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.

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.

Sialyl-Tn serves as a potential therapeutic target for ovarian cancer.

BACKGROUND: Ovarian cancer remains the deadliest of the gynecologic cancers in the United States. There have been limited advances in treatment strategies that have seen marked increases in overall survival. Thus, it is essential to continue developing and validating new treatment strategies and markers to identify patients who would benefit from the new strategy. In this report, we sought to further validate applications for a novel humanized anti-Sialyl Tn antibody-drug conjugate (anti-STn-ADC) in ovarian cancer. METHODS: We aimed to further test a humanized anti-STn-ADC in sialyl-Tn (STn) positive and negative ovarian cancer cell line, patient-derived organoid (PDO), and patient-derived xenograft (PDX) models. Furthermore, we sought to determine whether serum STn levels would reflect STn positivity in the tumor samples enabling us to identify patients that an anti-STn-ADC strategy would best serve. We developed a custom ELISA with high specificity and sensitivity, that was used to assess whether circulating STn levels would correlate with stage, progression-free survival, overall survival, and its value in augmenting CA-125 as a diagnostic. Lastly, we assessed whether the serum levels reflected what was observed via immunohistochemical analysis in a subset of tumor samples. RESULTS: Our in vitro experiments further define the specificity of the anti-STn-ADC. The ovarian cancer PDO, and PDX models provide additional support for an anti-STn-ADC-based strategy for targeting ovarian cancer. The custom serum ELISA was informative in potential triaging of patients with elevated levels of STn. However, it was not sensitive enough to add value to existing CA-125 levels for a diagnostic. While the ELISA identified non-serous ovarian tumors with low CA-125 levels, the sample numbers were too small to provide any confidence the STn ELISA would meaningfully add to CA-125 for diagnosis. CONCLUSIONS: Our preclinical data support the concept that an anti-STn-ADC may be a viable option for treating patients with elevated STn levels. Moreover, our STn-based ELISA could complement IHC in identifying patients with whom an anti-STn-based strategy might be more effective.

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.

Long-Term Effect of Salt Substitution for Cardiovascular Outcomes : A Systematic Review and Meta-Analysis.

BACKGROUND: Salt substitution is a simple yet increasingly promising strategy to improve cardiovascular outcomes. PURPOSE: To evaluate the long-term effects of salt substitution on cardiovascular outcomes. DATA SOURCES: PubMed, EMBASE, Cochrane CENTRAL, and CINAHL searched from inception to 23 August 2023. Trial registries, citation analysis, and hand-search were also done. STUDY SELECTION: Randomized controlled trials (RCTs) comparing provision of or advice to use a salt substitute with no intervention or use of regular salt among adults for 6 months or longer in total study duration. DATA EXTRACTION: Two authors independently screened articles, extracted data, and assessed risk of bias. Primary outcomes include mortality, major cardiovascular events (MACE), and adverse events at 6 months or greater. Secondary and post hoc outcomes include blood pressure, cause-specific mortality, and urinary excretion at 6 months or greater. Random-effects meta-analyses were done and certainty of effect estimates were assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). DATA SYNTHESIS: Of the 16 included RCTs, 8 reported on primary outcomes. Most (n = 7 of 8) were done in China or Taiwan, 3 were done in residential facilities, and 7 included populations of older age (average 62 years) and/or with higher-than-average cardiovascular risk. In this population, salt substitute may reduce risk for all-cause mortality (6 RCTs; 27 710 participants; rate ratio [RR], 0.88 [95% CI, 0.82 to 0.93]; low certainty) and cardiovascular mortality (4 RCTs; 25 050 participants; RR, 0.83 [CI, 0.73 to 0.95]; low certainty). Salt substitute may result in a slight reduction in MACE (3 RCTs; 23 215 participants; RR, 0.85 [CI, 0.71 to 1.00]; very low certainty), with very low-certainty evidence of serious adverse events (6 RCTs; 27 995 participants; risk ratio, 1.04 [CI, 0.87 to 1.25]). LIMITATIONS: The evidence base is dominated by a single, large RCT. Most RCTs were from China or Taiwan and involved participants with higher-than-average cardiovascular risk; therefore, generalizability to other populations is very limited. CONCLUSION: Salt substitution may reduce all-cause or cardiovascular mortality, but the evidence for reducing cardiovascular events and for not increasing serious adverse events is uncertain, particularly for a Western population. The certainty of evidence is higher among populations at higher cardiovascular risk and/or following a Chinese diet. PRIMARY FUNDING SOURCE: National Health and Medical Research Council. (PROSPERO: CRD42022327566).

