Distribution changes of cutaneous leishmaniasis: A postulated risk of disease transmission in Hambantota, Sri Lanka.

BACKGROUND OBJECTIVES: Leishmaniasis is caused by various species of parasite Leishmania. Approximately twenty of them are pathogenic to mammals. In Sri Lanka, cutaneous leishmaniasis (CL) is an established vector-borne disease. CL originates and spreads mainly through sandfly bite in many endemic countries. The aim of the present study was to compare the geographical distribution and demographic features of CL cases in Hambantota district, Sri Lanka in 2014 and 2016. METHODS: The patients who were presented to the Tangalle Base Hospital from June to December in 2014 and 2016 were examined and a descriptive study was carried out using a structured-questionnaire. Slit-skin smears were collected from each patient, Giemsa-stained and examined under the light microscope to identify Leishmania amastigotes. RESULTS: Out of 256 and 314 suspected CL patients, 156 and 155 were identified positive for the year 2014 and 2016, respectively. Out of 12 District Secretary Divisions (DSD) in Hambantota district, the highest number of CL cases, 85 and 86 was reported from Tangalle DSD in 2014 and 2016 respectively. Number of identified CL patients in Beliatta DSD had increased from 50 to 67 during the study period. In both years, majority of CL patients were ≥50 years old with males more infected than females. Although CL association with occupations were insignificant, housewives were the highly (23%) infected occupants in this area. INTERPRETATION CONCLUSION: Based on the present findings, geographical distribution within DSDs in Hambantota district had changed. This emphasizes the importance of CL as a health problem in Hambantota district.

Genetic association between antipsychotic induced weight gain and FTO gene in a Sri Lankan population

Background: About 30% of patients treated with second generation antipsychotics (SGA) experience weight gain. Although there is evidence that the FTO gene is associated with obesity its role in antipsychotic induced weight gain is not so clear. Methods: A genetic association study was carried out to identify the association between FTO rs9939609 and antipsychotic induced weight gain. Sample consisted of 180 cases and 120 controls. Cases were patients diagnosed with schizophrenia or schizoaffective disorder, treated with second-generation antipsychotics for a minimum of 3 months, and had gained at least 10% of body weight. Controls were patients with schizophrenia treated with second-generation antipsychotics for a minimum of 3 months but had not gained ≥10% of body weight. Genomic DNA was extracted from whole blood. Polymerase chain reaction of the samples was done. Real-time quantitative PCR (qPCR) was carried out using BIO-RAD CFX96 Touch TM PCR detection system. Results: Females were significantly more among cases (58.3%) than controls (35%). Cases (52.4%) were significantly more likely to be overweight or obese than controls (13.8%). Genotype distribution was in Hardy-Weinberg equilibrium (p=0.43). Cochran-Armitage trend test was not significant. Risk of antipsychotic induced weight gain in the AA genotype [OR 1.69 (95% CI 0.74-3.86)] and AT genotype [OR 1.1 (95% CI 0.67-1.79)] were not significantly higher than the TT genotype. Recessive model showed that AA/AT genotypes were at significantly higher risk of being obese/overweight [OR 1.84 (95% CI 1.05-3.2)]. Conclusions: There was no significant association between FTO rs9939609 and antipsychotic induced weight gain. AA/AT genotypes had significantly higher risk of overweight/obesity.

Clinico-pathological characteristics and outcome of upper urinary tract urothelial carcinoma presenting to a tertiary care urology unit in Sri Lanka

