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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 National Healthcare Safety Network Long-term Care Facility Component early reporting experience: January 2013-December 2015.

Background: In 2012, the Centers for Disease Control and Prevention launched the Long-term Care Facility (LTCF) Component of the National Healthcare Safety Network (NHSN) designed for LTCFs to monitor Clostridium difficile infections (CDIs), urinary tract infections (UTIs), infections due to multidrug-resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA), and infection prevention process measures.

Methods: We describe characteristics and reporting patterns of facilities enrolled in the first 3 years of the surveillance system and rate estimates for CDI, UTI, and MRSA data submitted between 2013 and 2015.

Results: From 2013-2015, 279 LTCFs were enrolled and eligible to report to the NHSN with variability in reporting from year to year.

Measuring Antibiotic Appropriateness for Urinary Tract Infections in Nursing Home Residents.

We assessed the appropriateness of initiating antibiotics in 49 nursing home (NH) residents receiving antibiotics for urinary tract infection (UTI) using 3 published algorithms. Overall, 16 residents (32%) received prophylaxis, and among the 33 receiving treatment, the percentage of appropriate use ranged from 15% to 45%. Opportunities exist for improving UTI antibiotic prescribing in NH.