A Hybrid Approach for Screening Endothelial Dysfunction using Photoplethysmography and Digital Thermal Monitoring.

Cardiovascular diseases(CVDs) are the world's leading cause of death. Endothelial Dysfunction is an early stage of cardiovascular diseases and can effectively be used to detect the presence of the CVDs, monitor its progress and investigate the effectiveness of the treatment given. This study proposes a reliable approach for the screening of endothelial dysfunction via machine learning, using features extracted from a combination of Plethysmography, Digital Thermal Monitoring, biological features (age and gender) and anthropometry (BMI and pulse pressure). This case control study includes 55 healthy subjects and 45 subjects with clinically verified CVDs. Following the feature engineering stage, the results were subjected to dimension reduction and 5-fold cross-validation where it was observed that models Logistic Regression and Linear Discriminant provided the highest accuracies of 84% and 81% respectively. We propose that this study can be used as an efficient guide for the non-invasive screening of endothelial dysfunction.

Glycemic and cardiometabolic effects of exercise in South Asian Sri Lankans with type 2 diabetes mellitus: A randomized controlled trial Sri Lanka diabetes aerobic and resistance training study (SL-DARTS).

BACKGROUND AND AIMS: To examine the effects of aerobic training (AT) and resistance training (RT) compared to standard care on glycemic control in South Asian Sri Lankan adults with Type 2 Diabetes Mellitus (T2DM). METHODS: Randomized controlled trial (RCT) with parallel-group design recruited 86 sedentary Sri Lankans (aged 35-65 years) with T2DM into aerobic training (AT, n = 28), resistance training (RT, n = 28) and control (CN, n = 30) groups. Supervised progressive exercise training consisting of 75 min per session, 2 days per week for 12 weeks was conducted. The primary outcome was pre- and post-intervention absolute change in hemoglobin A1c (HBA1c). Secondary outcomes were serum lipids, liver enzymes, chronic inflammatory status, anthropometry, body composition and blood pressure. RESULTS: The absolute change in HbA1c of RT vs. CN was -0.08% (95% CI, 0.8% to -0.7%, p = 0.8) and AT vs. CN was -0.22% (95% CI, 0.95% to -0.5%). Subgroup analysis (n = 49) with a high baseline HbA1c (>7.5%), absolute reduction in HbA1c in exercise groups were statistically significant (RT vs. CN was -0.37%; 95% CI 1.3% to -0.6%, p = 0.04 and AT vs. CN was -0.57%; 95% CI 1.7% to -0.6%, p = 0.03). The effect sizes (total and subgroup HbA1c >7.5%) ranged from 0.7 to 1.0 in AT, 0.4 to 1.1 in RT compared to 0.35 to 0.6 for the CN. Secondary outcomes did not significantly differ among groups. CONCLUSIONS: Exercise training 2 days/week improved glycemic control in Sri Lankan adults with T2DM and the effects were significant in high baseline HbA1c (>7.5%) groups (RT > AT).

Pharmacokinetic, pharmacodynamic, and pharmacogenetic assays to monitor clopidogrel therapy.

Clopidogrel is the most common and widely used antiplatelet agent for patients with coronary artery disease following confirmation by electrocardiographic studies. The nonresponsiveness of patients to clopidogrel and the possibility of testing for clopidogrel resistance by platelet function assays (PFA) are contentious issues. Light transmission aggregometry (LTA) is considered as the gold standard test among all PFA. In this review, the most commonly used PFA used for monitoring the effect of clopidogrel, LTA, vasodilator-stimulated phosphoprotein assay phosphorylation, rotational thromboelastometry (ROTEM) delta and ROTEM platelet, thromboelastography, PFA-100, VerifyNow P2Y12 assay, Multiplate analyzer, Plateletworks assay and pharmacogenetic studies, are comparatively discussed including their principles of action, advantages, and disadvantages. VerifyNow P2Y12 assay can be accepted as the ideal point of care test out of the discussed assays. However, modified assays are required which could overcome the limitations associated with currently available assays.

Sublingual nitroglycerin for early blood pressure control in hypertensive emergencies: observations from an emergency department clinical audit in Sri Lanka.