Introduction: Upper urinary tract urothelial cancers account for 5% of urothelial tumours. In the West, the majority affect the pelvicalyceal system, with pyelocalyceal to ureteric ratio of 3:1. This study aims to describe the clinico-pathological features and outcome of upper urinary tract urothelial cancer treated surgically in a tertiary care unit in Sri Lanka. Methods: A retrospective analysis of all patients who underwent nephroureterectomy for upper urinary tract urothelial cancer at the Urology Unit at National Hospital of Sri Lanka between January1997 and December 2016 was carried out. Results: There were 43 patients. Male: female=1.87. Median age was 65 years (range:42-83). Macroscopic haematuria was the commonest presentation (n=29; 67.4%). Median duration of symptoms was 3 months (range 0.5-6). In the majority (n=20;46.5%) the tumour was confined to the ureter. Thirty-three (75.6%) were papillary tumours. Twenty-one had non-muscle invasive tumours (pTa: n=6(14%), pT1: n=15(34.9%) and others had invasive cancers (pT2: n=11(25.6%), pT3: n=7(16.3%) and pT4: n=4(9.3%)). Majority were low grade tumours (n=23;53.5%). Twelve (27.9%) had preceding urothelial bladder cancer. Nineteen (44.2%) were lost to follow up after surgery. Median follow up duration of the rest was 40 months (range:4-224months). Of them, 9(20.9%) developed metachronous bladder tumours. Nine had recurrence free survival of ≥5years and 15 had overall survival of ≥5 years. Of them, 4 patients survived ≥10 years. Older age (p=0.015) and presence of necrosis(p=0.05) were the only clinico-pathological parameters predictive of tumour recurrence. Conclusions: A relatively higher number females and high number of ureteric tumours were noted compared to similar studies from Asia.

Validity of the Sinhala version of the centre for epidemiological studies depression scale (CES-D) in out-patients.

OBJECTIVES: To translate and validate the Sinhala version of the Centre for Epidemiological Studies Depression scale (CES-D) for diagnosing depression in out-patients. DESIGN: A combined qualitative and quantitative approach was used for the translation of the CES-D. Sample size was calculated to detect a targeted sensitivity and specificity of 85%. The sample consisted of 75 participants diagnosed with major depressive disorder according to DSM IV criteria and 75 gender matched controls. Criterion validity was assessed using receiver operating charact-eristic (ROC) analysis. The Structured Clinical Interview for DSM-IV (SCID-II) conducted by a psychiatrist was used as the gold standard. RESULTS: Mean age of the sample was 33 years. There were 91 females (60.7%). There was significant difference in the mean CES-D scores between cases (13.94) and controls (6.58) [t=14.50, df=148, p<0.001]. A score of ≥ 16 gave a sensitivity of 84% and specificity of 92%. A score of ≥ 21 gave a sensitivity of 73.3% and specificity of 96%. The Cronbach's alpha was 0.93. The four items that were reverse coded had poor correlation with total scores. The average correlation coefficient for the reverse-scored items was 0.35 and for the rest of the items 0.63. Principal component analysis with oblique rotation identified four factors. Factor 1 corresponds to the "depressed affect" and "somatic complaints" in the original model proposed by Radloff. Factor 2 corresponds to the interpersonal concerns. Factors 3 and 4 loaded the reversed coded items. CONCLUSIONS: The Sinhala version of the CES-D is a valid and reliable instrument for diagnosing major depressive disorder.

Geographical variation in admissions due to poisoning in Sri Lanka: a time series analysis.

OBJECTIVES: To carry out time series analyses of hospital admissions for poisoning between 1995-2008 in all districts in Sri Lanka to identify trends and geographical variations in the substances used in poisoning. METHODS: Data of hospital admissions from 1995-2008 due to poisoning were obtained from the Annual Health Bulletins published by the Ministry of Health. Data were converted to annual rates per 100,000 population. Time trends in the rates of suicide and self-poisoning were calculated using univariate time series analysis. RESULTS: All districts except Kilinochchi and Mullaitivu showed an increase in the rates of admissions due to poisoning with drugs, medicaments and biological substances. Colombo, Hambantota, Kalutara and Anuradhapura showed an exponential increase. Hambantota, Monaragala, Nuwara Eliya and Colombo show an increase in the rate of admissions after pesticide poisoning. All other districts showed a linear decrease. Admissions due to all types of poisoning showed a negative trend in Anuradhapura, Polonnaruwa, Ampara, Matale and Batticoloa districts. Other districts show a positive trend in the rate of admissions for all types of poisoning. CONCLUSIONS: Results should be viewed with caution because they are based on analysis of secondary data. Although the rate of suicides has reduced since 1995, admissions due to self poisoning have increased in almost all districts. While pesticide poisoning is becoming less, there is a gradual shift to the use of drugs and medicaments in self poisoning. Poisoning with drugs, medicaments and biological substances are increasing both in urban and rural areas.

