The impact of propranolol on nitric oxide and total antioxidant capacity in patients with resistant hypertension-evidence from the APPROPRIATE trial.

OBJECTIVES: The objective was to assess the effect of propranolol on oxidative stress and anti-oxidant potential in patients with resistant hypertension as a secondary analysis of the APPROPRIATE trial. This randomized double blinded clinical trial recruited patients with resistant hypertension and allocated forty patients to propranolol and placebo in 1:1 ratio. The pro-oxidant state (nitrate and nitrite) was assessed using modified Griess assay. The total anti-oxidant capacity was measured using ABTS assay. RESULTS: Analysis was performed for 18 patients from the propranolol group and 15 from the placebo group. A decline in end point ambulatory blood pressure (p = 0.031) and greater mean reduction in office SBP (29.7 ± 13.0 mmHg, p = 0.021) was noted in the propranolol arm. Nitrate and nitrite levels were lower at the end of a 90 day follow up period in both arms, with a greater mean reduction with propranolol. A significant increase in the AOC was noted in both arms with higher incremental value with Propranolol. The findings of this study do not demonstrate a statistically significant effect of propranolol on the oxidative stress/antioxidant balance in patients with resistant hypertension. The observed trends merit further evaluation.

Evaluation of the accuracy and precision of glucometers currently used in Sri Lanka.

AIMS: Life threatening macrovascular and microvascular complications of diabetes can be minimized by effective glycaemic control. Self monitoring of blood glucose with glucometers is recognized as a cost effective strategy to improve glycaemic control. However accuracy and precision of glucometers will determine the effectiveness of this strategy. We aimed to evaluate accuracy and precision of commonly used glucometers in Sri Lanka. MATERIALS AND METHODS: An observational study was conducted in a tertiary care setting including patients with diabetes and healthy volunteers. Eight commonly used glucometers were used. Blood glucose was measured in 50 participants (16 healthy volunteers, 34 patients with diabetes) in finger prick capillary blood using glucometers and venous blood using standard laboratory methods, and were compared to determine accuracy. Repeated measurements from same glucometer with a single finger prick were made and compared to determine precision. RESULTS: Only one glucometer showed insignificant difference to venous plasma glucose values. Only one glucometer met ADA recommended bias of <5%. None of the glucometers fell within the ISO recommendations for accuracy. CONCLUSION: Majority of commonly used glucometers in Sri Lanka do not meet the ADA recommendations and ISO standards for accuracy and precision. However their variations are unlikely to make significant adverse impact on patient management.

Amphotericin B for treatment of visceral leishmaniasis: systematic review and meta-analysis of prospective comparative clinical studies including dose-ranging studies.

OBJECTIVES: To evaluate the evidence for use of different formulations of amphotericin B (AmB), minimum effective dose for each formulation and its comparative efficacy against other drugs in achieving definitive cure of visceral leishmaniasis. METHODS: This systematic review and meta-analysis included following data sources: PubMed, Embase, Scopus, Web of Science and CINAHL. Controlled prospective clinical trials (randomized or nonrandomized, including dose-ranging studies) conducted between 1996 and 2017 with at least one treatment group receiving AmB were included (published data only). The primary outcome was definitive cure at 6 months. Adverse events and mortality were assessed as secondary outcomes. The PROSPERO registration number for this review is CRD42017067488. RESULTS: Thirty-one studies (26 from India) that enrolled 6903 patients into 84 study groups met the selection criteria. In India, liposomal AmB was not inferior to AmB deoxycholate (relative risk 1.00, 95% confidence interval (CI) 0.96-1.03, two randomized controlled trials (RCTs), 514 participants, high-quality evidence), and a single dose of the earlier formulation as low as 3.75 mg/kg achieved a cure rate of over 89% (95% CI 70.6-97.2). AmB deoxycholate was as effective as miltefosine (relative risk 0.99, 95% CI 0.95-1.03, two trials, 523 participants, high-quality evidence) and may be better than paromomycin (relative risk 1.04, 95% CI 1.02-1.07, one trial, 667 participants, low-quality evidence) in achieving definitive cure. CONCLUSIONS: AmB is an efficacious drug in the Indian subcontinent. Further evidence is needed from prospective clinical trials in other endemic geographical regions.

Closing the theory to practice gap for newly qualified doctors: evaluation of a peer-delivered practical skills training course for newly qualified doctors in preparation for clinical practice.

PURPOSE: The Good Intern Programme (GIP) in Sri Lanka has been implemented to bridge the 'theory to practice gap' of doctors preparing for their internship. This paper evaluates the impact of a 2-day peer-delivered Acute Care Skills Training (ACST) course as part of the GIP. STUDY DESIGN: The ACST course was developed by an interprofessional faculty, including newly graduated doctors awaiting internship (pre-intern), focusing on the recognition and management of common medical and surgical emergencies. Course delivery was entirely by pre-intern doctors to their peers. Knowledge was evaluated by a pre- and post-course multiple choice test. Participants' confidence (post-course) and 12 acute care skills (pre- and post-course) were assessed using Likert scale-based questions. A subset of participants provided feedback on the peer learning experience. RESULTS: Seventeen courses were delivered by a faculty consisting of eight peer trainers over 4 months, training 320 participants. The mean (SD) multiple choice questionnaire score was 71.03 (13.19) pre-course compared with 77.98 (7.7) post-course (p<0.05). Increased overall confidence in managing ward emergencies was reported by 97.2% (n=283) of respondents. Participants rated their post-course skills to be significantly higher (p<0.05) than pre-course in all 12 assessed skills. Extended feedback on the peer learning experience was overwhelmingly positive and 96.5% would recommend the course to a colleague. CONCLUSIONS: A peer-delivered ACST course was extremely well received and can improve newly qualified medical graduates' knowledge, skills and confidence in managing medical and surgical emergencies. This peer-based model may have utility beyond pre-interns and beyond Sri Lanka.

