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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Larger size of Conn's adenoma is associated with lower cure rates post adrenalectomy(Springer-Verlag, 2024-11) XinYao , O. H.; Leong, E. K. F.; Chan, W.T.; Lee, J. W. K; Pinto, D; Yuan, N. K.; Parameswaran, R.BACKGROUND The cure for patients with primary hyperaldosteronism (PHA) secondary to solitary adrenal adenoma is adrenalectomy. We investigated the impact of size of Conns' tumour on hypertension resolution in a multi-ethnic South East Asian Cohort.METHODS Retrospective cohort study of patients who underwent surgery for PHA between January 2010 to December 2022 was performed. Clinicopathological parameters that included tumour size, blood pressure parameters, class and dosage of drugs, biochemical indices and details of surgery were collected. Cure of hypertension was defined as normal blood pressure post-adrenalectomy. Statistical significance was defined as a P value of < 0.05.RESULTS 94 patients (40 female:54 male; 102 women; age 49.3 ± 11.8 years) with PHA were operated on laparoscopically (79 trans-abdominal and 15 retroperitoneal approach). Tumour size ranged from 0.4 to 4.6 cm (mean 1.5 ± 0.6 cm). Hypertension Grades were Grade 1 in 38 (40%), Grade 2 in 45 (48%) and Grade 3 in 11 (12%) patients. Patients were on a mean of 3 classes of drugs prior to surgery and this decreased to mean of 1 class of drug post adrenalectomy. All patients were rendered normokalaemic and overall cure of the patients from hypertension was 82.0%. Large adenoma (defined as greater than 1.5 cm) resulting in a greater decrease in blood pressure (mean decrease of 32mmHg systolic, 15mmHg diastolic and MAP 20mmHg) in comparison to smaller adenomas (p = 0.003), but with lower cure rates of hypertension (p = 0.038).CONCLUSIONS Large Conn's adenomas result in a greater reduction in blood pressure post-adrenalectomy but with decreased cure rates of hypertension compared to the small adenomas.Item Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial(Elsevier, 2024-10) Rodgers, A.; Salam, A.; Schutte, A.E.; Cushman, W.C.; De Silva, H.A.; Tanna, G.L.D.; Grobbee, D.E.; Narkiewicz, K.; Ojji, D.B.; Poulter, N.R.; Schlaich, M.P.; Oparil, S.; Spiering, W.; Williams, B.; Jr, J.T.W.; Lakshman, P.; Uluwattage, W.; Hay, P.; Pereira, T.; Amarasena, N.; Ranasinghe, G.; Gianacas, C.; Shanthakumar, M.; Liu, X.; Wang, N.; Gnanenthiran, S.R.; Whelton, P.K.; GMRx2 InvestigatorsBACKGROUND Single-pill combinations (SPCs) of three low-dose antihypertensive drugs can improve hypertension control but are not widely available. A key issue for any combination product is the contribution of each component to efficacy and tolerability. This trial compared a new triple SPC called GMRx2, containing telmisartan, amlodipine, and indapamide, with dual combinations of components for efficacy and safety.METHODS In this international, randomised, double-blind, active-controlled trial, we enrolled adults with hypertension receiving between zero and three antihypertensive drugs, with a screening systolic blood pressure (SBP) ranging from 140-179 mm Hg (on no drugs) to 110-150 mm Hg (on three drugs). Participants were recruited from Australia, the Czech Republic, New Zealand, Poland, Sri Lanka, the UK, and the USA. In a 4-week active run-in, existing medications were switched to GMRx2 half dose (telmisartan 20 mg, amlodipine 2·5 mg, and indapamide 1·25 mg). Participants were then randomly allocated (2:1:1:1) to continued GMRx2 half dose or to each possible dual combination of components at half doses (telmisartan 20 mg with amlodipine 2·5 mg, telmisartan 20 mg with indapamide 1·25 mg, or amlodipine 2·5 mg with indapamide 1·25 mg). At week 6, doses were doubled in all groups, unless there was a clinical contraindication. The primary efficacy outcome was mean change in home SBP from baseline to week 12, and the primary safety outcome was withdrawal of treatment due to an adverse event from baseline to week 12. Secondary efficacy outcomes included differences in clinic and home blood pressure levels and control rates. This study is registered with ClinicalTrials.gov, NCT04518293, and is