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.

Clinical trials and their impact on policy during COVID-19: a review.

Background: Of over 8,000 recorded randomised trials addressing COVID-19, around 80% were of treatments, and 17% have reported results. Approximately 1% were adaptive or platform trials, with 25 having results available, across 29 journal articles and 10 preprint articles. Methods: We conducted an extensive literature review to address four questions about COVID-19 trials, particularly the role and impact of platform/adaptive trials and lessons learned. Results: The key findings were: Q1. Social value in conducting trials and uptake into policy? COVID-19 drug treatments varied substantially and changed considerably, with drugs found effective in definitive clinical trials replacing unproven drugs. Dexamethasone has likely saved ½-2 million lives, and was cost effective across a range of countries and populations, whereas the cost effectiveness of remdesivir is uncertain. Published economic and health system impacts of COVID-19 treatments were infrequent. Q2. Issues with adaptive trial designs. Of the 77 platform trials registered, 6 major platform trials, with approximately 50 treatment arms, recruited ~135,000 participants with funding over $100 million. Q3. Models of good practice. Streamlined set-up processes such as flexible and fast-track funding, ethics, and governance approvals are vital. To facilitate recruitment, simple and streamlined research processes, and pre-existing research networks to coordinate trial planning, design, conduct and practice change are crucial to success. Q4. Potential conflicts to avoid? When treating patients through trials, balancing individual and collective rights and allocating scarce resources between healthcare and research are challenging. Tensions occur between commercial and non-commercial sectors, and academic and public health interests, such as publication and funding driven indicators and the public good. Conclusion: There is a need to (i) reduce small, repetitive, single centre trials, (ii) increase coordination to ensure robust research conducted for treatments, and (iii) a wider adoption of adaptive/platform trial designs to respond to fast-evolving evidence landscape.

Evaluating appetite/satiety hormones and eating behaviours as predictors of weight loss maintenance with GLP-1RA therapy in adolescents with severe obesity.

INTRODUCTION: Whilst glucagon-like peptide-1 receptor agonists (GLP1-RAs) are effective for treating adolescent obesity, weight loss maintenance (WLM; preventing weight regain) remains a challenge. Our goal was to investigate appetite/satiety hormones and eating behaviours that may predict WLM with exenatide (a GLP1-RA) versus placebo in adolescents with severe obesity. METHODS: Adolescents who had ≥5% body mass index (BMI) reduction with meal replacement therapy were randomized to 52 weeks of once-weekly exenatide extended release or placebo. In this secondary analysis, eating behaviours and appetite/satiety regulation hormones post-meal replacement therapy (pre-randomization to exenatide or placebo) were evaluated as possible predictors of WLM. Percent change in BMI from randomization to 52 weeks served as the primary measure of WLM. RESULTS: The analysis included 66 adolescents (mean age 16.0 years; 47% female). Lower leptin response to meal testing was associated with greater WLM in terms of BMI percent change in those receiving exenatide compared to placebo (p = 0.007) after adjusting for sex, age and BMI. There were no other significant predictors of WLM. CONCLUSIONS: Prior to exenatide, lower leptin response to meals was associated with improved WLM with exenatide compared to placebo. The mostly null findings of this study suggest that GLP1-RA treatment may produce similar WLM for adolescents with obesity regardless of age, BMI, sex and eating behaviours.

Digital health interventions for postoperative recovery in children: a systematic review.

