Associations between Present-on-Admission Do-Not-Resuscitate Orders and Short-Term Outcomes in Patients with Pneumonia.

OBJECTIVES: Do-not-resuscitate (DNR) orders are used to express patient preferences for cardiopulmonary resuscitation. This study examined whether early DNR orders are associated with differences in treatments and outcomes among patients hospitalized with pneumonia. METHODS: This is a retrospective cohort study of 768,015 adult patients hospitalized with pneumonia from 2010 to 2015 in 646 US hospitals. The exposure was DNR orders present on admission. Secondary analyses stratified patients by predicted in-hospital mortality. Main outcomes included in-hospital mortality, length of stay, cost, intensive care admission, invasive mechanical ventilation, noninvasive ventilation, vasopressors, and dialysis initiation. RESULTS: Of 768,015 patients, 94,155 (12.3%) had an early DNR order. Compared with those without, patients with DNR orders were older (mean age 80.1 ± 10.6 years vs 67.8 ± 16.4 years), with higher comorbidity burden, intensive care use (31.6% vs 30.6%), and in-hospital mortality (28.2% vs 8.5%). After adjustment via propensity score weighting, these patients had higher mortality (odds ratio [OR] 2.39, 95% confidence interval [CI] 2.33-2.45) and lower use of intensive therapies such as vasopressors (OR 0.83, 95% CI 0.81-0.85) and invasive mechanical ventilation (OR 0.68, 95% CI 0.66-0.70). Although there was little relationship between predicted mortality and DNR orders, among those with highest predicted mortality, DNR orders were associated with lower intensive care use compared with those without (66.7% vs 80.8%). CONCLUSIONS: Patients with early DNR orders have higher in-hospital mortality rates than those without, but often receive intensive care. These orders have the most impact on the care of patients with the highest mortality risk.

Diagnostic prediction models to identify patients at risk for healthcare-facility-onset Clostridioides difficile: A systematic review of methodology and reporting.

OBJECTIVE: To systematically review the methodology, performance, and generalizability of diagnostic models for predicting the risk of healthcare-facility-onset (HO) Clostridioides difficile infection (CDI) in adult hospital inpatients (aged ≥18 years). BACKGROUND: CDI is the most common cause of healthcare-associated diarrhea. Prediction models that identify inpatients at risk of HO-CDI have been published; however, the quality and utility of these models remain uncertain. METHODS: Two independent reviewers evaluated articles describing the development and/or validation of multivariable HO-CDI diagnostic models in an inpatient setting. All publication dates, languages, and study designs were considered. Model details (eg, sample size and source, outcome, and performance) were extracted from the selected studies based on the CHARMS checklist. The risk of bias was further assessed using PROBAST. RESULTS: Of the 3,030 records evaluated, 11 were eligible for final analysis, which described 12 diagnostic models. Most studies clearly identified the predictors and outcomes but did not report how missing data were handled. The most frequent predictors across all models were advanced age, receipt of high-risk antibiotics, history of hospitalization, and history of CDI. All studies reported the area under the receiver operating characteristic curve (AUROC) as a measure of discriminatory ability. However, only 3 studies reported the model calibration results, and only 2 studies were externally validated. All of the studies had a high risk of bias. CONCLUSION: The studies varied in their ability to predict the risk of HO-CDI. Future models will benefit from the validation on a prospective external cohort to maximize external validity.

Derivation and external validation of a prediction model for pneumococcal urinary antigen test positivity in patients with community-acquired pneumonia.

Objective: Derive and externally validate a prediction model for pneumococcal urinary antigen test (pUAT) positivity. Methods: Retrospective cohort study of adults admitted with community-acquired pneumonia (CAP) to 177 U.S. hospitals in the Premier Database (derivation and internal validation samples) or 12 Cleveland Clinic hospitals (external validation sample). We utilized multivariable logistic regression to predict pUAT positivity in the derivation dataset, followed by model performance evaluation in both validation datasets. Potential predictors included demographics, comorbidities, clinical findings, and markers of disease severity. Results: Of 198,130 Premier patients admitted with CAP, 27,970 (14.1%) underwent pUAT; 1962 (7.0%) tested positive. The strongest predictors of pUAT positivity were history of pneumococcal infection in the previous year (OR 6.99, 95% CI 4.27-11.46), severe CAP on admission (OR 1.76, 95% CI 1.56-1.98), substance abuse (OR 1.57, 95% CI 1.27-1.93), smoking (OR 1.23, 95% CI 1.09-1.39), and hyponatremia (OR 1.35, 95% CI 1.17-1.55). Negative predictors included IV antibiotic use in past year (OR 0.65, 95% CI 0.52-0.82), congestive heart failure (OR 0.72, 95% CI 0.63-0.83), obesity (OR 0.71, 95% CI 0.60-0.85), and admission from skilled nursing facility (OR 0.60, 95% CI 0.45-0.78). Model c-statistics were 0.60 and 0.67 in the internal and external validation cohorts, respectively. Compared to guideline-recommended testing of severe CAP patients, our model would have detected 23% more cases with 5% fewer tests. Conclusion: Readily available data can identify patients most likely to have a positive pUAT. Our model could be incorporated into automated clinical decision support to improve test efficiency and antimicrobial stewardship.

