Telehealth versus face-to-face delivery of speech language pathology services: A systematic review and meta-analysis.

BACKGROUND: There is an increasing demand for the provision of speech language pathology (SLP) services via telehealth. Therefore, we systematically reviewed randomized controlled trials comparing telehealth to face-to-face provision of SLP services. METHODS: We searched Medline, Embase and Cochrane, clinical trial registries, and conducted a citation analysis to identify trials. We included randomized trials comparing similar care delivered live via telehealth (phone or video), to face-to-face. Primary outcomes included: % syllables stuttered (%SS) (for individuals who stutter); change in sound pressure levels monologue (for individuals with Parkinson's disease); and key function scores (for other areas). Where data were sufficient, mean differences were calculated. RESULTS: Nine randomized controlled trials were included; eight evaluated video and one evaluated phone telehealth. Risk of bias was generally low or unclear, excepting blinding. There were no significant differences at any time-point up to 18 months for %SS (mean difference, MD 0.1, 95% CI -0.4 to 0.6, p = 0.70). For people with Parkinson's disease, there was no difference between groups in change in sound pressure levels (monologue) (MD 0.6, 95% CI -1.2 to 2.5, p = 0.49). Four trials investigated interventions for speech sound disorder, voice disorder and post-stroke dysphagia and aphasia; they found no differences between telehealth service delivery and face-to-face delivery. CONCLUSIONS: Evidence suggests that the telehealth provision of SLP services may be a viable alternative to their provision face-to-face, particularly to people who stutter and people with Parkinson's disease. The key limitation is the small number of randomized controlled trials, as well as evidence on the quality of life, well-being and satisfaction and economic outcomes.

A Case of Persistent Intra-Abdominal Stenotrophomonas maltophilia Infection Despite Bacteriophage Therapy.

Multidrug resistant infections are a challenge in the health care setting and a cause of patient morbidity and mortality. Bacteriophages (phages) are viruses that target and kill bacteria and have been used in patients to treat bacterial infections. We present a case of disseminated Stenotrophomonas maltophilia infection, with pulmonary, intra-abdominal and bloodstream involvement. The patient was treated with a combination of antibiotics and personalized phage therapy, administered daily for 12 days both intravenously as well as via intra-abdominal drains. Phage therapy was well-tolerated, the patient cleared S. maltophilia from their bloodstream and their intra-abdominal abscesses were stable or decreased in size. However, the intra-abdominal fluid cultures remained positive for S. maltophilia. Unfortunately, the patient passed away 2 months after completion of phage therapy due to multiorgan failure. These data highlight the difficulty of treating critically ill patients and clearing complex, biofilm mediated infections, even with phages. More information is needed regarding the optimal treatment protocols for phage therapy in complex multifocal infections.

The effect of carbapenem-resistant versus carbapenem-susceptible Enterobacterales infections on patient outcomes at an academic medical center.

Objective: We sought to compare patient outcomes between carbapenem-resistant Enterobacterales (CRE) and carbapenem-susceptible Enterobacterales (CSE) infections at our academic medical center. Design: We conducted a retrospective cohort study of adult patients with a positive culture of E. coli, E. cloacae, K. aerogenes, K. oxytoca, and/or K. pneumoniae admitted at UK HealthCare (January 1, 2010-December 31, 2019). Based on the type of pathogen on the date of the first culture (index date), patients were included in the CRE (i.e., exposed) group, or the CSE (comparator) group. Exclusion criteria were age < 18 years old, pregnancy, endocarditis, osteomyelitis, necrotizing fasciitis, or cystic fibrosis. We evaluated the impact of CRE vs CSE on a composite outcome of 30-day of all-cause mortality or discharge to hospice using Kaplan-Meier survival curves and Cox proportional hazard regression with inverse probability of treatment weights (IPTW). Results: Of 17,839 hospitalized patients, 128 and 6,953 patients were included in the CRE and CSE groups, respectively. Baseline differences existed in sex-assigned-at-birth, admission source, time-to-index culture, and infection type/severity. Most CRE index cultures observed (76%) only exhibited resistance to ertapenem. IPTW-adjusted HR [95% CI] of composite outcome was 0.99 [0.65, 1.51] after 30 days. Follow-up analysis in patients with carbapenem-non-susceptible Enterobacteralesbloodstream infections on index yielded an HR of 1.38 [0.85, 2.24]. Conclusions: Risk of composite outcome was not estimated to differ between patients with CRE and CSE in the overall analysis. Although follow-up analysis identified an increased risk, we cannot statistically distinguish this from a null effect.

