Propensity Score-Weighted Analysis of Postoperative Infection in Patients With and Without Preoperative Urine Culture.

Importance: Although recent guidelines recommend against performance of preoperative urine culture before nongenitourinary surgery, many clinicians still order preoperative urine cultures and prescribe antibiotics for treatment of asymptomatic bacteriuria in an effort to reduce infection risk. Objective: To assess the association between preoperative urine culture testing and postoperative urinary tract infection (UTI) or surgical site infection (SSI), independent of baseline patient characteristics or type of surgery. Design, Setting, and Participants: This cohort study analyzed surgical procedures performed from January 1, 2017, to December 31, 2019, at any of 112 US Department of Veterans Affairs (VA) medical centers. The cohort comprised VA enrollees who underwent major elective noncardiac, nonurological operations. Machine learning and inverse probability of treatment weighting (IPTW) were used to balance the characteristics between those who did and did not undergo a urine culture. Data analyses were performed between January 2023 and January 2024. Exposures: Performance of urine culture within 30 days prior to surgery. Main Outcomes and Measures: The 2 main outcomes were UTI and SSI occurring within 30 days after surgery. Weighted logistic regression was used to estimate odds ratios (ORs) for postoperative infection based on treatment status. Results: A total of 250 389 VA enrollees who underwent 288 858 surgical procedures were included, with 88.9% (256 753) of surgical procedures received by males and 48.9% (141 340) received by patients 65 years or older. Baseline characteristics were well balanced among treatment groups after applying IPTW weights. Preoperative urine culture was performed for 10.5% of surgical procedures (30 384 of 288 858). The IPTW analysis found that preoperative urine culture was not associated with SSI (adjusted OR [AOR], 0.99; 95% CI, 0.90-1.10) or postoperative UTI (AOR, 1.18; 95% CI, 0.98-1.40). In analyses limited to orthopedic surgery and neurosurgery as a proxy for prosthetic implants, the adjusted risks for UTI and SSI were also not associated with preoperative urine culture performance. Conclusions and Relevance: This cohort study found no association between performance of a preoperative urine culture and lower risk of postoperative UTI or SSI. The results support the deimplementation of urine cultures and associated antibiotic treatment prior to surgery, even when using prosthetic implants.

Comparative effectiveness of daptomycin versus vancomycin among patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections: A systematic literature review and meta-analysis.

BACKGROUND: In the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs), vancomycin stands as the prevalent therapeutic agent. Daptomycin remains an alternative antibiotic to treat MRSA BSIs in cases where vancomycin proves ineffective. However, studies have conflicted on whether daptomycin is more effective than vancomycin among patients with MRSA BSI. OBJECTIVE: To compare the effectiveness of daptomycin and vancomycin for the prevention of mortality among adult patients with MRSA BSI. METHODS: Systematic searches of databases were performed, including Embase, PubMed, Web of Science, and Cochrane Library. The Newcastle Ottawa Scale (NOS) and Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) were used to assess the quality of individual observational and randomized control studies, respectively. Pooled odd ratios were calculated using random effects models. RESULTS: Twenty studies were included based on a priori set inclusion and exclusion criteria. Daptomycin treatment was associated with non-significant lower mortality odds, compared to vancomycin treatment (OR = 0.81; 95% CI, 0.62, 1.06). Sub-analyses based on the time patients were switched from another anti-MRSA treatment to daptomycin demonstrated that switching to daptomycin within 3 or 5 days was significantly associated with 55% and 45% decreased odds of all-cause mortality, respectively. However, switching to daptomycin any time after five days of treatment was not significantly associated with lower odds of mortality. Stratified analysis based on vancomycin minimum inhibitory concentration (MIC) revealed that daptomycin treatment among patients infected with MRSA strains with MIC≥1 mg/L was significantly associated with 40% lower odds of mortality compared to vancomycin treatment. CONCLUSION: Compared with vancomycin, an early switch from vancomycin to daptomycin was significantly associated with lower odds of mortality. In contrast, switching to daptomycin at any time only showed a trend towards reduced mortality, with a non-significant association. Therefore, the efficacy of early daptomycin use over vancomycin against mortality among MRSA BSIs patients may add evidence to the existing literature in support of switching to daptomycin early over remaining on vancomycin. More randomized and prospective studies are needed to assess this association.

