Outdoor air pollution, subtypes and severity of ischemic stroke – a small-area level ecological study

Background: Evidence linking outdoor air pollution and incidence of ischemic stroke subtypes and severity is limited. We examined associations between outdoor PM 10 and NO 2 concentrations modeled at a fine spatial resolution and etiological and clinical ischemic stroke subtypes and severity of ischemic stroke. Methods: We used a small-area level ecological study design and a stroke register set up to capture all incident cases of first ever stroke (1995 – 2007) occurring in a defined geographical area in South London (948 census output areas; population of 267839). Modeled PM 10 and NO 2 concentrations were available at a very fine spatial scale (20 meter by 20 meter grid point resolution) and were aggregated to output area level using postcode population weighted averages. Ischemic stroke was classified using the Oxford clinical classification, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) etiological classification, National Institutes of Health Stroke Scale (NIHSS) score and a pragmatic clinical severity classification based on Glasgow coma score, ability to swallow, urinary continence and death <2 days of stroke onset. Results: Mean (SD) concentrations were 25.1 (1.2) ug/m 3 (range 23.3-36.4) for PM 10 and 41.4 (3.0) ug/m 3 (range 35.4-68.0) for NO 2 . There were 2492 incident cases of ischemic stroke. We found no evidence of association between these pollutants and the incidence of ischemic stroke subtypes classified using the Oxford and TOAST classifications. We found no significant association with stroke severity using NIHSS severity categories. However, we found that outdoor concentrations of both PM 10 and NO 2 appeared to be associated with increased incidence of mild but not severe ischemic stroke, classified using the pragmatic clinical severity classification. For mild ischemic stroke, the rate ratio in the highest PM 10 category by tertile was 1.20 (1.05-1.38) relative to the lowest category. The rate ratio in the highest NO 2 category was 1.22 (1.06-1.40) relative to the lowest category. Conclusions: We found no evidence of association between outdoor PM 10 and NO 2 concentrations and ischemic stroke subtypes but there was a suggestion that living in areas with elevated outdoor PM 10 and NO 2 concentrations might be associated with increased incidence of mild, but not severe, ischemic stroke

Uptake, Accuracy, Safety, and Linkage into Care over Two Years of Promoting Annual Self-Testing for HIV in Blantyre, Malawi: A Community-Based Prospective Study

Background Home-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population. Methods and Findings Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test) to adult (≥16 y old) residents (n = 16,660) and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA) sample. Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover) residents self-tested during months 1–12, with adolescents (16–19 y) most likely to test. 10,614/14,004 (75.8%) participants shared results with volunteer-counsellors. Of 1,257 (11.8%) HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3%) newly accessed care with a median CD4 count of 250 cells/μl (interquartile range 159–426). HIVST uptake in months 13–24 was more rapid (70.9% uptake by 6 mo), with fewer (7.3%, 95% CI 6.8%–7.8%) positive participants. Being “forced to test”, usually by a main partner, was reported by 2.9% (95% CI 2.6%–3.2%) of 10,017 questionnaire respondents in months 1–12, but satisfaction with HIVST (94.4%) remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1,649 systematically selected (1 in 20) QA participants (99.4%), giving a sensitivity of 93.6% (95% CI 88.2%–97.0%) and a specificity of 99.9% (95% CI 99.6%–100%). Key limitations included use of aggregate data to report uptake of HIVST and being unable to adjust for population turnover. Conclusions Community-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings

Social deprivation and exposure to health promotion. A study of the distribution of health promotion resources to schools in England

This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2010 Chivu and ReidpathBACKGROUND: Area deprivation is a known determinant of health. It is also known that area deprivation is associated with lower impact health promotion. It is less well known, however, whether deprived areas are less responsive to health promotion, or whether they are less exposed. Using data from a national, school-based campaign to promote vaccination against the human papilloma virus (HPV), the relationship between area deprivation and exposure was examined. METHODS: Taking advantage of a health promotion campaign to provide information to schools about HPV vaccination, a cross sectional study was conducted to examine the relationship between area level, social deprivation, and take-up of (i.e., exposure to) available health promotion material. The sample was 4,750 schools across England, including government maintained and independent schools. The relationship between area deprivation and exposure was examined using bi- and multivariate logistic regression. RESULTS: It was found that schools in the least deprived quintile had 1.32 times the odds of requesting health promotion materials than schools in the most deprived areas (p = .01). This effect was independent of the school size, the type of school, and the geographic region. Conclusion The relationship between area deprivation and the impact of health promotion may be due, at least in part, to differential levels of exposure. The study was limited in scope, pointing to the need for more research, but also points to potentially important policy implications

