Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Effect of virgin coconut oil supplementation on cognition of individuals with mild-to-moderate alzheimer's disease in Sri Lanka (VCO-AD study): A randomized placebo-controlled trial(IOS Press, 2023) Fernando, M.G.; Silva, R.; Fernando, W.M.A.D.B.; de Silva, H.A.; Wickremasinghe, A.R.; Dissanayake, A.S.; Sohrabi, H.R.; Martins, R.N.; Williams, S.S.BACKGROUND: Virgin coconut oil (VCO) is a potential therapeutic approach to improve cognition in Alzheimer’s disease (AD) due to its properties as a ketogenic agent and antioxidative characteristics. OBJECTIVE: This study aimed to investigate the effect of VCO on cognition in people with AD and to determine the impact of apolipoprotein E (APOE) ɛ4 genotype on cognitive outcomes. METHODS: Participants of this double-blind placebo-controlled trial (SLCTR/2015/018, 15.09.2015) were 120 Sri Lankan individuals with mild-to-moderate AD (MMSE = 15-25), aged > 65 years, and they were randomly allocated to treatment or control groups. The treatment group was given 30 mL/day of VCO orally and the control group, received similar amount of canola oil, for 24 weeks. The Mini-Mental Sate Examination (MMSE) and Clock drawing test were performed to assess cognition at baseline and at the end of the intervention. Blood samples were collected and analyzed for lipid profile and glycated hemoglobin (HbA1 C) levels.∥ RESULTS: There were no significant difference in cognitive scores, lipid profile, and HbA1 C levels between VCO and control groups post-intervention. The MMSE scores, however, improved among APOE ɛ4 carriers who had VCO, compared to non-carriers (2.37, p = 0.021). APOE ɛ4 status did not influence the cognitive scores in the control group. The attrition rate was 30%.∥ CONCLUSION: Overall, VCO did not improve cognition in individuals with mild-to-moderate AD following a 24-week intervention, compared to canola oil. However, it improved the MMSE scores in APOE ɛ4 carriers. Besides, VCO did not compromise lipid profile and HbA1 C levels and is thus safe to consume.Item Pharmacoeconomics amidst a financial crisis(Sri Lanka College of Psychiatrists, 2023) Williams, S.S.; Medagedara, A.U.; de Silva, H.A.Cost effective strategies must be implemented amidst an economic crisis in Sri Lanka to mitigate ever increasing medicinal costs. Exploration of measures such as evidence based generic prescribing, cost effectiveness analysis, value-based pricing, identification of low cost, high value medication and being sensitive to the ability of the patient to purchase medicine is a necessity. Clinicians must be sensitised to this issue to contribute actively to the process. Policies in line with pharmacoeconomic realities must be pursued.Item Association of low-dose triple combination therapy vs usual care with time at target blood pressure: A secondary analysis of the TRIUMPH Randomized Clinical Trial(American Medical Association, 2022) Gnanenthiran, S.R.; Wang, N.; Luca Di Tanna, G.; Salam, A.; Webster, R.; de Silva, H.A.; Guggilla, R.; Jan, S.; Maulik, P.K.; Naik, N.; Selak, V.; Thom, S.; Prabhakaran, D.; Schutte, A.E.; Patel, A.; Rodgers, A.; TRIUMPH Study GroupImportance: Cumulative exposure to high blood pressure (BP) is an adverse prognostic marker. Assessments of BP control over time, such as time at target, have been developed but assessments of the effects of BP-lowering interventions on such measures are lacking. Objective: To evaluate whether low-dose triple combination antihypertensive therapy was associated with greater rates of time at target compared with usual care. Design, setting, and participants: The Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) trial was a open-label randomized clinical trial of low-dose triple BP therapy vs usual care conducted in urban hospital clinics in Sri Lanka from February 2016 to May 2017. Adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg or in patients with diabetes or chronic kidney disease, systolic BP >130 mm Hg and/or diastolic BP >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy were included. Patients were excluded if they were currently taking 2 or more blood pressure-lowering drugs or had severe or uncontrolled blood pressure, accelerated hypertension or physician-determined need for slower titration of treatment, a contraindication to the triple combination pill therapy, an unstable medical condition, or clinically significant laboratory values deemed by researchers to be unsuitable for the study. All 700 individuals in the original trial were included in the secondary analysis. This post hoc analysis was conducted from December 2020 to December 2021. Intervention: Once-daily fixed-dose triple combination