Validation of psoriasis disability index (PDI) questionnaire Sinhala version.

INTRODUCTION/OBJECTIVES: Psoriasis is a chronic inflammatory dermatosis with significant physical and psychological impact leading to negative influence on the quality of life among patients with psoriasis. Other than the disease characteristics many external factors could operate in South Asian context. Lack of a reliable disease-specific instrument prevents objective estimation and monitoring of disability in patients with psoriasis and hence we aim to validate assess the psychometric properties of the Sinhala version of PDI. METHODS: A cross-sectional study conducted at dermatology clinic at a tertiary care National Hospital in Sri Lanka. Patients with psoriasis and on therapy at least 4 weeks prior to enrollment, aged more than 18 years, were included while those with already diagnosed psoriatic arthritis and/or nail psoriasis alone without any skin involvement and generalized pustular psoriasis de novo were excluded. All patients were examined by dermatologist to obtain disease characteristics. The reliability was assessed by internal consistency using Cronbach's α and item-total correlation. Convergent validity was measured with the known groups. RESULTS: Of 199 patients studied, the PDI Sinhala version showed Cronbach's α of 0.86 (all 15 items) and ranged from 0.57 to 0.77 for subscales. PDI score and Dermatology Life Quality Index (DLQI) showed good correlation of coefficient 0.76 (p < 0.01). Positive associations were noted with extent and severity of psoriasis when using sample medians (p < 0.05). The dimensionality of the PDI was determined using exploratory factor analysis and four factors were structured. CONCLUSION: The PDI Sinhala version is proved to be valid and reliable tool to assess the burden of psoriasis among Sinhala conversant patients in Sri Lanka.

Validation of the Sinhala version of the Montreal Cognitive Assessment in screening for dementia.

OBJECTIVES: To validate the Sinhala version of the Montreal Cognitive Assessment (MoCA) scale in screening for dementia. METHODS: The MoCA translation and cultural adaptation was carried using a combined qualitative and quantitative approach. Sample size was calculated to detect a targeted sensitivity of 85% and a specificity of 85%. Sample consisted of 49 participants diagnosed with dementia of the Alzheimer's type (AD) according to DSM-IV criteria and 49 normal controls (NC) aged ≥50 years. All subjects were administered the Mini Mental State Examination (MMSE) and MoCA Sinhala version (MoCA-S). Concurrent validity was assessed using Pearson correlation coefficients between the MoCA-S scores and MMSE scores. Criterion validity was assessed using receiver operating characteristic (ROC) analysis. RESULTS: Mean MoCA scores between NC (26.71, SD 2.4) and AD group (16.78, SD 5.9) were significantly different (t=10.8, p<0.001). Cronbach's alpha of 0.818 indicated good internal consistency. Attention (digit span, sustained attention, and the serial 7 calculation task) had the highest discriminant ability followed by visuospatial skills (trail making, cube drawing and clock drawing). Naming had poor discriminant ability. There was a high, positive correlation between MoCA-S total scores and MMSE total scores. (r=0.907, p<0.001). The area under the ROC curve was 0.975 (95%CI 0.94-1.0) for the MoCA and 0.928 (95% CI 0.87-0.98) for MMSE. A cut-off value of 24 provided the best balance between sensitivity (98.0 7%) and specificity (79.6 %). CONCLUSION: MoCA-S is a valid and reliable instrument which can be used as a brief screening instrument for dementia in Sri Lanka.

