Medicine
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Item Alirocumab and cardiovascular outcomes according to sex and lipoprotein(a) after acute coronary syndrome: a report from the ODYSSEY OUTCOMES study(Elservier, 2024) 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, P.G.; Szarek, M.; ODYSSEY OUTCOMES Investigators; Bittner, V. A.Background: The ODYSSEY OUTCOMES trial (NCT01663402) compared the effects of the pro- protein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovas- cular 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 lipopro- teins, 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 lipopro- tein(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 sim- ilarly 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 base- line 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. Reduc- tion of total cardiovascular events was greater at higher baseline lipoprotein(a). ©2024 National Lipid Association. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )Item Ambulatory blood pressure levels in individuals with uncontrolled clinic hypertension across Bangladesh, Pakistan, and Sri Lanka(Wiley, 2024) Zhu, A.; Ostbye, T.; Naheed, A.; de Silva, H.A.; Jehan, I.; Gandhi, M.; Chakma, N.; Kasturiratne, A.; Samad, Z.; Jafar, T.H.Hypertension is a leading risk factor for cardiovascular disease in South Asia. The authors aimed to assess the cross-country differences in 24-h ambulatory, daytime, and nighttime systolic blood pressure (SBP) among rural population with uncontrolled clinic hypertension in Bangladesh, Pakistan, and Sri Lanka. The authors studied patients with uncontrolled clinic hypertension (clinic BP ≥ 140/90 mmHg) who underwent ambulatory blood pressure monitoring (ABPM) during the baseline assessment as part of a community-based trial. The authors compared the distribution of ABPM profiles of patients across the three countries, specifically evaluating ambulatory SBP levels with multivariable models that adjusted for patient characteristics. Among the 382 patients (mean age, 58.3 years; 64.7% women), 56.5% exhibited ambulatory hypertension (24-h ambulatory BP ≥ 130/80 mmHg), with wide variation across countries: 72.6% (Bangladesh), 50.0% (Pakistan), and 51.0% (Sri Lanka; P < .05). Compared to Sri Lanka, adjusted mean 24-h ambulatory, daytime, and nighttime SBP were higher by 12.24 mmHg (95% CI 4.28-20.20), 11.96 mmHg (3.87-20.06), and 12.76 mmHg (4.51-21.01) in Bangladesh, separately. However, no significant differences were observed between Pakistan and Sri Lanka (P > .05). Additionally, clinic SBP was significantly associated with 24-h ambulatory (mean 0.38, 95% CI 0.28-0.47), daytime (0.37, 0.27-0.47), and nighttime SBP (0.40, 0.29-0.50) per 1 mmHg increase. The authors observed substantial cross-country differences in the distribution of ABPM profiles among patients with uncontrolled clinic hypertension in rural South Asia. The authors findings indicated the need to incorporate 24-h BP monitoring to mitigate cardiovascular risk, particularly in Bangladesh.Item 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(Elsevier, 2023) 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.; LIVING Collaborative GroupAIM: 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).Item Post-intervention acceptability of multicomponent intervention for management of hypertension in rural Bangladesh, Pakistan, and Sri Lanka- a qualitative study(Public Library of Science, 2023) Jafar, T.H.; Tavajoh, S.; de Silva, H.A.; Naheed, A.; Jehan, I.; de Silva, C.K.; Chakma, N.; Huda, M.; Legido-Quigley, H.; COBRA-BPS Study Group.BACKGROUND: COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multicomponent, community health-worker (CHW)-led hypertension management program, has been shown to be effective in rural communities in South Asia. This paper presents the acceptability of COBRA-BPS multicomponent intervention among the key stakeholders. METHODS: We conducted post-implementation interviews of 87 stakeholder including 23 community health workers (CHWs), 19 physicians and 45 patients in 15 rural communities randomized to COBRA-BPS