Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis.

BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of osteoarthritis pain management. We aimed to assess the effectiveness of different preparations and doses of NSAIDs on osteoarthritis pain in a network meta-analysis. METHODS For this network meta-analysis, we considered randomised trials comparing any of the following interventions: NSAIDs, paracetamol, or placebo, for the treatment of osteoarthritis pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the reference lists of relevant articles for trials published between Jan 1, 1980, and Feb 24, 2015, with at least 100 patients per group. The prespecified primary and secondary outcomes were pain and physical function, and were extracted in duplicate for up to seven timepoints after the start of treatment. We used an extension of multivariable Bayesian random effects models for mixed multiple treatment comparisons with a random effect at the level of trials. For the primary analysis, a random walk of first order was used to account for multiple follow-up outcome data within a trial. Preparations that used different total daily dose were considered separately in the analysis. To assess a potential dose-response relation, we used preparation-specific covariates assuming linearity on log relative dose. FINDINGS We identified 8973 manuscripts from our search, of which 74 randomised trials with a total of 58 556 patients were included in this analysis. 23 nodes concerning seven different NSAIDs or paracetamol with specific daily dose of administration or placebo were considered. All preparations, irrespective of dose, improved point estimates of pain symptoms when compared with placebo. For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a prespecified minimum clinically important effect for pain reduction (effect size [ES] -0·37) was at least 95%. Among maximally approved daily doses, diclofenac 150 mg/day (ES -0·57, 95% credibility interval [CrI] -0·69 to -0·46) and etoricoxib 60 mg/day (ES -0·58, -0·73 to -0·43) had the highest probability to be the best intervention, both with 100% probability to reach the minimum clinically important difference. Treatment effects increased as drug dose increased, but corresponding tests for a linear dose effect were significant only for celecoxib (p=0·030), diclofenac (p=0·031), and naproxen (p=0·026). We found no evidence that treatment effects varied over the duration of treatment. Model fit was good, and between-trial heterogeneity and inconsistency were low in all analyses. All trials were deemed to have a low risk of bias for blinding of patients. Effect estimates did not change in sensitivity analyses with two additional statistical models and accounting for methodological quality criteria in meta-regression analysis. INTERPRETATION On the basis of the available data, we see no role for single-agent paracetamol for the treatment of patients with osteoarthritis irrespective of dose. We provide sound evidence that diclofenac 150 mg/day is the most effective NSAID available at present, in terms of improving both pain and function. Nevertheless, in view of the safety profile of these drugs, physicians need to consider our results together with all known safety information when selecting the preparation and dose for individual patients. FUNDING Swiss National Science Foundation (grant number 405340-104762) and Arco Foundation, Switzerland.

Influence of EMS-physician presence on survival after out-of-hospital cardiopulmonary resuscitation: systematic review and meta-analysis

BACKGROUND Evidence suggests that EMS-physician-guided cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OOHCA) may be associated with improved outcomes, yet randomized controlled trials are not available. The goal of this meta-analysis was to determine the association between EMS-physician- versus paramedic-guided CPR and survival after OOHCA. METHODS AND RESULTS Studies that compared EMS-physician- versus paramedic-guided CPR in OOHCA published until June 2014 were systematically searched in MEDLINE, EMBASE and Cochrane databases. All studies were required to contain survival data. Data on study characteristics, methods, and as well as survival outcomes were extracted. A random-effects model was used for the meta-analysis due to a high degree of heterogeneity among the studies (I (2)  = 44 %). Return of spontaneous circulation [ROSC], survival to hospital admission, and survival to hospital discharge were the outcome measures. Out of 3,385 potentially eligible studies, 14 met the inclusion criteria. In the pooled analysis (n = 126,829), EMS-physician-guided CPR was associated with significantly improved outcomes compared to paramedic-guided CPR: ROSC 36.2 % (95 % confidence interval [CI] 31.0 - 41.7 %) vs. 23.4 % (95 % CI 18.5 - 29.2 %) (pooled odds ratio [OR] 1.89, 95 % CI 1.36 - 2.63, p < 0.001); survival to hospital admission 30.1 % (95 % CI 24.2 - 36.7 %) vs. 19.2 % (95 % CI 12.7 - 28.1 %) (pooled OR 1.78, 95 % CI 0.97 - 3.28, p = 0.06); and survival to discharge 15.1 % (95 % CI 14.6 - 15.7 %) vs. 8.4 % (95 % CI 8.2 - 8.5 %) (pooled OR 2.03, 95 % CI 1.48 - 2.79, p < 0.001). CONCLUSIONS This systematic review suggests that EMS-physician-guided CPR in out-of-hospital cardiac arrest is associated with improved survival outcomes.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