Validation of Sinhala version of Psoriasis Epidemiology Screening Tool.

INTRODUCTION/OBJECTIVES: Psoriatic arthritis (PsA) occurs in one-third of patients with psoriasis and mostly remains undetected leading to debilitating deforming arthritis, eventually. The Psoriasis Epidemiology Screening Tool (PEST) is a quick and valid tool, widely used to detect PsA in clinical practice, and it has been validated to many languages. In this study, we intended to validate a Sinhala version of the PEST and assess its psychometric properties. METHODS: The Sinhala version of the questionnaire was tested on 199 patients with psoriasis attending the dermatology clinic at a tertiary care National Hospital in Sri Lanka. Patients who were detected to have PsA previously (n = 5) and those with other rheumatologic conditions (n = 12) were excluded. All patients were examined by a dermatologist, and demographic and disease characteristics were obtained. All patients were assessed by two rheumatologists who were blinded to the answers provided in the questionnaire. The diagnosis of PsA was made based on the CASPAR criteria. RESULTS: We observed the total PEST score of 3 or more to be the best cutoff value to screen for PsA. This cutoff value showed the highest Youden index (sensitivity = 0.89, specificity = 0.95). In the ROC analysis, the area under the curve of the PEST_sv was 0.95 (SE 0.02, p < 0.001). PEST_sv total score showed a significant correlation with body surface area involved but not with Dermatology Life Quality Index or Psoriasis area and severity index score. CONCLUSION: The Sinhala version of PEST demonstrated satisfactory performance as a screening tool for PsA. Key Points • Psoriatic arthritis (PsA) is the most debilitating complication of psoriasis and lack of quick, valid screening tool is a limiting factor for early identification in Sri Lankan context. • Sinhala version of the Psoriasis Epidemiology Screening Tool (PEST_sv) was tested on 199 patients with psoriasis and examined for the diagnosis of PsA according to Classification of Psoriatic Arthritis (CASPAR) criteria. • PEST_sv score of 3 or more was observed to be the best cutoff value to screen for PsA with sensitivity and specificity of 0.89 and 0.95 respectively. • PEST_sv demonstrated satisfactory performance as a screening tool for PsA.

A global geometric framework for nonlinear dimensionality reduction.

Scientists working with large volumes of high-dimensional data, such as global climate patterns, stellar spectra, or human gene distributions, regularly confront the problem of dimensionality reduction: finding meaningful low-dimensional structures hidden in their high-dimensional observations. The human brain confronts the same problem in everyday perception, extracting from its high-dimensional sensory inputs-30,000 auditory nerve fibers or 10(6) optic nerve fibers-a manageably small number of perceptually relevant features. Here we describe an approach to solving dimensionality reduction problems that uses easily measured local metric information to learn the underlying global geometry of a data set. Unlike classical techniques such as principal component analysis (PCA) and multidimensional scaling (MDS), our approach is capable of discovering the nonlinear degrees of freedom that underlie complex natural observations, such as human handwriting or images of a face under different viewing conditions. In contrast to previous algorithms for nonlinear dimensionality reduction, ours efficiently computes a globally optimal solution, and, for an important class of data manifolds, is guaranteed to converge asymptotically to the true structure.

Alcohol and tobacco use among males in two districts in Sri Lanka.

