Label-invariant models for the analysis of meta-epidemiological data.

Rich meta-epidemiological data sets have been collected to explore associations between intervention effect estimates and study-level characteristics. Welton et al proposed models for the analysis of meta-epidemiological data, but these models are restrictive because they force heterogeneity among studies with a particular characteristic to be at least as large as that among studies without the characteristic. In this paper we present alternative models that are invariant to the labels defining the 2 categories of studies. To exemplify the methods, we use a collection of meta-analyses in which the Cochrane Risk of Bias tool has been implemented. We first investigate the influence of small trial sample sizes (less than 100 participants), before investigating the influence of multiple methodological flaws (inadequate or unclear sequence generation, allocation concealment, and blinding). We fit both the Welton et al model and our proposed label-invariant model and compare the results. Estimates of mean bias associated with the trial characteristics and of between-trial variances are not very sensitive to the choice of model. Results from fitting a univariable model show that heterogeneity variance is, on average, 88% greater among trials with less than 100 participants. On the basis of a multivariable model, heterogeneity variance is, on average, 25% greater among trials with inadequate/unclear sequence generation, 51% greater among trials with inadequate/unclear blinding, and 23% lower among trials with inadequate/unclear allocation concealment, although the 95% intervals for these ratios are very wide. Our proposed label-invariant models for meta-epidemiological data analysis facilitate investigations of between-study heterogeneity attributable to certain study characteristics.

Applicability and feasibility of systematic review for performing evidence-based risk assessment in food and feed safety.

Food and feed safety risk assessment uses multi-parameter models to evaluate the likelihood of adverse events associated with exposure to hazards in human health, plant health, animal health, animal welfare, and the environment. Systematic review and meta-analysis are established methods for answering questions in health care, and can be implemented to minimize biases in food and feed safety risk assessment. However, no methodological frameworks exist for refining risk assessment multi-parameter models into questions suitable for systematic review, and use of meta-analysis to estimate all parameters required by a risk model may not be always feasible. This paper describes novel approaches for determining question suitability and for prioritizing questions for systematic review in this area. Risk assessment questions that aim to estimate a parameter are likely to be suitable for systematic review. Such questions can be structured by their "key elements" [e.g., for intervention questions, the population(s), intervention(s), comparator(s), and outcome(s)]. Prioritization of questions to be addressed by systematic review relies on the likely impact and related uncertainty of individual parameters in the risk model. This approach to planning and prioritizing systematic review seems to have useful implications for producing evidence-based food and feed safety risk assessment.

Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis.

We report safety, tolerability, and 12-week sustained virologic response with half-standard dose sofosbuvir and standard-dose simeprevir combination therapy in a hepatitis C virus genotype 1a-infected liver transplant recipient on hemodialysis - uncharted territory for sofosbuvir-based therapy. The patient was a non-responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill-splitting and administration of half-standard dose, 200 mg per day. No drug-drug interactions were noted with tacrolimus-based immunosuppression. Laboratory tests remained stable or improved during therapy. Our observation, if reproduced in a larger study, may lead to significant improvement in clinical outcomes and cost savings in this patient population.

Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data.

