Multi-signal regulation of the GSK-3ß homolog Rim11 controls meiosis entry in budding yeast.

Starvation in diploid budding yeast cells triggers a cell-fate program culminating in meiosis and spore formation. Transcriptional activation of early meiotic genes (EMGs) hinges on the master regulator Ime1, its DNA-binding partner Ume6, and GSK-3ß kinase Rim11. Phosphorylation of Ume6 by Rim11 is required for EMG activation. We report here that Rim11 functions as the central signal integrator for controlling Ume6 phosphorylation and EMG transcription. In nutrient-rich conditions, PKA suppresses Rim11 levels, while TORC1 retains Rim11 in the cytoplasm. Inhibition of PKA and TORC1 induces Rim11 expression and nuclear localization. Remarkably, nuclear Rim11 is required, but not sufficient, for Rim11-dependent Ume6 phosphorylation. In addition, Ime1 is an anchor protein enabling Ume6 phosphorylation by Rim11. Subsequently, Ume6-Ime1 coactivator complexes form and induce EMG transcription. Our results demonstrate how various signaling inputs (PKA/TORC1/Ime1) converge through Rim11 to regulate EMG expression and meiosis initiation. We posit that the signaling-regulatory network elucidated here generates robustness in cell-fate control.

Skin Antisepsis before Surgical Fixation of Extremity Fractures.

BACKGROUND: Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture). METHODS: In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications. RESULTS: A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial. In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00; P = 0.049). In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45). The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups. CONCLUSIONS: Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. (Funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research; PREPARE ClinicalTrials.gov number, NCT03523962.).

Telerehabilitation consultations with a physiotherapist for chronic knee pain versus in-person consultations in Australia: the PEAK non-inferiority randomised controlled trial.

BACKGROUND: Telerehabilitation whether perceived as less effective than in-person care for musculoskeletal problems. We aimed to determine if physiotherapy video conferencing consultations were non-inferior to in-person consultations for chronic knee pain. METHODS: In this non-inferiority randomised controlled trial, we recruited primary care physiotherapists from 27 Australian clinics. Using computer-generated blocks, participants with chronic knee pain consistent with osteoarthritis were randomly assigned (1:1, stratified by physiotherapist and clinic) in-person or telerehabilitation (ie, video conferencing) physiotherapist consultations. Participants and physiotherapists were unmasked to group assignment. Both groups had five consultations over 3 months for strengthening, physical activity, and education. Primary outcomes were knee pain (on a numerical rating scale of 0-10) and physical function (using the Western Ontario and McMaster Universities osteoarthritis index of 0-68) at 3 months after randomisation. Primary analysis was by modified intention-to-treat using all available data. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12619001240134. FINDINGS: Between Dec 10, 2019, and June 17, 2022, 394 adults were enrolled, with 204 allocated to in-person care and 190 to telerehabilitation. 15 primary care physiotherapists were recruited. At 3 months, 383 (97%) participants provided information for primary outcomes and both groups reported improved pain (mean change 2·98, SD 2·23 for in-person care and 3·14, 1·87 for telerehabilitation) and function (10·20, 11·63 and 10·75, 9·62, respectively). Telerehabilitation was non-inferior for pain (mean difference 0·16, 95% CI -0·26 to 0·57) and function (1·65, -0·23 to 3·53). The number of participants reporting adverse events was similar between groups (40 [21%] for in-person care and 35 [19%] for telerehabilitation) and none were serious. INTERPRETATION: Telerehabilitation with a physiotherapist is non-inferior to in-person care for chronic knee pain. FUNDING: National Health and Medical Research Council.

Characterizing Patients Presenting on Hospital Admission With Central Line-Associated Bloodstream Infections: A Multicenter Study.