Minimal intervention (removable splint or bandage) for the management of distal forearm fractures in children and adolescents: A scoping review.

INTRODUCTION: Distal forearm fractures are common in children and adolescents with a spectrum of severity. There are fracture patterns that are suitable for minimal interventions, such as a splint or bandage. The objective of this review was to identify which types of paediatric distal forearm fractures can be safely and effectively managed with a removable splint or bandage. MATERIALS AND METHODS: A scoping review was performed. Databases searched were PubMed, Embase, The Cochrane Library and CINAHL; two trial registries were also searched. All primary study designs with children <18 years of age with a distal forearm fracture that was managed in either a splint or bandage were included. Quality of evidence was determined using the GRADE tool. RESULTS: Twenty-two eligible articles were included from 20 unique studies: 12 randomised controlled trials, seven cohort studies and a case report. Twelve studies focused solely on buckle/torus fractures, with remaining studies including other fracture types, such as incomplete ('greenstick'), complete ('transverse'), or physeal (Salter-Harris). Twelve studies reported that participants with either bandage or splint had appropriate reduction in pain and recovery of function at completion of follow-up for all fracture types. All 20 studies reported minimal adverse events related to fracture management. One study reported worsening angulation with bandage immobilisation for complete fractures in two participants, which required manipulation under anaesthesia. DISCUSSION: There is high quality evidence to support the safety and effectiveness of a splint or bandage for treatment of distal radius buckle and non-displaced incomplete fractures. Several studies supported the use of minimal interventions for various distal radius cortical breach fracture types, with good outcomes, but were limited by heterogeneity (methodology, interventions, outcome measures, reference standard) and potential bias. CONCLUSIONS: Included studies confirmed the inherent stability of buckle fractures. The current literature gap to support minimal interventions for a range of other paediatric distal forearm fracture types was highlighted. High-quality evidence with well-designed, large, multicentre randomised control trials in defined age groups is required to identify which paediatric distal forearm fractures can be safely and effectively managed with either a removable splint or bandage.

Causally interpretable meta-analysis combining aggregate and individual participant data.

Recent work in causally-interpretable meta-analysis (CIMA) has bridged the gap between traditional meta-analysis and causal inference. While traditional meta-analysis results generally do not apply to any well-defined population, CIMA approaches specify a target population to which meta-analytic treatment effect estimates are transported. While theoretically attractive, these approaches currently have some practical limitations. Most assume that all studies in the meta-analysis have individual participant data (IPD), which is rare in practice because most trials share only aggregate data. We propose a method to perform CIMA using a combination of aggregate data and IPD. This method borrows information from studies with IPD to augment the aggregate data and create aggregate-matched synthetic IPD (AMSIPD), which can be used readily in the existing CIMA framework. By allowing use of both aggregate data and IPD, the method opens CIMA to more applications and can avoid biases arising from using only studies with IPD. We present a case study and simulations showing the AMSIPD approach is promising and merits further investigation as an advancement of CIMA.

Comparing the activity of broad-spectrum beta-lactams in combination with aminoglycosides against VIM-producing Enterobacteriaceae.

