Decomposing Racial and Ethnic Disparities in Nursing Home Influenza Vaccination

OBJECTIVES: Quantify how observable characteristics contribute to influenza vaccination disparities among White, Black, and Hispanic nursing home (NH) residents. DESIGN: Retrospective cohort. SETTING AND PARTICIPANTS: Short- and long-stay U.S. NH residents aged ≥65 years. METHODS: We linked Minimum Data Set (MDS) and Medicare data to LTCFocUS and other facility data. We included residents with 6-month continuous enrollment in Medicare and an MDS assessment between October 1, 2013, and March 31, 2014. Residents were classified as short-stay (<100 days in NH) or long-stay (≥100 days in NH). We fit multivariable logistic regression models to assess the relationships between 27 resident and NH-level characteristics and receipt of influenza vaccination. Using nonlinear Oaxaca-Blinder decomposition, we decomposed the disparity in influenza vaccination between White versus Black and White versus Hispanic NH residents. Analyses were repeated separately for short- and long-stay residents. RESULTS: Our study included 630,373 short-stay and 1,029,593 long-stay residents. Proportions vaccinated against influenza included 67.2% of White, 55.1% of Black, and 54.5% of Hispanic individuals among short-stay residents and 84.2%, 76.7%, and 80.8%, respectively among long-stay residents. Across 4 comparisons, the crude disparity in influenza vaccination ranged from 3.4 to 12.7 percentage points. By equalizing 27 prespecified characteristics, these disparities could be reduced 37.7% to 59.2%. Living in a predominantly White facility and proxies for NH quality were important contributors across all analyses. Characteristics unmeasured in our data (eg, NH staff attitudes and beliefs) may have also contributed significantly to the disparity. CONCLUSIONS AND IMPLICATIONS: The racial/ethnic disparity in influenza vaccination was most dramatic among short-stay residents. Intervening on factors associated with NH quality would likely reduce these disparities; however, future qualitative research is essential to explore potential contributors that were unmeasured in our data and to understand the degree to which these factors contribute to the overall disparity in influenza vaccination

Relationships between Community Virus Activity and Cardiorespiratory Rehospitalizations From Post-Acute Care

OBJECTIVES: Quantify the relationship between increasing influenza and respiratory syncytial virus (RSV) community viral activity and cardiorespiratory rehospitalizations among older adults discharged to skilled nursing facilities (SNFs). DESIGN: Retrospective cohort. SETTING AND PARTICIPANTS: Adults aged ≥65 years who were hospitalized and then discharged to a US SNF between 2012 and 2015. METHODS: We linked Medicare Provider Analysis and Review claims to Minimum Data Set version 3.0 assessments, PRISM Climate Group data, and the Centers for Disease Control and Prevention viral testing data. All data were aggregated to US Department of Health and Human Services regions. Negative binomial regression models quantified the relationship between increasing viral activity for RSV and 3 influenza strains (H1N1pdm09, H3N2, and B) and cardiorespiratory rehospitalizations from SNFs. Incidence rate ratios described the relationship between a 5% increase in circulating virus and the rates of rehospitalization for cardiorespiratory outcomes. Analyses were repeated using the same model, but influenza and RSV were considered "in season" or "out of season" based on a 10% positive testing threshold. RESULTS: Cardiorespiratory rehospitalization rates increased by approximately 1% for every 5% increase in circulating influenza A(H3N2), influenza B, and RSV, but decreased by 1% for every 5% increase in circulating influenza A(H1N1pdm09). When respiratory viruses were in season (vs out of season), cardiorespiratory rehospitalization rates increased by approximately 6% for influenza A(H3N2), 3% for influenza B, and 5% for RSV, but decreased by 6% for influenza A(H1N1pdm09). CONCLUSIONS AND IMPLICATIONS: The respiratory season is a particularly important period to implement interventions that reduce cardiorespiratory hospitalizations among SNF residents. Decreasing viral transmission in SNFs through practices such as influenza vaccination for residents and staff, use of personal protective equipment, improved environmental cleaning measures, screening and testing of residents and staff, surveillance of viral activity, and quarantining infected individuals may be potential strategies to limit viral infections and associated cardiorespiratory rehospitalizations