BACKGROUND: There are no systematic measures of central line-associated bloodstream infections (CLABSIs) in patients maintaining central venous catheters (CVCs) outside acute care hospitals. To clarify the burden of CLABSIs in these patients, we characterized patients with CLABSI present on hospital admission (POA). METHODS: Retrospective cross-sectional analysis of patients with CLABSI-POA in 3 health systems covering 11 hospitals across Maryland, Washington DC, and Missouri from November 2020 to October 2021. CLABSI-POA was defined using an adaptation of the acute care CLABSI definition. Patient demographics, clinical characteristics, and outcomes were collected via record review. Cox proportional hazard analysis was used to assess factors associated with the all-cause mortality rate within 30 days. RESULTS: A total of 461 patients were identified as having CLABSI-POA. CVCs were most commonly maintained in home infusion therapy (32.8%) or oncology clinics (31.2%). Enterobacterales were the most common etiologic agent (29.2%). Recurrent CLABSIs occurred in a quarter of patients (25%). Eleven percent of patients died during the hospital admission. Among patients with CLABSI-POA, mortality risk increased with age (hazard ratio vs age <20 years by age group: 20-44 years, 11.2 [95% confidence interval, 1.46-86.22]; 45-64 years, 20.88 [2.84-153.58]; ≥65 years, 22.50 [2.98-169.93]) and lack of insurance (2.46 [1.08-5.59]), and it decreased with CVC removal (0.57 [.39-.84]). CONCLUSIONS: CLABSI-POA is associated with significant in-hospital mortality risk. Surveillance is required to understand the burden of CLABSI in the community to identify targets for CLABSI prevention initiatives outside acute care settings.

Sample-to-Answer Detection of SARS-CoV-2 Viremia Using Thermally Responsive Alkane Partitions.

The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.e., sample-to-answer), compact, low-cost system. We recently reported the development of thermally responsive alkane partitions (TRAPs), which enable the complete automation of diagnostic assays with complex samples. Here we report the use of TRAPs for the sample-to-answer detection of viruses in blood using a low-cost portable device and easily manufacturable cassettes. Specifically, we demonstrate the detection of SARS-CoV-2 in spiked blood samples, and we show that our system detects viremia in COVID-19 patient samples with good agreement to conventional RT-qPCR. We anticipate that our sample-to-answer system can be used to rapidly diagnose SARS-CoV-2 viremia at the point of care, leading to better health outcomes for patients with severe COVID-19 disease, and that our system can be applied to the diagnosis of other life-threatening bloodborne viral diseases, including Hepatitis C and HIV.

Comparison of three rapid diagnostic tests for bloodstream infections using Benefit-risk Evaluation Framework (BED-FRAME).

Rapid diagnostic tests (RDTs) for bloodstream infections have the potential to reduce time to appropriate antimicrobial therapy and improve patient outcomes. Previously, an in-house, lipid-based, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) method, Fast Lipid Analysis Technique (FLAT MS), has shown promise as a rapid pathogen identification method. In this study, FLAT MS for direct from blood culture identification was evaluated and compared to FDA-cleared identification methods using the Benefit-risk Evaluation Framework (BED-FRAME) analysis. FLAT MS was evaluated and compared to Bruker Sepsityper and bioMérieux BioFire FilmArray BCID2 using results from a previous study. For this study, 301 positive blood cultures were collected from the University of Maryland Medical Center. The RDTs were compared by their sensitivities, time-to-results, hands-on time, and BED-FRAME analysis. The overall sensitivity of all platforms compared to culture results from monomicrobial-positive blood cultures was 88.3%. However, the three RDTs differed in their accuracy for identifying Gram-positive bacteria, Gram-negative bacteria, and yeast. Time-to-results for FLAT MS, Sepsityper, and BioFire BCID2 were all approximately one hour. Hands-on times for FLAT MS, Sepsityper, and BioFire BCID2 were 10 (±1.3), 40 (±2.8), and 5 (±0.25) minutes, respectively. BED-FRAME demonstrated that each RDT had utility at different pathogen prevalence and relative importance. BED-FRAME is a useful tool that can used to determine which RDT is best for a healthcare center.

Neurophysiological evidence of motor preparation in inner speech and the effect of content predictability.