OBJECTIVE: Hypertensive emergencies are potentially life threatening and require prompt blood pressure control with intravenous agents. Preparation of intravenous infusions is time consuming. Usefulness of sublingual nitroglycerin in this setting is not known. We aimed to assess the benefit of sublingual nitroglycerin as a bridge to IV therapy. In a clinical audit in an emergency department, patients presenting with hypertensive emergencies requiring intravenous nitroglycerin were administered single spray of sublingual nitroglycerin awaiting commencement of intravenous infusion. Blood pressure was monitored every 5 min to observe the degree and speed of reduction. RESULTS: Thirty-seven patients met the selection criteria. Mean age was 65.8 years (SD 7.04), and 29 were males (88.4%). Mean values of systolic, diastolic and mean blood pressures on admission were 217, 137, 163 mmHg. At 5 and 10 min after sublingual nitroglycerin, mean reduction of mean arterial blood pressure by 12.3 and 16.3% was achieved. Only 2 patients (5.4%) showed an overcorrection of blood pressure. Minimum of 15 min were required to set up a nitroglycerin intravenous infusion. Sublingual nitroglycerin spray allows rapid blood pressure control in hypertensive emergencies and is a useful bridge during the time to prepare intravenous infusion.

Prevalence, patterns, and associations of dyslipidemia among Sri Lankan adults-Sri Lanka Diabetes and Cardiovascular Study in 2005-2006.

BACKGROUND: Dyslipidemia is a major risk factor for cardiovascular disease. Prevalence patterns and determinants of dyslipidemia in Sri Lanka are unkown. OBJECTIVES: We aimed to determine the prevalence and correlates of dyslipidemia among Sri Lankan adults. METHODS: A nationally representative sample was recruited by multistage random cluster sampling in Sri Lanka Diabetes and Cardiovascular Study, a cross-sectional study. Data collected by an interviewer-administered questionnaire, physical examination, anthropometric measurements lipid analysis from take 12-hour fasting blood samples were used. RESULTS: Among 4451 participants 60.5% were women and mean age was 46 years. Mean (standard deviation) total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), triglycerides (TGs), and TC/HDLC levels were 206.7 mg/dL (±43.5), 46.8 mg/dL (±10.6), 135.5 mg/dL (±37.6), 121.7 mg/dL (±66.8), and 4.6 (±1.1), respectively. Women had higher mean TC, HDLC, LDLC, and TG values compared to men across all age groups. Mean TC, LDLC, and TGs increased with age in both genders; 77.4% of participants had some form of dyslipidemia. Low HDLC was the commonest type (49.6%) of dyslipidemia. Increasing age, female sex, living in urban sector, high body mass index, central obesity, diabetes, hypertension, insufficient physical activity, and smoking were associated with having some form of dyslipidemia. CONCLUSION: Three in four Sri Lankan adults have some form of dyslipidemia. Physical inactivity, obesity, hypertension, and diabetes are the leading modifiable risk factors.

Zinc supplementation in prediabetes: A randomized double-blind placebo-controlled clinical trial.

BACKGROUND: This study evaluated the effects of zinc supplementation on glycemic control, other cardiometabolic and anthropometric parameters, and disease progression in prediabetes. METHODS: A randomized double-blind placebo-controlled Phase 2 clinical trial was conducted over a 12-month period in 200 subjects (43% male; mean [± SD] age 51.8 ± 7.3 years), randomly assigned (1: 1) to the treatment or control group. The treatment group received zinc (20 mg daily). Subjects were evaluated at baseline and at 1, 3, 6, and 12 months. The primary outcome was the change in glycemic control from baseline. Multiple regression analyses were performed, with change in outcome variables after intervention from baseline used as continuous dependent variables. RESULTS: In both groups, mean serum zinc concentrations prior to the trial were below normal (15.29-21.41 µmol/L). During the 12-month follow-up, a significantly higher percentage of participants developed type 2 diabetes in the control compared with zinc-treated group (25.0% vs 11.0% respectively; P = 0.016). Fasting plasma glucose (FPG), 2-h glucose levels in the oral glucose tolerance test (OGTT), homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were significantly lower in the treated group, with significant improvement in ß-cell function. In all four regression models, the best predictor of the dependent variables (i.e. change in FPG, 2-h glucose in the OGTT, HOMA-IR, and homeostatic model assessment of ß-cell function) was zinc treatment. CONCLUSIONS: Zinc supplementation reduced blood glucose and insulin resistance while improving ß-cell function. Furthermore, supplementation reduced disease progression to diabetes and had beneficial effects on TC and LDL-C.