Intravenous Diltiazem Versus Metoprolol in Acute Rate Control of Atrial Fibrillation/Flutter and Rapid Ventricular Response: A Meta-Analysis of Randomized and Observational Studies.

BACKGROUND: Atrial fibrillation (AF) and/or atrial flutter (AFL) with rapid ventricular response (RVR) is a condition that often requires urgent treatment. Although guidelines have recommendations regarding chronic rate control therapy, recommendations on the best choice for acute heart rate (HR) control in RVR are unclear. METHODS: A systematic search across multiple databases was performed for studies evaluating the outcome of HR control (defined as HR less than 110 bpm and/or 20% decrease from baseline HR). Included studies evaluated AF and/or AFL with RVR in a hospital setting, with direct comparison between intravenous (IV) diltiazem and metoprolol and excluded cardiac surgery and catheter ablation patients. Hypotension (defined as systolic blood pressure less than 90 mmHg) was measured as a secondary outcome. Two authors performed full-text article review and extracted data, with a third author mediating disagreements. Random effects models utilizing inverse variance weighting were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the I2 test. RESULTS: A total of 563 unique titles were identified through the systematic search, of which 16 studies (7 randomized and 9 observational) were included. In our primary analysis of HR control by study type, IV diltiazem was found to be more effective than IV metoprolol for HR control in randomized trials (OR 4.75, 95% CI 2.50-9.04 with I2 = 14%); however, this was not found for observational studies (OR 1.26, 95% CI 0.89-1.80 with I2 = 55%). In an analysis of observational studies, there were no significant differences between the two drugs in odds of hypotension (OR 1.12, 95% CI 0.51-2.45 with I2 = 18%). CONCLUSION: While there was a trend toward improved HR control with IV diltiazem compared with IV metoprolol in randomized trials, this was not seen in observational studies, and there was no observed difference in hypotension between the two drugs.

Implementing strategies to prevent infections in acute-care settings.

This document introduces and explains common implementation concepts and frameworks relevant to healthcare epidemiology and infection prevention and control and can serve as a stand-alone guide or be paired with the "SHEA/IDSA/APIC Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2022 Updates," which contain technical implementation guidance for specific healthcare-associated infections. This Compendium article focuses on broad behavioral and socio-adaptive concepts and suggests ways that infection prevention and control teams, healthcare epidemiologists, infection preventionists, and specialty groups may utilize them to deliver high-quality care. Implementation concepts, frameworks, and models can help bridge the "knowing-doing" gap, a term used to describe why practices in healthcare may diverge from those recommended according to evidence. It aims to guide the reader to think about implementation and to find resources suited for a specific setting and circumstances by describing strategies for implementation, including determinants and measurement, as well as the conceptual models and frameworks: 4Es, Behavior Change Wheel, CUSP, European and Mixed Methods, Getting to Outcomes, Model for Improvement, RE-AIM, REP, and Theoretical Domains.

Obesity in Refugees post-resettlement in a high-income country: a meta-analysis.

BACKGROUND: Refugees have a high prevalence of obesity post resettlement, but few studies have compared their risk of obesity to those of the host population. We systematically investigated the association between refugee status and obesity after resettlement in a high-income nation. METHODS: We searched PubMed, Embase, OpenGrey and bibliographies of retrieved articles, with no date, location, and language restrictions, for observational studies assessing obesity rates in resettled refugees compared to the host population. RESULTS: Nine studies were analyzed. We found no evidence of increased risk of obesity among refugees compared to the host population, with significant heterogeneity across studies. However, the risk of obesity among refugee men were significantly lower than the host population. DISCUSSION: The heterogeneity between studies calls for more high-quality research to examine the risk of obesity among refugees compared to the host population in high-income countries. This will enable results to be pooled to provide more decisive evidence about obesity trends among refugees post migration in a high-income nation.