Self-generated overt actions are preceded by a slow negativity as measured by electroencephalogram, which has been associated with motor preparation. Recent studies have shown that this neural activity is modulated by the predictability of action outcomes. It is unclear whether inner speech is also preceded by a motor-related negativity and influenced by the same factor. In three experiments, we compared the contingent negative variation elicited in a cue paradigm in an active vs. passive condition. In Experiment 1, participants produced an inner phoneme, at which an audible phoneme whose identity was unpredictable was concurrently presented. We found that while passive listening elicited a late contingent negative variation, inner speech production generated a more negative late contingent negative variation. In Experiment 2, the same pattern of results was found when participants were instead asked to overtly vocalize the phoneme. In Experiment 3, the identity of the audible phoneme was made predictable by establishing probabilistic expectations. We observed a smaller late contingent negative variation in the inner speech condition when the identity of the audible phoneme was predictable, but not in the passive condition. These findings suggest that inner speech is associated with motor preparatory activity that may also represent the predicted action-effects of covert actions.

Food consumption patterns, seasonal dietary diversity, and factors affecting food intake in rural Eastern Uganda: A mixed-methods cross-sectional study.

This mixed-methods cross-sectional study examines food consumption patterns, dietary diversity, and factors affecting food intake and malnutrition in the rural Mbale District in Eastern Uganda, during both wet and dry seasons. Participants (n = 100; 66% females) completed a food frequency questionnaire identifying foods and beverages consumed in the preceding 12 months. Individual interviews (n = 8) were conducted with key workers. Analysis of seventeen food items revealed seasonal variations in carbohydrate and protein sources. During the dry season, staples like matooke (mashed boiled plantains) and sweet and Irish potatoes were affected, while protein-rich foods such as beans and groundnuts saw increased consumption in the wet season. Fruit and vegetable intake also rose during the wet season. The main causes of malnutrition that emerged from the interviews were the lack of knowledge about food and nutrition, financial struggles, climate impact, and cultural beliefs. The last theme covered strategies to combat malnutrition. Although carbohydrate intake remains consistent throughout seasons due to reliance on posho (maize flour porridge) and cassava, variations in the number of meals and protein sources, particularly beans and groundnuts, were observed. Both of these, being the primary protein sources in rural households' diets, are highly susceptible to climate fluctuations. This may pose significant implications for food security, as heightened climate instability may impede their production. Solutions to combat malnutrition discussed by the interviewees include education, employment, family planning, and healthcare improvements. Professionals emphasise the need for comprehensive approaches to address these complex issues. In addition, data on food consumption during the dry and wet seasons should be collected as a difference in food consumption during the seasons may become more prominent with the need to implement tailored interventions.

Effectiveness of a telehealth-delivered clinician-supported exercise and weight loss program for hip osteoarthritis - protocol for the Better Hip randomised controlled trial.

BACKGROUND: Hip osteoarthritis (OA) is a leading cause of chronic pain and disability worldwide. Self-management is vital with education, exercise and weight loss core recommended treatments. However, evidence-practice gaps exist, and service models that increase patient accessibility to clinicians who can support lifestyle management are needed. The primary aim of this study is to determine the effectiveness of a telehealth-delivered clinician-supported exercise and weight loss program (Better Hip) on the primary outcomes of hip pain on walking and physical function at 6 months, compared with an information-only control for people with hip OA. METHODS: A two-arm, parallel-design, superiority pragmatic randomised controlled trial. 212 members from a health insurance fund aged 45 years and over, with painful hip OA will be recruited. Participants will be randomly allocated to receive: i) Better Hip; or ii) web-based information only (control). Participants randomised to the Better Hip program will have six videoconferencing physiotherapist consultations for education about OA, prescription of individualised home-based strengthening and physical activity programs, behaviour change support, and facilitation of other self-management strategies. Those with a body mass index > 27 kg/m2, aged < 80 years and no specific health conditions, will also be offered six videoconferencing dietitian consultations to undertake a weight loss program. Participants in the control group will be provided with similar educational information about managing hip OA via a custom website. All participants will be reassessed at 6 and 12 months. Primary outcomes are hip pain on walking and physical function. Secondary outcomes include measures of pain; hip function; weight; health-related quality of life; physical activity levels; global change in hip problem; willingness to undergo hip replacement surgery; rates of hip replacement; and use of oral pain medications. A health economic evaluation at 12 months will be conducted and reported separately. DISCUSSION: Findings will determine whether a telehealth-delivered clinician-supported lifestyle management program including education, exercise/physical activity and, for those with overweight or obesity, weight loss, is more effective than information only in people with hip OA. Results will inform the implementation of such programs to increase access to core recommended treatments. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ACTRN12622000461796).