Association of social vulnerability and influenza vaccination rates for Annual Medicare Enrollees at the county-level in the United States.

INTRODUCTION: Influenza is a preventable acute respiratory illness with a high potential to cause serious complications and is associated with high mortality and morbidity in the US. We aimed to determine the specific community-level vulnerabilities for different race/ethnic communities that are most predictive of influenza vaccination rates. METHODS: We conducted a machine learning analysis (XGBoost) to identify community-level social vulnerability features that are predictive of influenza vaccination rates among Medicare enrollees across counties in the US and by race/ethnicity. RESULTS: Population density per square mile in a county is the most important feature in predicting influenza vaccination in a county, followed by unemployment rates and the percentage of mobile homes. The gain relative importance of these features are 11.6%, 9.2%, and 9%, respectively. Among whites, population density (17% gain relative importance) was followed by the percentage of mobile homes (9%) and per capita income (8.7%). For Black/African Americans, the most important features were population density (12.8%), percentage of minorities in the county (8.0%), per capita income (6.9%), and percent of over-occupied housing units (6.8%). Finally, for Hispanics, the top features were per capita income (8.4%), percentage of mobile homes (8.0%), percentage of non-institutionalized persons with a disability (7.9%), and population density (7.6%). CONCLUSIONS: Our study may have implications for the success of large vaccination programs in counties with high social vulnerabilities. Further, our findings suggest that policies and interventions seeking to increase rates of vaccination in race/ethnic minority communities may need to be tailored to address their specific socioeconomic vulnerabilities.

A Type IV Extension Supracondylar Fracture With Comminuted Fracture Pattern: A Case Report.

CASE: A three year, 11 month old girl sustained a right displaced extension supracondylar fracture (ESF) of the humerus with comminution of the lateral column after an indoor fall. At surgery, fracture reduction showed multidirectional instability. Adequate reduction was achieved by applying longitudinal traction of the arm with partial elbow flexion and forearm supination. One percutaneous medial pin, followed by one lateral cross pin, was used to immobilize the fracture. Normal posterolateral new periosteal bone formation was seen on radiograph on the lateral side. At 5-year follow-up, she had full range of asymptomatic and symmetrical elbow motion. CONCLUSION: This case report shows a displaced ESF with a comminuted lateral humeral column, which contributed to a lack of adequate lateral pin purchase on bone. A modified pin fixation technique first with a medial pin and followed by a lateral pin with both placed through the medial column was used for stable fracture fixation. In addition, this case showed that fracture comminution was a contributory factor to the rare multidirectional instability of the Gartland Type IV fracture.

Advising Orthopaedic Hopefuls in the Wake of a Pass/Fail US Medical Licensing Examination Step 1: A Proposed Method for Predicting US Medical Licensing Examination Step 2 Clinical Knowledge Outcomes.