Estimated Cardiorespiratory Hospitalizations Attributable to Influenza and Respiratory Syncytial Virus Among Long-term Care Facility Residents

IMPORTANCE: Older adults residing in long-term care facilities (LTCFs) are at a high risk of being infected with respiratory viruses, such as influenza and respiratory syncytial virus (RSV). Although these infections commonly have many cardiorespiratory sequelae, the national burden of influenza- and RSV-attributable cardiorespiratory events remains unknown for the multimorbid and vulnerable LTCF population. OBJECTIVE: To estimate the incidence of cardiorespiratory hospitalizations that were attributable to influenza and RSV among LTCF residents and to quantify the economic burden of these hospitalizations on the US health care system by estimating their associated cost and length of stay. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used national Medicare Provider Analysis and Review inpatient claims and Minimum Data Set clinical assessments for 6 respiratory seasons (2011-2017). Long-stay residents of LTCFs were identified as those living in the facility for at least 100 days (index date), aged 65 years or older, and with 6 months of continuous enrollment in Medicare Part A were included. Follow-up occurred from the resident’s index date until the first hospitalization, discharge from the LTCF, disenrollment from Medicare, death, or the end of the study. Residents could re-enter the sample; thus, long-stay episodes of care were identified. Data analysis was performed between January 1 and September 30, 2020. EXPOSURES: Seasonal circulating pandemic 2009 influenza A(H1N1), human influenza A(H3N2), influenza B, and RSV. MAIN OUTCOMES AND MEASURES: Cardiorespiratory hospitalizations (eg, asthma exacerbation, heart failure) were identified using primary diagnosis codes. Influenza- and RSV-attributable cardiorespiratory events were estimated using a negative binomial regression model adjusted for weekly circulating influenza and RSV testing data. Length of stay and costs of influenza- and RSV-attributable events were then estimated. RESULTS: The study population comprised 2 909 106 LTCF residents with 3 138 962 long-stay episodes and 5 079 872 person-years of follow-up. Overall, 10 939 (95% CI, 9413-12 464) influenza- and RSV-attributable cardiorespiratory events occurred, with an incidence of 215 (95% CI, 185-245) events per 100 000 person-years. The cost of influenza- and RSV-attributable cardiorespiratory events was $91 055 393 (95$77 885 316-$104 225 470), and the length of stay was 56 858 (95% CI, 48 757-64 968) days. CONCLUSIONS AND RELEVANCE: This study found that many cardiorespiratory hospitalizations among LTCF residents in the US were attributable to seasonal influenza and RSV. To minimize the burden these events place on the health care system and residents of LTCFs and to prevent virus transmission, additional preventive measures should be implemented

Effect of BMAP-28 Antimicrobial Peptides on Leishmania major Promastigote and Amastigote Growth: Role of Leishmanolysin in Parasite Survival

Protozoan parasites are the causative agent of much disease in tropical areas of the world. Currently, the control of these diseases is dependent on outdated drug treatment, with associated high toxicity and drug resistance. There is an urgent need for novel anti-parasitic therapies. One emerging anti-parasitic therapies is Host defence peptides (HDPs). Here we test the HDP BMAP-28 as an anti-leishmanial therapy against two lifecycle stages of Leishmania major, the promastigotes (insect infective form) and the intracellular amastigote (mammalian infective form). Two stereoisomers of BMAP-28, the D-amino acid form (D-BMAP-28) and the retro-inverso form (RI-BMAP-28), were also tested for anti-leishmanial activity. The BMAP-28 form (L-form) was susceptible to degradation by GP63, the metalloproteinase that covers the promastigotes cell surface. However, the BMAP-28 isomers, the D-form and RI-form were resistant, and therefore more potent against the promastigote parasite. Though other anti-leishmanial HDP studies focus on the promastigote form of the parasite, it is the mammalian infective form, the amastigote, which causes the disease symptoms. Here we demonstrate that BMAP-28 and its isomers D-BMAP-28 and RI-BMAP-28 are effective against the amastigote form of the parasite using a macrophage infection model. These findings show that BMAP-28 has excellent potential as a novel anti-leishmanial therapeutic

