Medicine
Permanent URI for this communityhttp://repository.kln.ac.lk/handle/123456789/12
This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
Browse
15 results
Search Results
Item Rationale for a new low-dose triple single pill combination for the treatment of hypertension(Elsevier, 2024) Rodgers, A.; Salam, A.; Cushman, W.; de Silva, A.; Tanna, G.L.D.; Gnanenthiran, S.R.; Grobbee, D.; Narkiewicz, K.; Ojji, D.; Oparil, S.; Poulter, N.; Schlaich, M.P.; Schutte, A.E.; Spiering, W.; Williams, B.; Wright, J.T.Jr.; Whelton, P.Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these 'hypertension polypills' were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.Item Assessing reversibility of liver fibrosis in patients with transfusion-dependent beta thalassaemia following intensive chelation(Sri Lanka Medical Association, 2023) Padeniya, A.G.P.M.; Ediriweera, D.; Niriella, M.A.; de Silva, A.; Premawardhena, A.P.INTRODUCTION: Transfusion-related iron overload is a leading cause of hepatic fibrosis in transfusion-dependent thalassaemia (TDT). OBJECTIVES: This study aimed to evaluate the reversibility of liver fibrosis with intensive chelation therapy in TDT. METHODS: Forty-five patients were included. Serum ferritin, hepatic fibrosis & steatosis (assessed by Transient Elastography), and liver iron concentration/LIC (estimated by FerriScan) were recorded at recruitment and after 2 ½ years of intensive chelation. Compliance for iron chelators was monitored and recorded as good (gc), moderate compliance (mc), and poor (pc) compliance based on the number of days the iron chelators were used. RESULTS: 22/45 (49%) were males [mean age (SD)-19 (4.78) years]. There were 23 (51%), 12 (27%), and 10 (22%) patients with gc, mc, and pc with iron chelators, respectively. The LIC decreased in 36 (80%) patients. The median LIC reduction after 2 ½ years was as follows: gc group-13.5 to 5.1 mg Fe/g dw (P=0.0002); mc group-25.5 to 17.75 mg Fe/g dw (P=0.001). In the pc group, the LIC increased by 10.4 mg Fe/g dw (P =0.058). Liver fibrosis declined in 23 (51%) patients. The liver stiffness at recruitment and after 2 ½ years was 7.6 and 7.1 kPa (P=0.08) in the gc group. In both mc and pc groups, liver fibrosis increased on follow-up [significantly worsened in the pc group (P=0.04)]. CONCLUSION: The reduction of LIC in TDT was related to compliance with chelation therapy; substantial reductions were achieved in those with gc and mc. However, only those with gc managed to arrest the fibrosis progression.Item The third intensive care bundle with blood pressure reduction in acute cerebral haemorrhage trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial(Elsevier, 2023) Ma, L.; Hu, X.; Song, L.; Chen, X.; Ouyang, M.; Billot, L.; Li, Q.; Malavera, A.; Li, X.; Muñoz-Venturelli, P.; de Silva, A.; Thang, N.H.; Wahab, K.W.; Pandian, J.D.; Wasay, M.; Pontes-Neto, O.M.; Abanto, C.; Arauz, A.; Shi, H.; Tang, G.; Zhu, S.; She, X.; Liu, L.; Sakamoto, Y.; You, S.; Han, Q.; Crutzen, B.; Cheung, E.; Li, Y.; Wang, X.; Chen, C.; Liu, F.; Zhao, Y.; Li, H.; Liu, Y.; Jiang, Y.; Chen, L.; Wu, B.; Liu, M.; Xu, J.; You, C.; Anderson, C.S.; INTERACT3 InvestigatorsBACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.Item Recurrent vaginal vault dehiscence and evisceration following total laparoscopic hysterectomy, successfully repaired with polypropylene mesh and sacrocolpopexy(Oxford University Press, 2022) Rathigashini, R.; Wanniarachchi, W.A.D.P.; de Silva, A.; Herath, R.P.Recurrent vault dehiscence is a rare and potentially serious complication following hysterectomy. We report a rare case of recurrent vault dehiscence and evisceration following a total laparoscopic hysterectomy (TLH) which was successfully repaired with polypropylene mesh and sacro-colpopexy. A 47-year-old multiparous woman underwent TLH for adenomyosis. During the surgery, vaginal wall was incised with monopolar diathermy and sutured with synthetic absorbable barbed suture in a single layer. She presented 12 weeks later with vault dehiscence and evisceration of omentum. Laparoscopically, eviscerated omental part was removed and the vaginal cuff was repaired vaginally with absorbable synthetic suture. She came with a recurrence in 3 months with vault dehiscence and a vault prolapse without any evisceration. She underwent laparoscopic mesh repair of the vault combined with laparoscopic Sacro-colpopexy with complete recovery. Incidence of vault dehiscence is found to be higher in TLH than abdominal or vaginal hysterectomy. Treatment options for recurrent vault dehiscence involve strengthening the vault with tissues, or with a prosthesis.Item Effects of a Lifestyle Intervention to Prevent Deterioration in Glycemic Status Among South Asian Women With Recent Gestational Diabetes: A Randomized Clinical Trial(American Medical Association, 2022) Tandon, N.; Gupta, Y.; Kapoor, D.; Lakshmi, J.K.; Praveen, D.; Bhattacharya, A.; Billot, L.; Naheed, A.; de Silva, A.; Gupta, I.; Farzana, N.; John, R.; Ajanthan, S.; Divakar, H.; Bhatla, N.; Desai, A.; Pathmeswaran, A.; Prabhakaran, D.; Joshi, R.; Jan, S.; Teede, H.; Zoungas, S.; Patel, A.; LIVING Collaborative Group.Importance: Women with recent gestational diabetes (GDM) have increased risk of developing type 2 diabetes. Objective: To investigate whether a resource-appropriate and context-appropriate lifestyle intervention