INTRODUCTION: Matching into orthopaedic residency has become difficult, and the US Medical Licensing Examination Step 1 transition to pass/fail scoring has complicated the process. Advisors' ability to mentor students has decreased, and program directors may rely on Step 2 Clinical Knowledge (CK) scores in selecting which candidates to interview. This study aims to offer a method to predict Step 2 CK outcomes based on preadmission and preclinical performance. METHODS: The study investigated 486 students from a US medical school who enrolled in 2017 and 2018. Data on demographics, preadmission, and preclinical performance were collected. Before model creation, it was found that sex, Medical College Admission Test scores, Comprehensive Basic Science Examination performance, and preclinical curriculum performance produced optimal models. Multivariate ordinal logistic regression models were built to predict probabilities of four outcome levels of Step 2 CK: <235, 235 to 249, 250 to 265, and >265. Finally, nomograms were created to visualize probability calculations. RESULTS: Each model's odds ratios revealed that female sex, higher MCAT scores, and better Comprehensive Basic Science Examination and preclinical performance were associated with an increased likelihood of being in higher Step 2 CK scoring groups. Preclinical performance had a profound effect, especially for those in the top 1/3. Models were successful in assigning higher probabilities to students in higher Step 2 CK scoring groups in more than 80% of instances. Nomograms presented provide examples of how to apply these models to an individual student. DISCUSSION: This study presents a novel method for predicting probabilities of Step 2 CK outcomes that can be used to mentor students at a time point when Step 1 previously filled this role. It may assist in identifying orthopaedic hopefuls at risk of performing poorly on Step 2 CK and can foster the development of individualized guidance and mitigation strategies.

Reducing antimicrobial overuse through targeted therapy for patients with community-acquired pneumonia: a study protocol for a cluster-randomized factorial controlled trial (CARE-CAP).

BACKGROUND: Community-acquired pneumonia (CAP) is a significant public health concern and a leading cause of hospitalization and inpatient antimicrobial use in the USA. However, determining the etiologic pathogen is challenging because traditional culture methods are slow and insensitive, leading to prolonged empiric therapy with extended-spectrum antibiotics (ESA) that contributes to increased hospital length of stay, and antimicrobial resistance. Two potential ways to reduce the exposure to ESA are (a) rapid diagnostic assays that can provide accurate results within hours, obviating the need for empiric therapy, and (b) de-escalation following negative bacterial cultures in clinically stable patients. METHODS: We will conduct a large pragmatic 2 × 2 factorial cluster-randomized controlled trial across 12 hospitals in the Cleveland Clinic Health System that will test these two approaches to reducing the use of ESA in adult patients (age ≥ 18 years) with CAP. We will enroll over 12,000 patients and evaluate the independent and combined effects of routine use of rapid diagnostic testing at admission and pharmacist-led de-escalation after 48 h for clinically stable patients with negative cultures vs usual care. We hypothesize that both approaches will reduce days on ESA. Our primary outcome is the duration of exposure to ESA therapy, a key driver of antimicrobial resistance. Secondary outcomes include detection of respiratory viruses, treatment with anti-viral medications, positive pneumococcal urinary antigen test, de-escalation by 72 h from admission, re-escalation to ESA after de-escalation, total duration of any antibiotic, 14-day in-hospital mortality, intensive care unit transfer after admission, healthcare-associated C. difficile infection, acute kidney injury, total inpatient cost, and hospital length-of-stay. DISCUSSION: Our study aims to determine whether identifying an etiological agent early and pharmacist-led de-escalation (calling attention to negative cultures) can safely reduce the use of ESA in patients with CAP. If successful, our findings should lead to better antimicrobial stewardship, as well as improved patient outcomes and reduced healthcare costs. Our findings may also inform clinical guidelines on the optimal management of CAP. TRIAL REGISTRATION: ClinicalTrials.gov NCT05568654 . Registered on October 4, 2022.

Prevalence of Comorbid Factors in Patients With Recurrent Clostridioides difficile Infection in ECOSPOR III, a Randomized Trial of an Oral Microbiota-Based Therapeutic.

BACKGROUND: Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter "VOS," formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI. METHODS: Adults with rCDI were randomized to receive VOS or placebo (4 capsules daily for 3 days) following standard-of-care antibiotics. In this post hoc analysis, the rate of rCDI through week 8 was assessed in VOS-treated participants compared with placebo for subgroups including (i) Charlson comorbidity index (CCI) score category (0, 1-2, 3-4, ≥5); (ii) baseline creatinine clearance (<30, 30-50, >50 to 80, or >80 mL/minute); (iii) number of CDI episodes, inclusive of the qualifying episode (3 and ≥4); (iv) exposure to non-CDI-targeted antibiotics after dosing; and (v) acid-suppressing medication use at baseline. RESULTS: Of 281 participants screened, 182 were randomized (59.9% female; mean age, 65.5 years). Comorbidities were common with a mean overall baseline age-adjusted CCI score of 4.1 (4.1 in the VOS arm and 4.2 in the placebo arm). Across all subgroups analyzed, VOS-treated participants had a lower relative risk of recurrence compared with placebo. CONCLUSIONS: In this post hoc analysis, VOS reduced the risk of rCDI compared with placebo, regardless of baseline characteristics, concomitant medications, or comorbidities.