BACKGROUND: Digital health interventions offer a promising approach for monitoring during postoperative recovery. However, the effectiveness of these interventions remains poorly understood, particularly in children. The objective of this study was to assess the efficacy of digital health interventions for postoperative recovery in children. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with the use of automation tools for searching and screening. We searched five electronic databases for randomised controlled trials or non-randomised studies of interventions that utilised digital health interventions to monitor postoperative recovery in children. The study quality was assessed using Cochrane Collaboration's Risk of Bias tools. The systematic review protocol was prospectively registered with PROSPERO (CRD42022351492). RESULTS: The review included 16 studies involving 2728 participants from six countries. Tonsillectomy was the most common surgery and smartphone apps (WeChat) were the most commonly used digital health interventions. Digital health interventions resulted in significant improvements in parental knowledge about the child's condition and satisfaction regarding perioperative instructions (standard mean difference=2.16, 95% confidence interval 1.45-2.87; z=5.98, P<0.001; I2=88%). However, there was no significant effect on children's pain intensity (standard mean difference=0.09, 95% confidence interval -0.95 to 1.12; z=0.16, P=0.87; I2=98%). CONCLUSIONS: Digital health interventions hold promise for improving parental postoperative knowledge and satisfaction. However, more research is needed for child-centric interventions with validated outcome measures. Future work should focus development and testing of user-friendly digital apps and wearables to ease the healthcare burden and improve outcomes for children. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022351492).

Draft genome sequences of Pseudomonas strains zfem001-005 isolated from the intestine of larval zebrafish Danio rerio.

Here, we report the draft genome sequences of Pseudomonas strains zfem001-005, five isolates from the intestinal microbiota of healthy larval zebrafish Danio rerio at a developmental age of 7 days post fertilization. The isolates have been identified as Pseudomonas sediminis, Pseudomonas japonica, Pseudomonas otitidis, Pseudomonas sichuanensis, and Pseudomonas tohonis, respectively.

Cardiovascular disease risk communication and prevention: a meta-analysis.

BACKGROUND AND AIMS: Knowledge of quantifiable cardiovascular disease (CVD) risk may improve health outcomes and trigger behavioural change in patients or clinicians. This review aimed to investigate the impact of CVD risk communication on patient-perceived CVD risk and changes in CVD risk factors. METHODS: PubMed, Embase, and PsycINFO databases were searched from inception to 6 June 2023, supplemented by citation analysis. Randomized trials that compared any CVD risk communication strategy versus usual care were included. Paired reviewers independently screened the identified records and extracted the data; disagreements were resolved by a third author. The primary outcome was the accuracy of risk perception. Secondary outcomes were clinician-reported changes in CVD risk, psychological responses, intention to modify lifestyle, and self-reported changes in risk factors and clinician prescribing of preventive medicines. RESULTS: Sixty-two trials were included. Accuracy of risk perception was higher among intervention participants (odds ratio = 2.31, 95% confidence interval = 1.63 to 3.27). A statistically significant improvement in overall CVD risk scores was found at 6-12 months (mean difference = -0.27, 95% confidence interval = -0.45 to -0.09). For primary prevention, risk communication significantly increased self-reported dietary modification (odds ratio = 1.50, 95% confidence interval = 1.21 to 1.86) with no increase in intention or actual changes in smoking cessation or physical activity. A significant impact on patients' intention to start preventive medication was found for primary and secondary prevention, with changes at follow-up for the primary prevention group. CONCLUSIONS: In this systematic review and meta-analysis, communicating CVD risk information, regardless of the method, reduced the overall risk factors and enhanced patients' self-perceived risk. Communication of CVD risk to patients should be considered in routine consultations.

Evaluating Sex Differences in the Characteristics and Outcomes of Lupus Nephritis: A Systematic Review and Meta-Analysis.

Introduction: More frequent and severe lupus nephritis (LN) has been reported in men compared to women, but data are limited and inconsistent. We conducted a meta-analysis of the literature to compare the histopathologic findings and outcomes between men and women with biopsy-proven LN. Methods: A systematic search of MEDLINE, Embase, Cochrane, and Web of Science databases was conducted through February 2021. Clinical information was extracted and synthesized from 25 studies that met inclusion criteria (1,210 men and 6,635 women). Pooled odds ratios (OR) with corresponding 95% confidence intervals (CIs) were generated via meta-analysis, and meta-regression was performed to assess the impact of several covariates, both using random-effects models. Results: Twenty studies reported kidney histopathology, eleven reported kidney outcomes, and eight reported mortality rates. Men had greater odds of class IV ± V LN (OR 1.26, 95% CI: 1.01-1.56), and the composite of end-stage kidney disease, persistent eGFR <15 mL/min or doubling of serum creatinine (OR 2.20, 95% CI: 1.59-3.06), and lower odds of complete remission (OR 0.52, 95% CI: 0.39-0.68). Mortality was not statistically significantly different between sexes (OR 1.50, 95% CI: 0.92-2.46). Meta-regression did not reveal statistically significant study-level relationships between sex differences in any of the covariates that could account for the greater odds of worse kidney outcome in males. Conclusion: Our analysis confirms the association between male sex and increased severity of LN as well as worse kidney outcomes. Larger prospective studies are needed to validate this association and inform treatment strategies adapted to this population.

