Safety profile of oxcarbazepine: results from a prescription-event monitoring study

Purpose: To monitor safety of oxcarbazepine, prescribed in primary care in England, using prescription-event monitoring (PEM). Methods: Postmarketing surveillance using observational cohort technique of PEM. Exposure data were obtained from dispensed British National Health Service prescriptions issued by general practitioners (GPs) March 2000–July 2003. Demographic, drug utilization, and clinical event data were collected from questionnaires posted to GPs at least 6 months after first prescription date for each patient. Incidence densities (IDs) (number of first reports per 1,000 patient-months of treatment) were calculated and differences for events reported in month 1 (ID1) and months 2–6 (ID2–6) (99% confidence intervals) were examined for changes in event rates. Follow-up and causality assessment of medically significant events were undertaken. Results: The cohort comprised 2,243 patients [mean age 40.4 years; range 2–99 years; standard deviation (SD) 18.8; 46.3% (n = 1,038) male]. Most frequently reported primary indications were epilepsy, convulsion (n = 1,111; 49.5%, n = 209; 9.3%, respectively). GPs recorded 932 reasons for stopping medication in 698 (31.1%) patients; most frequent clinical reason “drowsiness/sedation” (n = 57; 2.5% of cohort). Clinical events (excluding indication) associated with starting treatment (lower 99% CI > 0) included: “drowsiness/sedation” (ID1-ID2–6 = 14.2), “nausea/vomiting” (ID1-ID2–6 = 13.0), and dizziness (ID1-ID2–6 = 11.6). Events followed up and assessed as probably related to oxcarbazepine use included rash (7 of 11) and hyponatremia (15 of 38). Discussion:  There were no serious adverse drug reactions reported during this study. Results of the study should be taken in context with other epidemiologic studies

Circulating antigen tests and urine reagent strips for diagnosis of active schistosomiasis in endemic areas

Background: Point-of-care (POC) tests for diagnosing schistosomiasis include tests based on circulating antigen detection and urine reagent strip tests. If they had sufficient diagnostic accuracy they could replace conventional microscopy as they provide a quicker answer and are easier to use. Objectives: To summarise the diagnostic accuracy of: a) urine reagent strip tests in detecting activeSchistosoma haematobium infection, with microscopy as the reference standard; and b) circulating antigen tests for detecting active Schistosoma infection in geographical regions endemic for Schistosoma mansoni or S. haematobium or both, with microscopy as the reference standard. Search methods: We searched the electronic databases MEDLINE, EMBASE, BIOSIS, MEDION, and Health Technology Assessment (HTA) without language restriction up to 30 June 2014. Selection criteria We included studies that used microscopy as the reference standard: for S. haematobium, microscopy of urine prepared by filtration, centrifugation, or sedimentation methods; and for S. mansoni, microscopy of stool by Kato-Katz thick smear. We included studies on participants residing in endemic areas only. Data collection and analysis: Two review authors independently extracted data, assessed quality of the data using QUADAS-2, and performed meta-analysis where appropriate. Using the variability of test thresholds, we used the hierarchical summary receiver operating characteristic (HSROC) model for all eligible tests (except the circulating cathodic antigen (CCA) POC for S. mansoni, where the bivariate random-effects model was more appropriate). We investigated heterogeneity, and carried out indirect comparisons where data were sufficient. Results for sensitivity and specificity are presented as percentages with 95% confidence intervals (CI). Main results; We included 90 studies; 88 from field settings in Africa. The median S. haematobiuminfection prevalence was 41% (range 1% to 89%) and 36% for S. mansoni (range 8% to 95%). Study design and conduct were poorly reported against current standards. Tests for S. haematobium Urine reagent test strips versus microscopy Compared to microscopy, the detection of microhaematuria on test strips had the highest sensitivity and specificity (sensitivity 75%, 95% CI 71% to 79%; specificity 87%, 95% CI 84% to 90%; 74 studies, 102,447 participants). For proteinuria, sensitivity was 61% and specificity was 82% (82,113 participants); and for leukocyturia, sensitivity was 58% and specificity 61% (1532 participants). However, the difference in overall test accuracy between the urine reagent strips for microhaematuria and proteinuria was not found to be different when we compared separate populations (P = 0.25), or when direct comparisons within the same individuals were performed (paired studies; P = 0.21). When tests were evaluated against the higher quality reference standard (when multiple samples were analysed), sensitivity was marginally lower for microhaematuria (71% vs 75%) and for proteinuria (49% vs 61%). The specificity of these tests was comparable. Antigen assay Compared to microscopy, the CCA test showed considerable heterogeneity; meta-analytic sensitivity estimate was 39%, 95% CI 6% to 73%; specificity 78%, 95% CI 55% to 100% (four studies, 901 participants). Tests for S. mansoni Compared to microscopy, the CCA test meta-analytic estimates for detecting S. mansoni at a single threshold of trace positive were: sensitivity 89% (95% CI 86% to 92%); and specificity 55% (95% CI 46% to 65%; 15 studies, 6091 participants) Against a higher quality reference standard, the sensitivity results were comparable (89% vs 88%) but specificity was higher (66% vs 55%). For the CAA test, sensitivity ranged from 47% to 94%, and specificity from 8% to 100% (four studies, 1583 participants). Authors' conclusions: Among the evaluated tests for S. haematobium infection, microhaematuria correctly detected the largest proportions of infections and non-infections identified by microscopy. The CCA POC test for S. mansoni detects a very large proportion of infections identified by microscopy, but it misclassifies a large proportion of microscopy negatives as positives in endemic areas with a moderate to high prevalence of infection, possibly because the test is potentially more sensitive than microscopy

