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

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Abnormal functions of pottasium channels in the platelets of patients with Alzheimer's disease
(Lancet Publishing Group, 1998) de Silva, H.A.; Aronson, J.K.; Grahame-Smith, D.G.; Jobst, K.A.; Smith, A.D.
BACKGROUND:Reports of abnormalities of potassium-channel function in various cultured cells of Alzheimer's disease patients led us to attempt to characterise the pharmacological characteristics of the abnormal channel.METHODS: We studied platelets from 14 patients with Alzheimer-type dementia and 14 non-demented controls matched for age and sex. The effects of specific inhibitors of K+ channels on the efflux of rubidium-86 ions, a radioactive analogue of K+, from the platelets were measured.FINDINGS: Normal platelets contain three types of K+ channel, sensitive to the inhibitory actions of apamin (small-conductance calcium-dependent potassium channels), charybdotoxin (of less specificity, but probably intermediate-conductance calcium-dependent K+ channels), and alpha-dendrotoxin (voltage-sensitive K+ channels). However, 8Rb+ efflux from the platelets of patients with Alzheimer-type dementia was not inhibited by either apamin or charybdotoxin. By contrast, inhibition by alpha-dendrotoxin did occur. INTERPRETATION: Our results suggest that calcium-dependent K+ channels in platelets are selectively impaired in Alzheimer's disease. A similar abnormality in neurons could contribute to the pathophysiology of the disorder.
Acceptance and attitudes of healthcare staff towards the introduction of clinical pharmacy service: a descriptive cross-sectional study from a tertiary care hospital in Sri Lanka
(Biomed Central, 2017) Shanika, L.G.T.; Wijekoon, C.N.; Jayamanne, S.; Coombes, J.; Mamunuwa, N.; Dawson, A.H.; de Silva, H.A.
BACKGROUND: Multidisciplinary patient management including a clinical pharmacist shows an improvement in patient quality use of medicine. Implementation of a clinical pharmacy service represents a significant novel change in practice in Sri Lanka. Although attitudes of doctors and nurses are an important determinant of successful implementation, there is no Sri Lankan data about staff attitudes to such changes in clinical practice. This study determines the level of acceptance and attitudes of doctors and nurses towards the introduction of a ward-based clinical pharmacy service in Sri Lanka. METHODS: This is a descriptive cross-sectional sub-study which determines the acceptance and attitudes of healthcare staff about the introduction of a clinical pharmacy service to a tertiary care hospital in Sri Lanka. The level of acceptance of pharmacist's recommendations regarding drug-related problems (DRPs) was measured. Data regarding attitudes were collected through a pre-tested self-administered questionnaires distributed to doctors (baseline, N =13, post-intervention period, N = 12) and nurses (12) worked in professorial medical unit at baseline and post-intervention period. RESULTS: A total of 274 (272 to doctors and 2 to nurses) recommendations regarding DRPs were made. Eighty three percent (225/272) and 100% (2/2) of the recommendations were accepted by doctors and nurses, respectively. The rate of implementation of pharmacist's recommendations by doctors was 73.5% (200/272) (95% CI 67.9 - 78.7%; P < 0.001). The response rate of doctors was higher at the post-intervention period (92.3%; 12/13) compared to the baseline (66.7%; 8/12). At the post-intervention survey 91.6% of doctors were happy to work with competent clinical pharmacists and accepted the necessity of this service to improve standards of care. The nurses' rate of response at baseline and post-intervention surveys were 80.0 and 0.0% respectively. Their perceptions on the role of clinical pharmacist were negative at baseline survey. CONCLUSIONS: There was high acceptance and implementation of clinical pharmacist's recommendations regarding DRPs by the healthcare team. The doctors' views and attitudes were positive regarding the inclusion of a ward-based pharmacist to the healthcare team. However there is a need to improve liaison between clinical pharmacist and nursing staff.