BACKGROUND: Many randomised controlled trials have investigated the effect of adjuvant chemotherapy in operable non-small-cell lung cancer. We undertook two comprehensive systematic reviews and meta-analyses to establish the effects of adding adjuvant chemotherapy to surgery, or to surgery plus radiotherapy. METHODS: We included randomised trials, not confounded by additional therapeutic differences between the two groups and that started randomisation on or after Jan 1, 1965, which compared surgery plus adjuvant chemotherapy versus surgery alone, or surgery plus adjuvant radiotherapy and chemotherapy versus surgery plus adjuvant radiotherapy. Updated individual patient data were collected, checked, and included in meta-analyses stratified by trial. The primary endpoint was overall survival, defined as time from randomisation until death by any cause. All analyses were by intention to treat. FINDINGS: The first meta-analysis of surgery plus chemotherapy versus surgery alone was based on 34 trial comparisons and 8447 patients (3323 deaths). We recorded a benefit of adding chemotherapy after surgery (hazard ratio [HR] 0.86, 95% CI 0.81-0.92, p<0.0001), with an absolute increase in survival of 4% (95% CI 3-6) at 5 years (from 60% to 64%). The second meta-analysis of surgery plus radiotherapy and chemotherapy versus surgery plus radiotherapy was based on 13 trial comparisons and 2660 patients (1909 deaths). We recorded a benefit of adding chemotherapy to surgery plus radiotherapy (HR 0.88, 95% CI 0.81-0.97, p=0.009), representing an absolute improvement in survival of 4% (95% CI 1-8) at 5 years (from 29% to 33%). In both meta-analyses we noted little variation in effect according to the type of chemotherapy, other trial characteristics, or patient subgroup. INTERPRETATION: The addition of adjuvant chemotherapy after surgery for patients with operable non-small-cell lung cancer improves survival, irrespective of whether chemotherapy was adjuvant to surgery alone or adjuvant to surgery plus radiotherapy. FUNDING: UK Medical Research Council, Institut Gustave-Roussy, Programme Hospitalier de Recherche Clinique (AOM 05 209), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.

Effect of lactic acid bacteria probiotic culture treatment timing on Salmonella Enteritidis in neonatal broilers.

In the present study, a series of experiments were conducted to evaluate the ability of a combination of 3 ATCC lactobacilli (LAB3) or a commercially available probiotic culture (PROB) to reduce Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) in broiler chicks. Additionally, we varied the timing of PROB administration in relationship to Salmonella challenge and determined the influence on recovery of enteric Salmonella. In experiments 1 to 3, chicks were randomly assigned to treatment groups and were then challenged via oral gavage with Salmonella Enteritidis. Chicks were treated 1 h after Salmonella Enteritidis challenge with LAB3 or PROB. Twenty-four hours posttreatment, cecal tonsils were collected for recovery of enteric Salmonella. In experiments 4 to 7, day-of-hatch chicks were randomly assigned to treatment groups and were then treated with PROB via oral gavage and placed into pens. Chicks were challenged with Salmonella Enteritidis 24 h after treatment via oral gavage. At 24 h after Salmonella Enteritidis challenge, cecal tonsils were collected and recovery of enteric Salmonella was determined. In experiments 8 to 10, 1-d-old chicks were randomly assigned to treatment groups and were then challenged via oral gavage with Salmonella Enteritidis and placed into pens. Chicks were treated 24 h after challenge with PROB via oral gavage. Twenty-four hours post PROB treatment, cecal tonsils were collected and enriched as described above. It was found that PROB significantly reduced cecal Salmonella Enteritidis recovery 24 h after treatment as compared with controls or LAB3-treated chicks in experiments 1 to 3 (P<0.05). Administration of PROB 24 h before Salmonella Enteritidis challenge significantly reduced recovery of Salmonella Enteritidis in 2 out of 4 experiments and no reduction in cecal Salmonella Enteritidis was observed when chicks were challenged with Salmonella Enteritidis and treated 24 h later with PROB. These data demonstrate that PROB more effectively reduced Salmonella Enteritidis than LAB3, and the timing of PROB treatment affects Salmonella Enteritidis-associated reductions.

Brain Network Disruption in Whiplash.

BACKGROUND AND PURPOSE: Whiplash-associated disorders frequently develop following motor vehicle collisions and often involve a range of cognitive and affective symptoms, though the neural correlates of the disorder are largely unknown. In this study, a sample of participants with chronic whiplash injuries were scanned by using resting-state fMRI to assess brain network changes associated with long-term outcome metrics. MATERIALS AND METHODS: Resting-state fMRI was collected for 23 participants and used to calculate network modularity, a quantitative measure of the functional segregation of brain region communities. This was analyzed for associations with whiplash-associated disorder outcome metrics, including scales of neck disability, traumatic distress, depression, and pain. In addition to these clinical scales, cervical muscle fat infiltration was quantified by using Dixon fat-water imaging, which has shown promise as a biomarker for assessing disorder severity and predicting recovery in chronic whiplash. RESULTS: An association was found between brain network structure and muscle fat infiltration, wherein lower network modularity was associated with larger amounts of cervical muscle fat infiltration after controlling for age, sex, body mass index, and scan motion (t = -4.02, partial R 2 = 0.49, P < .001). CONCLUSIONS: This work contributes to the existing whiplash literature by examining a sample of participants with whiplash-associated disorder by using resting-state fMRI. Less modular brain networks were found to be associated with greater amounts of cervical muscle fat infiltration suggesting a connection between disorder severity and neurologic changes, and a potential role for neuroimaging in understanding the pathophysiology of chronic whiplash-associated disorders.