Evaluation of pharmacodynamic properties and safety of Cinnamomum zeylanicum (Ceylon cinnamon) in healthy adults: a phase I clinical trial.

BACKGROUND: Cinnamon is considered as a treatment for many ailments in native medicine. Evidence suggests that Cinnamomum zeylanicum (CZ) has anti-microbial, anti-parasitic, anti-oxidant, blood glucose lowering properties and beneficial cardiovascular effects. The present study aims to evaluate Pharmacodynamic properties and safety of CZ in healthy adults using a Phase I Clinical Trial. METHODS: This phase I clinical trial was conducted at the Department of Pharmacology, Faculty of Medicine, University of Colombo, Sri Lanka. Thirty healthy adults were recruited for the study, conducted for a period of 3 months, with the dose of CZ (water extract) increased at monthly intervals (85 mg, 250 mg and 500 mg). Data collection was carried out at baseline and during each monthly follow up visit. Anthropometric, clinical and biochemical assessments were done at baseline and during follow up. Adverse effects and drug compliance was also evaluated. RESULTS: Twenty eight subjects completed the three months follow up. Mean age was 38.8 ± 10.4 years and 50% were males. There were no significant changes in the anthropometric parameters during the three months follow up. Both systolic and diastolic blood pressure reduced significant during the 1st month and this reduction was sustained throughout follow up. Full blood count, renal function tests, liver function tests, fasting blood glucose, HDL-c, VLDL-d and triglycerides remained within the normal range without any significant alteration during the 3 months. A significant reduction in the TC (p < 0.05) and LDL-c (p < 0.001) was noted at the end of the 3 months follow up period. There were no serious adverse effects (including hypersensitivity) noted. In two participants dyspepsia necessitated the discontinuation of study participation. Drug compliance was between 85 and 95% during the study period. CONCLUSIONS: This is the first phase I clinical trial in health adults evaluating efficacy and safety of CZ. Our results demonstrate no significant side effects and toxicity of CZ, including hepatotoxicity and anti-coagulation properties. CZ demonstrated beneficial anti-hyperlipidaemic and blood pressure lowering effects among healthy adults. Further studies with larger samples and longer durations may be able to elucidate other side effects and better describe the pharmacodynamic properties. TRIAL REGISTRATION: SLCTR/2013/001 (Sri Lanka Clinical Trials Registry: http://www.slctr.lk/trials/106 ) (Date of Registration: 01/01/2013).

Peer assisted learning among Sri Lankan medical undergraduates: a cross sectional study.

OBJECTIVE: The objectives of this study were to; (a) evaluate the current practices of peer assisted learning among second year and final year medical students of Faculty of Medicine, University of Colombo, Sri Lanka; (b) identify reasons for engaging in peer assisted learning; (c) identify perceived weaknesses in current learning activities; and (d) determine student characteristics associated with engaging in peer assisted learning. RESULTS: This cross sectional study interviewed two hundred and eighty-four eligible students. Average number of hours spent on peer assisted learning during a week was significantly greater among second year students compared to final year students (15.1 vs. 7.1 h, p < 0.05). Overall, female students were more likely to engage in peer assisted learning than male students. In second year, most common method of peer assisted learning was mass lectures offered by batch mates or seniors, while in final year it was group discussions. This reflected a transition to more focused, interactive, active learning among senior students.

Cinnamomum zeylanicum (Ceylon cinnamon) as a potential pharmaceutical agent for type-2 diabetes mellitus: study protocol for a randomized controlled trial.

