148 research outputs found

    HLA-DQA1-HLA-DRB1 polymorphism is a major predictor of azathioprine-induced pancreatitis in patients with inflammatory bowel disease

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    Background: Azathioprine (AZA)-induced pancreatitis is an unpredictable and dose-independent adverse event affecting 2%-7% of patients with inflammatory bowel disease (IBD) patients treated with AZA. There are no tools in clinical practice to identify at-risk individuals; however, a genome wide association study (GWAS) identified a strong association between the Class II HLA gene region polymorphism (rs2647087) and thiopurine-induced pancreatitis. Aim: To independently confirm the findings of the GWAS in an IBD cohort, to evaluate its utility in clinical practice and to offer a novel AZA treatment algorithm for IBD based on pharmacogenomic principles. Methods: A retrospective cohort study evaluated 373 AZA-exposed IBD patients from a tertiary care academic centre in London, Canada. Due to the limited number of patients taking mercaptopurine (MP), such patients were not included this cohort. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype and were sub-divided based on the presence (n = 13) or absence (n = 360) of an AZA-induced pancreatitis diagnosis. The risk of AZA-induced pancreatitis was assessed based on rs2647087 genotype. Results: The risk of pancreatitis during AZA-therapy was highly predictable and genotype dependent: 0.53% for wild type (A/A), 4.25% (OR = 4.19, 95% CI 1.02-36.45, P = 0.044) for heterozygous (A/C), and 14.63% (OR = 15.83, 95% CI 3.80-145.26, P = 0.0001) for homozygous variant (C/C) patients. Conclusions: The class II HLA region (at rs2647087) is an important marker of AZA-induced pancreatitis risk. We propose a simple and clinically implementable algorithm based on rs2647087 and TPMT genotypes for AZA selection and dosing for patients with IBD

    Remote monitoring and discrete data capture of joint pain and other parameters via the NokiaN900 device: Enhancing patient/physician interaction

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    The new generation cellular phones have multi-functional capabilities such as imaging, video, audio recording and messaging in addition to providing internet access. In this paper we present an innovative application in the field of remote health monitoring using N900 Nokia tablet, which will serve as a communicating device between the patient and healthcare providers like doctors and nurses. Patients with arthritis require regular objective monitoring of their affected joints by healthcare providers requiring that patients report their subjective pain levels to their physicians. The application has a patient's module allowing the patient to select their pain level on a sliding scale from a graphical representation of various human joints and send this as an SMS to the doctor. The healthcare providers can review the pain level, save it to a database and make an informed decision about possible recommendations based on the data received via SMS. The doctor's module allows the doctor to capture all the attributes of an affected joint discretely using the graphical representation of the joints and associated dialog boxes. The complete Graphical User Interface (GUI) development and data base design are discussed and test cases are presented. We plan to evaluate the application in a real healthcare environment for usability, its role in improving patient satisfaction and health outcomes

    Pharmacokinetic profiles for oral and subcutaneous methotrexate in patients with Crohn\u27s disease

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    Background Methotrexate (MTX) is administered subcutaneously to Crohn\u27s Disease (CD) patients. There are very few studies evaluating the use of oral (PO) MTX in CD. A drug and its pharmaceutical alternative are equivalent (bioequivalence) when the bioavailability of the alternative falls within 80-125% of the bioavailability of the standard (US Food and Drug Administration - FDA). Aim To compare the pharmacokinetic (PK) profiles of PO and subcutaneous (SC) MTX in CD patients to determine the bioequivalence of these two routes. Methods Eleven patients received a PO and an SC MTX dose (25 mg) separated by one week over a two-week interval. Blood samples were collected at specified times over a 24-h period for each patient on two separate days. MTX plasma levels were obtained using sensitive mass spectrometry. Areas under the curve (AUC) were compared between the two routes. Results The mean AUC values were 3375 ng/mL × h (PO MTX) and 3985 ng/mL × h (SC MTX). The mean AUC ratio (PO/SC) was 0.86 (0.62-1.08). This correlates with a relative PO bioavailability of 86% in comparison to SC. The 90% confidence interval for the mean AUC (PO/SC) ratio is (0.785, 0.929). There were no adverse events. Conclusions The mean MTX AUC (PO/SC) in these patients falls outside the 90% confidence interval for the bioequivalence limit. SC MTX is more bioavailable than PO MTX; however, the mean relative MTX bioavailability (PO/SC) nearly met the FDA bioequivalence standard and PO MTX could be proposed in responders who would prefer this route. © 2012 Blackwell Publishing Ltd

    5′′-(4-Chloro­benzyl­idene)-1′,1′′-dimethyl-3′-phenyl­acenaphthene-1-spiro-2′-pyrrolidine-3′-spiro-3′′-pyridine-2,4′′-dione

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    In the title compound, C34H28Cl2N2O2, the five-membered pyrrolidine ring adopts an envelope conformation and the six-membered piperidinone ring is in a distorted half-chair conformation. The mol­ecular structure shows three intra­molecular C—H⋯O inter­actions and the crystal packing is stabilized through inter­molecular C—H⋯O and C—H⋯π inter­actions

    Systematic review and meta-analysis: prevalence of alcohol use among young people in eastern Africa.