Metallo-beta-lactamase (MBL)-producing carbapenem-resistant Enterobacteriaceae (CRE) infections continue to pose a serious threat to healthcare. Due to their unique active site, MBLs evade the activity of many novel beta-lactam/beta-lactamase inhibitor combinations, which have been specifically targeted toward those carbapenemases with serine active sites. Furthermore, resistance to most, if not all, other clinically relevant antimicrobial classes leaves few reliable therapeutic options. Combination therapy has thus played a vital role in the treatment of MBL-producing CRE infections. In this study, we utilized the static time-kill assay to investigate clinically relevant concentrations of cefepime, piperacillin-tazobactam, and meropenem alone and in combination with either amikacin or the novel plazomicin to determine if combinations of routinely used beta-lactam therapy with an aminoglycoside would achieve bactericidal activity against eight clinically isolated Verona integron-encoded MBL (VIM)-producing CRE. Furthermore, we compared this activity to the combination of aztreonam/avibactam, which has shown potent activity against MBL-producing CRE. Both aztreonam/avibactam and meropenem with either aminoglycoside were rapidly bactericidal within 4 hours and remained bactericidal through 24 hours against all isolates with few exceptions. Combinations including cefepime and piperacillin-tazobactam were also rapidly bactericidal, but activity after 24 hours was inconsistent depending upon the partner aminoglycoside and isolate. Further investigation is warranted to elucidate optimal antibiotic exposures against MBL-producing CRE, including novel agents in the pipeline.IMPORTANCECarbapenem-resistant Enterobacterales (CRE) are one of the most pressing antimicrobial-resistant threats at present. In addition to exhibiting resistance to many, if not all, commonly used antimicrobial agents, CRE achieves these resistant phenotypes through a variety of mechanisms, each of which can uniquely affect available treatment options. The present study is an in vitro investigation of several Verona integron-encoded metallo-beta-lactamase (VIM)-producing CRE isolated from patients at our academic medical center. Because metallo-beta-lactamases (MBLs) are inherently resistant to many of the novel treatments designed to treat CRE due to their different active site composition, we tested several antimicrobial combinations containing routinely utilized broad-spectrum beta-lactams and aminoglycosides. Our results further our understanding of combination therapy options against VIM-producing CRE, including with non-carbapenem-beta-lactams cefepime and piperacillin. By optimizing combinations of existing antimicrobial agents, we hope to expand the available armamentarium against these resistant pathogens.

Automation of duplicate record detection for systematic reviews: Deduplicator.

BACKGROUND: To describe the algorithm and investigate the efficacy of a novel systematic review automation tool "the Deduplicator" to remove duplicate records from a multi-database systematic review search. METHODS: We constructed and tested the efficacy of the Deduplicator tool by using 10 previous Cochrane systematic review search results to compare the Deduplicator's 'balanced' algorithm to a semi-manual EndNote method. Two researchers each performed deduplication on the 10 libraries of search results. For five of those libraries, one researcher used the Deduplicator, while the other performed semi-manual deduplication with EndNote. They then switched methods for the remaining five libraries. In addition to this analysis, comparison between the three different Deduplicator algorithms ('balanced', 'focused' and 'relaxed') was performed on two datasets of previously deduplicated search results. RESULTS: Before deduplication, the mean library size for the 10 systematic reviews was 1962 records. When using the Deduplicator, the mean time to deduplicate was 5 min per 1000 records compared to 15 min with EndNote. The mean error rate with Deduplicator was 1.8 errors per 1000 records in comparison to 3.1 with EndNote. Evaluation of the different Deduplicator algorithms found that the 'balanced' algorithm had the highest mean F1 score of 0.9647. The 'focused' algorithm had the highest mean accuracy of 0.9798 and the highest recall of 0.9757. The 'relaxed' algorithm had the highest mean precision of 0.9896. CONCLUSIONS: This demonstrates that using the Deduplicator for duplicate record detection reduces the time taken to deduplicate, while maintaining or improving accuracy compared to using a semi-manual EndNote method. However, further research should be performed comparing more deduplication methods to establish relative performance of the Deduplicator against other deduplication methods.

