Hepatitis C Virus Testing, Infection, and Cases Reported Through Public Health Surveillance During Expanded Screening Recommendations, United States, 2013-2021.

OBJECTIVES: Hepatitis C virus (HCV) infection is the most common bloodborne infection in the United States. We assessed trends in HCV testing, infection, and surveillance cases among US adults. METHODS: We used Quest Diagnostics data from 2013-2021 to assess trends in the numbers tested for HCV antibody and proportion of positivity for HCV antibody and HCV RNA. We also assessed National Notifiable Diseases Surveillance System 2013-2020 data for trends in the number and proportion of hepatitis C cases. We applied joinpoint regression for trends testing. RESULTS: Annual HCV antibody testing increased from 1.7 million to 4.8 million from 2013 to 2021, and the positivity proportion declined (average, 0.2% per year) from 5.5% to 3.7%. The greatest percentage-point increase in HCV antibody testing occurred in hospitals and substance use disorder treatment facilities and among addiction medicine providers. HCV RNA positivity was stable at about 60% in 2013-2015 and declined to 41.0% in 2021 (2015-2021 average, -3.2% per year). Age-specific HCV RNA positivity was highest among people aged 40-59 years during 2013-2015 and among people aged 18-39 years during 2016-2021. The number of reported hepatitis C cases (acute and chronic) declined from 179 341 in 2015 to 105 504 in 2020 (average decline, -13 177 per year). The proportion of hepatitis C cases among those aged 18-39 years increased by an average of 1.4% per year during 2013-2020; among individuals aged 40-59 years, it decreased by an average of 2.3% per year during 2013-2018. CONCLUSIONS: HCV testing increased, suggesting improved universal screening. Various data sources are valuable for monitoring elimination progress.

Hepatitis B Care Continuum Models-Data to Inform Public Health Action.

The application of a care continuum model (CCM) can identify gaps in diagnosis, care, and treatment of populations with a common condition, but challenges are inherent in developing a CCM for chronic hepatitis B. In contrast with treatment for HIV or hepatitis C, treatment is not indicated for all people with chronic hepatitis B, clinical endpoints are not clear for those receiving treatment, and those for whom treatment is not indicated remain at risk for complications. This topical review examines the data elements necessary to develop and apply chronic hepatitis B CCMs at the jurisdictional health department level. We conducted a nonsystematic review of US-based publications in Ovid MEDLINE (1946-present), Ovid Embase (1974-present), and Scopus (not date limited) databases, which yielded 724 publications for review. Jurisdictional health departments, if properly supported, could develop locale-specific focused CCMs using person-level chronic hepatitis B registries, updated longitudinally using electronic laboratory reporting data and case reporting data. These CCMs could be applied to identify disparities and improve rates in testing and access to care and treatment, which are necessary to reduce liver disease and chronic hepatitis B mortality. Investments in public health surveillance infrastructure, including substantial enhancements in electronic laboratory reporting and case reporting and the use of supplementary data sources, could enable jurisdictional health departments to develop modified CCMs for chronic hepatitis B that focus, at least initially, on "early" CCM steps, which emphasize optimization of hepatitis B diagnosis, linkage to care, and ongoing clinical follow-up of diagnosed people, all of which can lead to improved outcomes.

Frequency of Children Diagnosed with Perinatal Hepatitis C, United States, 2018-2020.

We describe hepatitis C testing of 47 (2%) of 2,266 children diagnosed with perinatal hepatitis C who were exposed during 2018-2020 in 7 jurisdictions in the United States. Expected frequency of perinatal transmission is 5.8%, indicating only one third of the cases in this cohort were reported to public health authorities.

Assessing Pathogen Transmission Opportunities: Variation in Nursing Home Staff-Resident Interactions.

