Risk Analysis of Respiratory Syncytial Virus Among Infants in the United States by Birth Month.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among U.S. infants. A child's calendar birth month determines their age at first exposure(s) to RSV. We estimated birth month-specific risk of medically attended (MA) RSV lower respiratory tract infection (LRTI) among infants during their first RSV season and first year of life. METHODS: We analyzed infants born in the USA between July 2016 and February 2020 using three insurance claims databases (two commercial, one Medicaid). We classified infants' first MA RSV LRTI episode by highest level of care incurred (outpatient, emergency department, or inpatient), employing specific and sensitive diagnostic coding algorithms to define index RSV diagnoses. In our main analysis we focused on infants' first RSV season. In our secondary analysis we compared the risk of MA RSV LRTI during infants' first RSV season to that of their first year of life. RESULTS: Infants born from May through September generally had the highest risk of first-season MA RSV LRTI-approximately 6%-10% under the specific RSV index diagnosis definition and 16%-26% under the sensitive. Infants born between October and December had the highest risk of RSV-related hospitalization during their first season. The proportion of MA RSV LRTI events classified as inpatient ranged from 9%-54% (specific) and 5%-33% (sensitive) across birth month and comorbidity group. Through the first year of life, the overall risk of MA RSV LRTI is comparable across birth months within each claims database (6%-11% under the specific definition, 17%-30% under the sensitive), with additional cases progressing to care at outpatient or ED settings. CONCLUSIONS: Our data support recent national recommendations for the use of nirsevimab in the USA. For infants born at the tail end of an RSV season who do not receive nirsevimab, a dose administered prior to the onset of their second RSV season could reduce the incidence of outpatient and ED-related events.

Geospatial Distribution of Racial Disparities in Influenza Vaccination in Nursing Homes.

OBJECTIVES: This study aimed to assess the distribution of racial disparities in influenza vaccination between White and Black short-stay and long-stay nursing home residents among states and hospital referral regions (HRRs). DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: We included short-stay and long-stay older adults residing in US nursing homes during influenza seasons between 2011 and 2018. Included residents were aged ≥65 years and enrolled in Traditional Medicare. Analyses were conducted using resident-seasons, whereby residents could contribute to one or more influenza seasons if they resided in a nursing home across multiple seasons. METHODS: Our comparison of interest was marginalized vs privileged racial group membership measured as Black vs White race. We obtained influenza vaccination documentation from resident Minimum Data Set assessments from October 1 through June 30 of a particular influenza season. Nonparametric g-formula was used to estimate age- and sex-standardized disparities in vaccination, measured as the percentage point (pp) difference in the proportions of individuals vaccinated between Black and White nursing home residents within states and HRRs. RESULTS: The study included 7,807,187 short-stay resident-seasons (89.7% White and 10.3% Black) in 14,889 nursing homes and 7,308,111 long-stay resident-seasons (86.7% White and 13.3% Black) in 14,885 nursing homes. Among states, the median age- and sex-standardized disparity between Black and White residents was 10.1 percentage points (pps) among short-stay residents and 5.3 pps among long-stay residents across seasons. Among HRRs, the median disparity was 8.6 pps among short-stay residents and 5.0 pps among long-stay residents across seasons. CONCLUSIONS AND IMPLICATIONS: Our analysis revealed that the magnitudes of vaccination disparities varied substantially across states and HRRs, from no disparity in vaccination to disparities in excess of 25 pps. Local interventions and policies should be targeted to high-disparity geographic areas to increase vaccine uptake and promote health equity.

Predicting Seasonal Influenza Hospitalizations Using an Ensemble Super Learner: A Simulation Study.

Accurate forecasts can inform response to outbreaks. Most efforts in influenza forecasting have focused on predicting influenza-like activity, with fewer on influenza-related hospitalizations. We conducted a simulation study to evaluate a super learner's predictions of 3 seasonal measures of influenza hospitalizations in the United States: peak hospitalization rate, peak hospitalization week, and cumulative hospitalization rate. We trained an ensemble machine learning algorithm on 15,000 simulated hospitalization curves and generated weekly predictions. We compared the performance of the ensemble (weighted combination of predictions from multiple prediction algorithms), the best-performing individual prediction algorithm, and a naive prediction (median of a simulated outcome distribution). Ensemble predictions performed similarly to the naive predictions early in the season but consistently improved as the season progressed for all prediction targets. The best-performing prediction algorithm in each week typically had similar predictive accuracy compared with the ensemble, but the specific prediction algorithm selected varied by week. An ensemble super learner improved predictions of influenza-related hospitalizations, relative to a naive prediction. Future work should examine the super learner's performance using additional empirical data on influenza-related predictors (e.g., influenza-like illness). The algorithm should also be tailored to produce prospective probabilistic forecasts of selected prediction targets.

Geographic Variation in Racial Disparities in Receipt of High-Dose Influenza Vaccine Among US Older Adults.