Cranberry Juice, Cranberry Tablets, or Liquid Therapies for Urinary Tract Infection: A Systematic Review and Network Meta-analysis.

BACKGROUND AND OBJECTIVE: With over 50% of women suffering from at least one episode of urinary tract infection (UTI) each year and an increasing prevalence of antimicrobial resistance, efforts need to be made to clearly identify the evidence supporting potential non-drug interventions. This study aims to compare the effects of cranberry juice, cranberry tablets, and increased liquids for the management of UTIs. METHODS: PubMed, Embase, and Cochrane CENTRAL were searched for randomised controlled trials. The primary outcome was the number of UTIs, and the secondary outcomes were UTI symptoms and antimicrobial consumption. A risk of bias assessment was performed using the Cochrane risk of bias tool, and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. KEY FINDINGS AND LIMITATIONS: A total of 20 trials (3091 participants) were included, with 18 studies highlighting a 54% lower rate of UTIs with cranberry juice consumption than no treatment and a 27% lower rate than placebo liquid. Cranberry juice also resulted in a 49% lower rate of antibiotic use than placebo liquid and a 59% lower rate than no treatment, based on a network meta-analysis of six studies. The use of cranberry compounds also reduced the prevalence of symptoms associated with UTIs. CONCLUSIONS AND CLINICAL IMPLICATIONS: With moderate to low certainty, the evidence supports the use of cranberry juice for the prevention of UTIs. While increased liquids reduce the rate of UTIs compared with no treatment, cranberry in liquid form provides even better clinical outcomes in terms of reduction in UTIs and antibiotic use and should be considered for the management of UTIs. PATIENT SUMMARY: With the increasing prevalence of antimicrobial-resistant UTIs, alternate non-drug treatment options for its management are required. Available evidence supports the use of cranberry compounds and increases in fluid intake for managing UTIs.

Accelerating evidence synthesis for safety assessment through ClinicalTrials.gov platform: a feasibility study.

BACKGROUND: Standard systematic review can be labor-intensive and time-consuming meaning that it can be difficult to provide timely evidence when there is an urgent public health emergency such as a pandemic. The ClinicalTrials.gov provides a promising way to accelerate evidence production. METHODS: We conducted a search on PubMed to gather systematic reviews containing a minimum of 5 studies focused on safety aspects derived from randomized controlled trials (RCTs) of pharmacological interventions, aiming to establish a real-world dataset. The registration information of each trial from eligible reviews was further collected and verified. The meta-analytic data were then re-analyzed by using 1) the full meta-analytic data with all trials and 2) emulated rapid data with trials that had been registered and posted results on ClinicalTrials.gov, under the same synthesis methods. The effect estimates of the full meta-analysis and rapid meta-analysis were then compared. RESULTS: The real-world dataset comprises 558 meta-analyses. Among them, 56 (10.0%) meta-analyses included RCTs that were not registered in ClinicalTrials.gov. For the remaining 502 meta-analyses, the median percentage of RCTs registered within each meta-analysis is 70.1% (interquartile range: 33.3% to 88.9%). Under a 20% bias threshold, rapid meta-analyses conducted through ClinicalTrials.gov achieved accurate point estimates ranging from 77.4% (using the MH model) to 83.1% (using the GLMM model); 91.0% to 95.3% of these analyses accurately predicted the direction of effects. CONCLUSIONS: Utilizing the ClinicalTrials.gov platform for safety assessment with a minimum of 5 RCTs holds significant potential for accelerating evidence synthesis to support urgent decision-making.

The impact of telehealth care on escalation to emergency care: A systematic review and meta-analysis.

