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Background: Severe cardiac glycoside cardiotoxicity after ingestion of yellow oleander seeds is an important problem in rural areas of Sri Lanka. Currently, patients must be transferred to the capital for temporary cardiac pacing. We did a randomised controlled trial to investigate whether anti-digoxin Fab could reverse serious oleander-induced arrhythmias.Methods: After a preliminary dose-finding study, 66 patients who presented to hospital with a serious cardiac arrhythmia were randomised to receive either 1200 mg of anti-digoxin Fab or a saline placebo. A 12-lead electrocardiogram, 3 min rhythm strip, and blood sample for measurement of electrolytes and cardiac glycosides were taken before treatment and at 12 timepoints thereafter.Findings: 34 patients received anti-digoxin Fab and 32 received placebo. The presenting arrhythmia had resolved completely after 2 h in 15 antibody-treated patients and two controls (p<0.001); 24 and five patients, respectively, were in sinus rhythm at 8 h (p<0.001). Kaplan-Meier analysis of time to first reversal showed a significant response to anti-digoxin Fab. The heart rate increased in cases, from 49.1 per min at baseline to 66.8 at 2 h, but not in controls (50.6 per min at baseline to 51.5; p<0.001). Mean serum potassium concentrations decreased from 4.9 mmol/L to 4.1 mmol/L at 2 h in cases; no such decrease occurred in controls.Interpretation: Anti-digoxin Fab fragments are a safe and effective treatment for serious cardiac arrhythmias induced by yellow oleander. Their use in small rural hospitals in Sri Lanka should minimise costly transfer of patients and reduce the numbers of deaths; however, further study will be required to confirm this reduction. [ABSTRACT FROM AUTHOR]

Background and objectives: Acute coronary syndrome (ACS) is a leading cause of death. Correct implementation of evidence-based guidelines should improve outcome. We conducted this study to determine to what extent management of ACS in a tertiary care medical ward in Sri Lanka adhered to current guidelines. Study methods: This prospective observational study was carried out in the University Medical Unit of the National Hospital, Colombo, Sri Lanka, for a 5-month period commencing April 2008. All patients presenting with ACS to the unit were included. Results: During the period of study, there were 101 admissions of confirmed ACS. Thirty-one (30·6%) and 40 (39·6%) patients had not received the required correct loading dose of aspirin and clopidogrel, respectively. There were 34 cases of ST-elevation myocardial infarction (STEMI); 26 patients were eligible for thrombolysis and streptokinase was given to 22 (84·6%). The rest were treated with low-molecular-weight heparin (LMWH). Of the 67 patients who did not have STEMI, 66 received the correct dose of LMWH. Fifty-two patients (51·4%) were started on a β-blocker at presentation. None of the patients received intravenous β-blockers. Seventy-four patients (73·2%) were started on either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker on presentation. None of the patients underwent primary percutaneous intervention. Conclusion: Adherence to guidelines is limited by lack of funds and resources in our setting; however, attention must be paid to non-costly easily correctable deficits. [ABSTRACT FROM AUTHOR]

SummaryBackground: Severe cardiac glycoside cardiotoxicity after ingestion of yellow oleander seeds is an important problem in rural areas of Sri Lanka. Currently, patients must be transferred to the capital for temporary cardiac pacing. We did a randomised controlled trial to investigate whether anti-digoxin Fab could reverse serious oleander-induced arrhythmias.Methods: After a preliminary dose-finding study, 66 patients who presented to hospital with a serious cardiac arrhythmia were randomised to receive either 1200 mg of anti-digoxin Fab or a saline placebo. A 12-lead electrocardiogram, 3 min rhythm strip, and blood sample for measurement of electrolytes and cardiac glycosides were taken before treatment and at 12 timepoints thereafter.Findings: 34 patients received anti-digoxin Fab and 32 received placebo. The presenting arrhythmia had resolved completely after 2 h in 15 antibody-treated patients and two controls (p<0.001); 24 and five patients, respectively, were in sinus rhythm at 8 h (p<0.001). Kaplan-Meier analysis of time to first reversal showed a significant response to anti-digoxin Fab. The heart rate increased in cases, from 49.1 per min at baseline to 66.8 at 2 h, but not in controls (50.6 per min at baseline to 51.5; p<0.001). Mean serum potassium concentrations decreased from 4.9 mmol/L to 4.1 mmol/L at 2 h in cases; no such decrease occurred in controls.Interpretation: Anti-digoxin Fab fragments are a safe and effective treatment for serious cardiac arrhythmias induced by yellow oleander. Their use in small rural hospitals in Sri Lanka should minimise costly transfer of patients and reduce the numbers of deaths; however, further study will be required to confirm this reduction. [ABSTRACT FROM AUTHOR]