multicomponent intervention in in Bangladesh, Pakistan, and Sri Lanka. We used Theoretical Framework for Acceptability framework (TFA) with a focus on affective attitude, burden, ethicality, intervention coherence, opportunity cost, perceived effectiveness and self-efficacy. RESULTS: COBRA-BPS multicomponent intervention was acceptable to most stakeholders. Despite some concerns about workload, most CHWs were enthusiastic and felt empowered. Physicians appreciated the training sessions and felt trusted by their patients. Patients were grateful to receive the intervention and valued it. However, patients in Pakistan and Bangladesh expressed the need for supplies of free medicines from the primary health facilities, while those in Sri Lanka were concerned about supplies' irregularities. All stakeholders favoured scaling-up COBRA-BPS at a national level. CONCLUSIONS: COBRA-BPS multicomponent intervention is acceptable to the key stakeholders in Bangladesh, Pakistan and Sri Lanka. Community engagement for national scale-up of COBRA-BPS is likely to be successful in all three countries.Item A cluster-randomized, placebo-controlled trial to evaluate the efficacy of a spatial repellent (Mosquito Shield™) against Aedes-borne virus infection among children ≥ 4-16 years of age in the Gampaha District, Sri Lanka: study protocol (the AEGIS program)(BioMed Central, 2023) Tissera, H.; Dheerasinghe, D.S.A.F.; Malavige, N.; de Silva, H.A.; Morrison, A.C.; Scott, T.W.; Reiner, R.C. Jr.; Grieco, J.P.; Achee, N.L.BACKGROUND: Spatial repellents (SRs) have been widely used for prevention of mosquito bites, but their efficacy in reducing Aedes-borne viruses (ABV) has not been tested rigorously at large scale in Asia. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a transfluthrin SR, was developed in Gampaha District of Sri Lanka across three Medical Officer of Health areas; i.e., Negombo, Wattala, and Kelaniya. METHODS: This trial is a cluster-randomized, placebo-controlled, double-blinded clinical trial. A total of ~14,430 subjects aged ≥ 6 months in 30 clusters (15 intervention, 15 placebo) from ~3900 households (HH) will be randomly selected for enrolment into a "febrile surveillance cohort." A subset of the surveillance cohort, ~3570 subjects aged ≥4-16 years that test seronegative (naïve) or are serologically positive for a previous single dengue virus (DENV) infection (monotypic) at baseline sampling, will be enrolled into a "longitudinal cohort" for measuring DENV infection based on laboratory-confirmed seroconversion during the trial. Persons identified positive for antibodies against multiple DENV serotypes (multitypic) at baseline will be monitored for secondary analyses. Active ABV disease will be assessed using an enhanced passive surveillance system with case ascertainment performed in designated healthcare facilities. Serum samples will be taken from longitudinal cohort subjects within 1-2 weeks of when intervention is first deployed (T0) with additional samples taken ~12 (T1) and ~24 months (T2) from baseline sampling. DENV seroconversion and ABV active disease rates from baseline (pre-intervention) and follow-up (post-intervention) samples will be compared between intervention and placebo clusters. Participating houses will be monitored entomologically (indoor adult Aedes aegypti population densities and adult female blood fed status) within 3 months before intervention deployment and monthly during the intervention phase. Entomological surveys will monitor indoor adult Ae. aegypti population densities and blood fed status. Dengue incidence in each cohort will be estimated and compared to determine the public health benefit of using an SR. Entomological parameters will be measured to determine if there are entomological correlates of SR efficacy that may be useful for the evaluation of new SR products. DISCUSSION: The trial will serve as an efficacy assessment of SR products in South Asia. Results will be submitted to the World Health Organization Vector Control Advisory Group for assessment of public health value towards an endorsement to recommend inclusion of SRs in ABV