OBJECTIVE: We compared the impact of accessing healthcare (1) by telehealth (via telephone or video) vs face-to-face; and (2) by telephone vs video telehealth care, on escalation to emergency care. METHODS: We searched Medline, Embase and Cochrane CENTRAL to 24 July 2023; and conducted a citation analysis on 19 September 2023. We included randomised controlled trials. Risk of bias was assessed using Cochrane Tool 2. We calculated risk ratios for dichotomous outcomes and standardised mean difference for continuous outcomes. RESULTS: Ten trials compared telehealth (five telephone, four video, one both) to face-to-face care. Six were overall low, three some concerns and one high risk of bias. There were no differences between telehealth and face-to-face for visits to the emergency department (RR 1.07, 95% CI 0.89 to 1.29), hospitalisations up to 12 months (RR 0.89, 95% CI 0.56 to 1.41), deaths or other adverse events. Costs of care were similar, as were patient satisfaction scores.Six trials compared telephone to video telehealth: three were overall low, two some concerns, and one high risk of bias. There were no differences between telephone and video for visits to the emergency department (RR 0.67, 95% CI 0.41 to 1.12), hospitalisations (RR 1.04, 95% CI 0.73 to 1.48), deaths, other adverse events, costs, or patient satisfaction. Healthcare provider satisfaction was high. CONCLUSIONS: Telehealth care - delivered by telephone or by video - may be an appropriate alternative to face-to-face provision of care, as it does not increase the likelihood of escalation of care to the emergency department for patients in primary care, hospital outpatients, post-discharge patients or residents in aged care.

Vaccines against extraintestinal pathogenic Escherichia coli (ExPEC): progress and challenges.

The emergence of antimicrobial resistance (AMR) is a principal global health crisis projected to cause 10 million deaths annually worldwide by 2050. While the Gram-negative bacteria Escherichia coli is commonly found as a commensal microbe in the human gut, some strains are dangerously pathogenic, contributing to the highest AMR-associated mortality. Strains of E. coli that can translocate from the gastrointestinal tract to distal sites, called extraintestinal E. coli (ExPEC), are particularly problematic and predominantly afflict women, the elderly, and immunocompromised populations. Despite nearly 40 years of clinical trials, there is still no vaccine against ExPEC. One reason for this is the remarkable diversity in the ExPEC pangenome across pathotypes, clades, and strains, with hundreds of genes associated with pathogenesis including toxins, adhesins, and nutrient acquisition systems. Further, ExPEC is intimately associated with human mucosal surfaces and has evolved creative strategies to avoid the immune system. This review summarizes previous and ongoing preclinical and clinical ExPEC vaccine research efforts to help identify key gaps in knowledge and remaining challenges.

Effectiveness and predictors of weight loss response to phentermine plus lifestyle modifications among youth in a paediatric weight management clinical setting.

BACKGROUND: Anti-obesity medications (AOMs) are promising lifestyle modification (LSM) adjuncts for obesity treatment, and phentermine is commonly prescribed in paediatric weight management clinics. Determining 'real-world' AOM effectiveness and characteristics predicting response is important. OBJECTIVES: We sought to describe phentermine plus LSM effectiveness and identify baseline characteristics predicting response. METHODS: This was a retrospective cohort study among youth seen in a US academic-based weight management clinic from 2012 to 2020. Baseline characteristics (e.g., body mass index (BMI), liver transaminases, eating-related behaviours) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, %BMI change, weight) were determined through electronic health records and intake surveys. RESULTS: Among 91 youth prescribed phentermine plus LSM over 8 years (mean %BMIp95 150%), %BMIp95 was statistically significantly reduced at 1.5, 3, 6 and 12 months (peak reduction 10.9 percentage points at 6 months; p < 0.001). Considering multiple comparisons, the presence of baseline elevated alanine aminotransferase was associated with statistically significant smaller 1.5-month %BMIp95 reductions (p = 0.001) and higher food responsiveness with smaller 3- (p = 0.001) and 6-month (p < 0.001) reductions. CONCLUSIONS: Phentermine plus LSM reduced %BMIp95 among youth in a weight management clinic, and baseline characteristics may help determine those more or less likely to respond. Prospective studies are needed to further characterize effectiveness and confirm response predictors.