Assessment of a SARS-CoV-2 wastewater monitoring program in El Paso, Texas, from November 2020 to June 2022.

The border city of El Paso, Texas, and its water utility, El Paso Water, initiated a SARS-CoV-2 wastewater monitoring program to assess virus trends and the appropriateness of a wastewater monitoring program for the community. Nearly weekly sample collection at four wastewater treatment facilities (WWTFs), serving distinct regions of the city, was analyzed for SARS-CoV-2 genes using the CDC 2019-Novel coronavirus Real-Time RT-PCR diagnostic panel. Virus concentrations ranged from 86.7 to 268,000 gc/L, varying across time and at each WWTF. The lag time between virus concentrations in wastewater and reported COVID-19 case rates (per 100,00 population) ranged from 4-24 days for the four WWTFs, with the strongest trend occurring from November 2021 - June 2022. This study is an assessment of the utility of a geographically refined SARS-CoV-2 wastewater monitoring program to supplement public health efforts that will manage the virus as it becomes endemic in El Paso.

Appelmans protocol - A directed in vitro evolution enables induction and recombination of prophages with expanded host range.

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) present significant healthcare challenges due to limited treatment options. Bacteriophage (phage) therapy offers potential as an alternative treatment. However, the high host specificity of phages poses challenges for their therapeutic application. To broaden the phage spectrum, laboratory-based phage training using the Appelmans protocol was employed in this study. As a result, the protocol successfully expanded the host range of a phage cocktail targeting CRAB. Further analysis revealed that the expanded host range phages isolated from the output cocktail were identified as recombinant derivatives originating from prophages induced from encountered bacterial strains. These findings provide valuable genetic insights into the protocol's mechanism when applied to phages infecting A. baumannii strains that have never been investigated before. However, it is noteworthy that the expanded host range phages obtained from this protocol exhibited limited stability, raising concerns about their suitability for therapeutic purposes.

Comparison of Telephone and Video Telehealth Consultations: Systematic Review.

BACKGROUND: Telehealth has been used for health care delivery for decades, but the COVID-19 pandemic greatly accelerated the uptake of telehealth in many care settings globally. However, few studies have carried out a direct comparison among different telehealth modalities, with very few studies having compared the effectiveness of telephone and video telehealth modalities. OBJECTIVE: This study aimed to identify and synthesize randomized controlled trials (RCTs) comparing synchronous telehealth consultations delivered by telephone and those conducted by video with outcomes such as clinical effectiveness, patient safety, cost-effectiveness, and patient and clinician satisfaction with care. METHODS: PubMed (MEDLINE), Embase, and CENTRAL were searched via the Cochrane Library from inception until February 10, 2023, for RCTs without any language restriction. Forward and backward citation searches were conducted on included RCTs. The Cochrane Risk of Bias 2 tool was used to assess the quality of the studies. We included studies carried out in any health setting-involving all types of outpatient cohorts and all types of health care providers-that compared synchronous video consultations directly with telephone consultations and reported outcomes specified in the objective. We excluded studies of clinician-to-clinician telehealth consults, hospitalized patients, and asynchronous consultations. RESULTS: Sixteen RCTs-10 in the United States, 3 in the United Kingdom, 2 in Canada, and 1 in Australia involving 1719 participants-were included in the qualitative and quantitative analyses. Most of the telehealth interventions were for hospital-based outpatient follow-ups, monitoring, and rehabilitation (n=13). The 3 studies that were conducted in the community all focused on smoking cessation. In half of the studies, nurses delivered the care (n=8). Almost all included studies had high or unclear risk of bias, mainly due to bias in the randomization process and selection of reported results. The trials found no substantial differences between telephone and video telehealth consultations with regard to clinical effectiveness, patient satisfaction, and health care use (cost-effectiveness) outcomes. None of the studies reported on patient safety or adverse events. We did not find any study on telehealth interventions for diagnosis, initiating new treatment, or those conducted in a primary care setting. CONCLUSIONS: Based on a small set of diverse trials, we found no notable differences between telephone and video consultations for the management of patients with an established diagnosis. There is also a significant lack of telehealth research in primary care settings despite its high uptake.