BACKGROUND Panic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition. OBJECTIVES To assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults. SEARCH METHODS We conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status. SELECTION CRITERIA We included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The comparator interventions considered for this review were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP). For this review we considered four short-term (ST) outcomes (ST-remission, ST-response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT) outcome (LT-remission/response). DATA COLLECTION AND ANALYSIS As a first step, we conducted a systematic search of all relevant papers according to the inclusion criteria. For each outcome, we then constructed a treatment network in order to clarify the extent to which each type of therapy and each comparison had been investigated in the available literature. Then, for each available comparison, we conducted a random-effects meta-analysis. Subsequently, we performed a network meta-analysis in order to synthesise the available direct evidence with indirect evidence, and to obtain an overall effect size estimate for each possible pair of therapies in the network. Finally, we calculated a probabilistic ranking of the different psychological therapies and control conditions for each outcome. MAIN RESULTS We identified 1432 references; after screening, we included 60 studies in the final qualitative analyses. Among these, 54 (including 3021 patients) were also included in the quantitative analyses. With respect to the analyses for the first of our primary outcomes, (short-term remission), the most studied of the included psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10 studies), CT (three studies), SP (three studies) and PD (two studies).The quality of the evidence for the entire network was found to be low for all outcomes. The quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low, depending on the outcome. The majority of the included studies were at unclear risk of bias with regard to the randomisation process. We found almost half of the included studies to be at high risk of attrition bias and detection bias. We also found selective outcome reporting bias to be present and we strongly suspected publication bias. Finally, we found almost half of the included studies to be at high risk of researcher allegiance bias.Overall the networks appeared to be well connected, but were generally underpowered to detect any important disagreement between direct and indirect evidence. The results showed the superiority of psychological therapies over the WL condition, although this finding was amplified by evident small study effects (SSE). The NMAs for ST-remission, ST-response and ST-improvement on a continuous scale showed well-replicated evidence in favour of CBT, as well as some sparse but relevant evidence in favour of PD and SP, over other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over other psychological therapies in the short term. In the long term, CBT and PD showed the highest level of remission/response, suggesting that the effects of these two treatments may be more stable with respect to other psychological therapies. However, all the mentioned differences among active treatments must be interpreted while taking into account that in most cases the effect sizes were small and/or results were imprecise. AUTHORS' CONCLUSIONS There is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.

Hepatitis C in HIV-infected individuals: a systematic review and meta-analysis of estimated prevalence in Africa.

INTRODUCTION Although hepatitis C virus (HCV) screening is recommended for all HIV-infected patients initiating antiretroviral therapy, data on epidemiologic characteristics of HCV infection in resource-limited settings are scarce. METHODS We searched PubMed and EMBASE for studies assessing the prevalence of HCV infection among HIV-infected individuals in Africa and extracted data on laboratory methods used. Prevalence estimates from individual studies were combined for each country using random-effects meta-analysis. The importance of study design, population and setting as well as type of test (anti-HCV antibody tests and polymerase chain reactions) was examined with meta-regression. RESULTS Three randomized controlled trials, 28 cohort studies and 121 cross-sectional analyses with 108,180 HIV-infected individuals from 35 countries were included. The majority of data came from outpatient populations (55%), followed by blood donors (15%) and pregnant women (14%). Based on estimates from 159 study populations, anti-HCV positivity prevalence ranged between 3.3% (95% confidence interval (CI) 1.8-4.7) in Southern Africa and 42.3% (95% CI 4.1-80.5) in North Africa. Study design, type of setting and age distribution did not influence this prevalence significantly. The prevalence of replicating HCV infection, estimated from data of 29 cohorts, was 2.0% (95% CI 1.5-2.6). Ten studies from nine countries reported the HCV genotype of 74 samples, 53% were genotype 1, 24% genotype 2, 14% genotype 4 and 9% genotypes 3, 5 or 6. CONCLUSIONS The prevalence of anti-HCV antibodies is high in HIV-infected patients in Africa, but replicating HCV infection is rare and varies widely across countries.