Adverse drug reactions in a cohort of Sri Lankan patients with non-communicable chronic diseases
(Sri Lanka Medical Association, 2016) Shanika, L.G.T.; Wijekoon, C.N.; Jayamanne, S.; Coombes, J.; de Silva, H.A.; Dawson, A.
INTRODUCTION AND OBJECTIVES: Adverse drug reactions (ADRs) are a major problem in drug utilization. The study aimed to describe the incidence and nature of ADRs in a cohort of Sri Lankan patients with non-communicable chronic diseases (NCCDs). METHOD: This prospective observational study conducted in a tertiary-care hospital recruited in-ward patients with NCCDs. All ADRs that occurred during the index hospital admission and in the 6-month period following discharge were detected by active surveillance. Details were recorded using the ADR reporting form, developed based on the publication of the Clinical Center, Pharmacy Department, National Institutes of Health. RESULTS: 715 patients were studied (females-50.3%, mean age–57.6 years). The mean number of medicines given per patient was 6.11±2.97. The most prevalent NCCDs were hypertension (48.4%; 346/715), diabetes (45.3%; 324/715) and ischemic heart disease (29.4%; 210/715). 112 patients (15.7%) experienced at least one ADR. In the 112 patients, 154 ADRs (33 during index hospital admission; 121 during 6-month period following discharge) were detected. 51.9% (80/154) of them were potentially avoidable. 47% (73/154) of ADR swere Serious Adverse Events (SAEs); 13 were life threatening, 46 caused hospitalization and 14 caused disability. The most common causes for re-hospitalization due to ADRs were hypoglycemia due to anti-diabetic drugs (17/46), bleeding due to warfarin (14/46) and hypotension due to anti-hypertensives (6/46). CONCLUSIONS: Incidence of ADRs was high in the study population. A large proportion of them were SAEs. The majority of ADRs that required re-hospitalization were caused by widely used medicines and were potentially avoidable.
Adverse reactions to snake antivenom, and their prevention and treatment.
(Wiley-Blackwell, 2016) de Silva, H.A.; Ryan, N.M.; de Silva, H.J.
Antivenom is the mainstay of treatment of snakebite envenoming. However, adverse reactions to snake antivenom that is available are common in many parts of the world where snakebite is prevalent; both acute (anaphylactic or pyrogenic) and delayed (serum sickness type) reactions occur. Acute reactions are usually mild but severe systemic anaphylaxis may develop, often within an hour or so of exposure to antivenom. Serum sickness after antivenom has a delayed onset between 5 and 14 days after its administration. Ultimately, the prevention reactions will depend mainly on improving the quality of antivenom. Until these overdue improvements take place, doctors will have to depend on pharmacological prophylaxis, where the search for the best prophylactic agent is still on-going, as well as careful observation of patients receiving antivenom in preparation for prompt management of acute as well as delayed reactions when they occur. This article is protected by copyright. All rights reserved.
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/ )
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 Investigators
BACKGROUND: 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.
Alzheimer disease in Sri Lanka
(2007) de Silva, H.A.
Alzheimer's disease in Sri Lanka
(Ceylon College of Physicians, 2003) de Silva, H.A.
Alzheimer's disease with cerebrovascular disease: current status in the Asia-Pacific region
(Wiley-Blackwell, 2016) Chen, C.; Homma, A.; Mok, V.C.; Krishnamoorthy, E.; Alladi, S.; Meguro, K.; Abe, K.; Dominguez, J.; Marasigan, S.; Kandiah, N.; Kim, S.Y.; Lee, D.Y.; de Silva, H.A.; Yang, Y.H.; Pai, M.C.; Senanarong, V.; Dash, A.
BACKGROUND: There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well-defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia. METHODS: Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available. RESULTS: AD accounts for up to 60% and AD+CVD accounts for 10-20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First-line therapy is usually an acetylcholinesterase inhibitor such as donepezil. CONCLUSION: AD+CVD is likely to be under-recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease.