Adjusting trial results for biases in meta-analysis: combining data-based evidence on bias with detailed trial assessment.

Flaws in the conduct of randomized trials can lead to biased estimation of the intervention effect. Methods for adjustment of within-trial biases in meta-analysis include the use of empirical evidence from an external collection of meta-analyses, and the use of expert opinion informed by the assessment of detailed trial information. Our aim is to present methods to combine these two approaches to gain the advantages of both. We make use of the risk of bias information that is routinely available in Cochrane reviews, by obtaining empirical distributions for the bias associated with particular bias profiles (combinations of risk of bias judgements). We propose three methods: a formal combination of empirical evidence and opinion in a Bayesian analysis; asking experts to give an opinion on bias informed by both summary trial information and a bias distribution from the empirical evidence, either numerically or by selecting areas of the empirical distribution. The methods are demonstrated through application to two example binary outcome meta-analyses. Bias distributions based on opinion informed by trial information alone were most dispersed on average, and those based on opinions obtained by selecting areas of the empirical distribution were narrowest. Although the three methods for combining empirical evidence with opinion vary in ease and speed of implementation, they yielded similar results in the two examples.

Comparison of beak-trimming methods on early broiler breeder performance.

Beak trimming is necessary in commercial broiler breeders to prevent or decrease trauma as they mature. Two common beak-trimming methods were evaluated by early performance comparison with nontrimmed chicks (NBT). The robotic electrocautery device (ECD) trims and cauterizes the beak tip. The robotic infrared beak-trimming device (IBT) applies an infrared light beam to destroy the live basal tissue while leaving the hard corneum intact for the first approximately 10 d. In 2 experiments, day-of-hatch Ross 708 by-product chicks were obtained from a local hatchery, where 1/3 of the chicks were trimmed using IBT. All chicks were then transported to another hatchery where 1/3 were trimmed using ECD and 1/3 were NBT. Personnel at each hatchery were highly experienced and skilled with their respective technique. All chicks were then transported to University of Arkansas facilities. Before placement in each experiment, chicks were individually neck-tagged and weighed, and in experiment 1, beaks were measured using a digital caliper. A small but significant transient reduction in BW gain was observed at 14 d due to ECD as compared with NBT controls, although ECD was not different than IBT in experiment 1. In experiment 2, IBT birds were significantly heavier at 11 d by 7.8 and 8.7 g than the NBT or ECD, respectively. However, at d 21 and 42, no significant differences in BW or BW gain were observed. When beak trimming was performed on day of hatch by skilled and experienced personnel, little measurable effect on early performance was observed during the first 6 wk of life. Decreased broiler performance is generally considered a sensitive indication of physical or psychogenic stress. Given the marked reduction in beak-inflicted trauma with beak trimming birds as they reach sexual maturity, these results suggest that when properly performed, neither of these beak-trimming methods causes sufficient physical or psychogenic stress to markedly affect early growth rate.

Glutathione S-transferase M1 (GSTM1) polymorphisms and lung cancer: a literature-based systematic HuGE review and meta-analysis.