Implementation of a Prevention Bundle to Decrease Rates of Staphylococcus aureus Surgical Site Infection at 11 Veterans Affairs Hospitals.

Importance: While current evidence has demonstrated a surgical site infection (SSI) prevention bundle consisting of preoperative Staphylococcus aureus screening, nasal and skin decolonization, and use of appropriate perioperative antibiotic based on screening results can decrease rates of SSI caused by S aureus, it is well known that interventions may need to be modified to address facility-level factors. Objective: To assess the association between implementation of an SSI prevention bundle allowing for facility discretion regarding specific component interventions and S aureus deep incisional or organ space SSI rates. Design, Setting, and Participants: This quality improvement study was conducted among all patients who underwent coronary artery bypass grafting, cardiac valve replacement, or total joint arthroplasty (TJA) at 11 Veterans Administration hospitals. Implementation of the bundle was on a rolling basis with the earliest implementation occurring in April 2012 and the latest implementation occurring in July 2017. Data were collected from January 2007 to March 2018 and analyzed from October 2020 to June 2023. Interventions: Nasal screening for S aureus; nasal decolonization of S aureus carriers; chlorhexidine bathing; and appropriate perioperative antibiotic prophylaxis according to S aureus carrier status. Facility discretion regarding how to implement the bundle components was allowed. Main Outcomes and Measures: The primary outcome was deep incisional or organ space SSI caused by S aureus. Multivariable logistic regression with generalized estimating equation (GEE) and interrupted time-series (ITS) models were used to compare SSI rates between preintervention and postintervention periods. Results: Among 6696 cardiac surgical procedures and 16 309 TJAs, 95 S aureus deep incisional or organ space SSIs were detected (25 after cardiac operations and 70 after TJAs). While the GEE model suggested a significant association between the intervention and decreased SSI rates after TJAs (adjusted odds ratio, 0.55; 95% CI, 0.31-0.98), there was not a significant association when an ITS model was used (adjusted incidence rate ratio, 0.88; 95% CI, 0.32-2.39). No significant associations after cardiac operations were found. Conclusions and Relevance: Although this quality improvement study suggests an association between implementation of an SSI prevention bundle and decreased S aureus deep incisional or organ space SSI rates after TJAs, it was underpowered to see a significant difference when accounting for changes over time.

Effectiveness and acceptability of intranasal povidone-iodine decolonization among fracture fixation surgery patients to reduce Staphylococcus aureus nasal colonization.

We evaluated povidone-iodine (PVI) decolonization among 51 fracture-fixation surgery patients. PVI was applied twice on the day of surgery. Patients were tested for S. aureus nasal colonization and surveyed. Mean S. aureus concentrations decreased from 3.13 to 1.15 CFU/mL (P = .03). Also, 86% of patients stated that they felt neutral or positive about their PVI experience.

