Microenvironment M1/M2 macrophages and tumoral progression vary within C57BL/6 mice from same substrain in prostate cancer model.

Cancer mice models are critical for immune-oncology research; they provide conditions to explore tumor immunoenviroment aiming to advance knowledge and treatment development. Often, research groups breed their own mice colonies. To assess the effect of C57BL/6 mice breeding nuclei in prostate cancer development and intratumoral macrophage populations, an isotransplantation experiment was performed. C57BL/6J mice from two breeding nuclei (nA and nB) were employed for prostate adenocarcinoma TRAMP-C1 cell implantation; tumor growth period and intratumoral macrophage profile were measured. BL/6nB mice (54%) showed tumor implantation after 69-day growth period while BL/6nA implantation reached 100% across tumor growth period (28 days). No difference in total macrophage populations was observed between groups within several tumoral regions; significantly higher M2 macrophage profile was observed in tumor microenvironments from both mice groups. Nevertheless, BL/6nB tumors showed around twice the population of M1 profile (11-27%) than BL6nA (4-15%) and less non-polarized macrophages. The M1:M2 average ratio was 1:8 for group A and 1:4 for B. Our results demonstrate different tumor progression and intratumoral macrophage populations among mice from the same substrain. Data obtained in this study shows the relevance of animal source renewal for better control of murine cancer model variables.

Implementing nasal povidone-iodine decolonization to reduce infections in hemodialysis units: a qualitative assessment.

BACKGROUND: A substantial proportion of patients undergoing hemodialysis carry Staphylococcus aureus in their noses, and carriers are at increased risk of S. aureus bloodstream infections. Our pragmatic clinical trial implemented nasal povidone-iodine (PVI) decolonization for the prevention of bloodstream infections in the novel setting of hemodialysis units. OBJECTIVE: We aimed to identify pragmatic strategies for implementing PVI decolonization among patients in outpatient hemodialysis units. DESIGN: Qualitative descriptive study. SETTING: Outpatient hemodialysis units affiliated with five US academic medical centers. Units varied in size, patient demographics, and geographic location. INTERVIEWEES: Sixty-six interviewees including nurses, hemodialysis technicians, research coordinators, and other personnel. METHODS: We conducted interviews with personnel affiliated with all five academic medical centers and conducted thematic analysis of transcripts. RESULTS: Hemodialysis units had varied success with patient recruitment, but interviewees reported that patients and healthcare personnel (HCP) found PVI decolonization acceptable and feasible. Leadership support, HCP engagement, and tailored patient-focused tools or strategies facilitated patient engagement and PVI implementation. Interviewees reported both patients and HCP sometimes underestimated patients' infection risks and experienced infection-prevention fatigue. Other HCP barriers included limited staffing and poor staff engagement. Patient barriers included high health burdens, language barriers, memory issues, and lack of social support. CONCLUSION: Our qualitative study suggests that PVI decolonization would be acceptable to patients and clinical personnel, and implementation is feasible for outpatient hemodialysis units. Hemodialysis units could facilitate implementation by engaging unit leaders, patients and personnel, and developing education for patients about their infection risk.

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.

De-escalating axillary management after neoadjuvant chemotherapy in breast cancer: The ratio of positive sentinel lymph nodes matters.

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) patients diminishes sequelae without compromising cancer outcomes. Surgical management of the axilla is challenging after neoadjuvant treatment. We aimed to identify the factors associated with residual axillary disease amenable to lymphadenectomy in patients with positive sentinel lymph node biopsy (SLNB). METHODS: We conducted a retrospective observational study in Hospital 12 de Octubre (Spain). We included BC patients with positive SLNB who underwent axillary dissection after neoadjuvant chemotherapy. Univariate and multivariate logistic regression models were performed to identify independent predictors of residual axillary disease. We estimated the ratio of positive nodes in SLNB and assessed the diagnostic validity of this ratio in relation to residual axillary disease. RESULTS: We included 103 patients in the study. Residual axillary disease was identified in 54 patients (52.4%). Clinically node positive status at diagnosis (OR = 18.3, 95%CI: 4.0-83.6) and a ratio of positive nodes in SLNB ≥0.5 (OR = 6.5, 95%CI 41.7-23.7) were associated with residual axillary disease. The sensitivity and negative predictive value of a ratio of positive nodes in SLNB ≥0.5 were 87% (95%CI 75.1%-94.6%) and 75% (95%CI 55.1%-89.3%), respectively. CONCLUSIONS: In our study, for patients with positive SLNB after neoadjuvant chemotherapy, stage N+ at diagnosis and a ratio of positive nodes in SLNB ≥0.5 were independent risk factors of positive residual axillary disease. This ratio is a feasible measure with a good diagnostic validity for residual axillary disease and could be used as a guiding factor in the surgical management of these patients.

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.

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.

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.

Salivary Cortisol and Anxiety in Canadian Dentists over 1 Year of COVID-19.