OBJECTIVES: The Centers for Disease Control and Prevention (CDC) recommends implementing Enhanced Barrier Precautions (EBP) for all nursing home (NH) residents known to be colonized with targeted multidrug-resistant organisms (MDROs), wounds, or medical devices. Differences in health care personnel (HCP) and resident interactions between units may affect risk of acquiring and transmitting MDROs, affecting EBP implementation. We studied HCP-resident interactions across a variety of NHs to characterize MDRO transmission opportunities. DESIGN: 2 cross-sectional visits. SETTING AND PARTICIPANTS: Four CDC Epicenter sites and CDC Emerging Infection Program sites in 7 states recruited NHs with a mix of unit care types (≥30 beds or ≥2 units). HCP were observed providing resident care. METHODS: Room-based observations and HCP interviews assessed HCP-resident interactions, care type provided, and equipment use. Observations and interviews were conducted for 7-8 hours in 3-6-month intervals per unit. Chart reviews collected deidentified resident demographics and MDRO risk factors (eg, indwelling devices, pressure injuries, and antibiotic use). RESULTS: We recruited 25 NHs (49 units) with no loss to follow-up, conducted 2540 room-based observations (total duration: 405 hours), and 924 HCP interviews. HCP averaged 2.5 interactions per resident per hour (long-term care units) to 3.4 per resident per hour (ventilator care units). Nurses provided care to more residents (n = 12) than certified nursing assistants (CNAs) and respiratory therapists (RTs) (CNA: 9.8 and RT: 9) but nurses performed significantly fewer task types per interaction compared to CNAs (incidence rate ratio (IRR): 0.61, P < .05). Short-stay (IRR: 0.89) and ventilator-capable (IRR: 0.94) units had less varied care compared with long-term care units (P < .05), although HCP visited residents in these units at similar rates. CONCLUSIONS AND IMPLICATIONS: Resident-HCP interaction rates are similar across NH unit types, differing primarily in types of care provided. Current and future interventions such as EBP, care bundling, or targeted infection prevention education should consider unit-specific HCP-resident interaction patterns.

The MITRE trial protocol: a study to evaluate the microbiome as a biomarker of efficacy and toxicity in cancer patients receiving immune checkpoint inhibitor therapy.

BACKGROUND: The gut microbiome is implicated as a marker of response to immune checkpoint inhibitors (ICI) based on preclinical mouse models and preliminary observations in limited patient series. Furthermore, early studies suggest faecal microbial transfer may have therapeutic potential, converting ICI non-responders into responders. So far, identification of specific responsible bacterial taxa has been inconsistent, which limits future application. The MITRE study will explore and validate a microbiome signature in a larger scale prospective study across several different cancer types. METHODS: Melanoma, renal cancer and non-small cell lung cancer patients who are planned to receive standard immune checkpoint inhibitors are being recruited to the MITRE study. Longitudinal stool samples are collected prior to treatment, then at 6 weeks, 3, 6 and 12 months during treatment, or at disease progression/recurrence (whichever is sooner), as well as after a severe (≥grade 3 CTCAE v5.0) immune-related adverse event. Additionally, whole blood, plasma, buffy coat, RNA and peripheral blood mononuclear cells (PBMCs) is collected at similar time points and will be used for exploratory analyses. Archival tumour tissue, tumour biopsies at progression/relapse, as well as any biopsies from body organs collected after a severe toxicity are collected. The primary outcome measure is the ability of the microbiome signature to predict 1 year progression-free survival (PFS) in patients with advanced disease. Secondary outcomes include microbiome correlations with toxicity and other efficacy end-points. Biosamples will be used to explore immunological and genomic correlates. A sub-study will evaluate both COVID-19 antigen and antibody associations with the microbiome. DISCUSSION: There is an urgent need to identify biomarkers that are predictive of treatment response, resistance and toxicity to immunotherapy. The data generated from this study will both help inform patient selection for these drugs and provide information that may allow therapeutic manipulation of the microbiome to improve future patient outcomes. TRIAL REGISTRATION: NCT04107168 , ClinicalTrials.gov, registered 09/27/2019. Protocol V3.2 (16/04/2021).

Risk Factors for SARS-CoV-2 Infection Among US Healthcare Personnel, May-December 2020.

To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case-control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living.

Dynamic biomarker and imaging changes from a phase II study of pre- and post-surgical sunitinib.

