Hepatitis C viraemic and seroprevalence and risk factors for positivity in Northwest Cambodia: a household cross-sectional serosurvey.

BACKGROUND: Despite a dramatic reduction in HCV drug costs and simplified models of care, many countries lack important information on prevalence and risk factors to structure effective HCV services. METHODS: A cross-sectional, multi-stage cluster survey of HCV seroprevalence in adults 18 years and above was conducted, with an oversampling of those 45 years and above. One hundred forty-seven clusters of 25 households were randomly selected in two sets (set 1=24 clusters ≥18; set 2=123 clusters, ≥45). A multi-variable analysis assessed risk factors for sero-positivity among participants ≥45. The study occurred in rural Moung Ruessei Health Operational District, Battambang Province, Western Cambodia. RESULTS: A total of 5098 individuals and 3616 households participated in the survey. The overall seroprevalence was 2.6% (CI95% 2.3-3.0) for those ≥18 years, 5.1% (CI95% 4.6-5.7) for adults ≥ 45 years, and 0.6% (CI95% 0.3-0.9) for adults 18-44. Viraemic prevalence was 1.9% (CI95% 1.6-2.1), 3.6% (CI95% 3.2-4.0), and 0.5% (CI95% 0.2-0.8), respectively. Men had higher prevalence than women: ≥18 years male seroprevalence was 3.0 (CI95% 2.5-3.5) versus 2.3 (CI95% 1.9-2.7) for women. Knowledge of HCV was poor: 64.7% of all respondents and 57.0% of seropositive participants reported never having heard of HCV. Risk factor characteristics for the population ≥45 years included: advancing age (p< 0.001), low education (higher than secondary school OR 0.7 [95% CI 0.6-0.8]), any dental or gum treatment (OR 1.6 [95% CI 1.3-1.8]), historical routine medical care (medical injection after 1990 OR 0.7 [95% CI 0.6-0.9]; surgery after 1990 OR 0.7 [95% CI0.5-0.9]), and historical blood donation or transfusion (blood donation after 1980 OR 0.4 [95% CI 0.2-0.8]); blood transfusion after 1990 OR 0.7 [95% CI 0.4-1.1]). CONCLUSIONS: This study provides the first large-scale general adult population prevalence data on HCV infection in Cambodia. The results confirm the link between high prevalence and age ≥45 years, lower socio-economic status and past routine medical interventions (particularly those received before 1990 and 1980). This survey suggests high HCV prevalence in certain populations in Cambodia and can be used to guide national and local HCV policy discussion.

Generalizable Natural Language Processing Framework for Migraine Reporting from Social Media.

Migraine is a highly prevalent and disabling neurological disorder. However, information about migraine management in real-world settings is limited to traditional health information sources. In this paper, we (i) verify that there is substantial migraine-related chatter available on social media (Twitter and Reddit), self-reported by those with migraine; (ii) develop a platform-independent text classification system for automatically detecting self-reported migraine-related posts, and (iii) conduct analyses of the self-reported posts to assess the utility of social media for studying this problem. We manually annotated 5750 Twitter posts and 302 Reddit posts, and used them for training and evaluating supervised machine learning methods. Our best system achieved an F1 score of 0.90 on Twitter and 0.93 on Reddit. Analysis of information posted by our 'migraine cohort' revealed the presence of a plethora of relevant information about migraine therapies and sentiments associated with them. Our study forms the foundation for conducting an in-depth analysis of migraine-related information using social media data.

Comorbidities associated with the increasing burden of hepatitis C infection.

BACKGROUND: Hepatitis C virus (HCV) infection is implicated in an increasing number of liver transplantations, hospitalizations and healthcare costs. AIMS: We present an updated assessment of comorbidities associated with HCV in comparison to the general US population. METHODS: Cross-sectional retrospective review of data from 800 patients with HCV evaluated between January 1998 and November 2007. Patient data were prospectively collected using a standardized questionnaire completed at the first encounter and was compared with general US epidemiological data. Odds ratios and 95% confidence intervals (CI) are reported. RESULTS: HCV conferred a 44% (CI 1.16-1.78) and 25% (CI 1.01-1.54) increased risk of diabetes (12.5 vs. 7.3-8.4%; P=0.001) and obesity (23.9 vs. 19.8-33.1%; P=0.041), respectively, compared with the US population. Human immunodeficiency virus (HIV) (5.3 vs. 0.3%; P<0.001) and end-stage renal disease (ESRD) (4.5 vs. 0.2%; P<0.001) were 16- and 13-fold more prevalent in HCV. Interestingly, HCV bestowed 90% decreased odds (CI 0.09-0.15) for hyperlipidaemia (12.3 vs. 53.2-56.1%; P<0.001). The HCV population had a higher prevalence of significant alcohol consumption (41.5 vs. 4.7%; P<0.001), current smoking (57.7 vs. 18.8-20.8%; P<0.001), drug use (46.8 vs. 14.6-15.6%; P<0.001), incarceration (6.6 vs. 2.7%; P<0.001) and tattoos (20.3 vs. 14%; P=0.011), as well as chronic fatigue (44.6 vs. 11.3-19%; P<0.001) and depression (29.3 vs. 5.0-10.3%; P<0.001). CONCLUSION: HCV poses an increasing healthcare burden associated with increased prevalence of diabetes, obesity, HIV, ESRD, maladaptive lifestyle habits and poor quality of life. Practitioners should be cognizant of these trends in order to appropriately manage these comorbidities.