completed.FINDINGS The trial was conducted between July 9, 2021 and Sept 1, 2023. We randomly allocated 1385 participants to four groups: 551 to GMRx2, 276 to telmisartan-indapamide, 282 to telmisartan-amlodipine, and 276 to amlodipine-indapamide groups. The mean age was 59 years (SD 11), 712 (51%) participants self-reported as female and 673 (48·6%) male, and the mean clinic blood pressure at the screening visit was 142/85 mm Hg when taking an average of 1·6 blood pressure medications. Following the run-in on GMRx2 half dose, the mean clinic blood pressure level at randomisation was 133/81 mm Hg and the mean home blood pressure level was 129/78 mm Hg. At week 12, the mean home SBP was 126 mm Hg in the GMRx2 group, which was lower than for each of the dual combinations: -2·5 (95% CI -3·7 to -1·3, p<0·0001) versus telmisartan-indapamide, -5·4 (-6·8 to -4·1, p<0·0001) versus telmisartan-amlodipine, and -4·4 (-5·8 to -3·1, p<0·0001) versus amlodipine-indapamide. For the same comparisons, differences in clinic blood pressure at week 12 were 4·3/3·5 mm Hg, 5·6/3·7 mm Hg, and 6·3/4·5 mm Hg (all p<0·001). Clinic blood pressure control rate below 140/90 mm Hg at week 12 was superior with GMRx2 (74%) to with each dual combination (range 53-61%). Withdrawal of treatment due to adverse events occurred in 11 (2%) participants in the GMRx2 group, four (1%) in telmisartan-indapamide, three (1%) in telmisartan-amlodipine, and four (1%) in amlodipine-indapamide, with none of the differences being statistically significant.INTERPRETATION A novel low-dose SPC product of telmisartan, amlodipine, and indapamide provided clinically meaningful improvements in blood pressure reduction compared with dual combinations and was well tolerated. This SPC provides a new therapeutic option for the management of hypertension and its use could result in a substantial improvement in blood pressure control in clinical practice.Item Cross-fused right-to-left renal ectopia presenting as hypertension in a threeyear-old(Sri Lanka College of Paediatricians, 2023) Sandakelum, U.; Samararathna, R.; Kumarasiri, I.; Balasubramaniam, R.; Mettananda, S.No abstract availableItem 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 Sri Lankan infant with immunoglobulin resistant incomplete Kawasaki disease with a vesicular psoriasiform rash, hypertension and late onset small joint arthritis: a case report(BioMed Central, London, 2022) Hoole, T.J.; Athapathu, A.S.; Abeygunawardene, A.D.Background: Kawasaki disease (KD) is a medium and small vessel vasculitis which usually has a good response to immunoglobulin therapy (IVIG). We present a case of incomplete KD with IVIG resistance associated with an unusual combination of vesicular guttate-psoriasiform rash, hypertension and late onset small joint arthritis. Case presentation: A four-month-old male infant from Sri Lanka presented with high fever, conjunctival redness, pedal oedema and skin rash. He was found to have hypertension since admission with a high white cell count and high inflammatory markers. There was poor response to intravenous antibiotics and subsequent 2D echocardiogram revealed coronary artery aneurysms suggestive of KD. In the third week of illness he developed a vesiculo-papular rash involving face, trunk and limbs - which on biopsy revealed features of guttate psoriasis. Fever spikes continued and the coronary arteries showed progressive dilatation despite timely intravenous immunoglobulin administered on day 6 and methylprednisolone administered on day 10-13. Therapeutic response by means of reduction of fever was seen only after initiation of intravenous infliximab on day 28 of illness for which the fever responded within 24 hours. He developed a small joint arthritis of hands and feet on day 40 of illness which responded only after initiating methotrexate therapy. The hypertension persisted for 4 months after the onset of the illness before complete resolution. Conclusion: This case report depicts an unusual presentation of KD with a vesicular guttate-psoriasiform eruption, hypertension and late onset small joint arthritis. It highlights that clinicians should be aware of the fact that KD could present with such