination compared with placebo for initial treatment of hypertension
(Elsevier Biomedical, 2024) Rodgers, A.; Salam, A.; Schutte, A.E.; Cushman, W.C.; De Silva, H.A.; Tanna, G.L.D.; Grobbee, D.; Narkiewicz, K.; Ojji, D.B.; Poulter, N.R.; Schlaich, M.P.; Oparil, S.; Spiering, W.; Williams, B.; Jr, J.T.W.; Gutierez, A.; Sanni, A.; Lakshman, P.; McMullen, D.; Ranasinghe, G.; Gianacas, C.; Shanthakumar, M.; Liu, X.; Wang, N.; Whelton, P.
BACKGROUND Single-pill combinations of 3 or more low-dose blood pressure (BP)-lowering drugs hold promise for initial or early treatment of hypertension.OBJECTIVES We conducted a placebo-controlled trial of a new single-pill combination containing low doses of telmisartan, amlodipine, and indapamide in 2 dose options to assess efficacy and safety.METHODS This international, randomized, double-blind, placebo-controlled, parallel-group trial enrolled adults with hypertension receiving 0 to 1 BP-lowering drugs. After a 2-week placebo run-in during which any BP-lowering medication was stopped, participants were eligible if home systolic BP (SBP) was 130 to 154 mm Hg. Participants were randomized in a 2:2:1 ratio to GMRx2 ¼ dose (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), GMRx2 ½ dose (telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg), or placebo. The primary efficacy outcome was difference in change in home SBP from randomization to week 4, and primary safety outcome was treatment discontinuation due to an adverse event.RESULTS From June 14, 2021 to October 18, 2023, a total of 295 participants (mean age: 51 years; 56% female) were randomized and 96% completed the trial. Baseline mean home BP was 139/86 mm Hg and clinic BP was 138/86 mm Hg after placebo run-in. The placebo-corrected least square mean differences in home SBP at Week 4 were -7.3 mm Hg (95% CI: -4.5 to -10.2) for GMRx2 ¼ dose and -8.2 mm Hg (95% CI: -5.2 to -11.3) for GMRx2 ½ dose; reductions for clinic BP were 8.0/4.0 and 9.5/4.9 mm Hg. At Week 4, clinic BP control (<140/90 mm Hg) was 37%, 65%, and 70% for placebo, GMRx2 ¼ dose, and GMRx2 ½ dose, respectively (both doses P < 0.001 vs placebo). Placebo, GMRx2-triple ¼, and GMRx2 ½ treatment discontinuation due to an adverse event occurred in 1 (1.6%), 0, and 6 (5.1%), respectively; out of normal range serum sodium or potassium was observed in 4 (6.3%), 12 (10.6%), and 12 (10.1%), respectively, but no participant had a serum sodium <130/>150 mmol/L or potassium <3.0/>6.0 mmol/L. Serious adverse events were reported by 2 participants in the placebo and GMRx2 ½ groups and none in the GMRx2 ¼ group.CONCLUSIONS In a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo. (Efficacy and Safety of GRMx2 Compared to Placebo for the Treatment of Hypertension: NCT04518306).
The efficacy of interventions to prevent type 2 diabetes among women with recent gestational diabetes mellitus-A living systematic review and meta-analysis
(Blackwell Publishing Asia, 2024) Lee, V.Y.; Monjur, M.R.; Santos, J.A.; Patel, A.; Liu, R.; Tanna, G.L.D.; Gupta, Y.; Goyal, A.; Ajanthan, S.; Praveen, D.; Lakshmi, J.K.; De Silva, H.A.; Tandon, N.
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.
Post Pandemic Health Diplomacy in South Asia: A Case Study of SAARC’s Post - Covid Regional Reengagement with South Asian Nations
(Department of International Studies, Faculty of Social Sciences, University of Kelaniya, Sri Lanka, 2023) De Silva, H.A.
This paper examines the role played by South Asian Association for Regional Cooperation (SAARC) in the era that followed the covid-19 pandemic and the influence that it had in bringing post-pandemic resilience within the South Asian region. The objective of this study is to identify how South Asian Nations came together to work hand-in-hand with SAARC for the safety of their citizens and to identify the degree of influence that SAARC‟s policies had in healing a contaminated and unstable post-pandemic Asia. South Asia had long been engulfed in regional animosity followed by the India-Pakistan rivalry. Thus, the particular significance of the study is to elucidate how SAARC stands under the highlight amidst the other regional organizations in executing its reengagement policy which brought the South Asian nations together in strategic dialogue, with the aim of establishing a sustainable and healthy outreach to the mayhem caused by the Covid19 pandemic. The study which analyzes the post-pandemic policies of SAARC follows a qualitative approach based on secondary data sources gathered mainly through documents published by SAARC Secretariat. The findings of the research purports that SAARC has been able to configure a new post-pandemic architecture that has improved regional response rates of the nations and thereby has augmented the quality of life of South Asian people applied. All in all, it could be derived that, in spite of the inefficiencies and undiscerning policies of SAARC, it had been able to maintain a considerable amount of stability and resistance within the South Asian region followed by the Covid19 pandemic.