OBJECTIVE: To explore translational biological and imaging biomarkers for sunitinib treatment before and after debulking nephrectomy in the NeoSun (European Union Drug Regulating Authorities Clinical Trials Database [EudraCT] number: 2005-004502-82) single-centre, single-arm, single-agent, Phase II trial. PATIENTS AND METHODS: Treatment-naïve patients with metastatic renal cell carcinoma (mRCC) received 50 mg once daily sunitinib for 12 days pre-surgically, then post-surgery on 4 week-on, 2 week-off, repeating 6-week cycles until disease progression in a single arm phase II trial. Structural and dynamic contrast-enhanced magnet resonance imaging (DCE-MRI) and research blood sampling were performed at baseline and after 12 days. Computed tomography imaging was performed at baseline and post-surgery then every two cycles. The primary endpoint was objective response rate (Response Evaluation Criteria In Solid Tumors [RECIST]) excluding the resected kidney. Secondary endpoints included changes in DCE-MRI of the tumour following pre-surgery sunitinib, overall survival (OS), progression-free survival (PFS), response duration, surgical morbidity/mortality, and toxicity. Translational and imaging endpoints were exploratory. RESULTS: A total of 14 patients received pre-surgery sunitinib, 71% (10/14) took the planned 12 doses. All underwent nephrectomy, and 13 recommenced sunitinib postoperatively. In all, 58.3% (seven of 12) of patients achieved partial or complete response (PR or CR) (95% confidence interval 27.7-84.8%). The median OS was 33.7 months and median PFS was 15.7 months. Amongst those achieving a PR or CR, the median response duration was 8.7 months. No unexpected surgical complications, sunitinib-related toxicities, or surgical delays occurred. Within the translational endpoints, pre-surgical sunitinib significantly increased necrosis, and reduced cluster of differentiation-31 (CD31), Ki67, circulating vascular endothelial growth factor-C (VEGF-C), and transfer constant (KTrans , measured using DCE-MRI; all P < 0.05). There was a trend for improved OS in patients with high baseline plasma VEGF-C expression (P = 0.02). Reduction in radiological tumour volume after pre-surgical sunitinib correlated with high percentage of solid tumour components at baseline (Spearman's coefficient ρ = 0.69, P = 0.02). Conversely, the percentage tumour volume reduction correlated with lower baseline percentage necrosis (coefficient = -0.51, P = 0.03). CONCLUSION: Neoadjuvant studies such as the NeoSun can safely and effectively explore translational biological and imaging endpoints.

Practices and activities among healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection working in different healthcare settings-ten Emerging Infections Program sites, April-November 2020.

Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.

Comprehensive prediction of robust synthetic lethality between paralog pairs in cancer cell lines.

Pairs of paralogs may share common functionality and, hence, display synthetic lethal interactions. As the majority of human genes have an identifiable paralog, exploiting synthetic lethality between paralogs may be a broadly applicable approach for targeting gene loss in cancer. However, only a biased subset of human paralog pairs has been tested for synthetic lethality to date. Here, by analyzing genome-wide CRISPR screens and molecular profiles of over 700 cancer cell lines, we identify features predictive of synthetic lethality between paralogs, including shared protein-protein interactions and evolutionary conservation. We develop a machine-learning classifier based on these features to predict which paralog pairs are most likely to be synthetic lethal and to explain why. We show that our classifier accurately predicts the results of combinatorial CRISPR screens in cancer cell lines and furthermore can distinguish pairs that are synthetic lethal in multiple cell lines from those that are cell-line specific. A record of this paper's transparent peer review process is included in the supplemental information.

The rise and rise of protein degradation: Opportunities and challenges ahead.

The transformational mechanism of action underpinning targeted protein degradation strategies, including proteolysis-targeting chimeras (PROTACs), gives potential for potent in vivo pharmacology and has allowed projects to move rapidly to the clinic. Despite this remarkable progress, there remain many opportunities to improve current, first-generation approaches even further. Our expanding knowledge will allow discovery of new degrading mechanisms with potential to address several limitations of current approaches, including improving scope and efficiency of degradation, improving drug-like properties of degraders, and reducing potential for the emergence of acquired resistance. Here, we discuss potential routes to realize these advances to expand TPD utility even further.

Antimicrobial Use in a Cohort of US Nursing Homes, 2017.