could prevent glycemic deterioration among women with recent GDM in South Asia. Design, setting, and participants: This randomized, participant-unblinded controlled trial investigated a 12-month lifestyle intervention vs usual care at 19 urban hospitals in India, Sri Lanka, and Bangladesh. Participants included women with recent diagnosis of GDM who did not have type 2 diabetes at an oral glucose tolerance test (OGTT) 3 to 18 months postpartum. They were enrolled from November 2017 to January 2020, and follow-up ended in January 2021. Data were analyzed from April to July 2021. Interventions: A 12-month lifestyle intervention focused on diet and physical activity involving group and individual sessions, as well as remote engagement, adapted to local context and resources. This was compared with usual care. Main outcomes and measures: The primary outcome was worsening category of glycemia based on OGTT using American Diabetes Association criteria: (1) normal glucose tolerance to prediabetes (ie, impaired fasting glucose or impaired glucose tolerance) or type 2 diabetes or (2) prediabetes to type 2 diabetes. The primary analysis consisted of a survival analysis of time to change in glycemic status at or prior to the final patient visit, which occurred at varying times after 12 months for each patient. Secondary outcomes included new-onset type 2 diabetes and change in body weight. Results: A total of 1823 women (baseline mean [SD] age, 30.9 [4.9] years and mean [SD] body mass index, 26.6 [4.6]) underwent OGTT at a median (IQR) 6.5 (4.8-8.2) months postpartum. After excluding 160 women (8.8%) with type 2 diabetes, 2 women (0.1%) who met other exclusion criteria, and 49 women (2.7%) who did not consent or were uncontactable, 1612 women were randomized. Subsequently, 11 randomized participants were identified as ineligible and excluded from the primary analysis, leaving 1601 women randomized (800 women randomized to the intervention group and 801 women randomized to usual care). These included 600 women (37.5%) with prediabetes and 1001 women (62.5%) with normoglycemia. Among participants randomized to the intervention, 644 women (80.5%) received all program content, although COVID-19 lockdowns impacted the delivery model (ie, among 644 participants who engaged in all group sessions, 476 women [73.9%] received some or all content through individual engagement, and 315 women [48.9%] received some or all content remotely). After a median (IQR) 14.1 (11.4-20.1) months of follow-up, 1308 participants (81.2%) had primary outcome data. The intervention, compared with usual care, did not reduce worsening glycemic status (204 women [25.5%] vs 217 women [27.1%]; hazard ratio, 0.92; [95% CI, 0.76-1.12]; P = .42) or improve any secondary outcome. Conclusions and relevance: This study found that a large proportion of women in South Asian urban settings developed dysglycemia soon after a GDM-affected pregnancy and that a lifestyle intervention, modified owing to the COVID-19 pandemic, did not prevent subsequent glycemic deterioration. These findings suggest that alternate or additional approaches are needed, especially among high-risk individuals.Item Seven–minute neurocognitive test battery: A reliable test for dementia(Elsevier, Inc. (2020-Wiley), 2006) de Silva, A.; Pathmeswaran, A.; de-Jager, C.; Kuruppuarachi, L.A.BACKGROUND: The increasing prevalence of Alzheimer’s disease (AD) suggests that there is an increasing need for accurate and easily administered screening instruments to assess cognitive function. OBJECTIVE(S): To examine the reliability of the 7-minute screen as a cognitive screening instrument for AD in a Sri Lankan population. METHODS: 53 patients with mild-moderate AD, 34 with other dementias, 36 with mild cognitive impairment (MCI) referred to a memory clinic, and 60 patients with depression with no evidence of dementia and 56 healthy volunteers (controls) were recruited to the study after informed consent. All were community-dwelling and aged _60 years. Patients with severe dementia, receptive aphasia, visual and motor impairment, and severe depression were excluded. All diagnoses were made according to established criteria and the diagnosis of depression was confirmed after psychiatric evaluation. All subjects underwent cognitive assessment with the Mini Mental State Examination (MMSE) and the 7-minute screen. This screen consists of four components (enhanced cued recall, temporal orientation, verbal fluency, and clock drawing) that assess memory, orientation to time, fluency of expression, and executive function, cognitive functions typically compromised in AD. RESULTS: Baseline characteristics did not differ significantly in the five groups. (see the table). CONCLUSIONS: The 7-minute neurocognitive screen is a highly sensitive instrument to screen for AD and was more reliable than the MMSE to detect AD, MCI, and other dementias in this Sri Lankan population. However, the accuracy of the screen may be confounded by the presence of depression.Item INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial(BioMed Central, London, 2021) Song, L.; Hu, X.; Ma, L.; Chen, X.; Ouyang, M.; Billot, L.; Li, Q.; Muñoz-Venturelli, P.; Abanto, C.; Pontes-Neto, O.M.; Antonio, A.; Wasay, M.; de Silva, A.; Thang, N.H.; Pandian, J.D.; Wahab, K.W.; You, C.; Anderson, C.S.Background: Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH. Methods: INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (< 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic < 140 mmHg; glucose control, target 6.1-7.8 mmol/L and 7.8-10.0 mmol/L in those without and with diabetes mellitus, respectively; anti-pyrexia treatment to target body temperature ≤ 37.5 °C; and reversal of anticoagulation, target international normalized ratio < 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The sample size of 8360 subjects provides 90% power (α = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions. Discussion: As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established.Item Possible progression of an atypical leiomyoma to a leiomyosarcoma: a case report(Menopause Society of Sri Lanka, 2021) Ekanayake, C.D.; Herath, R.; Fernando, S.; Mahendra, G.; Balawardene, J.; de Silva, A.The spectrum of uterine smooth muscle cell tumours (SMT) ranges from leiomyomas to leiomyosarcomas (LMS). Atypical leiomyomas (AL) are a uterine SMT of a contentious nature due to its indeterminate malignant potential. Although the risk of recurrence is low there is limited experience on management. On the other hand, it is generally believed that the uterine LMS arises de novo, rather than from a precursor lesion.Item Estimating the treatment cost of selected diseases in three state sector hospitals(College of the Community Physicians of Sri Lanka, 2007) Kasturiratne, A.; Sugimoto, T.; de Silva, A.INTRODUCTION: Costing disease management is useful for appropriate resource allocation and improving accountability in the health system. Protocol based disease management is helpful in cost analysis, but well developed and accepted protocols to cover the entire disease spectrum are yet being developed in the Sri Lankan context. OBJECTIVE: To estimate treatment cost of acute severe asthma and Lower Segment Caesarean Section (LSCS) in three state sector hospitals. METHODS: This descriptive cross sectional study was conducted in Teaching Hospital, Kurunegala (THK), Base Hospital, Kuliyapitiya (BHK) and Colombo North Teaching Hospital, Ragama (CNTH), from September to December 2006. The study populations were Bed Head Tickets (BHTS) in BHK and THK, and patients in CNTH. All study populations fulfilled the same criteria. A time study was conducted at CNTH using direct observation of Clinical management. Results of the step down method, the time study and the data extracted from BHTS were used for estimating direct, para-medical and accommodation costs. RESULTS: The total sample consisted of 240 subjects. The average duration of hospital stay for patients with acute severe asthma was approximately 4 days in THK and BHK, and 7 days in CNTH. The total cost of management ranged from Rs.2520 (THK) to Rs.4933 (CNTH). The cost of a LSCS ranged from Rs.8268 (CNTH) to Rs.9429 (THK). The average duration of hospital stay was 7-8 days. Operation theatre overheads accounted for 20-40% of the total cost. The cost of the time Spent by Medical Officers in the theatre was about 10% of the total cost. For both conditions, the cost of accommodation was the largest contributor to the total cost. CONCLUSION: in the absence of disease management protocols, there is variation in the disease management cost between different levels of hospitals. This may be due to differences in resource availability, utilisation pattern and accepted practices.Item Combination burden of CVD through innovative strategies to improve BP control(Ceylon College of Physicians and Royal College of Physicians London, 2020) de Silva, A.ABSTRACT: Uncontrolled high blood pressure (BP) is the leading attributable risk factor for mortality globally. With over 1.3 billion people worldwide estimated to have hypertension, and just over one-third on any form of treatment, it has been estimated that approximately 20% of all deaths are attributable to non-optimal BP. Proportionately, more cardiovascular disease (CVD) deaths occur in LMICs and Asians have enhanced susceptibility to vascular disease. Control of BP reduces cardiovascular morbidity and Mortality. However, despite wide availability of effective and inexpensive medicines to treat hypertension, less than one-third of individuals with hypertension have controlled BP. Persistent use of monotherapy, which has modest efficacy, and inappropriate lifestyles with poor awareness of CVD risk factors and low patient compliance are considered to be the main contributory factors to inadequate BP control among patients with hypertension. There is, therefore, a need to challenge traditional paradigms that are unlikely to effectively address the CVD crisis and develop innovative strategies both in terms of clinical care and health systems responses to improve overall outcomes. One such strategy was evaluated by us in the TRIUMPH study. In this trial of 700 patients with mild or moderate hypertension, initial treatment with or escalation of monotherapy to low-dose triple combination therapy significantly improved achievement of blood pressure targets. The other study (COBRA-BPS) involving more than 2500 participants demonstrated a low-cost, multi-component intervention delivered at community level through existing primary healthcare infrastructure led to better BP control in rural communities. Both these recently published studies will be presented during the oration.