Objectives: To perform a comparative analysis of the extended APPROPRIATE trial of measures of reactive nitrogen species and antioxidant capacity in patients having resistant hypertension with controlled hypertension and healthy controls. Results: Mean serum NO2- and NOx levels were significantly lower and mean AOC was significantly higher in patients with controlled hypertension (n = 38) and healthy controls (n = 38) compared to resistant hypertension (RHTN) patients (n = 40) at the pre-intervention stage (p < 0.001). The serum NO2-, NOx and AOC levels of both controlled hypertension and healthy controls were comparable to those of the RHTN patients following treatment with propranolol (n = 18). Considering all samples (n = 114) we noted that there were significant weak and moderate positive correlations between NO2− levels with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (r = 0.396, p < 0.001 and r = 0.292, p = 0.004) as well as total NOx levels with SBP and DBP (r = 0.636 and r = 0.480 respectively, p < 0.001). Conversely, there was a significant negative correlation between AOC levels with SBP and DBP (r= -0.846 and r = -0.626 respectively, p < 0.001). [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism is a common endocrine disorder that exerts a substantial influence on people all over the world. Levothyroxine (LT-4) is the drug of choice for the treatment of hypothyroidism and the starting oral dose is typically ranging from 1.5 to 1.7 µg/kg/day. The target is to achieve an optimum serum TSH level of 0.4-4.0 mIU/L; hence, the dose is titrated accordingly. Once the LT-4 dose is adjusted to obtain the target TSH level, it usually remains stable for a long period of time in most cases. However, some of the patients require frequent dose adjustments and some of them require unusually high doses. Therefore, the aim of this study is to determine the association of pharmacogenomic, clinical and behavioural factors with the oral levothyroxine (LT-4) dose requirement of hypothyroid patients in Sri Lanka. Method: This study will be conducted as a matched case-control study and will involve primary hypothyroid patients who visit the diabetes and endocrinology clinic at the National Hospital, Kandy, Sri Lanka. We will recruit a total of 292 cases and select 292 controls from the clinic who are matched in terms of age, sex and Body Mass Index (BMI). An interviewer-administered questionnaire will be used to collect data from the participants (n = 584). Of the 584 patients, blood samples will be collected from a sub-sample (n = 150) for DNA extraction. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) will be performed for single nucleotide polymorphisms (SNP) analysis. Discussion: Frequent dose adjustments of levothyroxine cause a serious economic burden to the healthcare system. By identifying the root causes of the variations in LT-4 dosage, a more comprehensive comprehension of hypothyroidism and its management can be attained in Sri Lanka. Furthermore, upon identification of a positive association/correlation between genetic polymorphisms and the LT-4 dose, SNP profiles can be used as a possible genetic marker for dose adjustment determination in future patients. [ABSTRACT FROM AUTHOR]

Repurposing hydroxychloroquine (HCQ) and chloroquine (CQ) as antiviral agents is a re-emerging topic with the advent of new viral epidemics. To summarize evidence from human clinical studies for using HCQ or CQ as antiviral agents for any viral infection. PubMed, EMBASE, Scopus, Web of Science for published studies without time or language restrictions; Cochrane Clinical Trial Registry and Chinese Clinical Trials Registry for trials registered after 2015; MedRxiv for preprints within the last 12 months. Study eligibility criteria were interventional and prospective observational studies (with or without a control group). Participants were adults and children with a confirmed viral infection. Interventions included the use of CQ or HCQ as antiviral agent in one or more groups of the study. Two authors independently screened abstracts, and all authors agreed on eligible studies. A meta-analysis was planned if studies were available which were similar in terms of participants, intervention, comparator and outcomes. Nineteen studies (including two preprints) were eligible (HIV 8, HCV 2, dengue 2, chikungunya 1, COVID-19 6). Nine and ten studies assessed CQ and HCQ respectively. Benefits of either drug for viral load suppression in HIV are inconsistent. CQ is ineffective in curing dengue (high-certainty evidence) and may have little or no benefit in curing chikungunya (low-certainty evidence). The evidence for COVID-19 infection is rapidly evolving but at this stage we are unsure whether either CQ or HCQ has any benefit in clearing viraemia (very-low-certainty evidence). Using HCQ or CQ for HIV/HCV infections is now clinically irrelevant as other effective antivirals are available for viral load suppression (HIV) and cure (HCV). There is no benefit of CQ in dengue, and the same conclusion is likely for chikungunya. More evidence is needed to confirm whether either HCQ or CQ is beneficial in COVID-19 infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Investigates the existence of beetle marasmus in Sri Lanka. Infestation of dung-beetle; Growth levels of human and animal excrement in the human habitat; Faecal contamination among children.