Technical Efficiency in the Indian Textiles Industry: A Nonparametric Analysis of Firm-Level Data

The Indian textiles industry is now at the crossroads with the phasing out of quota regime that prevailed under the Multi-Fiber Agreement (MFA) until the end of 2004. In the face of a full integration of the textiles sector in the WTO, maintaining and enhancing productive efficiency is a precondition for competitiveness of the Indian firms in the new liberalized world market. In this paper we use data obtained from the Annual Survey of Industries for a number of years to measure the levels of technical efficiency in the Indian textiles industry at the firm level. We use both a grand frontier applicable to all firms and a group frontier specific to firms from any individual state, ownership, or organization type in order to evaluate their efficiencies. This permits us to separately identify how locational, proprietary, and organizational characteristics of a firm affect its performance.

Bayesian generalized linear models for meta-analysis of diagnostic tests

With the recognition of the importance of evidence-based medicine, there is an emerging need for methods to systematically synthesize available data. Specifically, methods to provide accurate estimates of test characteristics for diagnostic tests are needed to help physicians make better clinical decisions. To provide more flexible approaches for meta-analysis of diagnostic tests, we developed three Bayesian generalized linear models. Two of these models, a bivariate normal and a binomial model, analyzed pairs of sensitivity and specificity values while incorporating the correlation between these two outcome variables. Noninformative independent uniform priors were used for the variance of sensitivity, specificity and correlation. We also applied an inverse Wishart prior to check the sensitivity of the results. The third model was a multinomial model where the test results were modeled as multinomial random variables. All three models can include specific imaging techniques as covariates in order to compare performance. Vague normal priors were assigned to the coefficients of the covariates. The computations were carried out using the 'Bayesian inference using Gibbs sampling' implementation of Markov chain Monte Carlo techniques. We investigated the properties of the three proposed models through extensive simulation studies. We also applied these models to a previously published meta-analysis dataset on cervical cancer as well as to an unpublished melanoma dataset. In general, our findings show that the point estimates of sensitivity and specificity were consistent among Bayesian and frequentist bivariate normal and binomial models. However, in the simulation studies, the estimates of the correlation coefficient from Bayesian bivariate models are not as good as those obtained from frequentist estimation regardless of which prior distribution was used for the covariance matrix. The Bayesian multinomial model consistently underestimated the sensitivity and specificity regardless of the sample size and correlation coefficient. In conclusion, the Bayesian bivariate binomial model provides the most flexible framework for future applications because of its following strengths: (1) it facilitates direct comparison between different tests; (2) it captures the variability in both sensitivity and specificity simultaneously as well as the intercorrelation between the two; and (3) it can be directly applied to sparse data without ad hoc correction. ^

A systematic review and meta-analysis of diabetes disease management programs

Context. Despite the rapid growth of disease management programs, there are still questions about their efficacy and effectiveness for improving patient outcomes and their ability to reduce costs associated with chronic disease. ^ Objective. To determine the effectiveness of disease management programs on improving the results of HbA1c tests, lipid profiles and systolic blood pressure (SBP) readings among diabetics. These three quantitative measures are widely accepted methods of determining the quality of a patient's diabetes management and the potential for future complications. ^ Data Sources. MEDLINE and CINAHL were searched from 1950 to June 2008 using MeSH terms designed to capture all relevant studies. Scopus pearling and hand searching were also done. Only English language articles were selected. ^ Study Selection. Titles and abstracts for the 2347 articles were screened against predetermined inclusion and exclusion criteria, yielding 217 articles for full screening. After full article screening, 29 studies were selected for inclusion in the review. ^ Data Extraction. From the selected studies, data extraction included sample size, mean change over baseline, and standard deviation for each control and experimental arm. ^ Results. The pooled results show a mean HbA1c reduction of 0.64%, 95% CI (-0.83 to -0.44), mean SBP reduction of 7.39 mmHg (95% CI to -11.58 to -3.2), mean total cholesterol reduction of 5.74 mg/dL (95% CI, -10.01 to -1.43), and mean LDL cholesterol reduction of 3.74 mg/dL (95% CI, -8.34 to 0.87). Results for HbA1c, SBP and total cholesterol were statistically significant, while the results for LDL cholesterol were not. ^ Conclusions. The findings suggest that disease management programs utilizing five hallmarks of care can be effective at improving intermediate outcomes among diabetics. However, given the significant heterogeneity present, there may be fundamental differences with respect to study-specific interventions and populations that render them inappropriate for meta-analysis. ^