Importance: Controlling antimicrobial resistance in health care is a public health priority, although data describing antimicrobial use in US nursing homes are limited. Objective: To measure the prevalence of antimicrobial use and describe antimicrobial classes and common indications among nursing home residents. Design, Setting, and Participants: Cross-sectional, 1-day point-prevalence surveys of antimicrobial use performed between April 2017 and October 2017, last survey date October 31, 2017, and including 15 276 residents present on the survey date in 161 randomly selected nursing homes from selected counties of 10 Emerging Infections Program (EIP) states. EIP staff reviewed nursing home records to collect data on characteristics of residents and antimicrobials administered at the time of the survey. Nursing home characteristics were obtained from nursing home staff and the Nursing Home Compare website. Exposures: Residence in one of the participating nursing homes at the time of the survey. Main Outcomes and Measures: Prevalence of antimicrobial use per 100 residents, defined as the number of residents receiving antimicrobial drugs at the time of the survey divided by the total number of surveyed residents. Multivariable logistic regression modeling of antimicrobial use and percentages of drugs within various classifications. Results: Among 15 276 nursing home residents included in the study (mean [SD] age, 77.6 [13.7] years; 9475 [62%] women), complete prevalence data were available for 96.8%. The overall antimicrobial use prevalence was 8.2 per 100 residents (95% CI, 7.8-8.8). Antimicrobial use was more prevalent in residents admitted to the nursing home within 30 days before the survey date (18.8 per 100 residents; 95% CI, 17.4-20.3), with central venous catheters (62.8 per 100 residents; 95% CI, 56.9-68.3) or with indwelling urinary catheters (19.1 per 100 residents; 95% CI, 16.4-22.0). Antimicrobials were most often used to treat active infections (77% [95% CI, 74.8%-79.2%]) and primarily for urinary tract infections (28.1% [95% CI, 15.5%-30.7%]). While 18.2% (95% CI, 16.1%-20.1%) were for medical prophylaxis, most often use was for the urinary tract (40.8% [95% CI, 34.8%-47.1%]). Fluoroquinolones were the most common antimicrobial class (12.9% [95% CI, 11.3%-14.8%]), and 33.1% (95% CI, 30.7%-35.6%) of antimicrobials used were broad-spectrum antibiotics. Conclusions and Relevance: In this cross-sectional survey of a cohort of US nursing homes in 2017, prevalence of antimicrobial use was 8.2 per 100 residents. This study provides information on the patterns of antimicrobial use among these nursing home residents.

Combinatorial CRISPR screen identifies fitness effects of gene paralogues.

Genetic redundancy has evolved as a way for human cells to survive the loss of genes that are single copy and essential in other organisms, but also allows tumours to survive despite having highly rearranged genomes. In this study we CRISPR screen 1191 gene pairs, including paralogues and known and predicted synthetic lethal interactions to identify 105 gene combinations whose co-disruption results in a loss of cellular fitness. 27 pairs influence fitness across multiple cell lines including the paralogues FAM50A/FAM50B, two genes of unknown function. Silencing of FAM50B occurs across a range of tumour types and in this context disruption of FAM50A reduces cellular fitness whilst promoting micronucleus formation and extensive perturbation of transcriptional programmes. Our studies reveal the fitness effects of FAM50A/FAM50B in cancer cells.

International comparison of pressure ulcer measures in long-term care facilities: Assessing the methodological robustness of 4 approaches to point prevalence measurement.

INTRODUCTION: Pressure ulcer indicators are among the most frequently used performance measures in long-term care settings. However, measurement systems vary and there is limited knowledge about the international comparability of different measurement systems. The aim of this analysis was to identify possible avenues for international comparisons of data on pressure ulcer prevalence among residents of long-term care facilities. MATERIAL AND METHODS: A descriptive analysis of the four point prevalence measurement systems programs used in 28 countries on three continents was performed. The criteria for the description and analysis were based on the scientific literature on criteria for indicator selection, on issues in international comparisons of data and on specific challenges of pressure ulcer measurements. RESULTS: The four measurement systems use a prevalence measure based on very similar numerator and denominator definitions. All four measurement systems also collect data on patient mobility. They differ in the pressure ulcer classifications used and the requirements for a head-to-toe resident examination. The regional or country representativeness of long-term care facilities also varies among the four measurement systems. CONCLUSIONS: Methodological differences among the point prevalence measurement systems are an important barrier to reliable comparisons of pressure ulcer prevalence data. The alignment of the methodologies may be improved by implementing changes to the study protocols, such as aligning the classification of pressure ulcers and requirements for a head-to-toe resident skin assessment. The effort required for each change varies. All these elements need to be considered by any initiative to facilitate international comparison and learning.

