Sarah Thorning

Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication

Background: When prescribing antibiotics for common indications, clinicians need information about both harms and benefits, information that is currently available only from observational studies. We quantified the common harms of the most frequently prescribed antibiotic, amoxicillin, from randomized placebo-controlled trials. Methods: For this systematic review, we searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, without language restriction, for any randomized, participant-blinded, placebo-controlled trials of amoxicillin or amoxicillin–clavulanic acid for any indication, in any setting. Our main outcome was any reported adverse event. Results: Of 730 studies identified, we included 45 trials: 27 involving amoxicillin, 17 involving amoxicillin–clavulanic acid and 1 involving both. The indications for antibiotic therapy were variable. The risk of bias was low, although only 25 trials provided data suitable for assessment of harms, which suggested under-reporting. Diarrhea was attributed to amoxicillin only in the form of amoxicillin–clavulanic acid (Peto odds ratio [OR] 3.30, 95% confidence interval [CI] 2.23–4.87). The OR for candidiasis (3 trials) was significantly higher (OR 7.77, 95% CI 2.23–27.11). Rashes, nausea, itching, vomiting and abnormal results on liver function tests were not significantly increased. The results were not altered by sensitivity analyses, nor did funnel plots suggest publication bias. The number of courses of antibiotics needed to harm was 10 (95% CI 6–17) for diarrhea with amoxicillin–clavulanic acid and 27 (95% CI 24–42) for candidiasis with amoxicillin (with or without clavulanic acid). Interpretation: Diarrhea was caused by use of amoxicillin–clavulanic acid, and candidiasis was caused by both amoxicillin and amoxicillin–clavulanic acid. Harms were poorly reported in most trials, and their true incidence may have been higher than reported. Nevertheless, these rates of common harms associated with amoxicillin therapy may inform decisions by helping clinicians to balance harms against benefits.

The scatter of research: Cross sectional comparison of randomised trials and systematic reviews across specialties

Objective To estimate the degree of scatter of reports of randomised trials and systematic reviews, and how the scatter differs among medical specialties and subspecialties. Design Cross sectional analysis. Data source PubMed for all disease relevant randomised trials and systematic reviews published in 2009. Study selection Randomised trials and systematic reviews of the nine diseases or disorders with the highest burden of disease, and the broader category of disease to which each belonged. Results The scatter across journals varied considerably among specialties and subspecialties: otolaryngology had the least scatter (363 trials across 167 journals) and neurology the most (2770 trials across 896 journals). In only three subspecialties (lung cancer, chronic obstructive pulmonary disease, hearing loss) were 10 or fewer journals needed to locate 50% of trials. The scatter was less for systematic reviews: hearing loss had the least scatter (10 reviews across nine journals) and cancer the most (670 reviews across 279 journals). For some specialties and subspecialties the papers were concentrated in specialty journals; whereas for others, few of the top 10 journals were a specialty journal for that area. Generally, little overlap occurred between the top 10 journals publishing trials and those publishing systematic reviews. The number of journals required to find all trials or reviews was highly correlated (r=0.97) with the number of papers for each specialty/subspecialty. Conclusions Publication rates of speciality relevant trials vary widely, from one to seven trials per day, and are scattered across hundreds of general and specialty journals. Although systematic reviews reduce the extent of scatter, they are still widely scattered and mostly in different journals to those of randomised trials. Personal subscriptions to journals, which are insufficient for keeping up to date with knowledge, need to be supplemented by other methods such as journal scanning services or systems that cover sufficient journals and filter articles for quality and relevance. Few current systems seem adequate.

Determining the gaps between Cochrane reviews and trials of effectiveness of interventions for acute respiratory infections: an audit

BackgroundCochrane primarily aims to systematically review trials of effectiveness that are important to inform clinical decisions. Editorial groups support authors to achieve high-quality reviews and prioritise review proposals in their clinical domain that are submitted or elicited. Prioritising proposals requires two approaches, identifying (1) clinical practises for which the evidence of effectiveness is uncertain and (2) interventions in which there are trials of effectiveness (especially randomised controlled trials (RCTs)) not systematically reviewed. This study addresses this second approach for the Cochrane Acute Respiratory Infections Group (CARIG) in order to identify RCTs of acute respiratory infections that have not been systematically reviewed.MethodsWe exported, on the 9th of September 2014, and then compared the group’s trials register of RCTs against a list of current Cochrane ARI (systematic) Reviews to identify gaps in topics (the same intervention and health condition) where completed trials have not been systematically reviewed. We assigned a principle intervention and health condition to each of 157 Cochrane reviews (CRs) and 5393 RCTs.ResultsA majority of topics had been systematically reviewed; however, a substantial number (2174 or 41%) of RCTs were not included in any review. The topic that had been systematically reviewed the most was antibiotic vs placebo for pneumonia with 11 CRs and 205 RCTs. The topic that was the subject of most RCTs was vaccination for influenza with 525 RCTs and 6 CRs. Also, 6 CRs had no RCTs (‘empty reviews’).ConclusionsWe identified many RCT topics that have not been systematically reviewed. They need to be addressed in a separate process to establish their priority to clinicians.