Ascertainment, meta-analysis and reporting of adverse reactions in clinical trials of antibiotics

The ascertainment and analysis of adverse reactions to investigational agents presents a significant challenge because of the infrequency of these events, their subjective nature and the low priority of safety evaluations in many clinical trials. A one year review of antibiotic trials published in medical journals demonstrates the lack of standards in identifying and reporting these potentially fatal conditions. This review also illustrates the low probability of observing and detecting rare events in typical clinical trials which include fewer than 300 subjects. Uniform standards for ascertainment and reporting are suggested which include operational definitions of study subjects. Meta-analysis of selected antibiotic trials using multivariate regression analysis indicates that meaningful conclusions may be drawn from data from multiple studies which are pooled in a scientifically rigorous manner. ^

Análisis sobre la eficacia de niveles moderados de actividad física para reducir el riesgo de padecer enfermedades cardiovasculares : Un Meta-análisis

Objetivos: a. Determinar la eficacia de la actividad física en la reducción del riesgo de enfermedades cardiovasculares; b. Analizar los cambios relativos en los niveles de riesgo a padecer enfermedades cardiovasculares de acuerdo a diferentes intensidades (baja-moderada) de actividad física. Metodología: Se realizó un Meta-análisisde los estudios encontrados en la base de datos PUBMED. Se calculó el tamaño del efecto medio y se aplicó el test de Eggerpara descartar un posible sesgo de publicación. Al detectarse heterogeneidad, se procedió a realizar un análisis de las variables moderadoras. Resultados: Se obtuvo un tamaño del efecto medio de 0.762 (0.678-0857; 95 por ciento IC). El test de Egger arrojó un p-valor de 0.67 (I.C. 0.95), de manera tal que se confirmó la ausencia de sesgo de publicación. El análisis moderador determinó que los años de seguimiento (p=0.000; 95 por ciento IC) y los países de estudio (p=0.0096; 95 por ciento IC) son significativos. Conclusión: Se puede concluir en que la práctica de actividad física a intensidades moderadas ofrece un efecto protector sobre los individuos que la realizan disminuyendo el riesgo a padecer enfermedades cardiovasculares

Análisis sobre la eficacia de niveles moderados de actividad física para reducir el riesgo de padecer enfermedades cardiovasculares : Un Meta-análisis

Objetivos: a. Determinar la eficacia de la actividad física en la reducción del riesgo de enfermedades cardiovasculares; b. Analizar los cambios relativos en los niveles de riesgo a padecer enfermedades cardiovasculares de acuerdo a diferentes intensidades (baja-moderada) de actividad física. Metodología: Se realizó un Meta-análisisde los estudios encontrados en la base de datos PUBMED. Se calculó el tamaño del efecto medio y se aplicó el test de Eggerpara descartar un posible sesgo de publicación. Al detectarse heterogeneidad, se procedió a realizar un análisis de las variables moderadoras. Resultados: Se obtuvo un tamaño del efecto medio de 0.762 (0.678-0857; 95 por ciento IC). El test de Egger arrojó un p-valor de 0.67 (I.C. 0.95), de manera tal que se confirmó la ausencia de sesgo de publicación. El análisis moderador determinó que los años de seguimiento (p=0.000; 95 por ciento IC) y los países de estudio (p=0.0096; 95 por ciento IC) son significativos. Conclusión: Se puede concluir en que la práctica de actividad física a intensidades moderadas ofrece un efecto protector sobre los individuos que la realizan disminuyendo el riesgo a padecer enfermedades cardiovasculares

Análisis sobre la eficacia de niveles moderados de actividad física para reducir el riesgo de padecer enfermedades cardiovasculares : Un Meta-análisis