Efficacy of Diet on Fatigue and Quality of Life in Multiple Sclerosis: A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND AND OBJECTIVE: Emerging evidence suggests a role for diet in multiple sclerosis (MS) care; however, owing to methodological issues and heterogeneity of dietary interventions in preliminary trials, the current state of evidence does not support dietary recommendations for MS. The objective of this study was to assess the efficacy of different dietary approaches on MS-related fatigue and quality of life (QoL) through a systematic review of the literature and network meta-analysis (NMA). METHODS: Electronic database searches were performed in May 2021. Inclusion criteria were (1) randomized trial with a dietary intervention, (2) adults with definitive MS based on McDonald criteria, (3) patient-reported outcomes for fatigue and/or QoL, and (4) minimum intervention period of 4 weeks. For each outcome, standardized mean differences (SMDs) were calculated and included in random effects NMA to determine the pooled effect of each dietary intervention relative to each of the other dietary interventions. The protocol was registered at PROSPERO (CRD42021262648). RESULTS: Twelve trials comparing 8 dietary interventions (low-fat, Mediterranean, ketogenic, anti-inflammatory, Paleolithic, fasting, calorie restriction, and control [usual diet]), enrolling 608 participants, were included in the primary analysis. The Paleolithic (SMD -1.27; 95% CI -1.81 to -0.74), low-fat (SMD -0.90; 95% CI -1.39 to -0.42), and Mediterranean (SMD -0.89; 95% CI -1.15 to -0.64) diets showed greater reductions in fatigue compared with control. The Paleolithic (SMD 1.01; 95% CI 0.40-1.63) and Mediterranean (SMD 0.47; 95% CI 0.08-0.86) diets showed greater improvements in physical QoL compared with control. For improving mental QoL, the Paleolithic (SMD 0.81; 95% CI 0.26-1.37) and Mediterranean (SMD 0.36; 95% CI 0.06-0.65) diets were more effective compared with control. However, the NutriGRADE credibility of evidence for all direct comparisons is very low because of most of the included trials having high or moderate risk of bias, small sample sizes, and the limited number of studies included in this NMA. DISCUSSION: Several dietary interventions may reduce MS-related fatigue and improve physical and mental QoL; however, because of the limitations of this NMA, which are driven by the low quality of the included trials, these findings must be confirmed in high-quality, randomized, controlled trials.

Prevalence of One-Year Mortality after Implantable Cardioverter Defibrillator Placement: An Opportunity for Palliative Care?

Background: Current guidelines recommend against placement of implantable cardioverter defibrillators in patients with a life expectancy less than one year. These patients may benefit from early palliative care services; however, identifying this population is challenging. Objective: Determine whether a validated prognostic tool, based on patient factors and health care utilization from electronic medical records, accurately predicts one-year mortality at the time of implantable cardioverter defibrillator placement. Design: We used the United States (U.S.) Veterans Administration's "Care Assessment Needs" one-Year Mortality Score to identify patients at high risk of mortality (score ≥95) before their procedure. Data were extracted from the Corporate Data Warehouse. Logistic regression was used to assess the odds of mortality at different score levels. Setting/Subjects: Patients undergoing a new implantable cardioverter defibrillator procedure between October 1, 2015 and September 30, 2017 in the U.S. Veterans Administration. Results: Of 3194 patients with a new implantable cardioverter defibrillator placed, 657 (21.8%) had a score ≥95. The mortality rate among these patients was 151/657 (22.9%) compared with 281/3194 (8.8%) for all patients undergoing a new implantable cardioverter defibrillator procedure. Patients with a score ≥95 had 14.0 (95% confidence interval 8.0-24.4) higher odds of death within one year of the procedure compared with those with a score ≤60. Conclusions: The "Care Assessment Needs" Score is a valid predictor of one-year mortality following implantable cardioverter defibrillator procedures. Integrating its use into the management of Veterans Administration (VA) patients considering implantable cardioverter defibrillators may improve shared decision making and engagement with palliative care.

Comparative effectiveness of antibiotic therapy for carbapenem-resistant Enterobacterales (CRE) bloodstream infections in hospitalized US veterans.