Continuation or maintenance ECT for schizophrenia: A narrative review of case report data.

OBJECTIVE: This review aimed to address the limited evidence on the efficacy of continuation or maintenance electroconvulsive therapy (C/M-ECT) in schizophrenia, with a focus on international case reports and series due to the scarcity of randomised controlled trials. MATERIALS AND METHODS: Electronic database searches were conducted to identify case reports or series evaluating the efficacy of C/M-ECT in patients with schizophrenia or schizoaffective disorder. RESULTS: C/M-ECT treatment span varied from 3 months to 36 years (Median = 30 months; M = 43.9 months; SD = 63.0) and was effective in maintaining remission for most patients with schizophrenia in combination with antipsychotic medication. Reporting of adverse events including cognitive adverse effects was infrequent. CONCLUSIONS: Collation of case reports and series data indicated that C/M-ECT, when combined with antipsychotics, appears to be a safe and effective strategy for maintaining remission, even over several years. Caution is warranted due to the potential influence of publication bias.

Off-label prescribing of psychotropics in a psychiatric patient population in Australia.

BACKGROUND: This study aimed to investigate the practice of off-label prescribing in both in- and outpatient psychiatry practice. METHODS: One-hundred inpatient and 100 outpatient medical records from adult patients of an Australian psychiatry service from 2020 to 2021 were examined to determine the prevalence of off-label prescribing as defined by Therapeutic Goods Administration (TGA) indications, adherence to Royal Australian and New Zealand College of Psychiatrists (RANZCP) treatment guidelines, frequency of off-label prescription, and the quality of documentation and informed consent process. RESULTS: Most prescribing events in both in- and outpatient settings were either on-label or off-label but consistent with RANZCP guidelines. Patients with a schizoaffective disorder diagnosis or displaying aggression were most likely to receive off-label prescriptions. There was no significant difference between in- and outpatient groups in the quality of documentation or consent process. CONCLUSIONS: In general, off-label prescribing across groups was common, but many decisions were then in line with RANZCP recommendations. That there is a discrepancy between clinical and regulatory bodies has implications for how off-label status is decided.

The Next Generation: Mentoring and Diversity in the Antibacterial Resistance Leadership Group.

The Antibacterial Resistance Leadership Group (ARLG) Mentoring Program was established to develop and prepare the next generation of clinician-scientists for a career in antibacterial resistance research. The ARLG Diversity, Equity, and Inclusion Working Group partners with the Mentoring Committee to help ensure diversity and excellence in the clinician-scientist workforce of the future. To advance the field of antibacterial research while fostering inclusion and diversity, the Mentoring Program has developed a number of fellowships, awards, and programs, which are described in detail in this article.

Adherence to Antimicrobial Prophylaxis Guidelines for Elective Surgeries Across 825 US Hospitals, 2019-2020.

BACKGROUND: There are limited US data assessing adherence to surgical antimicrobial prophylaxis guidelines, particularly across a large, nationwide sample. Moreover, commonly prescribed inappropriate antimicrobial prophylaxis regimens remain unknown, hindering improvement initiatives. METHODS: We conducted a retrospective cohort study of adults who underwent elective craniotomy, hip replacement, knee replacement, spinal procedure, or hernia repair in 2019-2020 at hospitals in the PINC AI (Premier) Healthcare Database. We evaluated adherence of prophylaxis regimens, with respect to antimicrobial agents endorsed in the American Society of Health-System Pharmacist guidelines, accounting for patient antibiotic allergy and methicillin-resistant Staphylococcus aureus colonization status. We used multivariable logistic regression with random effects by hospital to evaluate associations between patient, procedural, and hospital characteristics and guideline adherence. RESULTS: Across 825 hospitals and 521 091 inpatient elective surgeries, 308 760 (59%) were adherent to prophylaxis guidelines. In adjusted analysis, adherence varied significantly by US Census division (adjusted OR [aOR] range: .61-1.61) and was significantly lower in 2020 compared with 2019 (aOR: .92; 95% CI: .91-.94; P < .001). The most common reason for nonadherence was unnecessary vancomycin use. In a post hoc analysis, controlling for patient age, comorbidities, other nephrotoxic agent use, and patient and procedure characteristics, patients receiving cefazolin plus vancomycin had 19% higher odds of acute kidney injury (AKI) compared with patients receiving cefazolin alone (aOR: 1.19; 95% CI: 1.11-1.27; P < .001). CONCLUSIONS: Adherence to antimicrobial prophylaxis guidelines remains suboptimal, largely driven by unnecessary vancomycin use, which may increase the risk of AKI. Adherence decreased in the first year of the COVID-19 pandemic.