control programs.Item Budget impact and cost-effectiveness analyses of the COBRA-BPS multicomponent hypertension management programme in rural communities in Bangladesh, Pakistan, and Sri Lanka(Elsevier, 2021) Finkelstein, E.A.; Krishnan, A.; Naheed, A.; Jehan, I.; de Silva, H.A.; Gandhi, M.; Lim, C.W.; Chakma, N.; Ediriweera, D.S.; Khan, J.; Kasturiratne, A.; Hirani, S.; Solayman, A.K.M.; Jafar, T.H.; COBRA-BPS study group.BACKGROUND: COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multi-component hypertension management programme that is led by community health workers, has been shown to be efficacious at reducing systolic blood pressure in rural communities in Bangladesh, Pakistan, and Sri Lanka. In this study, we aimed to assess the budget required to scale up the programme and the incremental cost-effectiveness ratios. METHODS: In a cluster-randomised trial of COBRA-BPS, individuals aged 40 years or older with hypertension who lived in 30 rural communities in Bangladesh, Pakistan, and Sri Lanka were deemed eligible for inclusion. Costs were quantified prospectively at baseline and during 2 years of the trial. All costs, including labour, rental, materials and supplies, and contracted services were recorded, stratified by programme activity. Incremental costs of scaling up COBRA-BPS to all eligible adults in areas covered by community health workers were estimated from the health ministry (public payer) perspective. FINDINGS: Between April 1, 2016, and Feb 28, 2017, 11 510 individuals were screened and 2645 were enrolled and included in the study. Participants were examined between May 8, 2016, and March 31, 2019. The first-year per-participant costs for COBRA-BPS were US$10•65 for Bangladesh, $10•25 for Pakistan, and $6•42 for Sri Lanka. Per-capita costs were $0•63 for Bangladesh, $0•29 for Pakistan, and $1•03 for Sri Lanka. Incremental cost-effectiveness ratios were $3430 for Bangladesh, $2270 for Pakistan, and $4080 for Sri Lanka, per cardiovascular disability-adjusted life year averted, which showed COBRA-BPS to be cost-effective in all three countries relative to the WHO-CHOICE threshold of three times gross domestic product per capita in each country. Using this threshold, the cost-effectiveness acceptability curves predicted that the probability of COBRA-BPS being cost-effective is 79•3% in Bangladesh, 85•2% in Pakistan, and 99•8% in Sri Lanka. INTERPRETATION: The low cost of scale-up and the cost-effectiveness of COBRA-BPS suggest that this programme is a viable strategy for responding to the growing cardiovascular disease epidemic in rural communities in low-income and middle-income countries where community health workers are present, and that it should qualify as a priority intervention across rural settings in south Asia and in other countries with similar demographics and health systems to those examined in this study. FUNDING: The UK Department of Health and Social Care, the UK Department for International Development, the Global Challenges Research Fund, the UK Medical Research Council, Wellcome Trust.Item Synergistic effect of combining MLC601 and rehabilitation on post-stroke recovery: The Chimes-E Study(Asia Pacific Stroke Organization, Hong Kong Stroke Society and Jiangsu Stroke Association & karger publishing, 2017) Suwanwela, N.; Lee, C.F.; Christopher, L.H.; Chen; Sherry, H.; Young; Tay, S.S.; Umapathi, T.; Lao, A.Y.; Gan, H.H.; Alejandro, C.; Baroque; Jose, C.; Navarro; Hang, H.M.; Joel, M.; Advincula; Muengtaweepongsa, S.; Chan, B.P.L.; Chua, C.L.C.; Wijekoon, N.; de Silva, H.A.; Hiyadan, J.H.B.; Wong, K.S.L.; Poungvarin, N.; Eow, G.B.; Venketasubramanian, N.BACKGROUND AND RATIONALE: MLC601 has been shown to enhance natural neuro-repair mechanisms after stroke and may also facilitate rehabilitation-stimulated recovery processes. We aimed to assess the effect of MLC601 and concomitant rehabilitation on stroke recovery in the CHIMES-E study to test the hypotheses that there would be a synergistic effect. METHODS: The CHIMES-E study recruited 880 subjects aged ≥18 years with acute ischemic stroke (AIS), National Institute of Health Stroke