Background: Carbapenem-resistant Enterobacterales bloodstream infections (CRE-BSI) increase mortality three-fold compared with carbapenem-susceptible bloodstream infections. Because these infections are rare, there is a paucity of information on mortality associated with different treatment regimens. This study examines treatment regimens and association with in-hospital, 30 day and 1 year mortality risk for patients with CRE-BSI. Methods: This retrospective cohort study identified hospitalized patients within the Veteran Affairs (VA) from 2013 to 2018 with a positive CRE blood culture and started antibiotic treatment within 5 days of culture. Primary outcomes were in-hospital, 30 day and 1 year all-cause mortality. Secondary outcomes were healthcare costs at 30 days and 1 year and Clostridioides difficile infection 6 weeks post culture date. The propensity for receiving each treatment regimen was determined. Multivariable regression assessed the association between treatment and outcomes. Results: There were 393 hospitalized patients from 2013 to 2018 included in the study. The cohort was male (97%) and elderly (mean age 71.0 years). Carbapenems were the most prescribed antibiotics (47%). In unadjusted analysis, ceftazidime/avibactam was associated with a lower likelihood of 30 day and 1 year mortality. After adjusting, ceftazidime/avibactam had a 30 day mortality OR of 0.42 (95% CI 0.17-1.02). No difference was found in C. difficile incidence at 6 weeks post-infection or total costs at 30 days or 1 year post culture date by any treatments. Conclusions: In hospitalized veterans with CRE-BSI, none of the treatments were shown to be associated with all-cause mortality. Ceftazidime/avibactam trended towards protectiveness against 30 day and 1 year all-cause mortality. Use of ceftazidime/avibactam should be encouraged for treatment of CRE-BSI.

The long-term effectiveness of coronavirus disease 2019 (COVID-19) vaccines: A systematic literature review and meta-analysis.

Background: Although multiple studies revealed high vaccine effectiveness of coronavirus disease 2019 (COVID-19) vaccines within 3 months after the completion of vaccines, long-term vaccine effectiveness has not been well established, especially after the δ (delta) variant became prominent. We performed a systematic literature review and meta-analysis of long-term vaccine effectiveness. Methods: We searched PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 2019 to November 15, 2021, for studies evaluating the long-term vaccine effectiveness against laboratory-confirmed COVID-19 or COVID-19 hospitalization among individuals who received 2 doses of Pfizer/BioNTech, Moderna, or AstraZeneca vaccines, or 1 dose of the Janssen vaccine. Long-term was defined as >5 months after the last dose. We calculated the pooled diagnostic odds ratio (DOR) with 95% confidence interval for COVID-19 between vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% × (1 - DOR). Results: In total, 16 studies including 17,939,172 individuals evaluated long-term vaccine effectiveness and were included in the meta-analysis. The pooled DOR for COVID-19 was 0.158 (95% CI: 0.157-0.160) with an estimated vaccine effectiveness of 84.2% (95% CI, 84.0- 84.3%). Estimated vaccine effectiveness against COVID-19 hospitalization was 88.7% (95% CI, 55.8%-97.1%). Vaccine effectiveness against COVID-19 during the δ variant period was 61.2% (95% CI, 59.0%-63.3%). Conclusions: COVID-19 vaccines are effective in preventing COVID-19 and COVID-19 hospitalization across a long-term period for the circulating variants during the study period. More observational studies are needed to evaluate the vaccine effectiveness of third dose of a COVID-19 vaccine, the vaccine effectiveness of mixing COVID-19 vaccines, COVID-19 breakthrough infection, and vaccine effectiveness against newly emerging variants.

Effectiveness and Optimal Duration of Adjunctive Rifampin Treatment in the Management of Staphylococcus aureus Prosthetic Joint Infections After Debridement, Antibiotics, and Implant Retention.

Background: Rifampin is recommended as adjunctive therapy for patients with a Staphylococcus aureus prosthetic joint infection (PJI) managed with debridement, antibiotics, and implant retention (DAIR), with no solid consensus on the optimal duration of therapy. Our study assessed the effectiveness and optimal duration of rifampin for S aureus PJI using Veterans Health Administration (VHA) data. Methods: We conducted a retrospective cohort study of patients with S aureus PJI managed with DAIR between 2003 and 2019 in VHA hospitals. Patients who died within 14 days after DAIR were excluded. The primary outcome was a time to microbiological recurrence from 15 days up to 2 years after DAIR. Rifampin use was analyzed as a time-varying exposure, and time-dependent hazard ratios (HRs) for recurrence were calculated according to the duration of rifampin treatment. Results: Among 4624 patients, 842 (18.2%) received at least 1 dose of rifampin; 1785 (38.6%) experienced recurrence within 2 years. Rifampin treatment was associated with significantly lower HRs for recurrence during the first 90 days of treatment (HR, 0.60 [95% confidence interval {CI}, .45-.79]) and between days 91 and 180 (HR, 0.16 [95% CI, .04-.66]) but no statistically significant protective effect was observed with longer than 180 days (HR, 0.57 [95% CI, .18-1.81]). The benefit of rifampin was observed for subgroups including knee PJI, methicillin-susceptible or -resistant S aureus infection, and early or late PJI. Conclusions: This study supports current guidelines that recommend adjunctive rifampin use for up to 6 months among patients with S aureus PJI treated with DAIR.