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm.

Ocular immune-related adverse events (IrAEs) associated with use of checkpoint inhibitors (CPIs) in cancer therapeutics are relatively rare, occurring in approximately 1% of treated patients. Recognition and early intervention are essential because the degree of tissue damage may be disproportionate to the symptoms, and lack of appropriate treatment risks permanent loss of vision. International guidelines on managing ocular IrAEs provide limited advice only. Importantly, local interventions can be effective and may avoid the need for systemic corticosteroids, thereby permitting the continuation of CPIs. We present a single institution case series of eight affected patients managed by our multidisciplinary team. Consistent with previously published series and case reports, we identified anterior uveitis as the most common ocular IrAE associated with CPIs requiring intervention. Based on our experience, as well as published guidance, we generated a simple algorithm to assist clinicians efficiently manage patients developing ocular symptoms during treatment with CPIs. In addition, we make recommendations for optimising treatment of uveitis and address implications for ongoing CPI therapy.

Antibiotic-resistant pathogens associated with urinary tract infections in nursing homes: Summary of data reported to the National Healthcare Safety Network Long-Term Care Facility Component, 2013-2017.

OBJECTIVE: Antibiotic resistance (AR) is a growing and highly prevalent problem in nursing homes. We describe selected AR phenotypes from pathogens causing urinary tract infections (UTIs) reported by nursing homes to the National Healthcare Safety Network (NHSN). DESIGN: Pathogens and antibiotic susceptibility testing results for UTI events in nursing homes between January 2013 and December 2017 were analyzed. The pathogen distribution and pooled mean proportion of isolates that tested resistant to select antibiotic agents are reported. SETTING AND PARTICIPANTS: US nursing homes voluntarily participating in the Long-Term Care Facility component of the NHSN. RESULTS: Overall, 243 nursing homes reported 1 or more UTIs: 121 (50%) were nonprofit facilities, median bed size was 91 (range: 9-801), and average occupancy was 87%. In total, 6,157 pathogens were reported for 5,485 UTI events. Moreover, 9 pathogens accounted for 90% of all reported UTIs; the 3 most frequently identified were Escherichia coli (41%), Proteus species (14%), and Klebsiella pneumoniae/oxytoca (13%). Among E. coli, fluoroquinolone, and extended-spectrum cephalosporin resistance were most prevalent (50% and 20%, respectively). Although Staphylococcus aureus and Enterococcus faecium represented <5% of pathogens reported, they had the highest rates of resistance (67% methicillin resistant and 60% vancomycin resistant, respectively). Multidrug resistance was most common in Pseudomonas aeruginosa (11%). For the resistant phenotypes we assessed, 36% of all UTIs reported were associated with a resistant pathogen. CONCLUSIONS: This is the first summary of AR among common pathogens causing UTIs reported to NHSN by nursing homes. Improved understanding of the resistance burden among common infections helps inform facility infection prevention and antibiotic stewardship efforts.

Facility-Wide Testing for SARS-CoV-2 in Nursing Homes - Seven U.S. Jurisdictions, March-June 2020.

Undetected infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) contributes to transmission in nursing homes, settings where large outbreaks with high resident mortality have occurred (1,2). Facility-wide testing of residents and health care personnel (HCP) can identify asymptomatic and presymptomatic infections and facilitate infection prevention and control interventions (3-5). Seven state or local health departments conducted initial facility-wide testing of residents and staff members in 288 nursing homes during March 24-June 14, 2020. Two of the seven health departments conducted testing in 195 nursing homes as part of facility-wide testing all nursing homes in their state, which were in low-incidence areas (i.e., the median preceding 14-day cumulative incidence in the surrounding county for each jurisdiction was 19 and 38 cases per 100,000 persons); 125 of the 195 nursing homes had not reported any COVID-19 cases before the testing. Ninety-five of 22,977 (0.4%) persons tested in 29 (23%) of these 125 facilities had positive SARS-CoV-2 test results. The other five health departments targeted facility-wide testing to 93 nursing homes, where 13,443 persons were tested, and 1,619 (12%) had positive SARS-CoV-2 test results. In regression analyses among 88 of these nursing homes with a documented case before facility-wide testing occurred, each additional day between identification of the first case and completion of facility-wide testing was associated with identification of 1.3 additional cases. Among 62 facilities that could differentiate results by resident and HCP status, an estimated 1.3 HCP cases were identified for every three resident cases. Performing facility-wide testing immediately after identification of a case commonly identifies additional unrecognized cases and, therefore, might maximize the benefits of infection prevention and control interventions. In contrast, facility-wide testing in low-incidence areas without a case has a lower proportion of test positivity; strategies are needed to further optimize testing in these settings.