pill (telmisartan 20 mg, amlodipine 2.5 mg, and chlorthalidone 12.5 mg) therapy vs usual care. Main outcomes and measures: Between-group differences in time at target were compared over 24 weeks of follow-up, with time at target defined as percentage of time at target BP. Results: There were a total of 700 randomized patients (mean [SD] age, 56 [11] years; 403 [57.6%] women). Patients allocated to the triple pill group (n = 349) had higher time at target compared with those in the usual care group (n = 351) over 24 weeks' follow-up (64% vs 43%; risk difference, 21%; 95% CI, 16-26; P < .001). Almost twice as many patients receiving triple pill therapy achieved more than 50% time at target during follow-up (64% vs 37%; P < .001). The association of the triple pill with an increase in time at target was seen early, with most patients achieving more than 50% time at target by 12 weeks. Those receiving the triple pill achieved a consistently higher time at target at all follow-up periods compared with those receiving usual care (mean [SD]: 0-6 weeks, 36.3% [30.9%] vs 21.7% [28.9%]; P < .001; 6-12 weeks, 5.2% [31.9%] vs 33.7% [33.0%]; P < .001; 12-24 weeks, 66.0% [31.1%] vs 43.5% [34.3%]; P < .001). Conclusions and relevance: To our knowledge, this analysis provides the first estimate of time at target as an outcome assessing longitudinal BP control in a randomized clinical trial. Among patients with mild to moderate hypertension, treatment with a low-dose triple combination pill was associated with substantially higher time at target compared with usual care.Item Polypills for the prevention of cardiovascular disease: a framework for wider use(Nature Publishing Company, 2022) Patel, A.; Ojji, D.; de Silva, H.A.; MacMahon, S.; Rodgers, A.No abstract availableItem Triple therapy prevention of recurrent intracerebral disease events trial: rationale, design and progress(Blackwell Publishing, 2022) Anderson, C.S.; Rodgers, A.; de Silva, H.A.; Martins, S.O.; Klijn, C.J.; Senanayake, B.; Freed, R.; Billot, L.; Arima, H.; Thang, N.H.; Zaidi, W.A.W.; Kherkheulidze, T.; Wahab, K.; Fisher, U.; Lee, T.H.; Chen, C.; Pontes-Neto, O.; Robinson, T.; Wang, J.; Naismith, S.; Song, L.; Schreuder, F.H.; Lindley, R.I.; Woodward, M.; MacMahon, S.; Salman, R.A.; Chow, C.K.; Chalmers, J.Background: Patients who suffer intracerebral hemorrhage (ICH) are at very high risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimize secondary prevention. Objectives: The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC "Triple Pill," three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH. Design: An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130-160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety. Results: Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required sample size should be achieved by 2024.Item Clinical research during the COVID-19 pandemic: Gastroenterology researchers' perspective(BMJ Publishing Group, 2020) Niriella, M.A.; de Silva, A.P.; de Silva, H.A.; de Silva, H.J.No Abstract availableItem Low-dose melatonin for sleep disturbances in early-stage cirrhosis: A randomized, placebo-controlled, cross-over trial(John Wiley & Sons Australia Ltd, 2020) de Silva, A.P.; Niriella, M.A.; Ediriweera, D.S.; de Alwis, J.P.N.; Liyanage, I.K.; Ettickan, U.; Liyanapathirana, K.V.; Undugodage, C.; de Silva, H.A.; de Silva, H.J.BACKGROUND AND AIM: Melatonin is used to treat sleep disturbances (SDs). The aim of this study was to investigate the safety and efficacy of low-dose melatonin for SDs in early-stage cirrhosis. METHODS: In a single-center, randomized, double-blind, placebo-controlled, cross-over clinical trial, patients with early-stage (Child-Turcotte-Pugh [CTP] class A or B) cirrhosis with SDs, without hepatic encephalopathy, were randomized to placebo or 3 mg of melatonin for 2 weeks. After 2 weeks, the patients were given a washout period of 1 week and crossed over to melatonin or placebo for a further 2 weeks. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to measure sleep quality and daytime sleepiness, respectively. Analysis of results was based on intention to treat, and linear mixed-effect models were used to evaluate the effect of melatonin. Analysis was conducted using R-programming language 3.5.1. RESULTS: Seventy-one patients were recruited (mean age: 61.9 ± 8.7 years, males: 46 [64.8%], and CTP Class A = 52 [73.2%] and Class B = 19 [26.8%]). Sixty patients completed the study (mean age: 61.7 ± 8.8 years, males: 40 [66.6%], and CTP Class A = 45 [75.0%] and Class-B = 15 [25.0%]). Two patients dropped out due to adverse events. Nine patients were lost to follow up. Patients given melatonin had a significantly lower PSQI and ESS compared to both pretreatment (P < 0.001) and postplacebo scores (P < 0.001). Incidence of adverse events was similar (two each of abdominal pain, one each of headache, one each of dizziness) in both groups. CONCLUSION: Melatonin seems safe and effective for use in patients with SDs in early-stage cirrhosis in the short term. However, larger and longer-term studies to assess efficacy and safety are required before its clinical use can be recommended. KEYWORDS: cirrhosis; clinical trial; melatonin; sleep disturbances; treatment.Item Combatting the Global Crisis of Cardiovascular Disease.