Patterns, Predictors, and Intercenter Variability in Empiric Gram-Negative Antibiotic Use Across 928 United States Hospitals.

BACKGROUND: Empiric antibiotic use among hospitalized adults in the United States (US) is largely undescribed. Identifying factors associated with broad-spectrum empiric therapy may inform antibiotic stewardship interventions and facilitate benchmarking. METHODS: We performed a retrospective cohort study of adults discharged in 2019 from 928 hospitals in the Premier Healthcare Database. "Empiric" gram-negative antibiotics were defined by administration before day 3 of hospitalization. Multivariable logistic regression models with random effects by hospital were used to evaluate associations between patient and hospital characteristics and empiric receipt of broad-spectrum, compared to narrow-spectrum, gram-negative antibiotics. RESULTS: Of 8 017 740 hospitalized adults, 2 928 657 (37%) received empiric gram-negative antibiotics. Among 1 781 306 who received broad-spectrum therapy, 30% did not have a common infectious syndrome present on admission (pneumonia, urinary tract infection, sepsis, or bacteremia), surgery, or an intensive care unit stay in the empiric window. Holding other factors constant, males were 22% more likely (adjusted odds ratio [aOR], 1.22 [95% confidence interval, 1.22-1.23]), and all non-White racial groups 6%-13% less likely (aOR range, 0.87-0.94), to receive broad-spectrum therapy. There were significant prescribing differences by region, with the highest adjusted odds of broad-spectrum therapy in the US West South Central division. Even after model adjustment, there remained substantial interhospital variability: Among patients receiving empiric therapy, the probability of receiving broad-spectrum antibiotics varied as much as 34+ percentage points due solely to the admitting hospital (95% interval of probabilities: 43%-77%). CONCLUSIONS: Empiric gram-negative antibiotic use is highly variable across US regions, and there is high, unexplained interhospital variability. Sex and racial disparities in the receipt of broad-spectrum therapy warrant further investigation.

Is Carbapenem Therapy Necessary for the Treatment of Non-CTX-M ESBL-Producing Enterobacterales Bloodstream Infections?

BACKGROUND: Investigations into antibiotics for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSIs) have focused on blaCTX-M genes. Outcomes of patients with non-CTX-M-producing ESBL-E BSIs and optimal treatment are unknown. METHODS: A multicenter observational study investigating 500 consecutive patients with ceftriaxone-resistant Enterobacterales BSIs during 2018-2022 was conducted. Broth microdilution and whole genome sequencing confirmed antibiotic susceptibilities and ESBL gene presence, respectively. Inverse probability weighting (IPW) using propensity scores was employed to ensure patients infected with non-CTX-M and CTX-M ESBL-E BSIs were similar prior to evaluation of outcomes. RESULTS: 396 patients (79.2%) were confirmed to have an ESBL-E BSI. ESBL gene family prevalence was as follows: blaCTX-M (n=370), blaSHV (n=16), blaOXY (n=12), and blaVEB (n=5). ESBL gene identification was not limited to Escherichia coli and Klebsiella species. In the IPW cohort, there was no difference in 30-day mortality or ESBL-E infection recurrence between the non-CTX-M and CTX-M groups (OR=.99, 95% CI 0.87-1.11; p=0.83) and (OR=1.10, 95% CI 0.85--1.42; p=0.47), respectively. In an exploratory analysis limited to the non-CTX-M group, 86% of the 21 patients receiving meropenem were alive on day 30; none of the 5 patients receiving piperacillin-tazobactam were alive on day 30. CONCLUSIONS: Our findings suggest that non-CTX-M and CTX-M ESBL-producing Enterobacterales BSIs are equally concerning and associated with similar clinical outcomes. Meropenem may be associated with improved survival in patients with non-CTX-M ESBL-E BSIs, underscoring the potential benefit of comprehensive molecular diagnostics to enable early antibiotic optimization for patients with ESBL-E BSI, beyond just blaCTX-M genes.