Citation Enrichment Improves Deduplication of Primary Evidence

Objective: To automatically detect duplicate citations in a bibliographical database. Background: Citations retrieved from multiple search databases have different forms making manual and automatic detection of duplicates difficult. Existing methods rely on fuzzy-similarity measures which are error-prone. Methods: We analysed four pairs of original search results from MEDLINE and EMBASE that were used to create systematic reviews. An automatic tool deduplicated citations by first enriching citations with Digital Object Identifiers DOI, and/or other unique identifiers. Duplication of records was then determined by comparing these unique identifiers. We compared our method with the duplicate detection function of a popular citation management desktop application in several configurations. Results: Citation Enrichment identified 93i¾?% range 86i¾?%---100i¾?% of the duplicates indexed online and erroneously marked 3i¾?% range 0i¾?%---6i¾?% documents as duplicates. The citation management application found 68i¾?% range 64i¾?%---72i¾?% without error using default setting. When set for highest deduplication, the citation management application found 94i¾?% of duplicates range 77i¾?%---100i¾?% and 4i¾?% error range 0i¾?%---8i¾?%. Conclusion: Citation enrichment using unique identifiers enhances automatic deduplication. On its own, the approach seems slightly superior to tools that compare citations without enrichment. Methods that combine citation enrichment with existing fuzzy-matching may substantially reduce resource requirements of evidence synthesis.

Scatter of orthopaedic research: can orthopods stay up-to-date with research?

The volume of orthopaedic literature is increasing exponentially, becoming more widely scattered among journals. The rate of increase in orthopaedics is greater than other specialties. We aimed to identify the number of different journals an orthopaedic surgeon would need to read to stay up‐to‐date with current evidence.

Vacunas para la prevención de la gripe en personas de edad avanzada

Resumen Antecedentes Durante las ultimas cuatro decadas, las vacunas han sido la principal arma global para disminuir la repercusion de la gripe en las personas de edad avanzada, y a nivel mundial se recomiendan para los individuos de 65 anos o mas de edad. El objetivo principal de la vacunacion contra la gripe en las personas de edad avanzada es reducir el riesgo de complicaciones en quienes son mas vulnerables. Objetivos Evaluar la efectividad de las vacunas sobre la prevencion de la gripe, la enfermedad similar a la gripe, los ingresos hospitalarios, las complicaciones y la mortalidad en las personas de edad avanzada. Identificar y evaluar los estudios comparativos que evaluan los efectos de las vacunas para la gripe en las personas de edad avanzada. Documentar los tipos y la frecuencia de los efectos adversos asociados con las vacunas contra la gripe en las personas de edad avanzada. Estrategia de busqueda Se realizaron busquedas en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials, CENTRAL), que contiene el Registro Especializado de Ensayos Controlados del Grupo Cochrane de Infecciones Respiratorias Agudas (Cochrane Acute Respiratory Infections [ARI]) (The Cochrane Library numero 4 de 2009), MEDLINE (enero de 1966 hasta la primera semana de octubre de 2009); EMBASE (1974 hasta octubre de 2009) y Web of Science (1974 hasta octubre de 2009). Criterios de seleccion Ensayos controlados aleatorios (ECAs), ensayos controlados cuasialeatorios, estudios de cohortes y estudios de casos y controles que evaluan la eficacia contra la gripe (casos confirmados por laboratorio), la efectividad contra la enfermedad similar a la gripe (ESG) o la seguridad. Se considero cualquier vacuna administrada de forma independiente, en cualquier dosis, preparacion o cronograma de administracion, comparada con placebo o ninguna intervencion. Obtencion y analisis de los datos Los informes se agruparon en primer lugar segun el contexto del estudio (comunidad o establecimientos de atencion a largo plazo) y luego por el nivel de circulacion virica y de pareamiento de la vacuna. Se estratifico adicionalmente por la administracion concomitante de la vacuna de polisacarido antineumococico (PPV) y por diferentes tipos de vacunas contra la gripe. Se analizaron los siguientes resultados: gripe, enfermedad similar a la gripe, ingresos hospitalarios, complicaciones y muertes. Resultados principales Se incluyeron 75 estudios. En general se identificaron 100 conjuntos de datos. Se identifico un ECA que evaluo la eficacia y la efectividad. Aunque el mismo parecio mostrar un efecto contra los sintomas de la gripe no tuvo poder estadistico suficiente para detectar efectos sobre las complicaciones (1348 participantes). La base de pruebas restante incluyo ensayos controlados no aleatorios. Debido a la baja calidad general de los ensayos controlados no aleatorios y la probable presencia de sesgos, que dificultan la interpretacion de estos datos y hacen que cualquier conclusion solida se torne potencialmente enganosa, no fue posible establecer conclusiones claras acerca de los efectos de las vacunas en las personas de edad avanzada. Conclusiones de los autores Las pruebas disponibles son de calidad deficiente y no proporcionan orientacion con respecto a la seguridad, la eficacia o la efectividad de las vacunas contra la gripe en las personas de 65 anos de edad o mas. Para resolver la incertidumbre se debe realizar un ensayo aleatorio controlado con placebo, con financiamiento publico y con poder estadistico adecuado, durante varias estaciones.