Porphyromonas gingivalis and Treponema denticola are periodontal pathogens that express virulence factors associated with the pathogenesis of periodontitis. In this paper we tested the hypothesis that P. gingivalis and T. denticola are synergistic in terms of virulence; using a model of mixed microbial infection in rats. Groups of rats were orally infected with either P. gingivalis or T. denticola or mixed microbial infections for 7 and 12 weeks. P. gingivalis genomic DNA was detected more frequently by PCR than T. denticola. Both bacteria induced significantly high IgG, IgG2b, IgG1, IgG2a antibody levels indicating a stimulation of Th1 and Th2 immune response. Radiographic and morphometric measurements demonstrated that rats infected with the mixed infection exhibited significantly more alveolar bone loss than shaminfected control rats. Histology revealed apical migration of junctional epithelium, rete ridge elongation, and crestal alveolar bone resorption; resembling periodontal disease lesion. These results showed that P. gingivalis and T. denticola exhibit no synergistic virulence in a rat model of periodontal disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Only a limited number of multiple synchronous primary malignancies of the pancreas have been reported in the medical literature. We report a case of two solid malignant tumors of the pancreas diagnosed preoperatively.Case Presentation: We describe a 65-year-old Sri Lankan woman who presented with progressive obstructive jaundice. Initial contrast-enhanced computed tomography imaging detected a malignant tumor at the tail of her pancreas. A second tumor of the pancreatic head was detected with integrated imaging using multidetector computed tomography and multimodal magnetic resonance imaging. She underwent total pancreaticoduodenectomy and splenectomy. Gross examination of the specimen confirmed the presence of two separate tumors. Histology of the ampullary tumor showed pancreatic-type adenocarcinoma and the tumor in the tail of her pancreas showed a colloid-type adenocarcinoma.Conclusion: The possibility of multiple primary malignant solid tumors of different types with malignant potential has to be considered even without background pathology when managing multiple tumors in the pancreas. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Uncontrolled studies suggest that magnesium sulphate controls spasms in patients with established tetanus. We performed a meta-analysis of controlled trials that compared magnesium sulphate with placebo or diazepam for the treatment of patients with tetanus. We searched PubMed, Scopus, Embase and the Cochrane clinical trials registry. Three studies met the inclusion criteria, containing 275 participants (199 male patients, 72.4%). Magnesium sulphate did not reduce mortality, relative risk (95% CI): vs placebo, 0.80 (0.41-1.58); vs diazepam, 1.11 (0.70-1.75). The data on duration of total intensive care unit stay, total hospital stay and the need for ventilatory support were conflicting and pooling of results could not be done due to methodological differences of individual trials. More controlled trials are needed to assess the effect of magnesium sulphate on reducing autonomic instability, spasms, duration of intensive care and hospital stays and the need for mechanical ventilation. [ABSTRACT FROM AUTHOR]

Damask roses are grown in several European and Asiatic countries for rose oil production. Twenty-six oil-bearing Rosa damascena Mill. accessions and 13 garden Damask roses were assayed by molecular markers. Microsatellite genotyping demonstrated that R. damascena Mill. accessions from Bulgaria, Iran, and India and old European Damask rose varieties possess identical microsatellite profiles, suggesting a common origin. At the same time, the data indicated that modern industrial oil rose cultivation is based on a very narrow genepool and that oil rose collections contain many genetically identical accessions. The study of long-term vegetative propagation of the Damask roses also reveals high somatic stability for the microsatellite loci analyzed. [ABSTRACT FROM AUTHOR]

There is a severe shortage of affordable antivenoms and antitoxins in the developing world. An anti-digoxin antitoxin for oleander poisoning was introduced in Sri Lanka in July, 2001, but because of its cost, stocks ran out in July, 2002. We looked at the effect of its introduction and withdrawal on case fatality, and determined its cost-effectiveness. The antitoxin strikingly reduced the case fatality; its absence resulted in a three-fold rise in deaths. At the present price of US2650 dollars per course, every life saved cost 10209 dollars and every life year cost 248 dollars. Reduction of the antitoxin's price to 400 dollars would reduce costs to 1137 dollars per life gained; a further reduction to 103 dollars would save money for every life gained. Treatments for poisoning and envenoming should be included in the present campaign to increase availability of affordable treatments in the developing world. [ABSTRACT FROM AUTHOR]

Several studies have shown that long term lithium use is associated with a subtle decline in estimated glomerular filtration rate (eGFR). Lithium can be a risk factor for chronic kidney disease in long term users. Objective To compare eGFR values of patients on long term lithium compared to controls matched for age, sex and confounding comorbidities Methods Patients with bipolar affective disorder, who are on lithium (for at least a year), were compared against controls matched (1:1) for age, gender and presence or absence of diabetes and hypertension. The eGFR was calculated according to the modification of diet in renal disease study formula. A meta-analysis was performed to compare our findings with similar studies in literature. Results Forty seven patients met the inclusion criteria. They were matched with 47 controls. The eGFR values of lithium users were significantly low (p = 0.04) compared to controls and the mean decline in eGFR was -2.7 ml/min/1.73m 2 (SD ± 9.8) per year. The significant difference in eGFR persisted between the subgroup without comorbidities (diabetes and hypertension) and their controls but disappeared for subgroup with comorbidities and their controls. Nevertheless, lithium users had a lower eGFR in both subgroups. A meta-analysis of 9 studies showed a significant lowering in the glomerular filtration rate in lithium users compared to controls [mean difference -10.3 ml/min (95% confidence interval: -15.13 to -5.55, p < 0.0001). Conclusions Lithium causes a subtle decline in glomerular filtration rate and renal functions need to be monitored in lithium using patients. [ABSTRACT FROM AUTHOR]