(Carlton, Vic., Australia : Blackwell Science Asia, 2019) Palagyi, A.; de Silva, H.A.; Praveen, D.; Patel, A.No abstract availableItem Blood pressure variability and outcome in acute ischemic and hemorrhagic stroke: a post hoc analysis of the HeadPoST study.(Scientific & Medical, Macmillan Press, 2019) Minhas, J. S.; Wang, X.; Lavados, P.M.; Moullaali, T.J.; Arima, H.; Billot, L.; Hackett, M.L.; Olavarria, V.V.; Middleton, S.; Pontes-Neto, O.; de Silva, H.A.; Lee, T. H.; Pandian, J. D.; Mead, G. E.; Watkins, C.; Chalmers, J.; Anderson, C.S.; Robinson, T.G.; HeadPoST InvestigatorsThe Head Positioning in Acute Stroke Trial (HeadPoST) is a pragmatic, international, cluster crossover randomized trial of 11,093 patients with acute stroke assigned to a lying-flat (0°) or sitting-up (head elevated ≥30°) position. This post hoc analysis aimed to determine the association between blood pressure variability (BPV) and outcomes for patients from a wide range of international clinical settings and how the association was modified by randomized head position. BPV was defined according to the standard criteria, with the key parameter considered the coefficient of variation (CV) of systolic BP (SBP) over 24 h. Outcome was ordinal 90-day Modified Rankin Scale (mRS) score. The association was analyzed by ordinal, logistic regression, hierarchical, mixed models with fixed intervention (lying flat vs. sitting up), and fixed period, random cluster, and random cluster-period, effects. Nine thousand one hundred and fifty six (8324 acute ischemic stroke and 817 intracerebral hemorrhage; mean age 68.1 years; 39.2% women) were included in the analysis. CV of SBP had a significant linear association with unfavorable shift of mRS at 90 days (adjusted odds ratio 1.06, 95% confidence interval 1.02–1.11; P = 0.01). There was no heterogeneity of the association by randomized head positioning. In addition, CV of diastolic BP (DBP) (1.08, 1.03–1.12; P = 0.001) over 24 h post stroke was significantly associated with 3-month poor outcome. The association was more apparent in sitting-up position (1.12, 1.06–1.19) compared with lying-flat position (1.03, 0.98–1.09) (P interaction = 0.005). BPV was associated with adverse stroke outcome, and the magnitude of the association was greater with sitting-up head positioning in terms of DBP variability.Item Alirocumab in patients with polyvascular disease and recent acute coronary syndrome: ODYSSEY OUTCOMES Trial.(Elsevier, 2019) Jukema, J.W.; Szarek, M.; Zijlstra, L.E.; de Silva, H.A.; Bhatt, D.L.; Bittner, V.A.; Diaz, R.; Edelberg, J.M.; Goodman, S.G.; Hanotin, C.; Harrington, H. A.; Karpov, Y.; Moryusef, A.; Pordy, R.; Prieto, J.C.; Roe, M.T.; White, H.D.; Zeiher, A. M.; Schwartz, G. G.; Steg, P.G.; ODYSSEY OUTCOMES Committees and InvestigatorsBACKGROUND: Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACE) and death. The impact of lipid-lowering by proprotein convertase subtilisin−kexin type 9 (PCSK9) inhibition in such patients is undetermined. OBJECTIVES: This pre-specified analysis from ODYSSEY OUTCOMES determined whether polyvascular disease (polyVD) influenced risks of MACE and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. METHODS: Patients were randomized to alirocumab or placebo 1−12 months after ACS. The primary MACE endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint.RESULTS: Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyVD in two beds (coronary and peripheral artery or cerebrovascular), and 149 had polyVD in three beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACE by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, corresponding absolute risk reduction (ARR [95% confidence interval]) was 1.4% (0.6, 2.3), 1.9% (−2.4%, 6.2%), and 13.0% (−2.0, 28.0). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; ARR with alirocumab was 0.4% (−0.1, 1.0), 1.3% (−1.8%, 4.3%), and 16.2% (5.5, 26.8). CONCLUSION: In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyVD is associated with high risks of MACE and death. The large absolute reductions in those risks with alirocumab are a potential benefit for this population.