atypical manifestations and could develop unusual complications.Item Validation of the World Health Organization/ International Society of Hypertension (WHO/ISH) cardiovascular risk predictions in Sri Lankans based on findings from a prospective cohort study(Public Library of Science, 2021) Thulani, U.B.; Mettananda, K.C.D.; Warnakulasuriya, D.T.D.; Peiris, T.S.G.; Kasturiratne, K.T.A.A.; Ranawaka, U.K.; Chakrewarthy, S.; Dassanayake, A.S.; Kurukulasooriya, S.A.F.; Niriella, M.A.; de Silva, S.T.; Pathmeswaran, A.; Kato, N.; de Silva, H.J.; Wickremasinghe, A.R.INTRODUCTION AND OBJECTIVES: There are no cardiovascular (CV) risk prediction models for Sri Lankans. Different risk prediction models not validated for Sri Lankans are being used to predict CV risk of Sri Lankans. We validated the WHO/ISH (SEAR-B) risk prediction charts prospectively in a population-based cohort of Sri Lankans. METHOD: We selected 40-64 year-old participants from the Ragama Medical Officer of Health (MOH) area in 2007 by stratified random sampling and followed them up for 10 years. Ten-year risk predictions of a fatal/non-fatal cardiovascular event (CVE) in 2007 were calculated using WHO/ISH (SEAR-B) charts with and without cholesterol. The CVEs that occurred from 2007-2017 were ascertained. Risk predictions in 2007 were validated against observed CVEs in 2017. RESULTS: Of 2517 participants, the mean age was 53.7 year (SD: 6.7) and 1132 (45%) were males. Using WHO/ISH chart with cholesterol, the percentages of subjects with a 10-year CV risk <10%, 10-19%, 20%-29%, 30-39%, ≥40% were 80.7%, 9.9%, 3.8%, 2.5% and 3.1%, respectively. 142 non-fatal and 73 fatal CVEs were observed during follow-up. Among the cohort, 9.4% were predicted of having a CV risk ≥20% and 8.6% CVEs were observed in the risk category. CVEs were within the predictions of WHO/ISH charts with and without cholesterol in both high (≥20%) and low(<20%) risk males, but only in low(<20%) risk females. The predictions of WHO/ISH charts, with-and without-cholesterol were in agreement in 81% of subjects (ĸ = 0.429; p<0.001). CONCLUSIONS: WHO/ISH (SEAR B) risk prediction charts with-and without-cholesterol may be used in Sri Lanka. Risk charts are more predictive in males than in females and for lower-risk categories. The predictions when stratifying into 2 categories, low risk (<20%) and high risk (≥20%), are more appropriate in clinical practice.Item Risk factors for Pregnancy induced Hypertension(College of the Community Physicians of Sri Lanka, 2007) Perera, N.; Abeysena, C.OBJECTIVE: TO determine the risk factors for pregnancy induced hypertension (PIH). METHODOLOGY: The study was a case control study which was carried out at Castle Street Hospital for Women during August to September 2006. Hundred mothers newly diagnosed as having PlH. were Chosen as cases and 100 with uncomplicated pregnancies as controls. Both cases and controls had a period of amenorrhoea of >20 weeks. Psychosocial Stress was measured using General Health Questionnaire -30 (GHQ) and Modified Life Event inventory. Maternal socio-demographic information and other data were collected using an interviewer administered questionnaire and a record sheet. Multivariate logistic regression analysis was applied to control for confounders and the results were expressed as odds ratios (OR) and 95% confidence intervals (95%Cl). RESULTS: After adjusting for confounding effect experience of ≥2 life events during pregnancy (OR:2.1, 95%Cl:1.1 - 10.9), a maternal BMl of ≥26kg/m2 (OR:2.4, 95%Cl:1.1- 5.0), maternal age of ≥28 years (OR:3.9, 95%Cl:2.0-7.5), history of ante partum haemorrhage (OR:3.4, 95%Clz1.1 - 10.9) and standing for >1.5 hours at one stretch per day (OR:3.4, 95%Cl:1.6 - 7.4) had statistically significant associations with developing PlH. A GHQ score of >5 was not associated with PlH (OR:3.0, 95%Cl: 1.0 -10.0). CONCLUSION: Experience of 22 life events during pregnancy, BMl ≥26 kg/m2, maternal age of ≥28 years, history of antepartum haemoghage and standing for more than 1.5 hours at one stretch per day were risk factors for PlH.Item Compliance with antihypertensive medications and its associations and knowledge on Hypertension-Hospital based