Evolution of adverse drug reactions reporting systems: paper based to software based.

OBJECTIVE: Adverse Drug Reactions (ADR) add a significant clinical and economic burden to the healthcare system of a country. We present an overview of the different approaches of ADR reporting systems worldwide and their evolution over time. METHODS: A systematic review of the literature was made based on PubMed and the Cochrane database of systematic reviews. The articles searched for included original articles, WHO and FDA reports and institute of medicine reports. Reporting ADRs is the cornerstone of detecting uncommon ADRs once the drugs are on the market. In many countries, ADR reporting is regulated by national regulatory bodies and various methods are employed to report ADRs. Direct reporting by healthcare professionals has been adopted by many developed and developing countries. With emerging new technologies in the field of medicine, there is a great potential to develop better ADR reporting systems in the countries where they have poor reporting. CONCLUSION: Development and acquisition of newer technologies to promote ADR monitoring and reporting is a necessity for an effective pharmacovigilance system in a country.

Frequently Relapsing Anterior Nodular Scleritis as the Initial Presentation of a Lethal Systemic Infection: Disseminated Tuberculosis with HIV Coinfection.

BACKGROUND: Scleritis is a painful inflammatory ocular disease often associated with an underlying systemic illness mostly having an autoimmune aetiology. Tuberculosis usually presents as pulmonary infection, and the ocular presentation is considered to be rare. Case presentation. We present a male who developed prolonged pyrexia following systemic steroids while being investigated for a frequently relapsing anterior scleritis. Biopsy of sclera demonstrated acid-fast bacilli, and histology of sclera and lymph node showed granulomatous inflammation with caseation. Contrast CT demonstrated mediastinal and visceral lymphadenopathy with pulmonary changes suggesting disseminated tuberculosis. Later, Western blot confirmed coinfection with HIV with a CD4 count of 71 cells/mm3. He was treated with antituberculous medications, and then HAART was initiated within two months. He showed good response and showed a partial resolution of scleritis at the end of two months. CONCLUSION: Tuberculosis tends to occur in unusual sites when coinfected with HIV. Scleritis is a rare extrapulmonary manifestation of tuberculosis. High degree of suspicion is critical in making diagnosis and commencing early treatment.

Severe Disabling Myalgia as an Initial Presentation of Polyarteritis Nodosa.

BACKGROUND: Polyarteritis nodosa (PAN) is a form of necrotizing vasculitis affecting medium or small blood vessels with multiorgan involvement. Although myalgia is a clinical feature of PAN, severe disabling myalgia as the initial presentation is rarely noted. CASE PRESENTATION: We present a case of 54-year-old male with recently detected chronic kidney disease admitted with progressive severe disabling muscular pains predominantly over calves with constitutional symptoms for seven weeks. He was weak to mobilize out of the bed. Later, he developed a vasculitic rash, unilateral ulnar claw, and bilateral foot drop. His skin and muscle biopsies showed evidence of vasculitis. His renal and mesenteric artery CT angiogram revealed stenosed segment of the celiac artery without evidence of visible aneurysms elsewhere. He completed six cycles of intravenous cyclophosphamide pulse therapy with high-dose oral prednisolone with good response. With continuation of aggressive immunosuppression and rehabilitation for five months, the patient improved and was able to walk without support. CONCLUSION: Musculoskeletal predominant PAN, even though rare, needs to be considered in patients presenting with disabling muscle pain and weakness. These features may herald over days to months along with constitutional symptoms before other systems getting affected. Early recognition of such symptoms and initiating specific treatment would be important for better outcomes.

A Comparison of the Prevalence of the Metabolic Syndrome among Sri Lankan Patients with Type 2 Diabetes Mellitus Using WHO, NCEP-ATP III, and IDF Definitions.

BACKGROUND: Presence of metabolic syndrome (MetS) in patients with type 2 diabetes mellitus (type 2 DM) increases the risk of cardiovascular morbidity and mortality. Therefore, recognition of MetS in type 2 DM is important in initiating the appropriate preventive and therapeutic measures. The commonly used definitions have similarities and discrepancies. Aims of this study was to investigate the prevalence of MetS among patients with type 2DM using all three well known (WHO, IDF, and NCEP-ATP III) definitions and to identify the concordance and the difference of these three definitions. METHODS: This cross-sectional study included patients with type 2 DM who were followed up at the regional diabetes centre in Galle, Sri Lanka. A total of 2913 type 2 DM patients were recruited by convenient sampling method, and their clinical and biochemical data were collected. RESULTS: The mean age (SD) of the sample was 49.9 (10.2) years and the mean duration of diabetes was 5.04 (5.71). Prevalence of MetS was highest by WHO (70%) followed by IDF (44%) and NCEP-ATP III (29%) definitions. The prevalence was significantly higher in women according to all three definitions, and the difference was most marked with NCEP-ATP III and IDF definitions. Around 25% were identified as having MetS by all three definitions whereas around 45% were recognized with MetS by two definitions. While concordances between WHO with IDF (0.37, p < 0.001) and NCEP-ATP III (0.24, p < 0.001) criteria were poor, they were average (0.53, p < 0.001) between NCEP-ATP III and IDF criteria. CONCLUSIONS: The prevalence of MetS among patients with type 2 DM can significantly be varied based on the definition used and the three definitions of MetS recognized different set of individuals. The highest prevalence of MetS was observed with WHO (70.6%) whereas lowest was observed with NCEP-ATP III definition.