Scale (NIHSS) 6–14, and pre-stroke modified Rankin Scale (mRS) ≤1 in a planned double-blind extension study of CHIMES trial with MLC601 or matching placebo given for 3 months in addition to standard stroke care and rehabilitation prescribed by the treating physicians. From Month (M) 3 to M24, mRS was compared between MLC601 and placebo. RESULTS: The study population had a mean age of 61.8 ± 11.3 with 318 (36%) women. Data on rehabilitation and mRS at M3 were available in 807 (91.7%) subjects. Treatment groups were balanced in baseline characteristics except for NIHSS mean score being higher in the rehabilitation group (Rehab) (p = 0.013). Stratification of subjects according to rehabilitation status (Rehab or NoRehab) showed a higher treatment effect of MLC601 on both mRS shift and dichotomy (0–1 vs. 2–6) from M3 to M24 in Rehab group, after adjusting for baseline differences and poorer prognosis factors. In the Rehab group, the adjusted odds of functional independence (mRS of ≤1) increased significantly over time in favor of MLC601 from M3 to M24, with the highest OR at M12 of 2.42 (1.53, 3.81). CONCLUSION: Combining MLC601 and rehabilitation increases improvement of functional recovery over 2 years, supporting a synergistic effect on brain neuro-repair processes after AIS, with more subjects improving to functional independence compared to placebo.Item Opportunities for pharmacists to optimise quality use of medicines in a Sri Lankan hospital: An observational, prospective, cohort study(Wiley-Blackwell, 2017) Perera, D.M.P.; Coombes, J.A.; Shanika, L.G.T.; Dawson, A.; Lynch, C.; Mohamed, F.; Kalupahana, N.; de Silva, H.A.; Jayamanne, S.F.; Peters, N.B.; Myers, B.; Coombes, I.D.BACKGROUND: Quality use of medicines (QUM) has been identified as a priority in Sri Lanka. Aim: To identify opportunities to optimise QUM, and evaluate medication appropriateness and medication information exchanged with patients and carers on discharge in a Sri Lankan tertiary care hospital. METHODS: An observational, prospective, cohort study of patients systematically sampled from two medical wards. A research pharmacist determined their pre-admission medication regimen via interview at time of discharge. Issues of poor adherence and discrepancies between the pre- and post-admission medication regimens were recorded. Drug-related problems were categorised into opportunities to optimise drug therapy. The appropriateness of discharge medications was evaluated using a validated tool. The patient or carer was interviewed after discharge regarding the quality of medicine information exchanged in hospital. RESULTS: The 578 recruited patients were taking 1756 medications prior to admission, and 657 (37.4%) of these medications were not continued during admission. Opportunities to optimise drug therapy were identified on 1496 occasions during admission (median, 2.0 opportunities/patient), 215 opportunities, (14.4%) were resolved spontaneously by the medical team prior to discharge. The median score for appropriateness of medications on discharge was 1.5 per patient (interquartile range, 0.0–3.5). Of 427 patients surveyed after discharge, 52% recalled being asked about their medications on admission to hospital, 75% about previous adverse medication reactions and 39% recalled being informed about changes to their medications on discharge. CONCLUSION: Significant opportunities exist for pharmacists to enhance quality use of medicines for patients in the current hospitalbased healthcare system in Sri Lanka. © 2017 The Society of Hospital Pharmacists of Australia.Item A Community based intervention for managing hypertension in rural South Asia(Massachusetts Medical Society., 2020) Jafar, T. H.; Gandhi, M.; de Silva, H.A.; Jehan, I.; Naheed, A.; Finkelstein, E.A.; Turner, E.L.; Morisky, D.; Kasturiratne, A.; Khan, A.H.; Clemens, J.D.; Ebrahim, S.; Assam, P.N.; Feng, L.; COBRA-BPS Study Group.