Management of unscheduled bleeding on HRT: A joint guideline on behalf of the British Menopause Society, Royal College Obstetricians and Gynaecologists, British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Faculty of Sexual and Reproductive Health, Royal College of General Practitioners and Getting it Right First Time.

Unscheduled bleeding on hormone replacement therapy (HRT) can affect up to 40% of users. In parallel with the increase in HRT prescribing in the UK, there has been an associated increase in referrals to the urgent suspicion of cancer pathway for unscheduled bleeding. On behalf of the British Menopause Society (BMS) an expert review panel was established, including primary and secondary care clinicians with expertise in the management of menopause, with representatives from key related organisations, including the Royal College of Obstetricians & Gynaecologists, the British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Royal College of General Practitioners and Faculty of Sexual and Reproductive Health, and service development partners from NHS England and GIRFT (Getting it Right First Time). For each topic, a focused literature review was completed to develop evidence led recommendations, where available, which were ratified by consensus review within the panel and by guideline groups.

Clinical effectiveness and predictors of response to topiramate plus lifestyle modification in youth with obesity seen in a weight management clinical setting.

Introduction: Obesity affects approximately 20% of U.S. youth. Anti-obesity medications (AOMs) are promising lifestyle modification adjuncts for obesity treatment, and topiramate is commonly prescribed in pediatric weight management clinics. It is important to determine "real-world" effectiveness of AOMs and, given shifts towards personalized approaches, characteristics potentially predicting better or worse response. We therefore sought to describe clinical effectiveness from topiramate plus lifestyle modification, and to determine if baseline phenotypic characteristics are associated with better or worse response. Methods: We performed a retrospective cohort study (2012-2020) among youth (<18 years old) followed in a U.S. academic-based weight management clinic. Baseline characteristics (i.e., body mass index (BMI), liver function tests, eating-related behaviors) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, percent %BMI change, weight) were determined through review of electronic health records and clinic intake survey data. Results: Among 282 youth prescribed topiramate plus lifestyle modifications (mean baseline age 12.7 years, %BMIp95 144%), %BMIp95 and percent BMI change were statistically significantly reduced at each time point (1.5-, 3-, 6-, and 12-month %BMIp95 reductions: -2.2, -3.9, -6.6, and -9.3 percentage points, respectively; percent BMI reduction: -1.2%, -1.9%, -3.2%, and -3.4%, respectively; all p<0.01). Considering multiple comparisons, no baseline characteristics statistically significantly predicted response at any time point. Conclusions: We found that topiramate plus lifestyle modification reduced %BMIp95 and BMI among youth in a weight management clinical setting, and that no baseline characteristics evaluated were associated with response. These results should be considered preliminary given the observational nature of this study, and prospective studies are needed to further characterize clinical effectiveness and identify and confirm potential predictors of response.

Anti-inflammatories as adjunct treatment for cellulitis: a systematic review and meta-analysis.

OBJECTIVES: Existing guideline recommendations suggest considering corticosteroids for adjunct treatment of cellulitis, but this is based on a single trial with low certainty of evidence. The objective was to determine if anti-inflammatory medication (non-steroidal anti-inflammatory drugs [NSAIDs], corticosteroids) as adjunct cellulitis treatment improves clinical response and cure. METHODS: Systematic review and meta-analysis including randomized controlled trials of patients with cellulitis treated with antibiotics irrespective of age, gender, severity and setting, and an intervention of anti-inflammatories (NSAIDs or corticosteroids) vs. placebo or no intervention. Medline (PubMed), Embase (via Elsevier), and Cochrane CENTRAL were searched from inception to August 1, 2023. Data extraction was conducted independently in pairs. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. Data were pooled using a random effects model. Primary outcomes are time to clinical response and cure. RESULTS: Five studies (n = 331) were included, all were adults. Three trials reported time to clinical response. There was a benefit with use of an oral NSAID as adjunct therapy at day 3 (risk ratio 1.81, 95%CI 1.42-2.31, I2 = 0%). There was no difference between groups at day 5 (risk ratio 1.19, 95%CI 0.62-2.26), although heterogeneity was high (I2 = 96%). Clinical cure was reported by three trials, and there was no difference between groups at all timepoints up to 22 days. Statistical heterogeneity was moderate to low. Adverse events (N = 3 trials) were infrequent. CONCLUSIONS: For patients with cellulitis, the best available data suggest that oral nonsteroidal anti-inflammatory drugs (NSAIDs) as adjunct therapy to antibiotics may lead to improved early clinical response, although this is not sustained beyond 4 days. There is insufficient data to comment on the role of corticosteroids for clinical response. These results must be interpreted with caution due to the small number of included studies. REGISTRATION: Open Science Framework:   https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .

RéSUMé: OBJECTIFS: Les recommandations existantes suggèrent d'envisager des corticostéroïdes pour le traitement complémentaire de la cellulite, mais cela est basé sur un seul essai avec une faible certitude des preuves. L'objectif était de déterminer si les anti-inflammatoires (anti-inflammatoires non stéroïdiens [AINS], corticostéroïdes) comme traitement d'appoint de la cellulite améliorent la réponse clinique et la guérison. MéTHODES: Revue systématique et méta-analyse comprenant des essais contrôlés randomisés de patients atteints de cellulite traités avec des antibiotiques, indépendamment de l'âge, du sexe, de la gravité et du contexte, et une intervention d'anti-inflammatoires (AINS ou corticostéroïdes) contre placebo ou sans intervention. Medline (PubMed), Embase (via Elsevier) et Cochrane CENTRAL ont été recherchés de la création au 1er août 2023. L'extraction des données a été effectuée indépendamment par paires. Le risque de biais a été évalué à l'aide de l'outil Cochrane sur le risque de biais 2. Les données ont été regroupées à l'aide d'un modèle à effets aléatoires. Les principaux résultats sont le temps de réponse clinique et de guérison. RéSULTATS: Cinq études (n = 331) ont été incluses, toutes des études adultes. Trois essais ont indiqué le délai de réponse clinique. Il y avait un avantage avec l'utilisation d'un AINS par voie orale comme traitement d'appoint au jour 3 (risque ratio 1,81, 95%CI 1,42 à 2,31, I2 = 0%). Il n'y avait pas de différence entre les groupes au jour 5 (rapport de risque 1,19, IC à 95% 0,62 à 2,26), bien que l'hétérogénéité était élevée (I2 = 96 %). La guérison clinique a été rapportée par trois essais, et il n'y avait aucune différence entre les groupes à tous les points de temps jusqu'à 22 jours. L'hétérogénéité statistique était modérée à faible. Les événements indésirables (N = 3 essais) étaient peu fréquents. CONCLUSIONS: Pour les patients atteints de cellulite, les meilleures données disponibles suggèrent que les anti-inflammatoires non stéroïdiens oraux (AINS) comme traitement d'appoint aux antibiotiques peuvent entraîner une amélioration de la réponse clinique précoce, bien que cela ne soit pas soutenu au-delà de quatre jours. Les données sont insuffisantes pour commenter le rôle des corticostéroïdes dans la réponse clinique. Ces résultats doivent être interprétés avec prudence en raison du petit nombre d'études incluses. ENREGISTREMENT: Cadre de la science ouverte:   https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .

Performance of ePlex® blood culture identification panels in clinical isolates and characterization of antimicrobial stewardship opportunities.