The dental profession has endured unprecedented disruption amid COVID-19. Novel stressors have included a high risk of occupational exposure to COVID-19, financial losses, and stricter infection prevention and control requirements. The present study investigated the longitudinal impact of COVID-19 on the stress and anxiety levels of a cohort of Canadian dentists (N = 222) between September 2020 and October 2021. Salivary cortisol was selected as a biomarker of mental stress, and 10 sets of monthly saliva samples (2,131 in total) were self-collected, sent to our laboratory in prepaid courier envelopes, and analyzed by enzyme-linked immunosorbent assay. To assess COVID-19 anxiety, 9 monthly online questionnaires were administered, comprising a general COVID-19 anxiety instrument and 3 items regarding the impact of dentistry-related factors. Bayesian log-normal mixed effect models were fitted to estimate the longitudinal trajectory of salivary cortisol levels and their association with the disease burden of COVID-19 in Canada. After accounting for age, sex, vaccination status, and the diurnal rhythm of cortisol secretion, a modest positive association was found between dentists' salivary cortisol levels and the count of COVID-19 cases in Canada (96% posterior probability). Similarly, the self-reported impact of dentistry-related factors, such as fear of getting COVID-19 from a patient or coworker, was greatest during peaks of COVID-19 waves in Canada; however, general COVID-19 anxiety decreased consistently throughout the study period. Interestingly, at all collection points, the majority of participants were not concerned about personal protective equipment. Overall, participants reported relatively low rates of psychological distress symptoms in relation to COVID-19, a result that should be reassuring for the dental community. Our findings strongly suggest a link between self-reported and biochemical measurements of stress and anxiety in Canadian dentists during the COVID-19 pandemic.

iPSC-derived retinal pigmented epithelial cells from patients with macular telangiectasia show decreased mitochondrial function.

Patient-derived induced pluripotent stem cells (iPSCs) provide a powerful tool for identifying cellular and molecular mechanisms of disease. Macular telangiectasia type 2 (MacTel) is a rare, late-onset degenerative retinal disease with an extremely heterogeneous genetic architecture, lending itself to the use of iPSCs. Whole-exome sequencing screens and pedigree analyses have identified rare causative mutations that account for less than 5% of cases. Metabolomic surveys of patient populations and GWAS have linked MacTel to decreased circulating levels of serine and elevated levels of neurotoxic 1-deoxysphingolipids (1-dSLs). However, retina-specific, disease-contributing factors have yet to be identified. Here, we used iPSC-differentiated retinal pigmented epithelial (iRPE) cells derived from donors with or without MacTel to screen for novel cell-intrinsic pathological mechanisms. We show that MacTel iRPE cells mimicked the low serine levels observed in serum from patients with MacTel. Through RNA-Seq and gene set enrichment pathway analysis, we determined that MacTel iRPE cells are enriched in cellular stress pathways and dysregulation of central carbon metabolism. Using respirometry and mitochondrial stress testing, we functionally validated that MacTel iRPE cells had a reduction in mitochondrial function that was independent of defects in serine biosynthesis and 1-dSL accumulation. Thus, we identified phenotypes that may constitute alternative disease mechanisms beyond the known serine/sphingolipid pathway.

Divergent amino acid and sphingolipid metabolism in patients with inherited neuro-retinal disease.

OBJECTIVES: The non-essential amino acids serine, glycine, and alanine, as well as diverse sphingolipid species, are implicated in inherited neuro-retinal disorders and are metabolically linked by serine palmitoyltransferase (SPT), a key enzyme in membrane lipid biogenesis. To gain insight into the pathophysiological mechanisms linking these pathways to neuro-retinal diseases we compared patients diagnosed with two metabolically intertwined diseases: macular telangiectasia type II (MacTel), hereditary sensory autonomic neuropathy type 1 (HSAN1), or both. METHODS: We performed targeted metabolomic analyses of amino acids and broad sphingolipids in sera from a cohort of MacTel (205), HSAN1 (25) and Control (151) participants. RESULTS: MacTel patients exhibited broad alterations of amino acids, including changes in serine, glycine, alanine, glutamate, and branched-chain amino acids reminiscent of diabetes. MacTel patients had elevated 1-deoxysphingolipids but reduced levels of complex sphingolipids in circulation. A mouse model of retinopathy indicates dietary serine and glycine restriction can drive this depletion in complex sphingolipids. HSAN1 patients exhibited elevated serine, lower alanine, and a reduction in canonical ceramides and sphingomyelins compared to controls. Those patients diagnosed with both HSAN1 and MacTel showed the most significant decrease in circulating sphingomyelins. CONCLUSIONS: These results highlight metabolic distinctions between MacTel and HSAN1, emphasize the importance of membrane lipids in the progression of MacTel, and suggest distinct therapeutic approaches for these two neurodegenerative diseases.

Insulin-regulated serine and lipid metabolism drive peripheral neuropathy.

Diabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves1,2. Although the onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidaemia3-7, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes8-10. Serine and glycine are closely related NEAAs whose levels are consistently reduced in patients with metabolic syndrome10-14, but the mechanistic drivers and downstream consequences of this metabotype remain unclear. Low systemic serine and glycine are also emerging as a hallmark of macular and peripheral nerve disorders, correlating with impaired visual acuity and peripheral neuropathy15,16. Here we demonstrate that aberrant serine homeostasis drives serine and glycine deficiencies in diabetic mice, which can be diagnosed with a serine tolerance test that quantifies serine uptake and disposal. Mimicking these metabolic alterations in young mice by dietary serine or glycine restriction together with high fat intake markedly accelerates the onset of small fibre neuropathy while reducing adiposity. Normalization of serine by dietary supplementation and mitigation of dyslipidaemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidaemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically.

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.