Multiple genes have been studied for potential associations with lung cancer. The gene most frequently associated with increased risk has been glutathione S-transferase M1 (GSTM1). The glutathione S-transferase enzyme family is known to catalyze detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. In this review, the authors summarize the available evidence associating lung cancer with the GSTM1 gene. They describe results from an updated meta-analysis of 98 published genetic association studies investigating the relation between the GSTM1 null variant and lung cancer risk including 19,638 lung cancer cases and 25,266 controls (counting cases and controls in each study only once). All studies considered, the GSTM1 null variant was associated with an increased risk of lung cancer (odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.14, 1.30), but no increase in risk was seen (OR = 1.01, 95% CI: 0.91, 1.12) when only the five largest studies (>500 cases each) were considered. Furthermore, while GSTM1 null status conferred a significantly increased risk of lung cancer to East Asians (OR = 1.38, 95% CI: 1.24, 1.55), such a genotype did not confer increased risk to Caucasians. More data regarding the predictive value of GSTM1 genetic testing are needed before population-based testing may be reasonably considered.

Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review.

UNLABELLED: We conducted a systematic review of genetic association studies for osteoarthritis of the peripheral joints (OA) and spinal degenerative disease (SDD). Electronic searches were carried out for any English language article reporting on a gene association study for either OA or SDD published up until the end of 2006. A team of seven reviewers used a standardised template to extract data in duplicate. In all, 90 studies fulfilled our inclusion criteria, reporting a total of 94 significant associations from 83 different genes. We found relatively few instances in which a specific gene-disease association had been analysed by more than one study, and there were 14 cases in which significant associations were replicated in independent studies (at joints associated with the AGC1, ASPN, COL9A2, COL9A3, COL11A2, ESR1, FZRB, HFE, IL1A, IL1RN, PTGS2 and VDR genes). METHOD: logical and reporting problems were widespread, including failure to report full results, missing population details, multiple testing, and over-reliance on subgroup analysis. In summary, the complex phenotypes of OA and SDD may have made it difficult for researchers to focus their efforts. The field is dominated by isolated analyses of disparate potential associations, a problem that is amplified by the frequent analysis of different polymorphisms within individual genes. Flaws in study methodology and interpretation undoubtedly increase the risk of publication bias. Closer adherence to published recommendations (in particular those produced by HuGENet) will help to ensure that future studies are well-designed and build on current understanding, rather than simply adding to the growing bank of potential associations.

Evaluation of Salmonella-lytic properties of bacteriophages isolated from commercial broiler houses.

Because of recent interest in bacteriophage therapy in poultry, information regarding the interaction of bacteriophages and potential host bacteria in the environment should be collected. The present studies were initiated with a rather typical commercial broiler integrator within the south-central United States to examine environmental Salmonella levels in two broiler complexes, attempt to isolate Salmonella-lytic bacteriophages, and elucidate a possible reason for differing apparent Salmonella prevalence. Significantly (P < 0.05) less Salmonella was isolated from houses in complex 1 (15/44 [34%] Salmonella-positive drag swabs) as compared to houses in complex 2 (22/24 [92%]). A total of seven Salmonella-lytic bacteriophages were isolated from Salmonella-positive environments, and two bacteriophages were isolated from a single Salmonella-negative house. During the initial bacteriophage isolation, individual bacteriophages did not replicate in the Salmonella host isolated from the same environment, and lysis of additional Salmonella hosts relied on high numbers of bacteriophage to be present. This suggests that the presence of these bacteriophages in the environment of a commercial broiler house had little to no effect on the presence of Salmonella. This study highlights the need to find additional bacteriophage sources, more effective isolation methods, and more innovative approaches to using bacteriophages to treat enteric disease.

Evaluation of a Lactobacillus-based probiotic culture for the reduction of Salmonella enteritidis in neonatal broiler chicks.