Causes and timing of 30-day rehospitalization from skilled nursing facilities after a hospital admission for pneumonia or sepsis

BACKGROUND: Pneumonia and sepsis are among the most common causes of hospitalization in the United States and often result in discharges to a skilled nursing facility (SNF) for rehabilitation. We described the timing and most common causes of 30-day unplanned hospital readmission following an index hospitalization for pneumonia or sepsis. METHODS AND FINDINGS: This national retrospective cohort study included adults ≥65 years who were hospitalized for pneumonia or sepsis and were discharged to a SNF between July 1, 2012 and July 4, 2015. We quantified the ten most common 30-day unplanned readmission diagnoses and estimated the daily risk of first unplanned rehospitalization for four causes of readmission (circulatory, infectious, respiratory, and genitourinary). The index hospitalization was pneumonia for 92,153 SNF stays and sepsis for 452,254 SNF stays. Of these SNF stays, 20.9% and 25.9%, respectively, resulted in a 30-day unplanned readmission. Overall, septicemia was the single most common readmission diagnosis for residents with an index hospitalization for pneumonia (16.7% of 30-day readmissions) and sepsis (22.4% of 30-day readmissions). The mean time to unplanned readmission was approximately 14 days overall. Respiratory causes displayed the highest daily risk of rehospitalization following index hospitalizations for pneumonia, while circulatory and infectious causes had the highest daily risk of rehospitalization following index hospitalizations for sepsis. The day of highest risk for readmission occurred within two weeks of the index hospitalization discharge, but the readmission risk persisted across the 30-day follow-up. CONCLUSION: Among older adults discharged to SNFs following a hospitalization for pneumonia or sepsis, hospital readmissions for infectious, circulatory, respiratory, and genitourinary causes occurred frequently throughout the 30-day post-discharge period. Our data suggests further study is needed, perhaps on the value of closer monitoring in SNFs post-hospital discharge and improved communication between hospitals and SNFs, to reduce the risk of potentially preventable hospital readmissions

Geographic variation in influenza vaccination among U.S. nursing home residents:A national study

OBJECTIVES: Estimates of influenza vaccine use are not available at the county level for U.S. nursing home (NH) residents but are critically necessary to guide the implementation of quality improvement programs aimed at increasing vaccination. Furthermore, estimates that account for differences in resident characteristics between counties are unavailable. We estimated risk‐standardized vaccination rates (RSVRs) among short‐ and long‐stay NH residents by U.S. county and identified drivers of geographic variation. METHODS: We conducted a retrospective cohort study utilizing 100% of 2013–2015 fee‐for‐service Medicare claims, Minimum Data Set assessments, Certification and Survey Provider Enhanced Reports, and Long‐Term Care: Facts on Care in the U.S. We separately evaluated short‐stay (<100 days) and long‐stay (≥100 days) residents aged 65 and older across the 2013–2014 and 2014–2015 influenza seasons. We estimated RSVRs via hierarchical logistic regression adjusting for 32 resident‐level covariates. We then used multivariable linear regression models to assess associations between county‐level NHs predictors and RSVRs. RESULTS: The study cohort consisted of 2,817,217 residents in 14,658 NHs across 2798 counties. Short‐stay residents had lower RSVRs than long‐stay residents (2013–2014: median [interquartile range], 69.6% [62.8–74.5] vs 84.0% [80.8–86.4]), and there was wide variation within each population (range, 11.4–89.8 vs 49.1–92.6). Several modifiable facility‐level characteristics were associated with increased RSVRs, including higher registered nurse to total nurse ratio and higher total staffing for licensed practical nurses, speech‐language pathologists, and social workers. Characteristics associated with lower RSVRs included higher percentage of residents restrained, with a pressure ulcer, and NH‐level hospitalizations per resident‐year. CONCLUSIONS: Substantial county‐level variation in influenza vaccine use exists among short‐ and long‐stay NH residents. Quality improvement interventions to improve vaccination rates can leverage these results to target NHs located in counties with lower risk‐standardized vaccine use