Effect of Vitamin D therapy on urinary albumin excretion, renal functions, and plasma renin among patients with diabetic nephropathy: A randomized, double-blind clinical trial.

BACKGROUND: Despite different management strategies, progression of proteinuria occurs in a sizable category of patients with diabetic nephropathy (DN). Increase in serum renin levels induced by the renin-angiotensin system (RAS) may contribute to this. Vitamin D therapy is found to have an inhibitory effect on the RAS. We aimed to study the effects of Vitamin D therapy on renal functions of patients with DN. METHODS: This was a double-blind, randomized, placebo-controlled study. Patients with DN (urinary albumin [UA] >30 mg/g of creatinine) whose estimated glomerular filtration rate (eGFR) was more than 30 mL/min were selected and their plasma renin, parathyroid hormone, serum Vitamin D, serum calcium, serum creatinine, fasting blood sugar were done as baseline measurements. Subjects were randomized into two groups and treatment group was given Vitamin D, 50000 IU (0.25 ml) intramuscularly (IM) monthly for 6 months; control group received distilled water IM. Investigations were repeated after 6 months of therapy. RESULTS: Of 155 patients invited, 85 were randomly assigned to two groups. After 6 months, mean reduction of UA to creatinine ratio in the treatment and control group was 51.8 mg/g (95% confidence interval [CI]; 66.1--37.5, P ≤ 0.001); 22.4 mg/g (95% CI; -45.7-0.8, P = 0.06), respectively (between group difference P = 0.001). Significant increase in the eGFR observed in the treatment group while eGFR remained unchanged in the control group (P = 0.03 for the between-group difference). Mean reduction in plasma renin in treatment group and control group was 5.85 pg/mL (95% CI; -6.7--4.6) (P < 0.001) and 0.95 pg/mL (95% CI; -1.4--0.14, P = 0.02), respectively. CONCLUSIONS: Vitamin D 50000 IU given IM monthly for 6 months reduces urine albumin, serum creatinine, and renin levels in patients with DN.

Potential use of telephone-based survey for non-communicable disease surveillance in Sri Lanka.

BACKGROUND: Telephone survey (TS) has been a popular tool for conducting health surveys, particularly in developed countries. However, the feasibility, and reliability of TS are not adequately explored in Sri Lanka. The main aim of this study is to assess the effectiveness of telephone-based survey in estimating the prevalence of common non-communicable diseases (NCDs) in Sri Lanka. METHODS: We carried out an observational cross-sectional study using telephone interview method in Galle district, Sri Lanka. The study participants were selected randomly from the residents living in the households with fixed land telephone lines. The prevalence of the main NCDs was estimated using descriptive statistics. RESULTS: Overall, 975 telephone numbers belonging to six main areas of Galle district were called, and 48% agreed to participate in the study. Of the non-respondents, 22% actively declined to participate. Data on NCDs were gathered from 1470 individuals. The most common self-reported NCD was hypertension (17.%), followed by diabetes (16.3%) and dyslipidaemia (15.6%). Smoking was exclusively seen in males (7.4%), and regular alcohol use was significantly more common in males (19.2%) than females (0.4%, P < .001). CONCLUSIONS: Our study revealed average response rate for telephone based interview in Sri Lankan setting. Overall prevalence of main NCDs in this study showed a comparable prevalence to studies used face to face interview method. This study supports the potential use of telephone-based survey to assess heath related information in Sri Lanka.

Knowledge, attitude and practice related to diabetes mellitus among the general public in Galle district in Southern Sri Lanka: a pilot study.