Addition of Propranolol in Resistant Arterial hypertension Treatment (APROPRIATE study): study protocol for a randomized double-blind placebo-controlled trial.

BACKGROUND: Resistant hypertension is defined as an uncontrolled blood pressure despite treatment at best-tolerated doses with at least three antihypertensive agents including a diuretic. It is an emerging public health problem. At present clinical trial data on management of resistant hypertension is limited. Management is largely based on observational studies and expert opinions. Propranolol is a nonselective beta blocker. Several studies have confirmed that propranolol has a significant hypotensive action, both when used alone and as an adjuvant therapy. At present there are no prospective, randomized, clinical studies evaluating the effectiveness of propranolol in patients with resistant hypertension. Therefore, we have designed a prospective randomized trial to evaluate the safety and efficacy of propranolol in patients with resistant hypertension. METHODS/DESIGN: The study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for a period of 3 months. The study has been approved by the Ethics Review Committee of the Faculty of Medicine, University of Colombo. A total of 200 adults with resistant hypertension will be recruited for the study. They will be randomly assigned to the test and placebo groups on a 1:1 ratio. The test group will receive propranolol 40 mg three times a day and the control group will receive an identical placebo capsule. The study drugs will be double blinded to both investigators and subjects. The visits and the evaluations will be done as follows: screening (visit 0), 1 month (visit 1), 2 months (visit 2) and 3 months (visit 3). The primary outcomes of the study is to find a statistically significant difference between the fall in mean systolic and mean diastolic blood pressure measured by ABPM (ambulatory blood pressure monitoring) from baseline between the two groups. Data will be analyzed using SPSS v16. DISCUSSION: To our knowledge this is one of the first randomized controlled trials evaluating the effects of propranolol in resistant hypertension. This study will provide the necessary groundwork for future large-scale, multicentered clinical trials. The result, positive or negative, should provide a step change in the evidence guiding current and future policies regarding treatment of resistant hypertension. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry, identifier: SLCTR/2016/002 . Registered on 27 January 2016; Study protocol version 2.1.

Clinicopathological correlates of chronic kidney disease of unknown etiology in Sri Lanka.

Chronic kidney disease of unknown etiology (CKDu) is a major healthcare issue in Sri Lanka. This study included 125 consecutive patients with a diagnosis of CKDu undergoing renal biopsy at one hospital from 2008 to 2012. Associations between renal outcome parameters, epidemiological data, and histopathological findings were examined and regression models constructed based on univariate associations with outcome variables as serum creatinine >1.2 and stage of CKD >3. The mean patient age was 46.21 years (standard deviation = 11.64). A marked male predominance was noted. A positive family history of CKD was seen in 35.8%. Prominent histopathological features were glomerular sclerosis (94.8%), interstitial infiltration (76%) with lymphocytic infiltration, interstitial fibrosis (71.2%), and tubular atrophy (70.4%). Importantly, significant histological changes were seen in patients with early CKDu. For CKD stage >3 independent associations were: interstitial fibrosis [P = 0.005; odds ratio (OR) =0.153] and interstitial infiltrate (P = 0.030; OR = 0.2440. For serum creatinine >1.2, independent predictors were >50% glomerular sclerosis (P = 0.041; OR = 0.92), tubular atrophy (P = 0.034; OR = 0.171, and more than 40 residential life years (P = 0.009; OR = 9.229). Chronic tubulointerstitial nephritis (TIN) appears to be the predominant histopathological finding in patients with CKDu, with significant renal pathology established early on in the course of the disease. Interstitial infiltration appears to be an independent association of advancing CKD, CKDu, histopathology, histology, and TIN.

Determinants of mortality and impact of therapy in patients with leptospirosis admitted for intensive care in a Sri Lankan hospital--a three year retrospective study.

INTRODUCTION: Leptospirosis is a disease of epidemic proportions in Sri Lanka. There is paucity of data on the determinants of mortality and impact of therapy in patients with leptospirosis admitted to critical care settings in endemic territories. METHODOLOGY: This retrospective cross-sectional study was performed in patients with serologically confirmed leptospirosis admitted to the intensive care unit of the General Hospital, Kalutara from January 2011 to April 2014. Associations between socio-epidemiological, clinical and laboratory parameters and patient mortality were examined. RESULTS: Forty-five patients were included. The mean age was 49.11(SD = 16.95) and majority (92%) were male. Percentage mortality was 44.4%. Patient mortality was associated with age > 40 (p = 0.012), symptoms of uremia (p = 0.017), evidence of CNS involvement (p = 0.039), presence of oliguria (p = 0.002) and anuria (p = 0.014), presence of multi-organ dysfunction syndrome (MODS) (p < 0.001), CRP > 96 (p = 0.036), platelet count < 20,000 (p = 0.045), Potassium > 5.0 (p = 0.05), metabolic acidosis with pH < 7.2 (p = 0.03), INR > 2 (p = 0.037) and requirement of mechanical ventilation (p < 0.001). Cox regression analysis revealed MODS and potassium > 5 to be independently associated with mortality. CONCLUSIONS: A high mortality rate is noted. The presence of MODS and serum potassium concentration > 5.0 was independently associated with mortality in this retrospective study of patients with confirmed leptospirosis in a critical care setting.