BACKGROUND: Previous studies have explored the anti-diabetic effects of Cinnamomum cassia extract in vivo and in vitro. However, there are no studies at present exploring the effects of the indigenous species of Sri Lankan cinnamon (Cinnamomum zeylanicum) in patients with diabetes mellitus. The present study aims to evaluate the potential effects of Cinnamomum zeylanicum extract as a pharmaceutical agent in patients with type-2 diabetes mellitus. METHODS/DESIGN: The study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for a period of 4 months at the Medical Clinic, University Medical Unit, National Hospital of Sri Lanka. A total of 210 subjects with diabetes, in three equal groups, will be recruited for the study. The patients will be randomized in a 1:1:1 ratio according to the method of block randomization and the subjects will be randomly and equally assigned into two test groups (n = 70 each) and one placebo group (n = 70). The population will be stratified at randomization based on age, gender and disease severity. The treatment drug is a capsule containing Cinnamomum zeylanicum extract as the active ingredient and the placebo capsule will contain lactose monohydrate. Two doses of Cinnamomum zeylanicum extracts (250 mg and 500 mg of the cinnamon extract) will be used. The study drugs will be double blinded to both investigators and participants. The visits and the evaluations will be done as follows: screening (visit 0), 1 month (visit 1), 2 months (visit 2), 3 months (visit 3) and 4 months (visit 4). The following primary outcome measures will be evaluated: glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG) and serum insulin. Secondary outcome measures include: Body Mass Index (BMI) and other anthropometric parameters, blood pressure, total cholesterol, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglycerides (TAG). Data will be analyzed using SPSS version 14. DISCUSSION: We describe the protocol for a clinical trial design evaluating the effects of Cinnamomum zeylanicum (Ceylon cinnamon) in patients with type-2 diabetes mellitus. The result of the present study, positive or negative, should provide a step change in the evidence guiding current and future policies regarding the use of cinnamon dietary supplementation in patients with diabetes. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry (SLCTR), identifier: SLCTR/2017/010 ( http://slctr.lk/trials/714 ). Registered on 5 April 2017; study protocol version 3.1 21 March 2017.

Zinc and diabetes mellitus: understanding molecular mechanisms and clinical implications.

BACKGROUND: Diabetes mellitus is a leading cause of morbidity and mortality worldwide. Studies have shown that Zinc has numerous beneficial effects in both type-1 and type-2 diabetes. We aim to evaluate the literature on the mechanisms and molecular level effects of Zinc on glycaemic control, ß-cell function, pathogenesis of diabetes and its complications. METHODS: A review of published studies reporting mechanisms of action of Zinc in diabetes was undertaken in PubMed and SciVerse Scopus medical databases using the following search terms in article title, abstract or keywords; ("Zinc" or "Zn") and ("mechanism" or "mechanism of action" or "action" or "effect" or "pathogenesis" or "pathology" or "physiology" or "metabolism") and ("diabetes" or "prediabetes" or "sugar" or "glucose" or "insulin"). RESULTS: The literature search identified the following number of articles in the two databases; PubMed (n = 1799) and SciVerse Scopus (n = 1879). After removing duplicates the total number of articles included in the present review is 111. Our results show that Zinc plays an important role in ß-cell function, insulin action, glucose homeostasis and the pathogenesis of diabetes and its complications. CONCLUSION: Numerous in-vitro and in-vivo studies have shown that Zinc has beneficial effects in both type-1 and type-2 diabetes. However further randomized double-blinded placebo-controlled clinical trials conducted for an adequate duration, are required to establish therapeutic safety in humans.

Cardiac involvement in dengue infection.

INTRODUCTION: Dengue is endemic in the tropics, and complications involving organ systems are seen with varying incidence. METHODOLOGY: We performed a systematic review. MEDLINE, EMBASE, Scopus SciVerse, Google Scholar, and LILACS were searched for papers providing information on cardiac involvement in dengue. RESULTS: Cardiac involvement is not uncommon in dengue infection and is often transient, but may be associated with significant morbidity and even mortality. Direct viral invasion, immune mechanisms, electrolyte imbalance, derangement of intracellular calcium ion storage, lactic acidosis, and ischemia due to hypotension all play a role in myocardial dysfunction. The manifestations of cardiac involvement include clinical, electrocardiographic, echocardiographic, cardiac enzyme, and histopathologic abnormalities. Echocardiography appears to be a useful tool for detecting myocardial involvement and should be performed in patients with electrocardiographic abnormalities or hemodynamic instability. Treatment is largely supportive, though there are some anecdotal reports of improvements with specific agents. CONCLUSIONS: Knowledge on cardiac manifestations in dengue is limited, and further studies are needed to establish the exact pathophysiology and role of specific agents in the prevention and treatment of cardiac complications in dengue.