We evaluated the effect of a Lactobacillus-based probiotic culture (FM-B11) for reduction of Salmonella Enteritidis in neonatal broiler chicks. In all experiments, chicks were challenged with approximately 10(4) cfu of Salmonella Enteritidis upon arrival at our laboratory, and the treatments were administered 1 h postchallenge. Cecal tonsil samples were obtained 24 h posttreatment and enriched for Salmonella Enteritidis recovery. The first experiment compared the effects of oral administration of doses of 10(4), 10(6), and 10(8) cfu/chick. In this experiment, doses of 10(6) and 10(8) both significantly reduced Salmonella Enteritidis recovery compared with controls (15 vs. 85% Salmonella Enteritidis positive), but 10(4) cfu did not significantly reduce Salmonella Enteritidis recovery. The second experiment compared the efficacy of oral administration of the live probiotic culture, with or without supernatant removed, to inactivated cultures or supernatant alone. Live probiotic organisms, with or without supernatant, significantly reduced Salmonella Enteritidis in this experiment, but inactivated or cell-free treatments did not reduce Salmonella Enteritidis. In the final 2 experiments, differing doses of probiotic culture were administered on the vent lips, where the treatment was taken into the lower gastrointestinal tract via cloacal drinking. Concentrations of probiotic culture from 10(2) to 10(7) cfu/chick significantly reduced Salmonella Enteritidis, and there was no difference in Salmonella Enteritidis recovery between treatment concentrations. These data suggest that this Lactobacillus-based probiotic culture may be efficacious for reduction of Salmonella Enteritidis in neonatal chicks.

Temporal effects of lactic acid bacteria probiotic culture on Salmonella in neonatal broilers.

We evaluated the ability of a commercially available lactic acid bacteria-based probiotic culture (LAB) to reduce Salmonella Enteritidis or Salmonella Typhimurium in day-of-hatch broiler chicks. In these experiments, chicks were challenged with Salmonella Enteritidis or Salmonella Typhimurium and treated with LAB 1-h postchallenge. Following treatment, cecal tonsils and ceca were aseptically collected for Salmonella Enteritidis or Salmonella Typhimurium enrichment or Salmonella Enteritidis enumeration, respectively. In experiments 1 to 3, LAB significantly reduced the incidence of Salmonella Enteritidis (60 to 70% reduction) or Salmonella Typhimurium (89 to 95% reduction) recovered from the cecal tonsils of day-old broiler chicks 24 h following treatment as compared with controls (P < 0.05). Additionally, administration of LAB caused a >2.9 log(10) reduction of total cecal Salmonella Enteritidis recovered 24 h following treatment as compared with controls (P < 0.05). In experiments 4 to 7, upon sample enrichment LAB significantly reduced the recovery of Salmonella Enteritidis from the cecal tonsils at 24 h, but not 6 or 12 h posttreatment (P < 0.05). However, in experiments 6 and 7, when total cecal Salmonella Enteritidis recovery was enumerated, a significant treatment-associated reduction was observed 12 h posttreatment, although in cecal tonsil samples there was no difference in Salmonella Enteritidis incidence at 12 h (P < 0.05). In these studies, LAB treatment significantly reduced recovery of Salmonella in day-of-hatch broilers.

Ability of bacteriophages isolated from different sources to reduce Salmonella enterica serovar enteritidis in vitro and in vivo.

Salmonella enterica serovar Enteritidis-lysing bacteriophages isolated from poultry or human sewage sources were used to reduce Salmonella Enteritidis in vitro and in experimentally infected chicks. Cocktails of 4 different bacteriophages obtained from commercial broiler houses (CB4Ø) and 45 bacteriophages from a municipal wastewater treatment plant (WT45Ø) were evaluated. In experiment 1, an in vitro crop assay was conducted with selected bacteriophage concentrations (10(5) to 10(9) pfu/mL) to determine ability to reduce Salmonella Enteritidis in the simulated crop environment. Following 2 h at 37 degrees C, CB4Ø or WT45Ø reduced Salmonella Enteritidis recovery by 1.5 or 5 log, respectively, as compared with control. However, CB4Ø did not affect total SE recovery after 6 h, whereas WT45Ø resulted in up to a 6-log reduction of Salmonella Enteritidis. In experiment 2, day-of-hatch chicks were challenged orally with 3 x 10(3) cfu/chick Salmonella Enteritidis and treated cloacally with 1 x 10(9) WT45Ø pfu/chick 1 h postchallenge. One hour later, chicks were treated or not with a commercially available probiotic (Floramax-B11). Both treatments significantly reduced Salmonella Enteritidis recovery from cecal tonsils at 24 h following vent lip application as compared with controls, but no additive effect was observed with the combination of bacteriophages and probiotic. In experiment 3, day-of-hatch chicks were challenged orally with 9 x 10(3) cfu/chick Salmonella Enteritidis and treated via oral gavage with 1 x 10(8) CB4Ø pfu/chick, 1.2 x 10(8) WT45Ø pfu/chick, or a combination of both, 1 h postchallenge. All treatments significantly reduced Salmonella Enteritidis recovered from cecal tonsils at 24 h as compared with untreated controls, but no significant differences were observed at 48 h following treatment. These data suggest that some bacteriophages can be efficacious in reducing SE colonization in poultry during a short period, but with the bacteriophages and methods presently tested, persistent reductions were not observed.