Intravenous to Oral Antibiotic Switch Therapy Among Patients Hospitalized With Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of hospital admissions and antimicrobial use. Clinical practice guidelines recommend switching from intravenous (IV) to oral antibiotics once patients are clinically stable. METHODS: We conducted a retrospective cohort study of adults admitted with CAP and initially treated with IV antibiotics at 642 US hospitals from 2010 through 2015. Switching was defined as discontinuation of IV and initiation of oral antibiotics without interrupting therapy. Patients switched by hospital day 3 were considered early switchers. We compared length of stay (LOS), in-hospital 14-day mortality, late deterioration (intensive care unit [ICU] transfer), and hospital costs between early switchers and others, controlling for hospital characteristics, patient demographics, comorbidities, initial treatments, and predicted mortality. RESULTS: Of 378 041 CAP patients, 21 784 (6%) were switched early, most frequently to fluoroquinolones. Patients switched early had fewer days on IV antibiotics, shorter duration of inpatient antibiotic treatment, shorter LOS, and lower hospitalization costs, but no significant excesses in 14-day in-hospital mortality or late ICU admission. Patients at a higher mortality risk were less likely to be switched. However, even in hospitals with relatively high switch rates, <15% of very low-risk patients were switched early. CONCLUSIONS: Although early switching was not associated with worse outcomes and was associated with shorter LOS and fewer days on antibiotics, it occurred infrequently. Even in hospitals with high switch rates, <15% of very low-risk patients were switched early. Our findings suggest that many more patients could be switched early without compromising outcomes.

Probiotics for primary prevention of Clostridioides difficile infection: revisiting the evidence.

Prophylactic probiotics have been shown to be effective in preventing Clostridioides difficile infection (CDI), according to multiple meta-analyses. However, different medical societies have varying recommendations on their use for preventing CDI. In this commentary, we discuss current evidence for probiotic use in primary prevention of CDI and the issues raised by professional societies when evaluating the evidence. We highlight four areas for future improvement: considering baseline risk for CDI, timing of probiotics with antibiotics, combining efficacy data from different probiotic strains, and safety. All societies agree on the need for more high-quality and adequately powered randomized controlled trials to further strengthen the evidence.

Can Electronic Clinical Decision Support Systems Improve the Diagnosis of Urinary Tract Infections? A Systematic Review and Meta-Analysis.

Background: Urinary tract infection (UTI) is a commonly misdiagnosed infectious syndrome. Diagnostic stewardship interventions can reduce rates of asymptomatic bacteriuria treatment but are often labor intensive, and thus an automated means of reducing unnecessary urine testing is preferred. In this systematic review and meta-analysis, we sought to identify studies describing interventions utilizing clinical decision support (CDS) to optimize UTI diagnosis and to characterize the effectiveness of these interventions. Methods: We conducted a comprehensive electronic search and manual reference list review for peer-reviewed articles published before July 2, 2021. Publications describing an intervention intending to enhance UTI diagnosis via CDS were included. The primary outcome was urine culture test rate. Results: The electronic search identified 5013 studies for screening. After screening and full-text review, 9 studies met criteria for inclusion, and a manual reference list review identified 5 additional studies, yielding a total of 14 studies included in the systematic review. The most common CDS intervention was urinalysis with reflex to urine culture based on prespecified urinalysis parameters. All 9 studies that provided statistical comparisons reported a decreased urine culture rate postintervention, 8 of which were statistically significant. A meta-analysis including 4 studies identified a pooled urine culture incidence rate ratio of 0.56 (95% confidence interval, .52-.60) favoring the postintervention versus preintervention group. Conclusions: In this systematic review and meta-analysis, CDS appeared to be effective in decreasing urine culture rates. Prospective trials are needed to confirm these findings and to evaluate their impact on antimicrobial prescribing, patient-relevant outcomes, and potential adverse effects.

Traumatic brain injuries in paediatric patients: individual vs. team sports-related hospitalizations.

