Six months therapy for tuberculous meningitis.

BACKGROUND Tuberculous meningitis (TBM) is the main form of tuberculosis that affects the central nervous system and is associated with high rates of death and disability. Most international guidelines recommend longer antituberculous treatment (ATT) regimens for TBM than for pulmonary tuberculosis disease to prevent relapse. However, longer regimens are associated with poor adherence, which could contribute to increased relapse, development of drug resistance, and increased costs to patients and healthcare systems. OBJECTIVES To compare the effects of short-course (six months) regimens versus prolonged-course regimens for people with tuberculous meningitis (TBM). SEARCH METHODS We searched the following databases up to 31 March 2016: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS; INDMED; and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists and contacted researchers in the field. SELECTION CRITERIA We included randomized controlled trials (RCTs) and prospective cohort studies of adults and children with TBM treated with antituberculous regimens that included rifampicin for six months or longer than six months. The primary outcome was relapse, and included studies required a minimum of six months follow-up after completion of treatment. DATA COLLECTION AND ANALYSIS Two review authors (SJ and HR) independently assessed the literature search results for eligibility, and performed data extraction and 'Risk of bias' assessments of the included studies. We contacted study authors for additional information when necessary. Most data came from single arm cohort studies without a direct comparison so we pooled the findings for each group of cohorts and presented them separately using a complete-case analysis. We assessed the quality of the evidence narratively, as using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was inappropriate with no direct comparisons between short- and prolonged-course regimens. MAIN RESULTS Four RCTs and 12 prospective cohort studies met our inclusion criteria, and included a total of 1881 participants with TBM. None of the included RCTs directly compared six months versus longer regimens, so we analysed all data as individual cohorts to obtain relapse rates in each set of cohorts.We included seven cohorts of participants treated for six months, with a total of 458 participants. Three studies were conducted in Thailand, two in South Africa, and one each in Ecuador and Papua New Guinea between the 1980s and 2009. We included 12 cohorts of participants treated for longer than six months (ranging from eight to 16 months), with a total of 1423 participants. Four studies were conducted in India, three in Thailand and one each in China, South Africa, Romania, Turkey and Vietnam, between the late 1970s and 2011.The proportion of participants classified as having stage III disease (severe) was higher in the cohorts treated for six months (33.2% versus 16.9%), but the proportion with known concurrent HIV was higher in the cohorts treated for longer (0/458 versus 122/1423). Although there were variations in the treatment regimens, most cohorts received isoniazid, rifampicin, and pyrazinamide during the intensive phase.Investigators achieved follow-up beyond 18 months after completing treatment in three out of the seven cohorts treated for six months, and five out of the 12 cohorts treated for eight to 16 months. All studies had potential sources of bias in their estimation of the relapse rate, and comparisons between the cohorts could be confounded.Relapse was an uncommon event across both groups of cohorts (3/369 (0.8%) with six months treatment versus 7/915 (0.8%) with longer), with only one death attributed to relapse in each group.Overall, the proportion of participants who died was higher in the cohorts treated for longer than six months (447/1423 (31.4%) versus 58/458 (12.7%)). However, most deaths occurred during the first six months in both treatment cohorts, which suggested that the difference in death rate was not directly related to duration of ATT but was due to confounding. Clinical cure was higher in the group of cohorts treated for six months (408/458 (89.1%) versus longer than six months (984/1336 (73.7%)), consistent with the observations for deaths.Few participants defaulted from treatment with six months treatment (4/370 (1.1%)) versus longer treatment (8/355 (2.3%)), and adherence was not well reported. AUTHORS' CONCLUSIONS In all cohorts most deaths occurred in the first six months; and relapse was uncommon in all participants irrespective of the regimen. Further inferences are probably inappropriate given this is observational data and confounding is likely. These data are almost all from participants who are HIV-negative, and thus the inferences will not apply to the efficacy and safety of the six months regimens in HIV-positive people. Well-designed RCTs, or large prospective cohort studies, comparing six months with longer treatment regimens with long follow-up periods established at initiation of ATT are needed to resolve the uncertainty regarding the safety and efficacy of six months regimens for TBM