The Impact of Universal Glove and Gown Use on Clostridioides Difficile Acquisition: A Cluster-Randomized Trial.

BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated infections in the United States. It is unknown whether universal gown and glove use in intensive care units (ICUs) decreases acquisition of C. difficile. METHODS: This was a secondary analysis of a cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from 4 January 2012 to 4 October 2012. After a baseline period, ICUs were randomized to standard practice for glove and gown use versus the intervention of all healthcare workers being required to wear gloves and gowns for all patient contact and when entering any patient room (contact precautions). The primary outcome was acquisition of toxigenic C. difficile determined by surveillance cultures collected on admission and discharge from the ICU. RESULTS: A total of 21 845 patients had both admission and discharge perianal swabs cultured for toxigenic C. difficile. On admission, 9.43% (2060/21 845) of patients were colonized with toxigenic C. difficile. No significant difference was observed in the rate of toxigenic C. difficile acquisition with universal gown and glove use. Differences in acquisition rates in the study period compared with the baseline period in control ICUs were 1.49 per 100 patient-days versus 1.68 per 100 patient-days in universal gown and glove ICUs (rate difference, -0.28; generalized linear mixed model, P = .091). CONCLUSIONS: Glove and gown use for all patient contact in medical and surgical ICUs did not result in a reduction in the acquisition of C. difficile compared with usual care. CLINICAL TRIALS REGISTRATION: NCT01318213.

Active Surveillance and Contact Precautions for Preventing Methicillin-Resistant Staphylococcus aureus Healthcare-Associated Infections During the COVID-19 Pandemic.

BACKGROUND: Statistically significant decreases in methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated infections (HAIs) occurred in Veterans Affairs (VA) hospitals from 2007 to 2019 using a national policy of active surveillance (AS) for facility admissions and contact precautions for MRSA colonized (CPC) or infected (CPI) patients, but the impact of suspending these measures to free up laboratory resources for testing and conserve personal protective equipment for coronavirus disease 2019 (COVID-19) on MRSA HAI rates is not known. METHODS: From July 2020 to June 2022 all 123 acute care VA hospitals nationwide were given the rolling option to suspend (or re-initiate) any combination of AS, CPC, or CPI each month, and MRSA HAIs in intensive care units (ICUs) and non-ICUs were tracked. RESULTS: There were 917 591 admissions, 5 225 174 patient-days, and 568 MRSA HAIs. The MRSA HAI rate/1000 patient-days in ICUs was 0.20 (95% confidence interval [CI], .15-.26) for facilities practicing "AS + CPC + CPI" compared to 0.65 (95% CI, .41-.98; P < .001) for those not practicing any of these strategies, and in non-ICUs was 0.07 (95% CI, .05-.08) and 0.12 (95% CI, .08-.19; P = .01) for the respective policies. Accounting for monthly COVID-19 facility admissions using a negative binomial regression model did not change the relationships between facility policy and MRSA HAI rates. There was no significant difference in monthly facility urinary catheter-associated infection rates, a non-equivalent dependent variable, in the policy categories in either ICUs or non-ICUs. CONCLUSIONS: Facility removal of MRSA prevention practices was associated with higher rates of MRSA HAIs in ICUs and non-ICUs.

Approach to schizophrenia.

Schizophrenia is the most common of a group of psychotic disorders that occur in approximately 3% of the population over the lifespan. It has clear genetic antecedents, which are shared across the spectrum of psychotic disorders; however, a range of other biological and social factors influence the onset and treatment of the disorder. Schizophrenia is diagnosed by a characteristic set of symptoms (positive, negative, disorganisation, cognitive and affective) accompanied by a functional decline. Investigations are used to exclude other organic causes of psychosis and to provide a baseline for the negative effects of pharmacological treatments. Treatment requires a combination of pharmacological and psychosocial interventions. Physical health is poor in this group of people and this is not helped by inconsistent care from health services. Although earlier intervention has improved the immediate outcomes, the longer-term outcome has not significantly shifted.