Non-invasive brain stimulation techniques for chronic pain

Copyright © 2014 The Cochrane Collaboration.Various devices are available that can electrically stimulate the brain without the need for surgery or any invasive treatment in order to manage chronic pain. There are four main treatment types: repetitive transcranial magnetic stimulation (rTMS) in which the brain is stimulated by a coil applied to the scalp, cranial electrotherapy stimulation (CES) in which electrodes are clipped to the ears or applied to the scalp, transcranial direct current stimulation (tDCS) and reduced impedance non-invasive cortical electrostimulation (RINCE) in which electrodes are applied to the scalp. These have been used to try to reduce pain by aiming to alter the activity of the brain, but the efficacy of these treatments is uncertain. This review update included 56 studies: 30 of rTMS, 11 of CES, 14 of tDCS and one of RINCE. We judged only three studies as having a low risk of bias. Low or very low-quality evidence suggests that low-frequency rTMS and rTMS applied to pre-frontal areas of the brain are not effective but that a single dose of high-frequency stimulation of the motor cortex area of the brain provides short-term pain relief. This effect appears to be small and may be exaggerated by a number of sources of bias. Studies that gave a course of multiple treatments of rTMS produced conflicting results with no overall effect seen when we pooled the results of these studies. Most studies of rTMS are small and there is substantial variation between studies in terms of the treatment methods used. Low-quality evidence does not suggest that CES or tDCS are effective treatments for chronic pain. A single small study of RINCE provided very low-quality evidence of a short-term effect on pain. For all forms of stimulation the evidence is not conclusive and uncertainty remains. The reporting of side effects varied across the studies. Of the studies that clearly reported side effects, short-lived and minor side effects such as headache, nausea and skin irritation were usually reported both after real and sham stimulation. There were two reports of seizure following real rTMS. While the broad conclusions for rTMS and CES have not changed substantially, the addition of this new evidence and the application of the GRADE system has modified some of our interpretation. Previous readers should re-read this update. More studies of rigorous design and adequate size are required to evaluate accurately all forms of non-invasive brain stimulation for the treatment of chronic pain

JAPANESE MILLERS' PREFERENCES FOR WHEAT AND FLOUR: A STATED PREFERENCE ANALYSIS

Japan imports 6.3 MMT of wheat annually and consumes almost 35 percent of this in the form of noodles. The purpose of this paper is to report on a study that evaluates the preferences of Japanese millers for the various characteristics of wheat and flour that are used in noodle making in Japan. The study used stated preference methodologies (SPM), that were developed and pre-tested through initial interviews with Japanese flour millers. In total, 57 purchase and quality managers for 22 Japanese milling companies were surveyed by means of direct interviews and 41 respondents completed the full SPM survey. Multinomial logit models of millers preferences were developed and tested and the parameter estimates of these are reported in the paper. This elicited their choices of wheat and flour with alternative combinations of characteristics, at specified levels, for various wheat classes and noodle flours. Data were also collected on stated choices for wheat sourced from different origins. Millers prefer wheat with test weights of minimum 80, dockage below 0.4 percent and falling numbers above 250. Preferences for protein, ash and color were specific for different wheat classes and for use in different noodle flours. Millers also display a preference for amylograph at minimum of 400 BU for noodle flour. For hard wheat millers preferred wheat of U.S. and Canadian origin, but for semi-hard and medium wheat, they preferred Australian origin wheat. These results may assist wheat breeders and traders in exporting nations in marketing their products and positioning these in this important and premium wheat market.Demand and Price Analysis,

Outcome of secondary root canal treatment: a systematic review of the literature.