BACKGROUND: Type 2 diabetes mellitus (DM) has become a global epidemic with significant disability and premature death. Identification of the level of knowledge, attitude and practice (KAP) related to diabetes among the general public is important in strategies for prevention of diabetes mellitus. METHODS: This study was conducted as a community based cross sectional study in three Medical Officers of Health (MOH) areas in Galle district. Previously healthy literate individuals who have not attended any diabetes education program in the last two years were selected for this study. RESULTS: A total of 277 participants were included in the study. The majority (77%) had either moderate (39%) or above moderate knowledge (38%) on diabetes mellitus. Even though, level of education was significantly and positively associated with knowledge (p = 0.001), the association of gender and age with knowledge was not significant. Unlike knowledge, the attitude towards diabetes was poor in majority (90%) and level of education had no significant effect on attitude. With regards to practices, more than half of study subjects never had their blood sugar checked and, about 65% used to take refined sugar liberally and a large majority (80%) had no regular exercise activity. CONCLUSIONS: Even though the majority (77%) had moderate or above moderate knowledge on diabetes, their attitudes towards diabetes was poor (88%). It appears that the higher knowledge on diabetes did not translate into good practices as over 50% of study subjects did not involve with any preventive measures. Therefore, more emphasis should be given to address the issue of poor attitude and practices towards diabetes mellitus among general public in Sri Lanka.

Use of HbA1c to diagnose type 2 diabetes mellitus among high risk Sri Lankan adults.

AIM: Even though, glycosylated hemoglobin (HbA1c) was found to be effective in predicting diabetes especially in Caucasians there is limited evidence of its diagnostic utility in high risk Sri Lankan adults. This study aimed to determine the optimal HbA1c cut-off points for detecting diabetes in a high risk population in Sri Lanka. MATERIALS AND METHODS: This community based study consisted of 254 previously healthy adults with history of diabetes in one or more first-degree relatives. Fasting plasma glucose (FPG) , glucose tolerance test (GTT) and HbA1c were measured in all and GTT was used as a reference to diagnose diabetes. Receiver operating characteristic curve was created to find the optimum HbA1c cut-off value to predict diabetes. RESULTS: Prevalence of diabetes was 12.2% (n=31) with FPG and 16.1% (n=41) with GTT. Prevalence rose to 27.6% (P<0.01) when HbA1c with cut-off of ≥6.5% was used as the diagnostic test. The ROC curves showed the HbA1c threshold of 6.3% provided the optimum balance between sensitivity (80.5%) and specificity (79%). In compared to GTT, FPG had only a modest sensitivity (65%) in diagnosing diabetes in this high risk population. CONCLUSION: Our study showed that optimum HbA1C cut-off for detecting diabetes was 6.3% and it had better sensitivity, but lower specificity than FPG. This study further showed that the prevalence of diabetes would become double if HbA1c is used over FPG to screen this high risk population.

Targeting postprandial blood sugar over fasting blood sugar: A clinic based comparative study.

INTRODUCTION: Recent studies indicate that modulation of post prandial blood sugar (PPBS) plays an important role in the long term glycemic control. Measurement of PPBS is more convenient for patients attending outpatient clinics than fasting blood sugar (FBS) as the former needs only two hours of fasting from the last meal. OBJECTIVE: To assess the value of PPBS monitoring in optimization of long term glycemic control among diabetic patients attending an outpatient clinic. METHODS: A total of 240 patients with type 2 diabetes (T2DM) attending an out-patient medical clinic were randomized to either PPBS or FBS monitoring. Those who selected to PPBS-group underwent blood sugar measurement 2-h after last meal on the day of their clinic visits and those in the FBS group underwent blood sugar measurement after fasting overnight (8-10h) in the morning of their clinic visits. Treating team was asked to optimize the anti-diabetic medications based on the available PPBS or FBS results. All patients were followed up monthly for six months. Glycemic control was assessed with glycosylated hemoglobin (HbA1c) at baseline and six months later. RESULTS: Baseline characteristics of the two arms including age, gender, and duration of T2DM were not significantly different. Mean HbA1c (SD) of FBS and PPBS arms at baseline were 7.20 (0.45), and 7.33 (0.43) and were not significantly different (P=0.115). During the study period, HbA1c dropped by 0.20 in FBS arm compared to 0.25 drop in PPBS arm (p=0.59). Incidence of hypoglycemia was similar in FBS (2.42%) and PPBS arms (2.70%). CONCLUSION: Monitoring of PPBS is a safe and effective alternative to FBS to optimize glycemic control in managing patients with T2DM attending outpatient clinics.

Comparison of McAuley/fasting insulin indices with ATP III clinical criteria for the diagnosis of insulin resistance in type 2 diabetes mellitus.