Alzheimer's disease--time to act is now
(Sri Lanka Medical Association, 2005) de Silva, H.A.
No Abstract Available
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.
Ante-mortem diagnosis of Alzheimer's disease (AD) by measuring medial temporal lobe (MTL) thickness on CT scans
(Sri Lanka Medical Association, 2003) de Silva, H.A.; Gunatilake, S.B.
Abstract Available
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 Group
Importance: 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.
Autonomic functions and gastric motility in children with functional abdominal pain disorders
(WJG Press, 2019) Karunanayake, A.; Rajindrajith, S.; de Silva, H.A.; Gunawardena, S.; Devanarayana, N.M.
BACKGROUND: Abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs) are the most common cause of recurrent abdominal pain in children. Despite its high prevalence, the underlying pathophysiology of this condition is poorly understood. AIM: To assess the role of gastric dysmotility and autonomic nervous system dysfunction in the pathophysiology of AP-FGIDs. METHODS: One hundred children, fulfilling Rome III criteria for AP-FGIDs, and 50 healthy controls, aged 5 to 12 years, were recruited after obtaining parental consent. All patients were investigated for underlying organic disorders. Gastric motility and cardiovascular autonomic functions were assessed using validated non-invasive techniques. RESULTS:The main gastric motility parameters assessed (gastric emptying rate [45.7 vs 59.6 in controls], amplitude [48.7 vs 58.2], frequency of antral contractions [8.3 vs 9.4], and antral motility index [4.1 vs 6.4]) were significantly lower in children with AP-FGIDs (P < 0.05). The post-prandial antral dilatation at 1 min after the test meal significantly correlated with the severity of abdominal pain (P < 0.05). Assessment of autonomic functions in AP-FGID patients showed neither a significant difference compared to the control group, nor a correlation with gastric motility abnormalities (P > 0.05). The duration of pain episodes negatively correlated with the parasympathetic tone (maladaptive parasympathetic tone) (P < 0.05).CONCLUSION: Children with AP-FGIDs have abnormal gastric motility but normal cardiovascular autonomic functions. There is no relationship between abnormal gastric motility and autonomic functions. The pathogenesis of AP-FGIDs is not related to cardiovascular autonomic dysfunction.
B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial.
