An outbreak investigation of typhoid fever in Pondicherry, South India, 2013

Background: Preliminary investigation at Pediatric ward of Indira Gandhi Medical College revealed admission of a cluster of typhoid cases who were residents of one particular street in a nearby locality. Objectives: This study was undertaken to estimate the magnitude of the outbreak, identify the source of infection, and, thereby, institute control measures. Materials and Methods: An investigation team including 10 MBBS students carried out a sanitary survey, house-to-house survey, data collection using epidemiological case sheets, and spot mapping. Typhoid diagnosis was confirmed as per the IDSP guidelines, i.e., either a blood culture growth positive for Salmonella typhi or a fourfold rise in antibody titer. An age- and gender-matched case–control study was conducted to find the association of occurrence of typhoid with various possible sources of infection. Water samples were collected from the affected households and public taps for investigation. Results: Rapid survey of all the 6 streets of Thilaspet covered 1106 people living in 283 households. All nine confirmed cases were residents of one particular street. The attack rate calculated was 3.4% in this street. A significant association of occurrence of typhoid was found only with consumption of raw drinking water (OR = 12.6, P = 0.01). Water samples only from the affected street tested positive for the presence of coliforms. The sanitary survey documented water pipeline breakage at the junction of this street. Further spread of disease was stopped by advocating drinking of boiled water and repair of pipeline. Conclusion: Strengthening of disease surveillance for early identification of localized outbreaks and instituting control measures can effectively control disease spread

COMPARATIVE EVALUATION OF FIRST ORDER, ABSORBANCE RATIO AND BIVARIATE SPECTROPHOTOMETRIC METHODS FOR DETERMINATION OF ATOVAQUONE AND PROGUANIL IN PHARMACEUTICAL FORMULATION MALARONE®

Objective: Three simple, rapid, accurate and precise spectrophotometric methods have been developed for the simultaneous estimation of atovaquone and proguanil hydrochloride in pharmaceutical preparations.Methods: The determination of drugs was carried out using the first order derivative, absorbance-ratio and bivariate spectrophotometric methods. The methods were validated for their linearity, accuracy and precision, recovery and ruggedness according to the ICH guidelines.Results: The linearity was established in the concentration range of 1.0-10 µg/ml for atovaquone and 0.5-8.0 µg/ml for proguanil hydrochloride by all three methods. The limit of detection (LOD) and the limit of quantitation (LOQ) of the methods varied from 0.252 to 0.270 µg/ml and 0.764 to 0.825 µg/ml for atovaquone and 0.119 to 0.156 µg/ml and 0.361 to 472 µg/ml for proguanil hydrochloride respectively. The intra-and inter-batch accuracy (% recovery) and precision (% RSD) ranged from 99.16 to 101.05 % and 0.603 to 1.048 for atovaquone and 99.74 to 101.12 % and 0.593 to 1.001 for proguanil respectively.Conclusion: The proposed methods were applied to a pharmaceutical formulation with acceptable accuracy and precision without any interference from commonly used excipients and additives. The results show that all three methods are comparable, cost effective and rapid and thus can be readily used in quality control labs for routine analysis of these drugs.Â

Simultaneous analysis of aliskiren and hydrochlorothiazide in pharmaceutical preparations and spiked human plasma by HPTLC

AbstractA simple, selective and precise method based on HPTLC has been developed for the simultaneous determination of aliskiren and hydrochlorothiazide in a fixed-dose tablet formulation and human plasma. The chromatography was performed on silica gel 60 GF254 plates, with a mobile phase consisting of methanol–chloroform (6:4, v/v). Densitometric analysis of the analytes was carried out at 225nm. Under optimized conditions, the Rf values were 0.26±0.02 and 0.71±0.02, and the resulting regression plots were linear (r2≥0.9997) in the concentration ranges of 1.00–10.0 and 0.10–1.00μgband−1 for aliskiren and hydrochlorothiazide. The limit of detection and limit of quantitation of the validated method were 0.206 and 0.624μgband−1 for aliskiren and 0.015 and 0.046μgband−1 for hydrochlorothiazide, respectively. The % expected content of aliskiren and hydrochlorothiazide in the commercial tablet formulation was 99.2% and 101.3%, respectively. For spiked plasma sample preparation, the analytes and nebivolol internal standard were extracted from 500μL of plasma sample by solid-phase extraction on LiChrosep® DVB-HL cartridges. The mean extraction recovery of aliskiren and hydrochlorothiazide from human plasma was 87.2% and 76.5%, respectively. In addition, the stability of the analytes in plasma was established under different storage conditions

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Prevalence and knowledge, attitude, practices about diabetes mellitus among elderly people in urban slums of Puducherry India

Background: Diabetes mellitus (DM) is a chronic metabolic disease which is prevalent globally. The World Health Organisation (WHO) has warned of an alarming increase in the population with type II diabetes mellitus both in developed and developing countries over the next two decades. This study is aimed at estimating the prevalence of diabetes mellitus among the elderly persons residing in urban slums of Pondicherry.Methods: A cross-sectional community based study was conducted with an objective to estimate the prevalence of diabetes and to assess the knowledge, attitude and practices regarding diabetes, treatment and control of diabetes, among elderly persons (60 years and above) residing in an urban slum. A house to house community based study was carried out among a randomly selected sample of 202 persons aged 60 years and above, from urban slum of Pondicherry. Results: Total 202 participants were interviewed, 103 (53%) were males and 99(49%) were females. The prevalence of impaired fasting blood glucose is 6.9 (7%), while prevalence of diabetes is found to be 20.3%. A total of 181(90%) of participants have heard about Diabetes Mellitus while 10% have not ever heard about Diabetes Mellitus, while 155 (77%) participants agreed that regular exercise keeps diabetes under control while almost equal number 149(73.4%) agreed that people with DM should control their weight and 144(71%) dietary modification is useful for keeping DM in control. A total of 177(88%) did not know whether complications can be prevented by timely investigations while just 12% knew that it is possible to prevent complications of diabetes mellitus with timely investigation. 77% knew that regular exercise keeps diabetes under control but during the last one month 106(50%) either rarely or never participated in any moderate physical exercise.Conclusions: Strengthening primary health care services in urban slums, with special emphasis on vulnerable population like elderly persons, is needed. Non-communicable diseases are a major cause of morbidity and mortality in this age group, and deserve special attention of policy makers and programme managers

Determination of cilostazol and its active metabolite 3,4-dehydro cilostazol from small plasma volume by UPLCâMS/MS

A simple, rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLCâMS/MS) method has been developed for the simultaneous determination of cilostazol and its pharmacologically active metabolite 3,4-dehydro cilostazol in human plasma using deuterated analogs as internal standards (ISs). Plasma samples were prepared using solid phase extraction and chromatographic separation was performed on UPLC BEH C18 (50 mmÃ2.1 mm, 1.7 µm) column. The method was established over a concentration range of 0.5â1000 ng/mL for cilostazol and 0.5â500 ng/mL for 3,4-dehydro cilostazol. Intra- and inter-batch precision (% CV) and accuracy for the analytes were found within 0.93â1.88 and 98.8â101.7% for cilostazol and 0.91â2.79 and 98.0â102.7% for the metabolite respectively. The assay recovery was within 95â97% for both the analytes and internal standards. The method was successfully applied to support a bioequivalence study of 100 mg cilostazol in 30 healthy subjects. Keywords: Cilostazol, 3,4-dehydro cilostazol, UPLCâMS/MS, Sensitive, High throughpu

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society