Modeling Odor Dispersion From a Swine Facility Using AERMOD

Meteorological conditions, odor emissions, and ambient odor levels at a four-barn, swine finishing facility in Iowa were measured in the summer and fall of 2004. This paper compares ambient odor levels measured using a Nasal Ranger® compared to those predicted by AERMOD, a relatively new air dispersion model. Scaling factors needed to adjust predicted odor levels to those observed ranged from 1.66 to 3.12, depending on the source configuration used by the model. Predicted odors levels from the point source configuration required the smallest scaling factor (1.66) and accounted for the greatest percentage of variability in the data when compared to Nasal Ranger readings

TNF-α promoter polymorphism: a factor contributing to the different immunological and clinical phenotypes in Japanese encephalitis

<p>Abstract</p> <p>Background</p> <p>More than three billion populations are living under the threat of Japanese encephalitis in South East Asian (SEA) countries including India. The pathogenesis of this disease is not clearly understood and is probably attributed to genomic variations in viral strains as well as the host genetic makeup. The present study is to determine the role of polymorphism of TNF-alpha promoter regions at positions -238G/A, -308G/A, -857C/T and -863C/A in the severity of Japanese encephalitis patients.</p> <p>Methods</p> <p>Total of 142 patients including 66 encephalitis case (IgM/RT-PCR positive), 16 fever cases (IgM positive) without encephalitis and 60 apparently healthy individuals (IgG positive) were included in the study. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) using site specific restriction enzymes were implemented for polymorphism study of TNF alpha promoter.</p> <p>Results</p> <p>Following the analysis of the digestion patterns of four polymorphic sites of the TNF- alpha promoter region, a significant association was observed between the allele -308A and -863C with the patients of Japanese encephalitis.</p> <p>Conclusions</p> <p>TNF- alpha 308 G/A has been shown to be associated with elevated TNF- alpha transcriptional activity. On the other hand, polymorphism at position -863C/A in the promoter region has been reported to be associated with reduced TNF- alpha promoter activity and lower plasma TNF levels. As per the literature search, this is the first study to identify the role of TNF- alpha promoter in JE infection. Our results show that subjects with - 308A and -863C alleles are more vulnerable to the severe form of JE infection.</p

Routing Questions to Experts in Community Question Answering Sites

In CQA sites, user can ask questions, which are answered by other users having expertise in that domain. These sites allow the knowledge exchange between users in terms of question and answers.This knowledge base of the question-answers which is getting created also serve as a reference to the other users who in later future may ran into similar problem. But due to large volume of these questions getting asked every hour, all questions do not end up getting answers. As a result, it can be useful to route a question to the potential answerer. A lot of prior work done in the field of the question routing, focuses on the static snapshot of data, whereas these sites are dynamic in nature i.e. users constantly join the site and user topic of interest might get change over time. Expertise �nding strategy used so far only considers the static nature of these datasets and do not model the change in the users behaviour. Some work [5] has been done on �nding availability of user at a particular point of time. In this paper, we propose a recommendation model that does tag network and temporal analysis to find the potential users who will answer the question. Our experiments over a large real-world datasets from Stack Exchange shows effectiveness of our approach over several baseline models. Our results shows that considering temporal information and community valuation of answer to compute user expertise provides improvement over the baseline models used so far for expertise recommendation, which shows the effectiveness of our proposed model

Limited incision and traditional open carpal tunnel release: Comparison of clinical and neurological outcomes

Background: Carpal Tunnel Syndrome (CTS) is the most common compression neuropathy of the upper extremity. Even though traditional open release has been considered as standard approach for median nerve decompression, various other techniques are gaining popularity. The aim of this study was to compare the clinical and neurological outcomes between traditional open approach and limited incision approach. Methods: Twenty-eight patients with isolated CTS have included in this study of which four patients had bilateral CTS thus constituting 32 hands (19-right; 13-left). The patients were divided for treatment into two groups, Group A included 21 hands underwent limited incision release, and Group B included 11 hands released by traditional open incision. Patient's were evaluated preoperatively and in six weeks and six months postoperatively, namely, (a) clinical outcomes including Boston carpal tunnel questionnaire (BCTQ), postoperative scar tenderness, hypertrophic scar, pillar pain &amp; quality of scar by Vancouver scar scale (VSS). (b) sensory testing using two-point discrimination (TPD) (c)motor testing using grip and pinch dynamometer, (d) neurological outcome measurement using nerve conduction study (NCS). Results: In each section of BCTQ outcomes, patients in group A showed significant improvement than in group B at both six weeks and six months follow up