Analytical method development and validation for simultaneous estimation of Moxifloxacin Hydrochloride and Ketorolac Tromethamine by using RP-HPLC

The main objectives of the present research were to develop the new method for the simultaneous estimation and validation of Moxifloxacin HCl and Ketorolac Tromethamine in pure form and in pharmaceutical dosage form by RP-HPLC. The chromatogram of Moxifloxacin HCl and Ketorolac Tromethamine was developed through column (Inertsil ODS C18), UV detection at 304 nm at a flow rate of 1.0 ml/min with Buffer (pH 4.0):Acetonitrile:Methanol (50:30:20) V/V as mobile phase. The method was validated by various validation parameters such as accuracy, precision, linearity, specificity as per the ICH guidelines. A linearity range of Moxifloxacin HCl and Ketorolac Tromethamine was found to be 60 to 140 µg/ml and 48 to 112 µg/ml respectively. The retention time of Moxifloxacin HCl and Ketorolac Tromethamine was found to be 2.07 min and 4.06 min respectively. % RSD of retention time and peak areas obtained in system precision for Moxifloxacin HCl was 0.21 and 0.80 respectively and for Ketorolac Tromethamine were 0.90 and 1.06 respectively. The % recovery of standard Moxifloxacin HCl and Ketorolac Tromethamine was found to be 100.18 to 100.08% and 99.97 to 99.93% respectively. The % recovery of Moxifloxacin HCl and Ketorolac Tromethamine in dosage form was found to be 98.73 to 100.92% and 98.10 to 100.77% respectively. This method was simple, accurate, precise, and sensitive. Hence, the developed method was employed for the routine analysis of Tenofovir in the pharmaceutical dosage form

A new RP-HPLC method for the determination of Tenofovir Disoproxil Fumarate in pure form and pharmaceutical formulation

The present study aimed to develop the new method for the estimation and validation of tenofovir in pure form and in pharmaceutical dosage form by RP-HPLC. The chromatogram of tenofovir was developed through column (Hyper ODS2 C18), UV detection at 260 nm at a flow rate of 1.2 ml/min with Methanol and Phosphate buffer (90:10) as mobile phase. The method was validated by various validation parameters such as accuracy, precision, linearity, specificity as per the ICH guidelines. A linearity range and retention time of Tenofovir were found to be 20-110 µg/ml and 2.1 min respectively. The % RSD of the Tenofovir was found to be 0.7. The % recovery was obtained as 99.7% for standard and 96.32% for tablets. This method was simple, accurate, precise and sensitive. Hence, the developed method was employed for the routine analysis of Tenofovir in the pharmaceutical dosage form

Simultaneous determination of levocetrizine and phenylpropanolamine hydrocholride by RP-HPLC

The aim of the present study was to develop the simple, selective, rapid, precise and economical reverse phase-high performance liquid chromatography (RP-HPLC) method for the simultaneous estimation of levocetirizine and phenylpropanolamine HCl in solid dosage forms. The method was carried out on a Phenomenex Luna C18 (25 cm × 4.6 mm i.d., 5 μ) column with a mobile phase consisting of acetonitrile: 0.5% triethylamine (70:30 v/v, pH 3.0) at a flow rate of 1.2 mL/min. Detection was carried out at 220 nm. The retention time (RT) 1.8 min and 2.6 min for phenylpropanolamine hydrocholride and levocetrizine respectively. The % recovery of standard phenylpropanolamine hydrocholride and levocetrizine was found to be 98.17 to 103.56 and 98.893 to 10.422 respectively. The % recovery of sample phenylpropanolamine hydrocholride and levocetrizine was found to be 101.30 and 100.63 respectively. The validation of the proposed method was also carried out. The proposed method can be used for the estimation of these drugs in combined dosage forms

Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

Loss of basal forebrain cholinergic neurons is an early and key feature of Alzheimer's disease, and magnetic resonance imaging (MRI) volumetric measurement of the basal forebrain has recently gained attention as a potential diagnostic tool for this condition. The aim of this study was to determine whether loss of basal forebrain cholinergic neurons underpins changes which can be detected through diffusion MRI using diffusion tensor imaging (DTI) and probabilistic tractography in a mouse model. To cause selective basal forebrain cholinergic degeneration, the toxin saporin conjugated to a p75 neurotrophin receptor antibody (mu-p75-SAP) was used. This resulted in similar to 25% loss of the basal forebrain cholinergic neurons and significant loss of terminal cholinergic projections in the hippocampus, as determined by histology. To test whether lesion of cholinergic neurons caused basal forebrain, hippocampal, or whole brain atrophy, we performed manual segmentation analysis, which revealed no significant atrophy in lesioned animals compared to controls (Rb-IgG-SAP). However, analysis by DTI of the basal forebrain area revealed a significant increase in fractional anisotropy (FA; + 7.7%), mean diffusivity (MD; + 6.1%), axial diffusivity (AD; + 8.5%) and radial diffusivity (RD; +4.0%) in lesioned mice compared to control animals. These parameters strongly inversely correlated with the number of choline acetyl transferase-positive neurons, with FA showing the greatest association (r(2) = 0.72), followed by MD (r(2) = 0.64), AD (r(2) = 0.64) and RD (r(2) = 0.61). Moreover, probabilistic tractography analysis of the septo-hippocampal tracts originating from the basal forebrain revealed an increase in streamline MD (+5.1%) and RD (+4.3%) in lesioned mice. This study illustrates that moderate loss of basal forebrain cholinergic neurons (representing only a minor proportion of all septo-hippocampal axons) can be detected by measuring either DTI parameters of the basal forebrain nuclei or tractography parameters of the basal forebrain tracts. These findings provide increased support for using DTI and probabilistic tractography as non-invasive tools for diagnosing and/or monitoring the progression of conditions affecting the integrity of the basal forebrain cholinergic system in humans, including Alzheimer's disease. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved

AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: economic evaluation protocol for a randomised controlled trial-based equivalence study.

INTRODUCTION: Cryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation. METHODS AND ANALYSIS: Country-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial. ETHICS AND DISSEMINATION: The AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings. TRIAL REGISTRATION: ISRCTN 7250 9687; Pre-results

FORMULATION AND EVALUATION OF FLOATING ORAL IN SITU GEL OF DILTIAZEM HYDROCHLORIDE

Objective: The objective of the present study was to formulate and evaluate the floating in-situ gelling system of diltiazem hydrochloride.Methods: Sodium alginate based diltiazem hydrochloride floating in situ gelling systems were prepared by dissolving hydroxyl propyl methyl cellulose (HPMC) in 25% of water, to which calcium carbonate and diltiazem hydrochloride were added with stirring to form, a proper and a homogenous dispersion of diltiazem hydrochloride. Meanwhile, 30% of water was heated to 60 ËšC on a hot plate to dissolve sodium alginate and cooled to 40 ËšC. The resulting solution was added to HPMC solution and mixed well. To 5% of water at 60 ËšC, sodium methyl paraben was added and dissolved and cooled to 40 ËšC and was added to the above mixture and mixed well. The volume was adjusted finally to 100% with distilled water. Prepared formulae were evaluated for physicochemical properties, drug content, pH, in vitro gelling capacity, in vitro buoyancy, viscosity, water uptake and in vitro drug release.Results: Formulation variables such as type and concentration of viscosity enhancing polymer (sodium alginate) and HPMC affected the formulation viscosity, gelling properties, floating behavior, and in vitro drug release. Formulation F5 and F6 showed the floating time of 5 min and more than 20 h respectively. A significant decrease in the rate and extent of the drug release was observed with the increase in polymer concentration in in-situ gelling preparation. Formulation F4, F5, F6 were shown to have extended drug release until the end of 7 h.Conclusion: The prepared in situ gelling formulations of diltiazem hydrochloride could float in the gastric conditions and released the drug in a sustained manner. The present formulation was non-irritant, easy to administer along with good retention properties, better patient compliant and with greater efficacy of the drug