Comparing proficiency of obstetrics and gynaecology trainees with general surgery trainees using simulated laparoscopic tasks in Health Education England, North-West: a prospective observational study.

BACKGROUND: Training programmes for obstetrics and gynaecology (O&G) and general surgery (GS) vary significantly, but both require proficiency in laparoscopic skills. We sought to determine performance in each specialty. DESIGN: Prospective, observational study. SETTING: Health Education England North-West, UK. PARTICIPANTS: 47 surgical trainees (24 O&G and 23 GS) were subdivided into four groups: 11 junior O&G, 13 senior O&G, 11 junior GS and 12 senior GS trainees. OBJECTIVES: Trainees were tested on four simulated laparoscopic tasks: laparoscopic camera navigation (LCN), hand-eye coordination (HEC), bimanual coordination (BMC) and suturing with intracorporeal knot tying (suturing). RESULTS: O&G trainees completed LCN (p<0.001), HEC (p<0.001) and BMC (p<0.001) significantly slower than GS trainees. Furthermore, O&G found fewer number of targets in LCN (p=0.001) and dropped a greater number of pins than the GS trainees in BMC (p=0.04). In all three tasks, there were significant differences between O&G and GS trainees but no difference between the junior and senior groups within each specialty. Performance in suturing also varied by specialty; senior O&G trainees scored significantly lower than senior GS trainees (O&G 11.4±4.4 vs GS 16.8±2.1, p=0.03). Whilst suturing scores improved with seniority among O&G trainees, there was no difference between the junior and senior GS trainees (senior O&G 11.4±4.4 vs junior O&G 3.6±2.1, p=0.004). DISCUSSION: GS trainees performed better than O&G trainees in core laparoscopic skills, and the structure of O&G training may require modification. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05116332).

Low-Value Surgical Procedures in Low- and Middle-Income Countries: A Systematic Scoping Review.

Importance: Overuse of surgical procedures is increasing around the world and harms both individuals and health care systems by using resources that could otherwise be allocated to addressing the underuse of effective health care interventions. In low- and middle-income countries (LMICs), there is some limited country-specific evidence showing that overuse of surgical procedures is increasing, at least for certain procedures. Objectives: To assess factors associated with, extent and consequences of, and potential solutions for low-value surgical procedures in LMICs. Evidence Review: We searched 4 electronic databases (PubMed, Embase, PsycINFO, and Global Index Medicus) for studies published from database inception until April 27, 2022, with no restrictions on date or language. A combination of MeSH terms and free-text words about the overuse of surgical procedures was used. Studies examining the problem of overuse of surgical procedures in LMICs were included and categorized by major focus: the extent of overuse, associated factors, consequences, and solutions. Findings: Of 4276 unique records identified, 133 studies across 63 countries were included, reporting on more than 9.1 million surgical procedures (median per study, 894 [IQR, 97-4259]) and with more than 11.4 million participants (median per study, 989 [IQR, 257-6857]). Fourteen studies (10.5%) were multinational. Of the 119 studies (89.5%) originating from single countries, 69 (58.0%) were from upper-middle-income countries and 30 (25.2%) were from East Asia and the Pacific. Of the 42 studies (31.6%) reporting extent of overuse of surgical procedures, most (36 [85.7%]) reported on unnecessary cesarean delivery, with estimated rates in LMICs ranging from 12% to 81%. Evidence on other surgical procedures was limited and included abdominal and percutaneous cardiovascular surgical procedures. Consequences of low-value surgical procedures included harms and costs, such as an estimated US $3.29 billion annual cost of unnecessary cesarean deliveries in China. Associated factors included private financing, and solutions included social media campaigns and multifaceted interventions such as audits, feedback, and reminders. Conclusions and Relevance: This systematic review found growing evidence of overuse of surgical procedures in LMICs, which may generate significant harm and waste of limited resources; the majority of studies reporting overuse were about unnecessary cesarean delivery. Therefore, a better understanding of the problems in other surgical procedures and a robust evaluation of solutions are needed.