Stage-specific requirement for Eomes in mature NK cell homeostasis and cytotoxicity

Natural killer (NK) cells are cytotoxic innate lymphoid cells (ILCs) that mediate antiviral and antitumor responses and require the transcriptional regulator Eomesodermin (Eomes) for early development. However, the role of Eomes and its molecular program in mature NK cell biology is unclear. To address this, we develop a tamoxifen-inducible, type-1-ILC-specific (Ncr1-targeted) cre mouse and combine this with Eomes-floxed mice. Eomes deletion after normal NK cell ontogeny results in a rapid loss of NK cells (but not ILC1s), with a particularly profound effect on penultimately mature stage III NK cells. Mechanisms responsible for stage III reduction include increased apoptosis and impaired maturation from stage II precursors. Induced Eomes deletion also decreases NK cell cytotoxicity and abrogates in vivo rejection of major histocompatibility complex (MHC)-class-I-deficient cells. However, other NK cell functional responses, and stage IV NK cells, are largely preserved. These data indicate that mature NK cells have distinct Eomes-dependent and -independent stages

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease

Risk of Ovarian Cancer and Inherited Variants in Relapse-Associated Genes

Background: We previously identified a panel of genes associated with outcome of ovarian cancer. The purpose of the current study was to assess whether variants in these genes correlated with ovarian cancer risk. Methods and Findings: Women with and without invasive ovarian cancer (749 cases, 1,041 controls) were genotyped at 136 single nucleotide polymorphisms (SNPs) within 13 candidate genes. Risk was estimated for each SNP and for overall variation within each gene. At the gene-level, variation within MSL1 (male-specific lethal-1 homolog) was associated with risk of serous cancer (p = 0.03); haplotypes within PRPF31 (PRP31 pre-mRNA processing factor 31 homolog) were associated with risk of invasive disease (p = 0.03). MSL1 rs7211770 was associated with decreased risk of serous disease (OR 0.81, 95 % CI 0.66–0.98; p = 0.03). SNPs in MFSD7, BTN3A3, ZNF200, PTPRS, and CCND1A were inversely associated with risk (p,0.05), and there was increased risk at HEXIM1 rs1053578 (p = 0.04, OR 1.40, 95 % CI 1.02–1.91). Conclusions: Tumor studies can reveal novel genes worthy of follow-up for cancer susceptibility. Here, we found that inherited markers in the gene encoding MSL1, part of a complex that modifies the histone H4, may decrease risk of invasiv

Vulnerability to climate change of managed stocks in the California Current large marine ecosystem

Introduction: Understanding how abundance, productivity and distribution of individual species may respond to climate change is a critical first step towards anticipating alterations in marine ecosystem structure and function, as well as developing strategies to adapt to the full range of potential changes. Methods: This study applies the NOAA (National Oceanic and Atmospheric Administration) Fisheries Climate Vulnerability Assessment method to 64 federally-managed species in the California Current Large Marine Ecosystem to assess their vulnerability to climate change, where vulnerability is a function of a species’ exposure to environmental change and its biological sensitivity to a set of environmental conditions, which includes components of its resiliency and adaptive capacity to respond to these new conditions. Results: Overall, two-thirds of the species were judged to have Moderate or greater vulnerability to climate change, and only one species was anticipated to have a positive response. Species classified as Highly or Very Highly vulnerable share one or more characteristics including: 1) having complex life histories that utilize a wide range of freshwater and marine habitats; 2) having habitat specialization, particularly for areas that are likely to experience increased hypoxia; 3) having long lifespans and low population growth rates; and/or 4) being of high commercial value combined with impacts from non-climate stressors such as anthropogenic habitat degradation. Species with Low or Moderate vulnerability are either habitat generalists, occupy deep-water habitats or are highly mobile and likely to shift their ranges. Discussion: As climate-related changes intensify, this work provides key information for both scientists and managers as they address the long-term sustainability of fisheries in the region. This information can inform near-term advice for prioritizing species-level data collection and research on climate impacts, help managers to determine when and where a precautionary approach might be warranted, in harvest or other management decisions, and help identify habitats or life history stages that might be especially effective to protect or restore