We assessed the performance of GenMark's ePlex® Blood Culture Identification (BCID) Panels for overall agreement of organism identification and resistance mechanism detection with standard microbiologic methods. This study included patients with a positive blood culture from May 2020 to January 2021. The primary outcomes were to assess concordance of ePlex® organism identification with standard identification methods and concordance of ePlex® genotypic resistance mechanism detection with standard phenotypic susceptibility testing. Secondary outcomes included panel specific performance and characterization of antimicrobial stewardship opportunities. The overall identification concordance rate in 1276 positive blood cultures was 98.1%. The overall concordance for the presence of resistance markers was 98.2% and concordance for the absence of resistance markers was 100%. A majority of ePlex® results (69.5%) represented opportunities for potential antimicrobial stewardship intervention. High concordance rates between the ePlex® BCID panels and standard identification and susceptibility methods enable utilization of results to guide rapid antimicrobial optimization.

Progress toward a vaccine for extraintestinal pathogenic E. coli (ExPEC) II: efficacy of a toxin-autotransporter dual antigen approach.

Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of worldwide morbidity and mortality, the top cause of antimicrobial-resistant (AMR) infections, and the most frequent cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The development of an effective and universal vaccine is complicated by this pathogen's pan-genome, its ability to mix and match virulence factors and AMR genes via horizontal gene transfer, an inability to decipher commensal from pathogens, and its intimate association and co-evolution with mammals. Using a pan virulome analysis of >20,000 sequenced E. coli strains, we identified the secreted cytolysin α-hemolysin (HlyA) as a high priority target for vaccine exploration studies. We demonstrate that a catalytically inactive pure form of HlyA, expressed in an autologous host using its own secretion system, is highly immunogenic in a murine host, protects against several forms of ExPEC infection (including lethal bacteremia), and significantly lowers bacterial burdens in multiple organ systems. Interestingly, the combination of a previously reported autotransporter (SinH) with HlyA was notably effective, inducing near complete protection against lethal challenge, including commonly used infection strains ST73 (CFT073) and ST95 (UTI89), as well as a mixture of 10 of the most highly virulent sequence types and strains from our clinical collection. Both HlyA and HlyA-SinH combinations also afforded some protection against UTI89 colonization in a murine UTI model. These findings suggest recombinant, inactive hemolysin and/or its combination with SinH warrant investigation in the development of an E. coli vaccine against invasive disease.

Hitting the target and missing the point? A BEME systematic review of evidence regarding the efficacy of statutory and mandatory training in health and care: BEME Guide No. 87.

BACKGROUND: Mandatory training is considered fundamental to establishing and maintaining high standards of professional practice. There is little evidence however, of the training either achieving its required learning outcomes, or delivering improvement in outcomes for patients. Whist organisations may be hitting their compliance target for mandatory training, is the purpose missing the point? This systematic review aims to synthesize and evaluate the efficacy of statutory and mandatory training. METHODS: PubMed, EMBASE, CNAHL, ERIC and Cochrane Central registers were searched on 23rd May 2023. All research designs were included and reported training had to specify an organisational mandate within a healthcare setting. Data was coded using a modified Kirkpatrick (KP) rating system. Critical appraisal was undertaken using the Modified Medical Education Research Study Quality Instrument, Critical Appraisal Skills Programme Qualitative Studies checklist and Mixed Methods Assessment Tool. RESULTS: Twenty-five studies were included, featuring 9132 participants and 1348 patient cases audited. Studies described evaluation of mandatory training according to Kirkpatrick's outcomes levels 1-4b, with the majority (68%) undertaken in the UK and within acute settings. Training duration varied from 5 min to 3 days. There is a lack of consensus regarding mandatory training rationale, core topics, duration, and optimum refresher training period. Currently, mandatory training does not consistently translate to widescale improvements in safe practice or improved patient outcomes. CONCLUSIONS: Due to the lack of international consensus regarding the need for mandated training, most papers originated from countries with centrally administered national health care systems. The rationale for mandating training programmes remains undefined. The assumption that mandatory training is delivering safe practice outcomes is not supported by studies included in this review. The findings of this review offer a basis for further research to be undertaken to assist with the design, facilitation, and impact of mandatory training.