Immediate versus delayed versus no antibiotics for respiratory infections.

BACKGROUND: Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost and antibacterial resistance. One proposed strategy to reduce antibiotic prescribing is to provide prescriptions, but to advise delay in antibiotic use with the expectation that symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007, and updated in 2010, 2013 and 2017. OBJECTIVES: To evaluate the effects on duration and/or severity of clinical outcomes (pain, malaise, fever, cough and rhinorrhoea), antibiotic use, antibiotic resistance and patient satisfaction of advising a delayed prescription of antibiotics in respiratory tract infections. SEARCH METHODS: From May 2017 until 20 August 2022, this was a living systematic review with monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL and Web of Science. We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov on 20 August 2022. Due to the abundance of evidence supporting the review's key findings, it ceased being a living systematic review on 21 August 2022. SELECTION CRITERIA: Randomised controlled trials involving participants of all ages with an RTI, where delayed antibiotics were compared to immediate or no antibiotics. We defined a delayed antibiotic as advice to delay the filling of an antibiotic prescription by at least 48 hours. We considered all RTIs regardless of whether antibiotics were recommended or not. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: For this 2022 update, we added one new trial enrolling 448 children (436 analysed) with uncomplicated acute RTIs. Overall, this review includes 12 studies with a total of 3968 participants, of which data from 3750 are available for analysis. These 12 studies involved acute RTIs including acute otitis media (three studies), streptococcal pharyngitis (three studies), cough (two studies), sore throat (one study), common cold (one study) and a variety of RTIs (two studies). Six studies involved only children, two only adults and four included both adults and children. Six studies were conducted in primary care, four in paediatric clinics and two in emergency departments. Studies were well reported and appeared to provide moderate-certainty evidence. Randomisation was not adequately described in two trials. Four trials blinded the outcome assessor, and three included blinding of participants and doctors. We conducted meta-analyses for pain, malaise, fever, adverse effects, antibiotic use and patient satisfaction. Cough (four studies): we found no differences amongst delayed, immediate and no prescribed antibiotics for clinical outcomes in any of the four studies. Sore throat (six studies): for the outcome of fever with sore throat, four of the six studies favoured immediate antibiotics, and two found no difference. For the outcome of pain related to sore throat, two studies favoured immediate antibiotics, and four found no difference. Two studies compared delayed antibiotics with no antibiotic for sore throat, and found no difference in clinical outcomes. Acute otitis media (four studies): two studies compared immediate with delayed antibiotics - one found no difference for fever, and the other favoured immediate antibiotics for pain and malaise severity on Day 3. Two studies compared delayed with no antibiotics: one found no difference for pain and fever severity on Day 3, and the other found no difference for the number of children with fever on Day 3. Common cold (two studies): neither study found differences for clinical outcomes between delayed and immediate antibiotic groups. One study found delayed antibiotics were probably favoured over no antibiotics for pain, fever and cough duration (moderate-certainty evidence). ADVERSE EFFECTS: there were either no differences for adverse effects or results may have favoured delayed over immediate antibiotics with no significant differences in complication rates (low-certainty evidence). Antibiotic use: delayed antibiotics probably resulted in a reduction in antibiotic use compared to immediate antibiotics (odds ratio (OR) 0.03, 95% confidence interval (CI) 0.01 to 0.07; 8 studies, 2257 participants; moderate-certainty evidence). However, a delayed antibiotic was probably more likely to result in reported antibiotic use than no antibiotics (OR 2.52, 95% CI 1.69 to 3.75; 5 studies, 1529 participants; moderate-certainty evidence). Patient satisfaction: patient satisfaction probably favoured delayed over no antibiotics (OR 1.45, 1.08 to 1.96; 5 studies, 1523 participants; moderate-certainty evidence). There was probably no difference in patient satisfaction between delayed and immediate antibiotics (OR 0.77, 95% CI 0.45 to 1.29; 7 studies, 1927 participants; moderate-certainty evidence). No studies evaluated antibiotic resistance. Reconsultation rates and use of alternative medicines were similar for delayed, immediate and no antibiotic strategies. In one of the four studies reporting use of alternative medicines, less paracetamol was used in the immediate group compared to the delayed group. AUTHORS' CONCLUSIONS: For many clinical outcomes, there were no differences between prescribing strategies. Symptoms for acute otitis media and sore throat were modestly improved by immediate antibiotics compared with delayed antibiotics. There were no differences in complication rates. Delaying prescribing did not result in significantly different levels of patient satisfaction compared with immediate provision of antibiotics (86% versus 91%; moderate-certainty evidence). However, delay was favoured over no antibiotics (87% versus 82%). Delayed antibiotics achieved lower rates of antibiotic use compared to immediate antibiotics (30% versus 93%). The strategy of no antibiotics further reduced antibiotic use compared to delaying prescription for antibiotics (13% versus 27%). Delayed antibiotics for people with acute respiratory infection reduced antibiotic use compared to immediate antibiotics, but was not shown to be different to no antibiotics in terms of symptom control and disease complications. Where clinicians feel it is safe not to prescribe antibiotics immediately for people with RTIs, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use while maintaining similar patient satisfaction and clinical outcomes to delayed antibiotics. Where clinicians are not confident in not prescribing antibiotics, delayed antibiotics may be an acceptable compromise in place of immediate prescribing to significantly reduce unnecessary antibiotic use for RTIs, while maintaining patient safety and satisfaction levels. Further research into antibiotic prescribing strategies for RTIs may best be focused on identifying patient groups at high risk of disease complications, enhancing doctors' communication with patients to maintain satisfaction, ways of increasing doctors' confidence to not prescribe antibiotics for RTIs, and policy measures to reduce unnecessary antibiotic prescribing for RTIs.