Effect of probiotic treatment in broiler chicks on intestinal macrophage numbers and phagocytosis of Salmonella enteritidis by abdominal exudate cells.

Previous data have indicated that a Lactobacillus-based probiotic culture (FM-B11) is efficacious in reducing Salmonella Enteritidis colonization within 24 h when administered within 1 h of challenge. We hypothesized that the innate immune system, specifically macrophages, may play a role in the observed reduction of Salmonella Enteritidis colonization with probiotic treatment. Day-of-hatch chicks were challenged with Salmonella Enteritidis and then treated with the probiotic culture 1 h later. Three other treatment groups were not treated (negative control), challenged only, or treated with probiotic only. In all experiments, probiotic treatment on the day of hatch reduced (P < 0.05) cecal Salmonella Enteritidis recovery as compared with the control treatment. In experiments 1 and 2, immunohistochemistry was used to evaluate the presence of macrophages (KUL01+) in the ileum and cecum of 7 to 10 chicks per group at 24 h posttreatment. In experiment 1, the number of macrophages observed per 10,000 microm(2) in the ileum of Salmonella Enteritidis-challenged chicks was higher (P < 0.05) than that of nonchallenged chicks (4.87 +/- 0.31 vs. 3.05 +/- 0.19). In the cecum, there were more (P < 0.05) macrophages per 10,000 microm(2) in chicks receiving probiotic treatment without challenge than in negative control chicks (5.32 +/- 0.41 vs. 3.66 +/- 0.35). However, in experiment 2 we found no differences among treatments in the numbers of macrophages for both the ileum and cecum. Experiments 3 and 4 were performed to evaluate the ability of Sephadex-elicited abdominal exudate cells (AEC) from chicks to phagocytose Salmonella Enteritidis in vitro. Abdominal exudate cells were isolated from the abdominal cavity, maintained in tissue culture plates overnight, and then assayed for phagocytic activity by coincubating with Salmonella Enteritidis. In experiment 3, more (P < 0.05) Salmonella Enteritidis was recovered from AEC derived from probiotic-treated chicks than in any other treatment. However, in experiment 4, all treatments resulted in similar levels of elicited AEC, and phagocytosis of Salmonella Enteritidis was at low levels in all groups. Although not conclusive, the modest differences detected in experiments 1 and 3, and the fact that those differences were not repeatedly detectable, suggest that these macrophage-related changes were not solely responsible for the reductions of Salmonella Enteritidis following probiotic treatment.

The quality of randomised controlled trials involving surgery from the hand to the elbow: a critical analysis of the literature.

AIMS: Our purpose was to determine the quality of current randomised controlled trials (RCTs) in hand surgery using standardised metrics. MATERIALS AND METHODS: Based on five-year mean impact factors, we selected the six journals that routinely publish studies of upper extremity surgery. Using a journal-specific search query, 62 RCTs met our inclusion criteria. Then three blinded reviewers used the Jadad and revised Coleman Methodology Score (RCMS) to assess the quality of the manuscripts. RESULTS: Based on the Jadad scale, 28 studies were of high quality and 34 were of low quality. Methodological deficiencies in poorly scoring trials included the absence of rate of enrolment, no power analysis, no description of withdrawal or dropout, and a failure to use validated outcomes assessments with an independent investigator. CONCLUSION: A large number of RCTs in hand, wrist, and elbow surgery were of suboptimal quality when judged against the RCMS and Jadad scales. Even with a high level of evidence, study design and execution of RCTs should be critically assessed. Methodological deficiencies may introduce bias and lead to statistically underpowered studies. Cite this article: Bone Joint J 2017;99-B:94-9.