(Lancet Pub. Group, 2010) Hankey, G.J.; Eikelboom, J.W.; Baker, R.I.; Gelavis, A.; Hickling, S.C.; Jamrozik, K.; van Bockxmeer, F.M.; Vasikaran, S.; Chen, C.; Eikelboom, J.W.; Lees, K.R.; Yi, Q.; Hankey, G.J.; Algra, A.; Chen, C.; Wong, M.C.; Cheung, R.; Wong, I.; Divjak, I.; Ferro, J.; De Freitas, G.; Gommans, J.; Groppa, S.; Hill, M.; Spence, J.D.; Lees, K.R.; Lisheng, L.; Navarro, J.; Ranawaka, U.; Ricci, S.; Schmidt, R.; Slivka, A.; Tan, A.; Tsiskaridze, A.; Uddin, W.; Vanhooren, G.; Xavier, D.; Armitage, J.; Hobbs, M.; Le, M.; Sudlow, C.; Wheatley, K.; Yi, Q.; Brown, W.; Bulder, M.; Eikelboom, J.W.; Hankey, G.J.; Ho, W.K.; Jamrozik, K.; Klijn, C.J.; Koedam, E.; Langton, P.; Nijboer, E.; Tuch, P.; Pizzi, J.; Tang, M.; Alaparthi, R.; Antenucci, M.; Chew, Y.; Chinnery, C.; Cockayne, C.; Holt, R.; Loh, K.; McMullin, L.; Mulholland, G.; Nahoo, B.; Read, E.; Smith, F.; Yip, C.Y.; Hankey, G.J.; Loh, K.; Crimmins, D.; Davis, T.; England, M.; Rakic, V.; Schultz, D.W.; Frayne, J.; Bladin, C.; Kokkinos, J.; Dunbabin, D.; Harper, J.; Rees, P.; Warden, D.; Levi, C.; Parsons, M.; Russell, M.; Spratt, N.; Clayton, P.; Nayagam, P.; Sharp, J.; Grainger, K.; De Wytt, C.; McDougall, A.; Donnan, G.A.; Grimley, R.; Neynens, E.; Reinhart, B.; Ropele, S.; Schmidt, R.; Stögerer, E.; Dedeken, P.; Schelstraete, C.; Vanhooren, G.; Veyt, A.; Andre, C.; De Freitas, G.R.; Gomes, S.E.; Mok, V.C.; Wong, A.; Wong, L.K.; Cheung, R.T.; Li, L.S.; Pais, P.; Xavier, D.; Joshi, S.; Parthasaradhi, S.; Roy, A.K.; Varghese, R.V.; Kochar, K.; Panwar, R.B.; Chidambaram, N.; Rajasekaharan, U.; Bala, S.; Pandian, J.D.; Singh, Y.; Karadan, U.; Salam, A.; Shivkumar, S.; Sundararajan, A.; Joshi, R.; Kalantri, S.P.; Singh, H.; Rath, A.; Balasubramanian, N.T.; Kalanidhi, A.; Babu, K.; Bharani, A.; Choudhary, P.; Jain, M.; Agarwal, A.; Singh, M.; Agarwal, R.R.; Gupta, R.; Kothari, S.; Mijar, S.; Wadia, R.S.; Paul, S.K.; Sekhar Nandi, S.; Mehndiratta, M.M.; Tukaram, U.; Mittal, K.; Rohatgi, A.; Kumar, S.; Vinayan, K.P.; Muralidharan, R.S.; Celani, M.G.; Favorito, I.; Mazzoli, T.; Ricci, S.; Righetti, E.; Blundo, M.; Carnemolla, A.; D'Asta, A.; Giordano, A.; Iemolo, F.; Favorito, L.; Mazzoli, T.; Ricci, S.; Righetti, E.; Gresele, P.; Guercini, F.; Caporalini, R.; De Dominicis, L.; Giovagnetti, M.; Giuliani, G.; Paoletti, S.; Pucci, E.; Cavallini, A.; Persico, A.; Casoni, F.; Costa, A.; Magoni, M.; Spezi, R.; Tortorella, R.; Venturelli, E.; Vergani, V.; Caprioli, S.; Provisione, M.; Zanotta, D.; Abdullah, J.M.; Damitri, T.; Idris, B.; Sayuthi, S.; Hong, J.J.; Tan, C.T.; Tan, K.S.; Dutca, G.; Grigor, V.; Groppa, S.; Manea, D.; Achterberg, S.; Algra, A.; Halkes, P.H.; Kappelle, L.J.; Boon, A.M.; Doelman, J.C.; Sips, R.; Visscher, F.; Kwa, V.I.; Ternede, O.A.; van der