Telehealth versus face-to-face delivery of cognitive behavioural therapy for insomnia: A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: This systematic review and meta-analysis compared the effectiveness of the delivery of care to patients with insomnia via telehealth to its delivery face-to-face. METHODS: We searched Medline, Embase, and Cochrane CENTRAL from inception to 11 January 2023, and conducted a citation analysis on 13 June 2023. No language restrictions were imposed. We included randomised controlled trials. Where feasible, mean differences were calculated; we used a random effects model. RESULTS: Four trials (239 patients) were included. There were no significant differences between telehealth and face-to-face for insomnia severity scores shortly post-intervention (MD 1.13, 95% CI -0.29-2.55) or at 3 months (mean difference (MD) 1.79, 95% CI -0.01-3.59). There were no differences in Short Form-36 physical and mental scores, Work and Social Adjustment scores, and sleep quality components. Depression scores did not differ post-intervention or at 3 months (MD 0.42, 95% CI -2.42-3.26). Functioning likewise did not differ post-intervention or at 3 months (standardised mean difference (SMD) 0.15, 95% CI -0.37-0.67, P = 0.58). Treatment satisfaction did not differ (one trial) or favoured the face-to-face group (one trial). CONCLUSIONS: Telehealth may be a viable alternative to the face-to-face provision of cognitive behavioural therapy for insomnia to patients with insomnia. However, the volume of the existing evidence is limited, therefore additional trials are needed, evaluating cognitive behavioural therapy for insomnia and other therapies for individuals for whom cognitive behavioural therapy for insomnia is not effective, and conducted with a wider range of populations, providers and settings.

Wastewater sequencing reveals community and variant dynamics of the collective human virome.

Wastewater is a discarded human by-product, but its analysis may help us understand the health of populations. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels while bypassing the difficulties and pit falls of individual testing. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. Here, we conduct a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Critical to detection is the use of a viral probe capture set targeting thousands of viral species or variants. Over 450 distinct pathogenic viruses from 28 viral families are observed, most of which have never been detected in such samples. Sequencing reads of established pathogens and emerging viruses correlate to clinical data sets of SARS-CoV-2, influenza virus, and monkeypox viruses, outlining the public health utility of this approach. Viral communities are tightly organized by space and time. Finally, the most abundant human viruses yield sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health.