Impact of Infectious Diseases Consultation on the Outcome of Patients With Enterococcal Bacteremia: A Systematic Literature Review and Meta-analysis.

Background: Enterococcal bacteremia carries significant mortality. While multiple studies have evaluated the impact of infectious disease consultation (IDC) on this condition, these studies were limited by the low numbers of patients enrolled. This systemic literature review and meta-analysis was conducted to determine whether IDC is associated with a mortality benefit among patients with enterococcal bacteremia. Methods: We performed a systematic literature search using 5 databases for studies evaluating IDC among patients with enterococcal bacteremia. We conducted a meta-analysis to assess whether IDC was associated with reduced mortality. Random-effects models were used to calculate pooled odds ratios (pORs). Heterogeneity was evaluated using I 2 estimation and the Cochran's Q statistic test. Results: The systematic literature review revealed 6496 reports, from which 18 studies were evaluated in the literature review and 16 studies in the meta-analysis. When all studies were pooled, the association between IDC and mortality was not statistically significant with a pOR of 0.81 (95% CI, 0.61-1.08) and substantial heterogeneity (I 2 = 58%). When the studies were limited to those reporting multivariate analysis including IDC, there was a significant protective effect of IDC (pOR, 0.40; 95% CI, 0.24-0.68) without heterogeneity (I 2 = 0%). Some studies also showed additional benefits to IDC, including appropriate antibiotic therapy and improved diagnostic use. Conclusions: IDC was associated with 60% lower odds of mortality when patients were well-matched, potentially through improvement in the care of patients with enterococcal bacteremia. IDC should be considered part of routine care for patients with enterococcal bacteremia.

The Effectiveness of Combination Therapy for Treating Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Systematic Literature Review and a Meta-Analysis.

BACKGROUND: This meta-analysis aims to evaluate the effectiveness of combination therapy for treating MSSA bacteremia. METHODS: We searched Ovid MEDLINE, EMBASE, Cochrane CENTRAL, and clinicaltrials.gov for studies including adults with MSSA bacteremia. The monotherapy group used a first-line antibiotic active against MSSA and the combination group used a first-line antibiotic plus additional antibiotic/s. The primary outcome was all-cause mortality. Secondary outcomes included persistent bacteremia, duration of bacteremia, relapse, and adverse events. Random-effects models with inverse variance weighting were used to estimate pooled risk ratios (pRR). Heterogeneity was assessed using the I2 value and the Cochrane's Q statistic. RESULTS: A total of 12 studies (6 randomized controlled trials [RCTs]) were included. Combination therapy did not significantly reduce 30-day mortality (pRR 0.92, 95% CI, 0.70-1.20), 90-day mortality (pRR 0.89, 95% CI, 0.74-1.06), or any-time mortality (pRR 0.91, 95% CI, 0.76-1.08). Among patients with deep-seated infections, adjunctive rifampicin may reduce 90-day mortality (3 studies with moderate-high risk of bias; pRR 0.62, 95% CI, 0.42-0.92). For secondary outcomes, combination therapy decreased the risk of relapse (pRR 0.38, 95% CI, 0.22-0.66), but this benefit was not maintained when pooling RCTs (pRR 0.54, 95% CI, 0.12-2.51). Combination therapy was associated with an increased risk of adverse events (pRR 1.74, 95% CI, 1.31-2.31). CONCLUSIONS: Combination therapy not only did not decrease mortality in patients with MSSA bacteremia, but also increased the risk of adverse events. Combination therapy may reduce the risk of relapse, but additional high-quality studies are needed.