Paediatric sport participation continues to increase in the United States, with a corresponding increase in sports-related concussions or traumatic brain injuries (TBIs). It is important to recognize which sports are at elevated risk and identify risk factors for hospital admission and length of stay (LOS). Paediatric patients (ages 5-18) from 2008 to 2014 were identified from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS). Eight hundred and ninety-four patients included those who were hospitalized with a TBI resulting from participation in an individual (451 patients) or team (443 patients) sport. We evaluated the differences in LOS and total charges between individual and team sports and found that compared to team sports, TBI patients in individual sports had significantly longer hospital stays compared to team sports (1.75 days versus 1.34 days, p < 0.001) and costlier ($27,333 versus $19,069, p < 0.001) hospital stays. This may be due to reduced awareness and reduced compliance with return-to-play protocols in individual sports. Safety education information at a young age, increased awareness of TBIs, and additional medical support for individual sports as well as team sports may help mitigate these findings.

Assessment of Quality of Life Among Patients With Recurrent Clostridioides difficile Infection Treated with Investigational Oral Microbiome Therapeutic SER-109: Secondary Analysis of a Randomized Clinical Trial.

Importance: Recurrent Clostridioides difficile infection (CDI) is a debilitating disease leading to poor health-related quality of life (HRQOL), loss of productivity, anxiety, and depression. The potential association of treatment with HRQOL has not been well evaluated. Objectives: To explore the association of SER-109 compared with placebo on HRQOL in patients with recurrent CDI up to week 8. Design, Setting, and Participants: This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial that took place at 56 sites in the US and Canada from July 2017 to April 2020 and included 182 patients randomized to SER-109 or placebo groups. Interventions: SER-109 or placebo (4 capsules once daily for 3 days) following antibiotics for CDI. Main Outcomes and Measures: Exploratory analysis of HRQOL using the disease specific Clostridioides difficile Quality of Life Survey (Cdiff32) assessed at baseline, week 1, and week 8. Results: In this study, 182 patients (109 [59.9%] female; mean age, 65.5 [16.5] years) were randomized to SER-109 (89 [48.9%]) or placebo (93 [51.1%]) groups and were included in the primary and exploratory analyses. Baseline Cdiff32 scores were similar between patients in the SER-109 and placebo groups (52.0 [18.3] vs 52.8 [18.7], respectively). The proportion of patients with overall improvement from baseline in the Cdiff32 total score was higher in the SER-109 arm than placebo at week 1 (49.4% vs 26.9%; P = .012) and week 8 (66.3% vs 48.4%; P = .001).Greater improvements in total and physical domain and subdomain scores were observed in patients in the SER-109 group compared with placebo as early as week 1, with continued improvements observed at week 8. Among patients in the placebo group, improvements in HRQOL were primarily observed in patients with nonrecurrent CDI while patients in the SER-109 group reported improvements in HRQOL, regardless of clinical outcome. Conclusions and Relevance: In this secondary analysis of a phase 3 clinical trial, SER-109, an investigational microbiome therapeutic was associated with rapid and steady improvement in HRQOL compared with placebo through 8 weeks, an important patient-reported outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03183128.

Association of fluoroquinolones or cephalosporin plus macrolide with Clostridioides difficile infection (CDI) after treatment for community-acquired pneumonia.

OBJECTIVE: Clostridioides difficile infection (CDI) is the most common cause of gastroenteritis, and community-acquired pneumonia (CAP) is the most common infection treated in hospitals. American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines recommend empiric therapy with a respiratory fluoroquinolone or cephalosporin plus macrolide combination, but the CDI risk of these regimens is unknown. We examined the association between each antibiotic regimen and the development of hospital-onset CDI. METHODS: We conducted a retrospective cohort study using data from 638 US hospitals contributing administrative including 177 also contributing microbiologic data to Premier, Inc. We included adults admitted with pneumonia and discharged from July 2010 through June 2015 with a pneumonia diagnosis code who received ≥3 days of either empiric regimen. Hospital-onset CDI was defined by a diagnosis code not present on admission and positive laboratory test on day 4 or later or readmission for CDI. Mixed propensity-weighted multiple logistic regression was used to estimate the associations of CDI with antibiotic regimens. RESULTS: Our sample included 58,060 patients treated with either cephalosporin plus macrolide (36,796 patients) or a fluoroquinolone alone (21,264 patients) and with microbiological data; 127 (0.35%) patients who received cephalosporin plus macrolide and 65 (0.31%) who received a fluoroquinolone developed CDI. After adjustment for patient demographics, comorbidities, risk factors for antimicrobial resistance, and hospital characteristics, CDI risks were similar for fluoroquinolones versus cephalosporin plus macrolide (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.70-1.38). CONCLUSION: Among patients with CAP at US hospitals, CDI was uncommon, occurring in ∼0.33% of patients. We did not detect a significant association between the choice of empiric guideline recommended antibiotic therapy and the development of CDI.