OBJECTIVE: To estimate the prevalence of insulin resistant syndrome (IRS) among newly diagnosed patients with type 2 diabetes and to test their validity against two indices of insulin resistance (IR). MATERIALS AND METHODS: Prevalence of IRS was estimated according to the criteria used by ATP III in newly diagnosed type 2 diabetic patients. Sensitivity and specificity of the ACE criteria were calculated against two indices of IR namely fasting insulin (FI) level > 12 mU/l and McAuley index (McA) < 5.8. [McA= exp [2.63--0.28 ln(insulin in mU/l) -- 0.31 ln(triglycerides in mmol/l)]. RESULTS: 35.7% of patients had IRS by ATP III criteria. 64.3% of patients were insulin resistant by FI and McA in each index. In patients who had IRS with ATP criteria, 80% and 86.6% were found to have McA and FI in the insulin resistant range. Out of the patients who were resistant by McA, only 40.6% had IR by ACE criteria and 93% had shown IR by FI. Out of all patients who did not fulfill the ATP III for IR, 74% and 59% were detected as having IR by fasting insulin and McA respectively. Sensitivity of the ACE criteria when tested against the FI and McA were 37.5% and 40.6%, specificity were 70% and 80%, respectively. CONCLUSIONS: IRS was common among the newly diagnosed patients with type 2 diabetes. ACE criteria showed an acceptable specificity but lack adequate sensitivity when compared with the two Indices of insulin resistance. More valid and clinically useful criteria should be available for the accurate diagnosis of IRS in clinical practice.

Prediction of total and visceral fat contents using anthropometric measures of adiposity in women.

BACKGROUND: Although techniques such as dual energy xray absorptiometry (DXA) and quantitative CT are available to estimate global and regional adiposity, anthropometric measurements are often used to detect adiposity in clinical practice. OBJECTIVES: To assess the association between the anthropometric measurements of obesity with total and regional fat mass determined by DXA. DESIGN: A cross-sectional, descriptive study. Patients and method 106 healthy women volunteers, aged between 30 and 54 years were studied. Anthropometric measurements including body mass index (BMI), waist circumference (WC), hip circumference (HC), height adjusted WC (WC/HT), waist-hip ratio (WHR), and skin-fold thickness (SFT) over triceps, infrascapular, and iliac regions were made. All women underwent assessment of total fat mass (TFM) and visceral fat mass (VFM) using a Hologic DXA scan. RESULTS: TFM and VFM showed positive correlations with all the anthropometric measurements examined, the strongest correlation was with BMI (r = 0.89 and 0.77 for TFM and VFM respectively, p < 0.001). Correlations of TFM with WC, HC, and WC/HT were 0.72, 0.87, and 0.65, (p < 0001 for all) respectively. Corresponding figures for VFM were 0.73, 0.74, and 0.68, (p < 0001 for all). WHR showed a poor correlation with TFM (r = 18, p = 0.09) and VFM (r = 0.33, p = 0.002). SFTs measured at three sites showed less strong correlations with TFM and VFM (r = 0.48 to 0.69, p < 0.001). CONCLUSIONS: BMI has the strongest association with total and visceral fat mass among these women. Waist and hip circumferences showed high correlations with total and visceral fat mass, but adjusting waist circumference for height did not improve the correlation.

Correlation between changes of blood pressure with insulin resistance in type 2 diabetes mellitus with 4 weeks of pioglitazone therapy.

OBJECTIVE: To examine effects of pioglitazone (PIO) on systolic, diastolic, pulse and mean blood pressures (SBP, DBP, PP and MP, respectively) in type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: One hundred and six normotensive patients with T2DM with mean fasting blood glucose (FBS; 183 +/- 6 mg/dl) were randomly divided into two groups. Test group was treated with 15 mg of PIO in addition to metformin 500 mg three times per day in both groups. SBP, DBP, PP and MP and fasting insulin, FBS and lipid profiles were measured before and after PIO therapy. RESULTS: There was a significant reduction in SBP (123 +/- 2 vs. 118 +/- 2 mmHg, P < 0.05), PP (41 +/- 1 vs. 37 +/- 1 mmHg, P < 0.05), and MP (95 +/- 1 vs. 91 +/- 1, P < 0.05). Clinical reduction in DBP was observed but not significant (82 +/- 2 vs. 81 +/- 1 mmHg, P > 0.05). There was a significant correlation between decline in SBP and DBP with respective baseline values (r = 0.76, P < 0.001 and r = 0.62, P < 0.001, respectively). Changes in PP and MP strongly correlated with baseline values (r = 0.51, P < 0.05 and r = 0.56, P < 0.05, respectively). There was a parallel reduction of FBS (183 +/- 2 vs. 121 +/- 3, P < 0.001) but reduction in IR or lipid profiles was not significant in test group. Changes in BP were not significant in control group ( P > 0.05). CONCLUSION: PIO treatment of T2DM showed early reduction of SBP and MP within first 4 weeks. Results suggest that pharmacodynamic effects of PIO mainly affect the systolic component. We hereby suggest that reduction of BP by PIO is independent from mechanisms of changes in IR and dyslipidaemia in normotensive diabetic patients.