Association of Nonobstructive Chronic Bronchitis With All-Cause Mortality: A Systematic Literature Review and Meta-analysis.

BACKGROUND: The effect of nonobstructive chronic bronchitis (CB) on mortality is unclear. RESEARCH QUESTION: Is nonobstructive CB associated with increased all-cause mortality? STUDY DESIGN AND METHODS: We conducted a systematic literature review and meta-analysis to assess the association of nonobstructive CB and all-cause mortality. We searched for articles that included both CB and mortality in the title, abstract, or both in PubMed and EMBASE. We excluded studies in which participants demonstrated obstructive spirometry findings and studies in which CB and mortality were not defined. We used the Newcastle-Ottawa Quality Assessment Scale to assess study quality. We pooled adjusted hazard ratios (HRs) using the random effects model and inverse variance weighting. We conducted stratified analysis by the definition of CB and smoking status. We used Cochran's Q and I2 to assess for heterogeneity. We assessed publication bias by visual inspection of a funnel plot. RESULTS: Of 5,014 titles identified, eight fulfilled the inclusion and exclusion criteria. Overall nonobstructive CB was associated with all-cause mortality (HR, 1.37; 95% CI, 1.26-1.50) with no statistically significant heterogeneity (P = .14; I2 = 29%). Nonobstructive CB was associated with increased mortality in studies that defined CB as any respiratory symptoms (broad definition; HR, 1.28; 95% CI, 1.10-1.48; I2 = 0%) as well as in the rest of the studies (HR, 1.40; 95% CI, 1.26-1.56; I2 = 37%). Nonobstructive CB was associated with increased mortality in ever smokers (HR, 1.49; 95% CI, 1.35-1.64; I2 = 0%), but was not associated with increased mortality in never smokers (HR, 1.22; 95% CI, 0.90-1.66), and moderate heterogeneity was found (P = .10; I2 = 49%). The funnel plot did not indicate evidence of a publication bias because it showed symmetrical distribution of studies. INTERPRETATION: Nonobstructive CB is associated with increased all-cause mortality, and this association seems to be present only in current and former smokers. Further research should investigate whether this high-risk population may benefit from early therapeutic intervention. TRIAL REGISTRY: PROSPERO; No.: CRD42021253596; URL: www.crd.york.ac.uk/prospero.

Short-term effectiveness of COVID-19 vaccines in immunocompromised patients: A systematic literature review and meta-analysis.

OBJECTIVES: We aimed to assess the short-term effectiveness of COVID-19 vaccines among immunocompromised patients to prevent laboratory-confirmed symptomatic COVID-19 infection. METHODS: Systematic review and meta-analysis. We calculated the pooled diagnostic odds ratio [DOR] (95% CI) for COVID-19 infection between immunocompromised patients and healthy people or those with stable chronic medical conditions. VE was estimated as 100% x (1-DOR). We also investigated the rates of developing anti-SARS-CoV-2 spike protein IgG between the 2 groups. RESULTS: Twenty studies evaluating COVID-19 vaccine response, and four studies evaluating VE were included in the meta-analysis. The pooled DOR for symptomatic COVID-19 infection in immunocompromised patients was 0.296 (95% CI: 0.108-0.811) with an estimated VE of 70.4% (95% CI: 18.9%- 89.2%). When stratified by diagnosis, IgG antibody levels were much higher in the control group compared to immunocompromised patients with solid organ transplant (pOR 232.3; 95% Cl: 66.98-806.03), malignant diseases (pOR 42.0, 95% Cl: 11.68-151.03), and inflammatory rheumatic diseases (pOR 19.06; 95% Cl: 5.00-72.62). CONCLUSIONS: We found COVID-19 mRNA vaccines were effective against symptomatic COVID-19 among the immunocompromised patients but had lower VE compared to the controls. Further research is needed to understand the discordance between antibody production and protection against symptomatic COVID-19 infection.