Mutations in FAM50A suggest that Armfield XLID syndrome is a spliceosomopathy.

Intellectual disability (ID) is a heterogeneous clinical entity and includes an excess of males who harbor variants on the X-chromosome (XLID). We report rare FAM50A missense variants in the original Armfield XLID syndrome family localized in Xq28 and four additional unrelated males with overlapping features. Our fam50a knockout (KO) zebrafish model exhibits abnormal neurogenesis and craniofacial patterning, and in vivo complementation assays indicate that the patient-derived variants are hypomorphic. RNA sequencing analysis from fam50a KO zebrafish show dysregulation of the transcriptome, with augmented spliceosome mRNAs and depletion of transcripts involved in neurodevelopment. Zebrafish RNA-seq datasets show a preponderance of 3' alternative splicing events in fam50a KO, suggesting a role in the spliceosome C complex. These data are supported with transcriptomic signatures from cell lines derived from affected individuals and FAM50A protein-protein interaction data. In sum, Armfield XLID syndrome is a spliceosomopathy associated with aberrant mRNA processing during development.

Assessment of Health Care Exposures and Outcomes in Adult Patients With Sepsis and Septic Shock.

Importance: Current information on the characteristics of patients who develop sepsis may help in identifying opportunities to improve outcomes. Most recent studies of sepsis epidemiology have focused on changes in incidence or have used administrative data sets that provided limited patient-level data. Objective: To describe sepsis epidemiology in adults. Design, Setting, and Participants: This retrospective cohort study reviewed the medical records, death certificates, and hospital discharge data of adult patients with sepsis or septic shock who were discharged from the hospital between October 1, 2014, and September 30, 2015. The convenience sample was obtained from hospitals in the Centers for Disease Control and Prevention Emerging Infections Program in 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee). Patients 18 years and older with discharge diagnosis codes for severe sepsis or septic shock were randomly selected. Data were analyzed between May 1, 2018, and January 31, 2019. Main Outcomes and Measures: The population's demographic characteristics, health care exposures, and sepsis-associated infections and pathogens were described, and risk factors for death within 30 days after sepsis diagnosis were assessed. Results: Among 1078 adult patients with sepsis (569 men [52.8%]; median age, 64 years [interquartile range, 53-75 years]), 973 patients (90.3%) were classified as having community-onset sepsis (ie, sepsis diagnosed within 3 days of hospital admission). In total, 654 patients (60.7%) had health care exposures before their hospital admission for sepsis; 260 patients (24.1%) had outpatient encounters in the 7 days before admission, and 447 patients (41.5%) received medical treatment, including antimicrobial drugs, chemotherapy, wound care, dialysis, or surgery, in the 30 days before admission. A pathogen associated with sepsis was found in 613 patients (56.9%); the most common pathogens identified were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Clostridioides difficile. After controlling for other factors, an association was found between underlying comorbidities, such as cirrhosis (odds ratio, 3.59; 95% CI, 2.03-6.32), immunosuppression (odds ratio, 2.52; 95% CI, 1.81-3.52), vascular disease (odds ratio, 1.54; 95% CI, 1.10-2.15), and 30-day mortality. Conclusions and Relevance: Most adults experienced sepsis onset outside of the hospital and had recent encounters with the health care system. A sepsis-associated pathogen was identified in more than half of patients. Future efforts to improve sepsis outcomes may benefit from examination of health maintenance practices and recent health care exposures as potential opportunities among high-risk patients.

Documentation of acute change in mental status in nursing homes highlights opportunity to augment infection surveillance criteria.

Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.