study in Sri Lanka(Sri Lanka College of Internal Medicine, 2019) Medagedara, A.U.; Thampoe, R.S.; Batagoda, B.M.S.M.; Mendis, W.A.S.; Martin, V.T.; Mettananda, K.C.D.BACKGROUND: Hypertension is the commonest preventable risk factor for the development of cardio and cerebrovascular disorders. Poor compliance with anti-hypertensive medications is an important yet often an under recognized risk factor for uncontrolled hypertension and rarely has this aspect been investigated thus far in Sri Lanka. OBJECTIVES: To determine the prevalence and associations of compliance with antihypertensive medications and the knowledge on hypertension among patients attending to medical clinics conducted by the Department of Medicine of the Faculty of Medicine, Ragama. METHODS: An interviewer-administered questionnaire and the patients' clinic records were utilized to collect data. Prevalence was assessed using SPSS 22 version. Associated factors were analyzed by binary logistic regression. RESULTS: Prevalence of medium and low compliance are 42.3% and 35.1% respectively. Factors significantly associated with poor compliance were not starting treatment at all due to the feeling that it's better not to start a treatment that they'll have to continue for the whole lifetime (p value 0.04), frequency at which medications have to be taken being too difficult to be followed (p value 0.00), finding it difficult to comprehend the instructions provided by the pharmacist (p value 0.00) and lack of knowledge on hypertension (p value 0.00). CONCLUSION: Compliance with antihypertensive medications can be enhanced by rectifying patients' misconceptions on hypertension.Item Validation of the World Health Organization/ International Society of Hypertension (WHO/ISH) cardiovascular risk predictions in Sri Lankans based on findings from a prospective cohort study(Ceylon College of Physicians, 2020) Thulani, U.B.; Mettananda, K.C.D.; Warnakulasuriya, D.T.D.; Peiris, T.S.G.; Kasturiratne, K.T.A.A.; Ranawaka, U.K.; Chackrewarthy, S.; Dassanayake, A.S.; Kurukulasooriya, S.A.F.; Niriella, M.A.; de Silva, S.T.; Pathmeswaran, A.P.; Kato, N.; de Silva, H.J.; Wickremasinghe, A.R.INTRODUCTION AND OBJECTIVES: There are no cardiovascular(CV)-risk prediction models specifically for Sri Lankans. Different risk prediction models not validated among Sri Lankans are being used to predict CV-risk of Sri Lankans. We validated the WHO/ISH (SEAR-B) risk prediction charts prospectively in a population-based cohort of Sri Lankans. METHOD: We selected participants between 40-64 years, by stratified random sampling of the Ragama Medical Officer of Health area in 2007 and followed them up for 10-years. Risk predictions for 10-years were calculated using WHO/ISH (SEAR-B) charts with- and without-cholesterol in 2007. We identified all new-onset cardiovascular events(CVE) from 2007-2017 by interviewing participants and perusing medical-records/death-certificates in 2017. We validated the risk predictions against observed CVEs. RESULTS: Baseline cohort consisted of 2517 participants (males 1132 (45%), mean age 53.7 (SD: 6.7 years). We observed 215 (8.6%) CVEs over 10-years. WHO/ISH (SEAR B) charts with and without-cholesterol predicted 9.3% (235/2517) and 4.2% (106/2517) to be of high CV-risk ≥20%), respectively. Risk predictions of both WHO/ISH (SEAR B) charts with- and without-cholesterol were in agreement in 2033/2517 (80.3%). Risk predictions of WHO/ISH (SEAR B) charts with and with out-cholesterol were in agreement with observed CVE percentages among all except in high risk females predicted by WHO/ISH (SEAR B) chart with-cholesterol (observed risk 15.3% (95% Cl 12.5 - 18.2%) and predicted risk 2::20%). CONCLUSIONS: WHO/ISH (SEAR B) risk charts provide good 10-year CV-risk predictions for Sri Lankans. The predictions of the two charts, with and without-cholesterol, appear to be in agreement but the chart with-cholesterol seems to be more predictive than the chart without-cholesterol. Risk charts are more predictive in males than in females. The predictive accuracy was best when stratified into two categories; low (<20%) and high (≥20%) risk.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.).