Validation of a Health-Related Quality of Life Questionnaire in Patients With Recurrent Clostridioides difficile Infection in ECOSPOR III, a Phase 3 Randomized Trial.

BACKGROUND: Debilitating symptoms of recurrent Clostridioides difficile infection (rCDI) often lead to long-term effects on health-related quality-of-life (HRQOL). In ECOSPOR III, SER-109, an investigational oral microbiome therapeutic, was superior to placebo in reducing rCDI. We investigated the validity, reliability, and responsiveness of a 32-item, CDI-specific questionnaire-the Clostridium difficile Quality of Life Survey (Cdiff32)-across mental, physical, and social domains in patients with rCDI. METHODS: In this post hoc analysis of a phase 3 clinical trial, 182 outpatients with rCDI completed Cdiff32 and EQ-5D at baseline and at 1 and 8 weeks. Cdiff32 was evaluated for item performance, internal reliability, and convergent validity. To assess known-groups validity, Cdiff32 scores were compared by disease recurrence status at week 1; internal responsiveness was evaluated in the nonrecurrent disease group by 8 weeks by means of paired t test. RESULTS: All 182 patients (mean age [standard deviation], 65.5 [16.5] years; 59.9% female) completed baseline Cdiff32. Confirmatory factor analysis identified 3 domains (physical, mental, and social relationships) with good item fit. High internal reliability was demonstrated (Cronbach α = 0.94 with all subscales >0.80). Convergent validity was evidenced by significant correlations between Cdiff32 subscales and EQ-5D (r = 0.29-0.37; P < .001). Cdiff32 differentiated patients by disease recurrence status at week 1 (effect sizes, 0.38-0.42; P < .05 overall), with significant improvement from baseline through week 8 in patients with nonrecurrent disease at week 1 (effect sizes, 0.75-1.02; P < .001 overall). CONCLUSIONS: Cdiff32 is a valid, reliable, and responsive disease-specific HRQOL questionnaire that is fit for purpose for interventional treatment trials. The significant improvement in patients with nonrecurrent disease by 8 weeks demonstrates the negative impact of rCDI on HRQOL.

A randomized trial of ultraviolet-C (UV-C) light versus sodium hypochlorite delivered by an electrostatic sprayer for adjunctive decontamination of hospital rooms.

In a randomized trial, adjunctive ultraviolet-C light treatment with a room decontamination device and sodium hypochlorite delivered via an electrostatic sprayer were similarly effective in significantly reducing residual healthcare-associated pathogen contamination on floors and high-touch surfaces after manual cleaning and disinfection. Less time until the room was ready to be occupied by another patient was required for electrostatic spraying.

Disease State Transition Probabilities Across the Spectrum of NAFLD: A Systematic Review and Meta-Analysis of Paired Biopsy or Imaging Studies.

BACKGROUND & AIMS: We conducted a meta-analysis to summarize the rates of progression to and regression of nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), and fibrosis in adults with nonalcoholic fatty liver disease (NAFLD). METHODS: We searched PubMed/Medline and 4 other databases from 1985 through 2020. We included observational studies and randomized controlled trials in any language that used liver biopsy or imaging to diagnose NAFLD in adults with a follow-up period ≥48 weeks. Rates were calculated as incident cases per 100 person-years and pooled using the random-effects Poisson distribution model. Heterogeneity was assessed using the I2 statistic. RESULTS: We screened 9744 articles and included 54 studies involving 26,738 patients. Among observational studies, 20% of healthy adults developed NAFL (incidence rate, 4.8/100 person-years) while 21% of people with fatty liver had resolution of NAFL (incidence rate, 2.4/100 person-years) after a median of approximately 4.5 years. In addition, 31% of patients developed NASH after 4.7 years (incidence rate, 7.4/100 person-years), whereas in 29% of those with NASH, resolution occurred after a median of 3.5 years (incidence rate, 5.1/100 person-years). Time to progress by 1 fibrosis stage was 9.9, 10.3, 13.3, and 22.2 years for F0, F1, F2, and F3, respectively. Time to regress by 1 stage was 21.3, 12.5, 20.4, and 40.0 years for F4, F3, F2, and F1, respectively. Rates estimated from randomized controlled trials were higher than those from observational studies. CONCLUSIONS: In our meta-analysis, progression to NASH was more common than regression from NASH. Rates of fibrosis progression were similar across baseline stage, but patients with advanced fibrosis were more likely to regress than those with mild fibrosis.