(Luke, N., de Silva, .C, Perera, M., Ranasinha, C.,Ediriweera, D)BACKGROUND: The burden of hypertension is escalating, and control rates are poor in low- and middle-income countries. Cardiovascular mortality is high in rural areas. METHODS: We conducted a cluster-randomized, controlled trial in rural districts in Bangladesh, Pakistan, and Sri Lanka. A total of 30 communities were randomly assigned to either a multicomponent intervention (intervention group) or usual care (control group). The intervention involved home visits by trained government community health workers for blood-pressure monitoring and counseling, training of physicians, and care coordination in the public sector. A total of 2645 adults with hypertension were enrolled. The primary outcome was reduction in systolic blood pressure at 24 months. Follow-up at 24 months was completed for more than 90% of the participants. RESULTS: At baseline, the mean systolic blood pressure was 146.7 mm Hg in the intervention group and 144.7 mm Hg in the control group. At 24 months, the mean systolic blood pressure fell by 9.0 mm Hg in the intervention group and by 3.9 mm Hg in the control group; the mean reduction was 5.2 mm Hg greater with the intervention (95% confidence interval [CI], 3.2 to 7.1; P<0.001). The mean reduction in diastolic blood pressure was 2.8 mm Hg greater in the intervention group than in the control group (95% CI, 1.7 to 3.9). Blood-pressure control (<140/90 mm Hg) was achieved in 53.2% of the participants in the intervention group, as compared with 43.7% of those in the control group (relative risk, 1.22; 95% CI, 1.10 to 1.35). All-cause mortality was 2.9% in the intervention group and 4.3% in the control group. CONCLUSIONS: In rural communities in Bangladesh, Pakistan, and Sri Lanka, a multicomponent intervention that was centered on proactive home visits by trained government community health workers who were linked with existing public health care infrastructure led to a greater reduction in blood pressure than usual care among adults with hypertension. (Funded by the Joint Global Health Trials scheme; COBRA-BPS ClinicalTrials.gov number, NCT02657746.).Item Prevalence and correlates of cardiometabolic multimorbidity among hypertensive individuals: a cross-sectional study in rural South Asia-Bangladesh, Pakistan and Sri Lanka.(BMJ Publishing Group Ltd, 2019) Feng, L.; Jehan, I.; de Silva, H.A.; Naheed, A.; Farazdaq, H.; Hirani, S.; Kasturiratne, A.; Ranasinha, C.D.; Islam, M.T.; Siddiquee, A.T.; Jafar, T.H.OBJECTIVE: To determinate the prevalence and correlates of cardiometabolic multimorbidity (CMM), and their cross-country variation among individuals with hypertension residing in rural communities in South Asia. DESIGN: A cross-sectional study. SETTING: Rural communities in Bangladesh, Pakistan and Sri Lanka. PARTICIPANTS: A total of 2288 individuals with hypertension aged ≥40 years from the ongoing Control of Blood Pressure and Risk Attenuation- Bangladesh, Pakistan and Sri Lanka clinical trial. MAIN OUTCOME MEASURES: CMM was defined as the presence of ≥2 of the conditions: diabetes, chronic kidney disease, heart disease and stroke. Logistic regression was done to evaluate the correlates of CMM. RESULTS: About 25.4% (95% CI 23.6% to 27.2%) of the hypertensive individuals had CMM. Factors positively associated with CMM included residing in Bangladesh (OR 3.42, 95% CI 2.52 to 4.65) or Sri Lankan (3.73, 95% CI 2.48 to 5.61) versus in Pakistan, advancing age (2.33, 95% CI 1.59 to 3.40 for 70 years and over vs 40-49 years), higher waist circumference (2.15, 95% CI 1.42 to 3.25) for Q2-Q3 and 2.14, 95% CI 1.50 to 3.06 for Q3 and above), statin use (2.43, 95% CI 1.84 to 3.22), and higher levels of triglyceride (1.01, 95% CI 1.01 to 1.02 per 5 mg/dL increase). A lower odds of CMM was associated with being physically active (0.75, 95% CI 0.57 to 0.97). A weak inverted J-shaped association between International Wealth Index and CMM was found (p for non-linear=0.058), suggesting higher risk in the middle than higher or lower socioeconomic strata. CONCLUSIONS: CMM is highly prevalent in rural South Asians affecting one in four individuals with hypertension. There is an urgent need for strategies to concomitantly manage hypertension, cardiometabolic comorbid conditions and associated determinants in South Asia.