Sande, J.J.; Frendin, T.; Gommans, J.; Anderson, N.E.; Bennett, P.; Charleston, A.; Spriggs, D.; Singh, J.; Bourke, J.; Bucknell, R.; McNaughton, H.; Anwar, A.; Murtaza, H.; Uddin, W.; Ismail, J.; Khan, N.U.; Navarro, J.C.; Amor, V.G.; Canete, M.T.; Lim, C.; Ravelo, E.B.; Siguenza, M.; Villahermosa, M.O.; Siguenza, M.; Canete, M.T.; Cardino, M.J.; Cenabre, R.; Gara, M.; Salas, Z.; Batac, A.; Canete, M.T.; Conde, L.; Dumdum, P.; Garcia, F.S.; Libarnes, S.; Matig-a, N.; Olanda, N.; Arcenas, R.; Canete, M.T.; Loraña, A.; Surdilla, A.; Araullo, M.L.; Lokin, J.; Maylem, G.; Marques, E.; Veloso, M.; Correia, M.; Lopes, G.; Canhão, P.; Ferro, J.M.; Melo, T.P.; Dias, A.; Sousa, A.P.; Tsiskaridze, A.; Vashadze, T.; Divjak, I.; Papic, V.; Chang, H.M.; Chen, C.P.; de Silva, D.A.; Tan, E.K.; Ranawaka, U.K.; Wijesekera, J.C.; de Silva, H.A.; Wijekoon, C.N.; Dawson, U.K.; Higgins, P.; Lees, K.R.; MacDonald, L.; McArthur, K.; McIlvenna, Y.; Quinn, T.; Walters, M.; Curless, R.; Dickson, J.; Murdy, J.; Scott, A.; Cameron, S.; Darnley, K.; Dennis, M.; Lyle, D.; Hunter, A.; Watt, M.; Watt, M.; Wiggam, I.; Murdy, J.; Rodgers, H.; Dick, F.; Macleod, M.; McKenzie, A.; Jones, P.; Jones, S.; Hussain, M.; Albazzaz, M.K.; Elliott, K.; Hardware, B.; Bacabac, E.; Martin, H.; Sharma, A.; Sutton, V.; Baht, H.; Cowie, L.; Gunathilagan, G.; Hargrove, D.R.; Smithard, D.J.; Adrian, M.; Bath, P.; Hammonds, F.; Maguire, H.; Roff, C.; Datta-chaudhuri, M.; Diyazee, K.; Krishnamoorthy, S.; McNulty, K.; Okwera, J.; Hilaire, C.; Kelly, D.; Barron, L.; James, M.; Wedge, N.; Bruce, M.; Macleod, M.; Barber, M.; Esson, D.; Ames, D.; Chataway, J.; Bulley, S.; Jenkins, K.; Rashed, K.; Dafalla, B.E.; Venugopalan, T.C.; Ball, M.; Punnoose, S.; Justin, F.; Sekaran, L.; Sethuraman, S.; Goddard, H.; Howard, J.; McIlmoyle, J.; Diver-Hall, C.; McCarron, M.; McNicholl, M.P.; Clamp, B.; Hunter, J.; Oke, A.; Weaver, A.; Fraser, P.; McAlpine, C.; Chambers, J.; Dymond, H.; Saunders, G.; Langhorne, P.; Stott, D.; Wright, F.; Adie, K.; Bland, R.; Courtauld, G.; Harrington, F.; James, A.; Mate, A.; Schofield, C.; Wroath, C.; Duberley, S.; Punekar, S.; Niranjan, K.; Sandler, D.; Krishna, P.; Moussouttas, M.; Notestine, M.A.; Slivka, A.; Vallini, D.; Hwang, T.; Saverance, M.; Booth, K.; Murphy, D.
BACKGROUND: Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye. METHODS: In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0.5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratified by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444. FINDINGS: Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk reduction 1.56%, -0.01 to 3.16). There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups. INTERPRETATION: Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins. FUNDING: Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, Singapore National Medical Research Council, Australia National Heart Foundation, Royal Perth Hospital Medical Research Foundation, and Health Department of Western Australia.
Baseline characteristics of the 4011 patients recruited into the Efficacy of Nitric Oxide in Stroke' (ENOS) trial.