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    OBJECTIVE: Systematic review and meta-analysis of published studies of alcohol use among young people (age 15-24 years) in eastern Africa to estimate prevalence of alcohol use and determine the extent of use of standardised screening questionnaires in alcohol studies. METHODS: Five databases (MEDLINE, EMBASE, Global Health, Africa-wide, and PsycINFO) were searched for publications until 30th June 2013. Results were summarised using the guidelines on preferred reporting items for systematic reviews and meta-analyses (PRISMA) and on quality assessment using the modified quality assessment tool for systematic reviews of observational studies (QATSO). Heterogeneity was assessed using the I(2) statistic (DerSimonian-Laird). RESULTS: We identified 2785 potentially relevant studies, of which 56 were eligible for inclusion. Only two studies (4%) used the standardised Alcohol Use Disorder Identification Test (AUDIT) questionnaire, and six studies (13%) used the Cut down, Annoyed, Guilt, Eye opener (CAGE) questionnaire. The reported median prevalence of alcohol use was ever-use 52% [interquartile range (IQR): 20-58%], use in the last month 28% (IQR: 17-37%), use in the last year 26% (IQR: 22-32%), and problem drinking as defined by CAGE or AUDIT 15% (IQR: 3-36%). We observed high heterogeneity between studies, with the highest prevalence of ever use of alcohol among university students (82%; 95%CI: 79-85%) and female sex workers (66%; 95%CI: 58-74%). Current use was most prevalent among male sex workers (69%; 95%CI: 63-75%). CONCLUSIONS: Reported alcohol use and problem drinking were common among diverse groups of young people in eastern Africa, indicating the urgent need for alcohol-focused interventions in this population. Few studies have used standardised alcohol screening questionnaires. Epidemiological research to investigate alcohol-focused interventions in young people should aim to apply such questionnaires that should be validated for use in this population

    Drivers of millet consumption among school aged children in central Tanzania

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    Open Access Journal; Published online: 06 Aug 2021Background: Iron and zinc deficiency are common public health problems in low-income countries largely due to poor consumption of iron and zinc rich foods. It has previously been observed that 57% of school aged children (SAC) in Tanzania suffer from anemia. In addition, estimates indicate that over 25% of the population have inadequate zinc intake. Pearlmillet is an example of a nutrient dense, resilient cereal crop, that can be promoted to diversify diets and combat iron and zinc deficiency. This study overall aim was to increase pearl millet consumption among school aged (5 – 12 years) children. As part of the study, we investigated, the drivers of food choice relating to pearl millet consumption. Methods: The study was a cross-sectional study of randomly selected households in Kongwa district, Dodoma region of Tanzania. In total, 128 women of reproductive age (20 – 49 years) were randomly selected for the study. A study questionnaire consisting of 66 items, was developed and validated. The constructs in the questionnaire were categorized in two groups: internal and external factors. Respondents were asked to indicate their level of agreement or disagreement with statements read to them by interviewers. The scores on intention and behavior constructs were based on the number of times caregivers intended to, or had fed their school going children with pearl millet in the referent month. Intention was considered high if it was higher than the median intention score of the group, and low if it was equal to or lower than the median scores. Correlations and multiple linear regressions were performed to measure association between constructs and to identify predictive constructs. The Mann-Whitney U test was used for score comparison. Results: There was a significant difference between intention and behavior among those who did not consume pearl millet (P = 0.003), and those who consumed pearl millet two or more times a week, in the same month (P = 0.01). Knowledge was significantly correlated with behavior identity (r = 0.58, P = 0.001), while health behavior identity was significantly correlated with intention (r = 0.31, P = 0.001). Intention of caregivers was significantly and positively correlated (r = 0.44, P = 0.001) with and predicted consumption of pearl millet (r = 0.87, P = 0.067). Conclusion: Increasing knowledge or awareness on nutritional benefits of pearl millet among caregivers may increase consumption of pearl millet by children of school going age
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