[Antidepressant pharmacotherapy: a review of pharmaco-economic research]. / Pharmacothérapie antidépressive: une synthèse des recherches pharmaco-économiques.

Recent pharmacotherapeutic advances in the treatment of depression have included the development of selective serotonin reuptake inhibitors (SSRIs), thereby providing an alternative to tricyclic antidepressants (TCAs). SSRIs have achieved a rapid acceptance by prescribers worldwide due to a superior safety profile to that observed with the TCAs, and the potential for once daily administration. However, to date there exists limited data regarding the effect of antidepressant pharmacotherapy on health service expenditures. Herein, we review the inherent strengths and weaknesses of the five study designs which have been employed in the economic appraisal of antidepressant pharmacotherapy: randomized controlled trials; meta-analyses stemming from the results of controlled clinical trials; decision-analytical models predicated on results stemming from randomized clinical trials and/or meta-analyses; retrospective data archive investigations; and prospective randomized naturalistic inquiry. What emerges is the necessity of establishing a portfolio of evidence as to the safety, efficacy, and effectiveness of a given pharmacotherapeutic category (e.g. SSRIs) and/or a specific medication. Thus, the economic appraisal of antidepressant pharmacotherapy will require an iterative process extending from the developmental through post-marketing phase.

[Pharmacokinetic criteria of the choice of antibiotic for antibiotic prophylaxis in surgery]. / Critères pharmacocinétiques du choix d'un antibiotique pour l'antibioprophylaxie en chirurgie.

The prevention of surgical infections with perioperative prophylactic antibiotics is experimentally and clinically well founded in both principle and practice. The evaluation of the role of antimicrobial agents in the success of failure of infection prophylaxis in surgery involves a discussion of both the pharmacokinetic and the pharmacodynamic properties of particular agents. A main concern in surgical prophylaxis is the relation between the respective time course of antibiotic concentrations in serum and in the tissue (wound). Several problems arise in both the measurement and the interpretation of drug concentrations in tissues and the results of this approach are still controversial. However, the knowledge of the numerous factors influencing the penetration into a tissue and the characteristics of the relative distribution of the antibiotic between the compartments inside the tissue, i.e. the vascular, interstitial and intracellular spaces, could allow a valuable approach to this problem. The concentrations of free drugs in serum are valuable predictors of the time course of unbound drug in interstitial fluid, where the bacteria are generally located. An increase in protein binding does not reduce the area under the curve (AUC) of free drug for beta lactam agents eliminated predominantly by glomerular filtration, but prolongs their elimination half life. Timing and route of administration are also important factors to consider in relation with the pharmacokinetic profile of the drug. Pharmacodynamic studies of persistent growth suppression and bactericidal activity predict that the period during which the free drug concentration exceeds the MIC is an important parameter of the efficacy of beta lactam antibiotics. In the opposite, the Cmax and/or the AUC are the major parameters of the efficacy of aminoglycosides and quinolones against Gram negative bacteria. Thus, the goal of prophylaxis with beta lactams could be to provide levels of free drug above the MIC for the whole surgical period, while the obtention of a high Cmax with a one-day therapy should be required for aminoglycosides. Further clinical trials are warranted to assess this approach.

Basis for the permeability barrier abnormality in lamellar ichthyosis.

The basis for the permeability barrier abnormality in lamellar ichthyosis (LI) is not known. LI is caused by mutations in the gene that encodes the enzyme, transglutaminase 1 (TGI), which is responsible for assembly of the cornified envelope (CE). TG1 also has been suggested recently to catalyze the covalent attachment of omega-hydroxyceramides (omega-OHCer) to the CE, forming the corneocyte-lipid envelope (CLE). We first assessed the barrier function and the permeability pathway of the water-soluble tracer, colloidal lanthanum, across the stratum corneum (SC) in patients with LI with absent (n = 4) or low (n = 2) TG1 activity/protein. Increased movement of tracer through the SC correlated with increased transcutaneous water loss, and tracer remained restricted to the SC interstices. Enhanced extracellular permeability, in turn, was explicable by truncation and fragmentation of extracellular lamellar membrane arrays. The resultant clefts in the SC interstices represent the likely pathway for increased water permeability. Moreover, tracer movement remained restricted to the interstices, despite the demonstration of increased corneocyte fragility associated with widespread variations in CE structure. Regardless of variability in CE structure, however, CLE structure and bound omega-OHCer content were normal. The normal CLE in LI may explain both the restriction of tracer to the SC interstices, as well as the presence of foreshortened membrane arrays with near-normal interlamellar dimensions. Finally, the demonstration of a normal CLE in LI also raises questions about the putative role of TG1 in forming the CLE. These results demonstrate: (1) the extracellular nature of increased permeability in LI; (2) discontinuities in extracellular membrane structures that account for the enhanced permeability in LI; (3) that these membrane abnormalities are both associated with and explained by abnormalities in the subjacent CE scaffold; and (4) an intact CLE is present in LI, despite abnormalities in the CE, which may restrict water movement to the SC interstices in LI.