Derivation and validation of a risk assessment model for drug-resistant pathogens in hospitalized patients with community-acquired pneumonia.

OBJECTIVE: To derive and validate a model for risk of resistance to first-line community-acquired pneumonia (CAP) therapy. DESIGN: We developed a logistic regression prediction model from a large multihospital discharge database and validated it versus the Drug Resistance in Pneumonia (DRIP) score in a holdout sample and another hospital system outside that database. Resistance to first-line CAP therapy (quinolone or third generation cephalosporin plus macrolide) was based on blood or respiratory cultures. SETTING: This study was conducted using data from 177 Premier Healthcare database hospitals and 11 Cleveland Clinic hospitals. PARTICIPANTS: Adults hospitalized for CAP. EXPOSURE: Risk factors for resistant infection. RESULTS: Among 138,762 eligible patients in the Premier database, 12,181 (8.8%) had positive cultures and 5,200 (3.8%) had organisms resistant to CAP therapy. Infection with a resistant organism in the previous year was the strongest predictor of resistance; markers of acute illness (eg, receipt of mechanical ventilation or vasopressors) and chronic illness (eg, pressure ulcer, paralysis) were also associated with resistant infections. Our model outperformed the DRIP score with a C-statistic of 0.71 versus 0.63 for the DRIP score (P < .001) in the Premier holdout sample, and 0.65 versus 0.58 (P < .001) in Cleveland Clinic hospitals. Clinicians at Premier facilities used broad-spectrum antibiotics for 20%-30% of patients. In discriminating between patients with and without resistant infections, physician judgment slightly outperformed the DRIP instrument but not our model. CONCLUSIONS: Our model predicting infection with a resistant pathogen outperformed both the DRIP score and physician practice in an external validation set. Its integration into practice could reduce unnecessary use of broad-spectrum antibiotics.

Adoption and Trends in Uptake of Updated ICD-10 Codes for Clostridioides difficile-A Retrospective Observational Study.

Background: In October 2017, the single International Classification of Diseases, Tenth Revision (ICD-10), code for Clostridioides difficile infection (CDI), A04.7, was replaced with 2 codes delineating "recurrent CDI" (rCDI; A04.71) and "nonrecurrent CDI" (nrCDI; A04.72). Methods: To evaluate and validate use of the updated codes, this retrospective study included inpatient encounters with a CDI-related ICD-10 code from October 2016 to May 2019 in the PINC AITM Healthcare Database (PHD). Encounters after the October 2017 code update were characterized by clinical, facility, and provider variables and whether coding was concordant or discordant to the 8-week recurrence period. Multivariable regression analysis assessed variables associated with concordant coding. Results: Widespread adoption of the updated CDI codes across PHD hospitals occurred in October 2017. After October 2017, 21 446 CDI-related encounters met sample selection criteria (concordance in 67% of rCDI and 25% of nrCDI encounters). Higher proportions of rCDI- vs nrCDI-coded encounters (P < .05) had emergency room admission, admission by a gastroenterologist or infectious disease specialist, and were prescribed fidaxomicin, bezlotoxumab, or fecal microbiota transfer (FMT), with no significant difference by coding concordance status. Encounters coded concordantly were significantly more likely to be for rCDI (odds ratio [OR], 5.67; 95% CI, 5.32-6.03), a nonelective admission (OR, 1.35-1.69), or prescribed fidaxomicin (OR, 1.11; 95% CI, 1.01-1.23) or FMT (OR, 1.29; 95% CI, 1.17-1.42). Conclusions: Our study findings suggest no delay in transition to the updated CDI-related codes. Treatment patterns for rCDI vs nrCDI encounters were consistent with Infectious Diseases Society of America guidelines, regardless of concordance status.

Homeostasis and injectivity: a reaction network perspective.

Homeostasis represents the idea that a feature may remain invariant despite changes in some external parameters. We establish a connection between homeostasis and injectivity for reaction network models. In particular, we show that a reaction network cannot exhibit homeostasis if a modified version of the network (which we call homeostasis-associated network) is injective. We provide examples of reaction networks which can or cannot exhibit homeostasis by analyzing the injectivity of their homeostasis-associated networks.