(Sage Publications, 2014) Bath, P.M.; Adami, A.; Bereczki, D.; Berge, E.; Beridze, M.; Cala, L.; Casado, A.; Caso, V.; Chang, H.M.; Christensen, H.; Collins, R.; Czlonkowska, A.; Dineen, R.A.; El Etribi, A.; Ghani, A. R.; Gommans, J.; Koumellis, P.; Laska, A. C.; Lees, K. R.; Navarro, J.; Ntaios, G.; Ozturk, S.; Phillips, S.; Pocock, S.; Prasad, K.; Scutt, P.; de Silva, H.A.; Szatmari, S.; Díez-Tejedor E; Utton, S.; Wang, Y. J.; Wardlaw, J.M.; Whynes, D.; Wong, L.; Woodhouse, L; Sprigg, N.; ENOS Trial Investigators(36)
BACKGROUND: High blood pressure is common in acute stroke and associated with a worse functional outcome. Many patients who present with acute stroke are taking prescribed antihypertensive therapy before their stroke. AIMS: ENOS tested whether lowering blood pressure and continuing pre-stroke antihypertensive therapy are each safe and effective. METHODS: This study is an international multi-centre prospective randomized single-blind blinded-endpoint parallel-group partial-factorial controlled trial of transdermal glyceryl trinitrate(a nitric oxide donor, given for seven-days) vs. no glyceryl trinitrate, and of continuing vs. stopping (temporarily for seven-days) pre-stroke antihypertensive drugs if relevant, in patients with acute ischaemic stroke or intracerebral haemorrhage and high systolic blood pressure (140–220 mmHg). RESULTS: Recruitment ran from July 2001 to October 2013. Four thousand eleven patients [2097 (52•3%) in the continue/stop arm] were recruited from 173 sites across 23 countries in 5 continents (Asia 14%, Continental Europe 16%, UK 64%). Baseline characteristics include: mean age 70 (standard deviation 12) years; male 57%; mean time from stroke to recruitment 26 (13) h; mean severity (Scandinavian Stroke Scale) 34(13) of 58; mean blood pressure 167 (19)/90 (13) mmHg; ischaemic stroke 83%; and intracerebral haemorrhage 16%. The main trial results will be presented in May 2014. The results will also be presented in updated Cochrane systematic reviews and included in individual patient data meta-analyses of all relevant randomized controlled trials. CONCLUSION: ENOS is a large completed international trial of blood pressure management in acute stroke and includes patients representative of many stroke services worldwide.
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 Investigators
The 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.
Breast examination of older women in a teaching hospital
(Sri Lanka Medical Association, 2001) de Silva, H.A.; Jayasekara, W.M.P.R.; Mangalika, H.A.R.
INTRODUCTION: Breast examination during routine physical examination may help detect breast cancer and effect early treatment. OBJECTIVE: To determine whether doctors routinely perform breast examination in older women, and to assess attitudes of patients and doctors to this examination. METHODS: A questionnaire based survey of 150 women over 65 years attending a teaching hospital, and 51 doctors working in this hospital. RESULTS: Very few women had a breast examination performed by a doctor. All thought breast examination was important, and would give consent for this examination. Although the great majority of doctors thought breast examination should be done routinely only very few do so. CONCLUSION: Older women have a positive attitude towards breast examination, but this is not reflected by the practice of doctors. There is a need for change in attitudes and training among doctors so that breast examination would be performed routinely.
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.
Case report: Opportunities for Medication Review and Reconciliation by a Clinical Pharmacist to Prevent Drug-Related Hospital Re-Admissions: Evidence from a Case Series in Sri Lanka
(Pharmaceutical Journal of Sri Lanka, 2018) Shanika, L.G.T.; Wijekoon, C.N.; Jayamanne, S.; Coombes, J.; Perera, D.; Pathiraja, V.M.; Mamunuwa, N.; Mohamed, F.; Coombes, I.; Lynch, C.; de Silva, H.A.; Dawson, A.H.
ABSTRACT: Medication review by a clinical pharmacist improves quality use of medicines in patients by identifying, reducing and preventing drug related problems and hospital re-admissions. This service is new to Sri Lanka. We present two cases from a non-randomized controlled trial conducted in a tertiary care hospital in Sri Lanka. The first case is from the control group where no clinical pharmacist was engaged and the next case is from the intervention group. The first case was a drug related hospital re-admission because of missing medicines in the discharge prescription and the second case was a re-admission which was prevented by the intervention of a ward pharmacist by performing a clinical medication review of the prescription.