OBJECTIVES: To investigate the prevalence and consumption of tobacco and alcohol among males in the Colombo and Polonnaruwa districts. DESIGN: A cross-sectional study based on multistage cluster sampling was carried out in four Medical Officer of Health (MOH) areas in the Colombo (urban) and Polonnaruwa (rural) districts to assess the prevalence of tobacco and alcohol use. The Public Health Midwife areas were considered as primary clusters. The sample consisted of males over 18 years. There were 1318 from the Colombo District and 1366 from the Polonnaruwa District. The quantity frequency method was used to assess consumption. RESULTS: Abstinence was significantly higher in the rural areas (75.2%) compared to urban areas (56.6%) (p < 0.001). Prevalence of current drinking in the urban areas (32.9%) was significantly higher than in rural areas (20.8%) (p < 0.001). Alcohol consumption in the urban areas (33.1 units/week) was significantly higher than in rural areas (20.9) (p < 0.004). 51.6/1000 males in the urban areas and 14.6/1000 males in rural areas consumed daily. The prevalence of current smoking was also higher in the urban areas (29.9%) than (p = 0.052) in rural areas (24.4%). CONCLUSION: High-risk alcohol consumption was prevalent especially in urban areas as indicated by the mean alcohol consumption and number who consumed spirits daily. The prevalence of smoking is much lower than in many Asian countries but similar to western Europe.

Growth hormone secretion and circulating insulin-like growth factor-I (IGF-I) and IGF binding protein-3 concentrations in children with sickle cell disease.

Impaired growth involving both height and weight accompanying sickle cell disease (SCD) poses diagnostic and therapeutic problems. We undertook this study to test the hypothesis that this impaired growth is associated with abnormalities of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF binding protein-3 (IGFBP-3) axis in 21 children with SCD and that SCD is associated with GH resistance. Nine of 21 children with SCD had a defective GH response to both clonidine and glucagon provocation (peak < 10 micrograms/L); these children differed from the 12 others in having slower linear growth velocity (GV and GVSDS), lower circulating concentrations of IGF-I and IGFBP-3, and either partial or complete empty sellae in computed tomographic scans of the hypothalamic-pituitary area. In this group of patients with SCD, it appears that defective GH secretion and consequent low IGF-I production are the major etiological factors causing the slow growth. The two groups with SCD did not differ significantly in dietary intake, body mass index (BMI), midarm circumferences, skinfold thickness, serum albumin concentration, or intestinal absorption of D-xylose. A single injection of GH produced a smaller increase in circulating IGF-I in children with SCD with or without defective GH secretion versus 10 age-matched children with idiopathic short stature (ISS) and 11 children with isolated GH deficiency (GHD), suggesting partial GH resistance in the SCD group. The presence of defective GH secretion, decreased IGF-I synthesis, and partial resistance to GH in short children with SCD suggests that treatment with IGF-I may be superior to GH therapy for improving growth.

Prevalence of microalbuminuria in Saudi Arabians with non-insulin-dependent diabetes mellitus: a clinic-based study.

Prevalence of diabetic nephropathy varies in different racial groups, being especially high in communities that have abandoned an active traditional living and embraced a modern but sedentary life-style. As a new and rapidly developing country, Saudi Arabia has witnessed impressive changes in socio-economic growth and development and concurrently, a disturbing trend in non-insulin-dependent diabetes mellitus (NIDDM). These observations therefore prompted us to investigate the prevalence of microalbuminuria among Saudi Arabians with NIDDM. Two hundred and eleven patients attending a large Diabetic Clinic in Riyadh were screened for microalbuminuria (30-300 mg/24 h). Twenty-seven subjects had clinical proteinuria (dipstick-positive) and were excluded, leaving 184 cases for analysis. Seventy-six subjects (76/184, 41.3%) had microalbuminuria. These subjects had higher fasting plasma glucose concentrations (P = 0.002) and greater body mass index (P = 0.049) than subjects with normal albumin excretion rate (< 30 mg/24 h). There were no significant differences between subjects with and without microalbuminuria with regards to fasting total plasma cholesterol and triglycerides concentrations, frequency of hypertension, duration of diabetes or type of therapy for diabetes. In multivariate analysis, glycaemia (P < 0.005) and years since diagnosis of diabetes (P = 0.05) remained independently associated with albumin excretion rate. We conclude that microalbuminuria is exceedingly common in a clinic-based population of Saudi Arabians with NIDDM and its presence is closely related to glycaemic control. Whether the prevalence of microalbuminuria is truly increased in the diabetic population at large in Saudi Arabia must now await further population-based studies.