Control of carbapenemase-producing Enterobacteriaceae outbreaks in acute settings: an evidence review.

BACKGROUND: In recent years, infections with carbapenemase-producing Enterobacteriaceae (CPE) have been increasing globally and present a major public health challenge. AIM: To review the international literature: (i) to describe CPE outbreaks in acute hospital settings globally; and (ii) to identify the control measures used during these outbreaks and report on their effectiveness. METHODS: A systematic search of MEDLINE and EMBASE databases, abstract lists for key conferences and reference lists of key reviews was undertaken, and information on unpublished outbreaks was sought for 2000-2015. Where relevant, risk of bias was assessed using the Newcastle-Ottawa scale. A narrative synthesis of the evidence was conducted. FINDINGS: Ninety-eight outbreaks were eligible. These occurred worldwide, with 53 reports from Europe. The number of cases (CPE infection or colonization) involved in outbreaks varied widely, from two to 803. In the vast majority of outbreaks, multi-component infection control measures were used, commonly including: patient screening; contact precautions (e.g. gowns, gloves); handwashing interventions; staff education or monitoring; enhanced environmental cleaning/decontamination; cohorting of patients and/or staff; and patient isolation. Seven studies were identified as providing the best-available evidence on the effectiveness of control measures. These demonstrated that CPE outbreaks can be controlled successfully using a range of appropriate, commonly used, infection control measures. However, risk of bias was considered relatively high for these studies. CONCLUSION: The findings indicate that CPE outbreaks can be controlled using combinations of existing measures. However, the quality of the evidence base is weak and further high-quality research is needed, particularly on the effectiveness of individual infection control measures.

Cognitive-behavioural interventions for children who have been sexually abused.

BACKGROUND: Despite differences in perceptions of what constitutes child sexual abuse there is a general consensus amongst clinicians and researchers that this is a substantial social problem which affects large numbers of children and young people worldwide. The effects of sexual abuse manifest themselves in a wide range of symptoms, including fear, anxiety, post-traumatic stress disorder and behaviour problems such as externalising or internalising, or inappropriate sexual behaviours. Child sexual abuse is associated with increased risk of psychological problems in adulthood. Knowing what is most likely to benefit children already traumatised by these events is important. OBJECTIVES: The aim of this review was to assess the efficacy of cognitive-behavioural approaches (CBT) in addressing the immediate and longer-term sequelae on children who have been sexually abused. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2005), MEDLINE (1966-November 2005); EMBASE (1980-November 2005); CINAHL (1982-November 2005), PsycINFO (1897-November 2005); LILACS (1982-November 2005); SIGLE (1980 to November 2005) and the register of the Cochrane Developmental, Psychosocial and Learning Problems Group (November 2005) were searched. SELECTION CRITERIA: Included studies were randomised or quasi-randomised controlled trials investigating the efficacy of cognitive behavioural therapy on children and adolescents up to age 18 years who had experienced sexual abuse. DATA COLLECTION AND ANALYSIS: Titles and abstracts identified in the search were independently assessed for eligibility by two reviewers (GM and PR). Data were extracted and entered into REVMAN (JH and GM), and synthesised and presented in both written and graphical form (forest plots). MAIN RESULTS: Ten trials, including 847 participants, were included in this review. Data suggest that CBT may have a positive impact on the sequelae of child sexual abuse, but most results were statistically non-significant. AUTHORS' CONCLUSIONS: The review confirms CBT's potential as a means of addressing the adverse consequences of child sexual abuse, but highlights the tenuousness of the evidence base and the need for more carefully conducted and better reported trials.