Promoting de-implementation of inappropriate antimicrobial use in cardiac device procedures by expanding audit and feedback: protocol for hybrid III type effectiveness/implementation quasi-experimental study.

BACKGROUND: Despite a strong evidence base and clinical guidelines specifically recommending against prolonged post-procedural antimicrobial use, studies indicate that the practice is common following cardiac device procedures. Formative evaluations conducted by the study team suggest that inappropriate antimicrobial use may be driven by information silos that drive provider belief that antimicrobials are not harmful, in part due to lack of complete feedback about all types of clinical outcomes. De-implementation is recognized as an important area of research that can lead to reductions in unnecessary, wasteful, or harmful practices, such as excess antimicrobial use following cardiac device procedures; however, investigations into strategies that lead to successful de-implementation are limited. The overarching hypothesis to be tested in this trial is that a bundle of implementation strategies that includes audit and feedback about direct patient harms caused by inappropriate prescribing can lead to successful de-implementation of guideline-discordant care. METHODS: We propose a hybrid type III effectiveness-implementation stepped-wedge intervention trial at three high-volume, high-complexity VA medical centers. The main study intervention (an informatics-based, real-time audit-and-feedback tool) was developed based on learning/unlearning theory and formative evaluations and guided by the integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) Framework. Elements of the bundled and multifaceted implementation strategy to promote appropriate prescribing will include audit-and-feedback reports that include information about antibiotic harms, stakeholder engagement, patient and provider education, identification of local champions, and blended facilitation. The primary study outcome is adoption of evidence-based practice (de-implementation of inappropriate antimicrobial use). Clinical outcomes (cardiac device infections, acute kidney injuries and Clostridioides difficile infections) are secondary. Qualitative interviews will assess relevant implementation outcomes (acceptability, adoption, fidelity, feasibility). DISCUSSION: De-implementation theory suggests that factors that may have a particularly strong influence on de-implementation include strength of the underlying evidence, the complexity of the intervention, and patient and provider anxiety and fear about changing an established practice. This study will assess whether a multifaceted intervention mapped to identified de-implementation barriers leads to measurable improvements in provision of guideline-concordant antimicrobial use. Findings will improve understanding about factors that impact successful or unsuccessful de-implementation of harmful or wasteful healthcare practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT05020418.

Self-controlled assessment of thromboembolic event (TEE) risk following intravenous immune globulin (IGIV) in the U.S. (2006-2012).

Since 2013, the U.S. Food and Drug administration (FDA) has required that intravenous immune globulin (IGIV) products carry a boxed warning concerning the risk of thromboembolic events (TEEs). This study assessed the incidence of TEEs attributable to IGIV in a large population-based cohort. A self-controlled risk interval design was used to quantify the transient increase in TEE risk during the risk interval (days 0-2 and 0-13 following IGIV for arterial and venous TEEs, respectively) relative to a later control interval (days 14-27 following IGIV). Potential IGIV-exposed TEE cases from 2006 to 2012 were identified from the FDA-sponsored Sentinel Distributed Database and confirmed through medical record review. Inpatient IGIV exposures were not included in the venous TEE analysis due to concerns about time-varying confounding. 19,069 new users of IGIV who received 93,555 treatment episodes were included. Charts were retrieved for 62% and 70% of potential venous and arterial cases, respectively. There was a transient increase in the risk of arterial TEEs during days 0-2 following IGIV treatment (RR = 4.69; 95% CI 1.87, 11.90; absolute increase in risk = 8.86 events per 10,000 patients, 95% CI 3.25, 14.6), but no significant increase in venous TEE risk during days 0-13 following outpatient IGIV treatments (RR = 1.07, 95% CI 0.34, 3.48). Our results suggest there is a small increase in the absolute risk of arterial TEEs following IGIV. However, lower-than-expected chart retrieval rates and the possibility of time-varying confounding mean that our results should be interpreted cautiously. Continued pharmacovigilance efforts are warranted.