FEEDBACK trial - A randomised control trial to investigate the effect of personalised feedback and financial incentives on reducing the incidence of road crashes.

BACKGROUND: Road crashes continue to pose a significant threat to global health. Young drivers aged between 18 and 25 are over-represented in road injury and fatality statistics, especially the first six months after obtaining their license. This study is the first multi-centre two-arm parallel-group individually randomised controlled trial (the FEEDBACK Trial) that will examine whether the delivery of personalised driver feedback plus financial incentives is superior to no feedback and no financial incentives in reducing motor vehicle crashes among young drivers (18 to 20 years) during the first year of provisional licensing. METHODS: A total of 3,610 young drivers on their provisional licence (P1, the first-year provisional licensing) will participate in the trial over 28 weeks, including a 4-week baseline, 20-week intervention and 4-week post-intervention period. The primary outcome of the study will be police-reported crashes over the 20-week intervention period and the 4-week post-intervention period. Secondary outcomes include driving behaviours such as speeding and harsh braking that contribute to road crashes, which will be attained weekly from mobile telematics delivered to a smartphone app. DISCUSSION: Assuming a positive finding associated with personalised driver feedback and financial incentives in reducing road crashes among young drivers, the study will provide important evidence to support policymakers in introducing the intervention(s) as a key strategy to mitigate the risks associated with the burden of road injury among this vulnerable population. TRIAL REGISTRATION: Registered under the Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12623000387628p on April 17, 2023.

Comparing Video-Based, Telehealth-Delivered Exercise and Weight Loss Programs With Online Education on Outcomes of Knee Osteoarthritis : A Randomized Trial.

BACKGROUND: Scalable knee osteoarthritis programs are needed to deliver recommended education, exercise, and weight loss interventions. OBJECTIVE: To evaluate two 6-month, telehealth-delivered exercise programs, 1 with and 1 without dietary intervention. DESIGN: 3-group, parallel randomized (5:5:2) trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000930280). SETTING: Australian private health insurance members. PARTICIPANTS: 415 persons with symptomatic knee osteoarthritis and a body mass index between 28 and 40 kg/m2 who were aged 45 to 80 years. INTERVENTION: All groups received access to electronic osteoarthritis information (control). The exercise program comprised 6 physiotherapist consultations via videoconference for exercise, self-management advice, and behavioral counseling, plus exercise equipment and resources. The diet and exercise program included an additional 6 dietitian consultations for a ketogenic very-low-calorie diet (2 formulated meal replacements and a low-carbohydrate meal daily) followed by a transition to healthy eating, as well as nutrition and behavioral resources. MEASUREMENTS: Primary outcomes were changes in knee pain (numerical rating scale [NRS] of 0 to 10, higher indicating worse) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]; scale, 0 to 68, higher indicating worse) at 6 months (primary time point) and 12 months. Secondary outcomes were weight, physical activity, quality of life, mental health, global change, satisfaction, willingness to have surgery, orthopedic appointments, and knee surgery. RESULTS: A total of 379 participants (91%) provided 6-month primary outcomes, and 372 (90%) provided 12-month primary outcomes. At 6 months, both programs were superior to control for pain (between-group mean difference in change on NRS: diet and exercise, -1.5 [95% CI, -2.1 to -0.8]; exercise, -0.8 [CI, -1.5 to -0.2]) and function (between-group mean difference in change on WOMAC: diet and exercise, -9.8 [CI, -12.5 to -7.0]; exercise, -7.0 [CI, -9.7 to -4.2]). The diet and exercise program was superior to exercise (pain, -0.6 [CI, -1.1 to -0.2]; function, -2.8 [CI, -4.7 to -0.8]). Findings were similar at 12 months. LIMITATION: Participants and clinicians were unblinded. CONCLUSION: Telehealth-delivered exercise and diet programs improved pain and function in people with knee osteoarthritis and overweight or obesity. A dietary intervention conferred modest additional pain and function benefits over exercise. PRIMARY FUNDING SOURCE: Medibank, the Medibank Better Health Foundation Research Fund, and a National Health and Medical Research Council Centre of Research Excellence.