Hypocalcemia is associated with disease severity in patients with dengue.

INTRODUCTION: Dengue hemorrhagic fever (DHF) is a major cause of morbidity and mortality in tropical regions. Serum free calcium (Ca2+) is known to be important in cardiac and circulatory function. We evaluated association between serum Ca2+ level and severity of dengue. METHODOLOGY: A cross-sectional study was carried out at a tertiary care private hospital in Sri Lanka. A probable case of dengue was diagnosed and classified according to World Health Organization criteria and confirmed by either IgM antibody, PCR, or NS1 antigen detection. Socio-demographic details were collected using an interviewer-administered questionnaire. RESULTS: The sample size was 135. The mean age was 26.1 years, and the majority were males (n = 80, 59.3%). DHF was diagnosed in 71 patients (52.6%). Mean serum Ca2+ level of the study population was 1.05 mmol/L (range 0.77-1.24). Mean serum Ca2+ was significantly higher in patients with dengue fever (DF) (1.09 mmol/L) than in those with DHF (1.02 mmol/L) (p < 0.05). A significant difference was observed between mean serum calcium levels of DHF I and DHF II. Prevalence of hypocalcemia in DHF and DF patients was 86.9% (n = 60) and 29.7% (n = 11), respectively (p < 0.05). CONCLUSIONS: Serum Ca2+ levels significantly correlated with dengue severity. Serum Ca2+ levels were significantly lower and hypocalcemia was more prevalent in patients with DHF than in patients with DF. Further studies are required to determine whether hypocalcemia can be utilized as a prognostic indicator and to evaluate effectiveness of calcium therapy in prevention of dengue complications.

The prevalence, predictors and associations of hypertension in Sri Lanka: a cross-sectional population based national survey.

We studied the community prevalence, patterns and predictors of hypertension in a large sub-population of South Asian adults with a view of identifying differential risk factors. Data were collected between years 2005-2006 and 5000 adults were invited for the study. The sample size was 4485, and about 39.5% were males. Mean systolic and diastolic blood pressures were 127.1 ± 19.8 mmHg and 75.4 ± 11.3 mmHg, respectively. Age-adjusted prevalence in all adults, males and females was 23.7%, 23.4% and 23.8%, respectively. Urban adults had a significantly higher prevalence of hypertension than rural adults. In the binary logistic-regression analysis, male gender (OR: 1.2), increasing age, Sri Lankan Moor ethnicity (OR: 1.6), physical inactivity (OR: 1.7), presence of diabetes (OR: 2.2) and central obesity (OR: 2.3) all were significantly associated with hypertension. In conclusion, nearly one-third of the Sri Lankan adult population is hypertensive. Hence, public health initiatives should encourage healthier lifestyles with emphasis on preventing obesity and increasing physical activity.

Medicinal properties of 'true' cinnamon (Cinnamomum zeylanicum): a systematic review.

BACKGROUND: In traditional medicine Cinnamon is considered a remedy for respiratory, digestive and gynaecological ailments. In-vitro and in-vivo studies from different parts of the world have demonstrated numerous beneficial medicinal effects of Cinnamomum zeylanicum (CZ). This paper aims to systematically review the scientific literature and provide a comprehensive summary on the potential medicinal benefits of CZ. METHODS: A comprehensive systematic review was conducted in the following databases; PubMed, Web of Science, SciVerse Scopus for studies published before 31st December 2012. The following keywords were used: "Cinnamomum zeylanicum", "Ceylon cinnamon", "True cinnamon" and "Sri Lankan cinnamon". To obtain additional data a manual search was performed using the reference lists of included articles. RESULTS: The literature search identified the following number of articles in the respective databases; PubMed=54, Web of Science=76 and SciVerse Scopus=591. Thirteen additional articles were identified by searching reference lists. After removing duplicates the total number of articles included in the present review is 70. The beneficial health effects of CZ identified were; a) anti-microbial and anti-parasitic activity, b) lowering of blood glucose, blood pressure and serum cholesterol, c) anti-oxidant and free-radical scavenging properties, d) inhibition of tau aggregation and filament formation (hallmarks of Alzheimer's disease), e) inhibitory effects on osteoclastogenesis, f) anti-secretagogue and anti-gastric ulcer effects, g) anti-nociceptive and anti-inflammatory activity, h) wound healing properties and i) hepato-protective effects. The studies reported minimal toxic and adverse effects. CONCLUSIONS: The available in-vitro and in-vivo evidence suggests that CZ has many beneficial health effects. However, since data on humans are sparse, randomized controlled trials in humans will be necessary to determine whether these effects have public health implications.