UNLABELLED: AIMS (I): To investigate the effects of study characteristics on the reported success rates of secondary root canal treatment (2 degrees RCT or root canal retreatment); and (ii) to investigate the effects of clinical factors on the success of 2 degrees RCT. METHODOLOGY: Longitudinal human clinical studies investigating outcome of 2 degrees RCT which were published upto the end of 2006 were identified electronically (MEDLINE and Cochrane database 1966-2006 Dec, week 4). Four journals (Dental Traumatology, International Endodontic Journal, Journal of Endodontics, Oral Surgery Oral Medicine Oral Pathology Endodontics Radiology), bibliographies of all relevant papers and review articles were hand-searched. Two reviewers (Y-LN, KG) independently assessed and selected the studies based on specified inclusion criteria and extracted the data onto a pre-designed proforma, independently. The criteria were: (i) Clinical studies on 2 degrees RCT; (ii) Stratified analyses available for 2 degrees RCT where 1 degrees RCT data included; (iii) Sample size given and larger than 10; (iv) At least 6-month post-operative review; (v) Success based on clinical and/or radiographic criteria (strict = absence of apical radiolucency; loose = reduction in size of radiolucency); and (vi) Overall success rate given or could be calculated from the raw data. Three strands of evidence or analyses were used to triangulate a consensus view. The reported findings from individual studies, including those excluded for quantitative analysis, were utilized for the intuitive synthesis which constituted the first strand of evidence. Secondly, the pooled weighted success rates by each study characteristic and potential prognostic factor were estimated using the random effect model. Thirdly, the effects of study characteristics and prognostic factors (expressed as odds ratios) on success rates were estimated using fixed and random effects meta-analysis with DerSimonean and Laird's methods. Meta-regression models were used to explore potential sources of statistical heterogeneity. Study characteristics considered in the meta-regression analyses were: decade of publication, study-specific criteria for success (radiographic, combined radiographic & clinical), unit of outcome measure (tooth, root), duration after treatment when assessing success ('at least 4 years' or '<4 years'), geographic location of the study (North American, Scandinavian, other countries), and qualification of the operator (undergraduate students, postgraduate students, general dental practitioners, specialist or mixed group). RESULTS: Of the 40 papers identified, 17 studies published between 1961 and 2005 were included; none were published in 2006. The majority of studies were retrospective (n = 12) and only five prospective. The pooled weighted success rate of 2 degrees RCT judged by complete healing was 76.7% (95% CI 73.6%, 89.6%) and by incomplete healing, 77.2% (95% CI 61.1%, 88.1%). The success rates by 'decade of publication' and 'geographic location of study' were not significantly different at the 5% level. Eighteen clinical factors had been investigated in various combinations in previous studies. The most frequently and thoroughly investigated were 'periapical status' (n = 13), 'size of lesion' (n = 7), and 'apical extent of RF' (n = 5) which were found to be significant prognostic factors. The effect of different aspects of primary treatment history and re-treatment procedures has been poorly tested. CONCLUSIONS: The pooled estimated success rate of secondary root canal treatment was 77%. The presence of pre-operative periapical lesion, apical extent of root filling and quality of coronal restoration proved significant prognostic factors with concurrence between all three strands of evidence whilst the effects of 1 degrees RCT history and 2 degrees RCT protocol have been poorly investigated

Evaluation of earlier versus later dietary management in long-chain 3-hydroxyacyl-CoA dehydrogenase or mitochondrial trifunctional protein deficiency::a systematic review

Background: Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid β-oxidation disorders. Without dietary management the conditions are life-threatening. We conducted a systematic review to investigate whether pre-symptomatic dietary management following newborn screening provides better outcomes than treatment following symptomatic detection. Methods: We searched Web of Science, Medline, Pre-Medline, Embase and the Cochrane Library up to 23rd April 2018. Two reviewers independently screened titles, abstracts and full texts for eligibility and quality appraised the studies. Data extraction was performed by one reviewer and checked by another. Results: We included 13 articles out of 7483 unique records. The 13 articles reported on 11 patient groups, including 174 people with LCHAD deficiency, 18 people with MTP deficiency and 12 people with undifferentiated LCHAD/MTP deficiency. Study quality was moderate to weak in all studies. Included studies suggested fewer heart and liver problems in screen-detected patients, but inconsistent results for mortality. Follow up analyses compared long-term outcomes of (1) pre-symptomatically versus symptomatically treated patients, (2) screened versus unscreened patients, and (3) asymptomatic screen-detected, symptomatic screen-detected, and clinically diagnosed patients in each study. For follow up analyses 1 and 2, we found few statistically significant differences in the long-term outcomes. For follow up analysis 3 we found a significant difference for only one comparison, in the incidence of cardiomyopathy between the three groups. Conclusions: There is some evidence that dietary management following screen-detection might be associated with a lower incidence of some LCHAD and MTP deficiency-related complications. However, the evidence base is limited by small study sizes, quality issues and risk of confounding. An internationally collaborative research effort is needed to fully examine the risks and the benefits to pre-emptive dietary management with particular attention paid to disease severity and treatment group.</p

Proactive SLA negotiation for service based systems: Initial implementation and evaluation experience

This paper describes a framework that we have developed to integrate proactive SLA negotiation with dynamic service discovery to provide cohesive runtime support for both these activities. The proactive negotiation of SLAs as part of service discovery is necessary for reducing the extent of interruptions during the operation of a service based system when the need for replacing services in it arises. The developed framework discovers alternative candidate constituent services for a service client application, and negotiates/agrees but does not activate SLAs with these services until the need for using a service becomes necessary. A prototype tool has been implemented to realize the framework. This prototype is discussed in the paper along with the results of the initial evaluation of the framework