Objetivos: a. Determinar la eficacia de la actividad física en la reducción del riesgo de enfermedades cardiovasculares; b. Analizar los cambios relativos en los niveles de riesgo a padecer enfermedades cardiovasculares de acuerdo a diferentes intensidades (baja-moderada) de actividad física. Metodología: Se realizó un Meta-análisisde los estudios encontrados en la base de datos PUBMED. Se calculó el tamaño del efecto medio y se aplicó el test de Eggerpara descartar un posible sesgo de publicación. Al detectarse heterogeneidad, se procedió a realizar un análisis de las variables moderadoras. Resultados: Se obtuvo un tamaño del efecto medio de 0.762 (0.678-0857; 95 por ciento IC). El test de Egger arrojó un p-valor de 0.67 (I.C. 0.95), de manera tal que se confirmó la ausencia de sesgo de publicación. El análisis moderador determinó que los años de seguimiento (p=0.000; 95 por ciento IC) y los países de estudio (p=0.0096; 95 por ciento IC) son significativos. Conclusión: Se puede concluir en que la práctica de actividad física a intensidades moderadas ofrece un efecto protector sobre los individuos que la realizan disminuyendo el riesgo a padecer enfermedades cardiovasculares

Profile of sediment echo sounding with links to ParaSound data files and swath sonar multibeam bathymetry during METEOR cruise M70/2b

Two highly active mud volcanoes located in 990-1,265 m water depths were mapped on the northern Egyptian continental slope during the BIONIL expedition of R/V Meteor in October 2006. High-resolution swath bathymetry and backscatter imagery were acquired with an autonomous underwater vehicle (AUV)-mounted multibeam echosounder, operating at a frequency of 200 kHz. Data allowed for the construction of ~1 m pixel bathymetry and backscatter maps. The newly produced maps provide details of the seabed morphology and texture, and insights into the formation of the two mud volcanoes. They also contain key indicators on the distribution of seepage and its tectonic control. The acquisition of high-resolution seafloor bathymetry and acoustic imagery maps with an AUV-mounted multibeam echosounder fills the gap in spatial scale between conventional multibeam data collected from a surface vessel and in situ video observations made from a manned submersible or a remotely operating vehicle.

New data on the ophiolitic VMS deposits of Moeche (Cabo Ortegal Complex, NW Spain)

As a result of the variscan collision, several allochtonous complexes were emplaced on the Iberian margin in Devonian times, among them the Cabo Ortegal Complex comprising the Moeche ophiolitic sequence. Copper has been won from several mines (Piquitos I & II, Barqueira, Maruxa) from disseminated ores and thin massive sulphide layers in the Moeche Unit, a strongly deformed meta-volcanic sequence comprising mainly quartz-chlorite schists and mylonites, which defines the top of the ophiolite. The ores were metamorphosed and strongly deformed under brittle conditions (for pyrite), but their textures are often apparently post-deformational, due to very common solution-transfer processes; they are composed mostly of pyrite and chalcopyrite, with minor sphalerite, pyrrhotite, etc., and with traces of native gold and PGE. The geology, mineralogy, and geochemistry of the orebodies relate closely to VMS of the Cu-Zn (Cyprus) type. Fluid inclusion studies allowed an estimation of metamorphic conditions at pressures of 2/2’5 kb and T 325/350ºC. New determinations using the chlorite geothermometer yield temperatures around 320 ºC, corresponding to pressures near 2 kb according to the isochores deduced from the fluid inclusion study, although in the Barqueira mine higher temperatures, up to 350 ºC, are found, corresponding to presssures up to 2’5 kb. Pb isotopic compositions of pyrite point to a double source of Pb, i.e. a main mantle and a subordinate crustal source. The values for 87SR/86Sr in pyrite support this interpretation, but some results suggest later mobilization in an open system, corresponding to solution-transfer. Age determinations of pyrite deduced from the Pb isotope uranogenic graph, ≈ 480 Ma, do not fit with the metamorphic ages published for the Moeche Unit, and might point to the age of Pb extraction from the mantle.

Data-Flow analysis of prolog programs with extra-logical features

Abstract interpretation-based data-flow analysis of logic programs is at this point relatively well understood from the point of view of general frameworks and abstract domains. On the other hand, comparatively little attention has been given to the problems which arise when analysis of a full, practical dialect of the Prolog language is attempted, and only few solutions to these problems have been proposed to date. Such problems relate to dealing correctly with all builtins, including meta-logical and extra-logical predicates, with dynamic predicates (where the program is modified during execution), and with the absence of certain program text during compilation. Existing proposals for dealing with such issues generally restrict in one way or another the classes of programs which can be analyzed if the information from analysis is to be used for program optimization. This paper attempts to fill this gap by considering a full dialect of Prolog, essentially following the recently proposed ISO standard, pointing out the problems that may arise in the analysis of such a dialect, and proposing a combination of known and novel solutions that together allow the correct analysis of arbitrary programs using the full power of the language.