Prevalence and risk factors for resistant hypertension among hypertensive patients from a developing country.

BACKGROUND: To study the prevalence and define deferential risk factors for 'Resistant' hypertension (RHT) in a hypertensive population of South Asian origin. METHODS: A descriptive cross-sectional study was carried out among hypertensive patients attending clinics at the Cardiology Unit, Colombo from July-October 2009. All the patients with hypertension who provided informed written consent were recruited to the study (n = 277). A pre-tested interviewer-administered questionnaire was used for data collection. A binary logistic-regression analysis was performed in all patients with 'presence of RHT' as the dichotomous dependent variable and other independent co-variants. RESULTS: Mean age was 61 ± 10.3 years and 50.2% were males. The mean of average systolic and diastolic blood pressures (BP) were 133.04 ± 12.91 mmHg and 81.07 ± 6.41 mmHg respectively. Uncontrolled BP was present in 41.1% (n = 114) of patients, of which RHT was present in 19.1% (n = 53). Uncontrolled BP were due to 'therapeutic inertia' in 27.8% of the study population. Those with diabetes mellitus, obesity (BMI > 27.5 kg/m2) and those who were older than 55 years were significantly higher in the RHT group than in the non-RHT group. In the binary logistic regression analysis older age (OR:1.36), longer duration of hypertension (OR:1.76), presence of diabetes mellitus (OR:1.67) and being obese (OR:1.84) were significantly associated with RHT. CONCLUSION: A significant proportion of the hypertensive patients were having uncontrolled hypertension. Nearly 1/5th of the population was suffering from RHT, which was significantly associated with the presence of obesity and diabetes mellitus. Therapeutic inertia seems to contribute significantly towards the presence of uncontrolled BP.

Electrocardiographic and echocardiographic manifestations of cardiac involvement in leptospirosis.

BACKGROUND: Cardiac involvement is known to occur in leptospirosis, however, data on the significance of electrocardiographic and echocardiographic findings is very limited. METHODS: Electrocardiographic and echocardiographic changes were studied in serologically confirmed patients with leptospirosis. RESULTS: Of 22 patients, 45% (10) had cardiac symptoms; 59% (13) had abnormalities on the ECG; 90% (9/10) of patients with cardiac symptoms had at least one electrocardiographic abnormality. Echocardiographic abnormalities were seen in 41% (9). Clinical and echocardiographic evidence of myocarditis was seen in two patients, but left ventricular function was preserved. CONCLUSIONS: Echocardiographic changes may be useful in identifying patients with myocarditis in leptospirosis, especially in symptomatic patients.

Reflex anuria following acute cardiac event.

BACKGROUND: Reflex anuria is an uncommon cause for acute renal failure, which occurs almost always after manipulation or irritation to kidneys, ureter, bladder or other pelvic organs. CASE PRESENTATION: Here we describe a case of acute renal failure due to reflex anuria following acute cardiac event. This patient had background history of urolithiasis. In the absence of other pre renal, renal or post- renal causes for acute kidney injury, we believe reflex anuria is the causative entity for acute renal failure in our patient. CONCLUSION: Acute renal failure due to reflex anuria is related to a reflex mechanism involving arteriolar vasoconstriction and urethral spasm. Patients with reflex anuria can be successfully managed with medical or surgical interventions. Our case suggests that reflex anuria should be considered as one of the differential diagnosis of acute renal failure following acute cardiac event, especially in patients with background urological problem.