Permanent neonatal diabetes mellitus: clinical presentation and epidemiology in Oman.

AIM: To estimate the accurate incidence and prevalence of permanent neonatal diabetes mellitus, and to determine the clinical profile of this condition in the Sultanate of Oman. METHODS: All children diagnosed as having permanent neonatal diabetes mellitus between 1991 and 1995 in Oman were included in the study. RESULTS: The mean incidence was 2.2 per 100 000 live births/year and the prevalence among under 5s during 1995 was 2.0/100 000. Intrauterine growth retardation was noted in all (mean birthweight 1.86 kg), and diabetic ketoacidosis (mean plasma glucose 34.4 (SD 8.7) mmol/l, mean pH 7.17 (SD 0.09) in 80%. Hypertriglyceridaemia (mean serum triglyceride 19.06 (6.13) mmol/) was constant. No infant had clinical or immunological evidence of congenital viral infections. None had C-peptide excretion or circulating islet cell antibody during diagnosis or follow up. The other important features were parental consanguinity in all, HLA DR3/DR4 association in 80%, development of autoimmune hypothyroidism in one and observation of autoimmune disorders (insulin dependent diabetes mellitus and Hashimoto's thyroiditis) in family members. CONCLUSIONS: These findings strongly suggest an immune mediated aetiology for diabetes mellitus. The reported incidence of permanent insulin dependent neonatal diabetes mellitus in Oman is the highest in the world.

Permanent neonatal diabetes mellitus: epidemiology, mode of presentation, pathogenesis and growth.

Permanent neonatal diabetes mellitus (PNIDDM) is a rare form of IDDM with unclear etiology and pathogenesis. We determined the incidence and prevalence rates and studied the clinical and biochemical features of PNIDDM in the Sultanate of Oman. The mean incidence rate during the study period from January 1989 to December 1994 was 1.788 +/- 0.82 per 100,000 live births per year. At the end of December 1994 the prevalence rate was 2.4 per 100,000 children below the age of 5 years. They constituted 41.6% of all cases of IDDM in this age group. Diarrhoea, fever, lethargy, poor feeding and failure to thrive were the most common presenting symptoms. Dehydration and tachypnoea were the most common signs. All patients who developed IDDM during the neonatal period had intrauterine growth retardation and 4.5 presented with diabetic ketoacidosis (plasma glucose 37 +/- 9 mmol/L, pH 7.12 +/- 0.1). Hypertriglyceridemia was a constant feature (19.4 +/- 4.8 mmol/L). They were products of consanguineous marriage with significantly high prevalence of IDDM and NIDDM in their family members. None of the infants had clinical or immunological evidence of congenital viral infection. Three of the five children had HLA-DR2, the diabetes resistance alleles. C-peptide secretion was absent during and after metabolic control of hyperglycemia in all the studied infants and none had circulating islet cell antibody at presentation or during the first year after diagnosis. Despite marked growth retardation at birth, there was a significant improvement of growth after initiating insulin therapy. Four of the 5 patients had normal developmental milestones, one had mild developmental delay following a severe and prolonged attack of hypoglycemia. None of the patients had exocrine pancreatic deficiency. In summary, the very high rate of parental consanguinity, occurrence in both sexes and in two siblings in the same family, absence of islet cell antibodies and the presence of HLA-DR2 loci in 3/5 of patients suggest that PNIDDM is a different disease process to standard IDDM in childhood and an autosomal recessive mode of transmission.

Clozapine-associated weight loss.

Clozapine is associated with weight gain. We report three patients with substantial weight loss following treatment with clozapine. The weight loss observed in the three patients was 33, 18 and 14.4 kg with percentage loss of body weight of 49, 18 and 21 respectively. Two patients had diabetes mellitus. History, physical examination and extensive investigations in the three patients did not reveal any cause that could account for the weight loss.