BACKGROUND: Racial disparities in receipt of high-dose influenza vaccine (HDV) have been documented nationally, but whether small-area geographic variation in such disparities exists remains unknown. We assessed the distribution of disparities in HDV receipt between Black and White traditional Medicare beneficiaries vaccinated against influenza within states and hospital referral regions (HRRs). METHODS: We conducted a nationally representative retrospective cohort study of 11,768,724 community-dwelling traditional Medicare beneficiaries vaccinated against influenza during the 2015-2016 influenza season (94.3% White and 5.7% Black). Our comparison was marginalized versus privileged racial group measured as Black versus White race. Vaccination and type of vaccine were obtained from Medicare Carrier and Outpatient files. Differences in the proportions of individuals who received HDV between Black and White beneficiaries within states and HRRs were used to measure age- and sex-standardized disparities in HDV receipt. We restricted to states and HRRs with ≥ 100 beneficiaries per age-sex strata per racial group. RESULTS: We detected a national disparity in HDV receipt of 12.8 percentage points (pps). At the state level, the median standardized HDV receipt disparity was 10.7 pps (minimum, maximum: 2.9, 25.6; n = 30 states). The median standardized HDV receipt disparity among HRRs was 11.6 pps (minimum, maximum: 0.4, 24.7; n = 54 HRRs). CONCLUSION: Black beneficiaries were less likely to receive HDV compared to White beneficiaries in almost every state and HRR in our analysis. The magnitudes of disparities varied substantially across states and HRRs. Local interventions and policies are needed to target geographic areas with the largest disparities to address these inequities.

Geographic Variation in Influenza Vaccination Disparities Between Hispanic and Non-Hispanic White US Nursing Home Residents.

Background: Disparities in influenza vaccination exist between Hispanic and non-Hispanic White US nursing home (NH) residents, but the geographic areas with the largest disparities remain unknown. We examined how these racial/ethnic disparities differ across states and hospital referral regions (HRRs). Methods: This retrospective cohort study included >14 million short-stay and long-stay US NH resident-seasons over 7 influenza seasons from October 1, 2011, to March 31, 2018, where residents could contribute to 1 or more seasons. Residents were aged ≥65 years and enrolled in Medicare fee-for-service. We used the Medicare Beneficiary Summary File to ascertain race/ethnicity and Minimum Data Set assessments for influenza vaccination. We calculated age- and sex-standardized percentage point (pp) differences in the proportions vaccinated between non-Hispanic White and Hispanic (any race) resident-seasons. Positive pp differences were considered disparities, where the proportion of non-Hispanic White residents vaccinated was greater than the proportion of Hispanic residents vaccinated. States and HRRs with ≥100 resident-seasons per age-sex stratum per racial/ethnic group were included in analyses. Results: Among 7 442 241 short-stay resident-seasons (94.1% non-Hispanic White, 5.9% Hispanic), the median standardized disparities in influenza vaccination were 4.3 pp (minimum, maximum: 0.3, 19.2; n = 22 states) and 2.8 pp (minimum, maximum: -3.6, 10.3; n = 49 HRRs). Among 6 758 616 long-stay resident-seasons (93.7% non-Hispanic White, 6.5% Hispanic), the median standardized differences were -0.1 pp (minimum, maximum: -4.1, 11.4; n = 18 states) and -1.8 pp (minimum, maximum: -6.5, 7.6; n = 34 HRRs). Conclusions: Wide geographic variation in influenza vaccination disparities existed across US states and HRRs. Localized interventions targeted toward areas with high disparities may be a more effective strategy to promote health equity than one-size-fits-all national interventions.

Correlation of long-term care facility vaccination practices between seasons and resident types.

BACKGROUND: Influenza vaccination varies widely across long-term care facilities (LTCFs) due to staff behaviors, LTCF practices, and patient factors. It is unclear how seasonal LTCF vaccination varies between cohabitating but distinct short-stay and long-stay residents. Thus, we assessed the correlation of LTCF vaccination between these populations and across seasons. METHODS: The study design is a national retrospective cohort using Medicare and Minimum Data Set (MDS) data. Participants include U.S. LTCFs. Short-stay and long-stay Medicare-enrolled residents age ≥ 65 in U.S. LTCFs from a source population of residents during October 1st-March 31st in 2013-2014 (3,042,881 residents; 15,683 LTCFs) and 2014-2015 (3,143,174, residents; 15,667 LTCFs). MDS-assessed influenza vaccination was the outcome. Pearson correlation coefficients were estimated to assess seasonal correlations between short-stay and long-stay resident vaccination within LTCFs. RESULTS: The median proportion of short-stay residents vaccinated across LTCFs was 70.4% (IQR, 50.0-82.7%) in 2013-2014 and 69.6% (IQR, 50.0-81.6%) in 2014-2015. The median proportion of long-stay residents vaccinated across LTCFs was 85.5% (IQR, 78.0-90.9%) in 2013-2014 and 84.6% (IQR, 76.6-90.3%) in 2014-2015. Within LTCFs, there was a moderate correlation between short-stay and long-stay vaccination in 2013-2014 (r = 0.50, 95%CI: 0.49-0.51) and 2014-2015 (r = 0.53, 95%CI: 0.51-0.54). Across seasons, there was a moderate correlation for LTCFs with short-stay residents (r = 0.54, 95%CI: 0.53-0.55) and a strong correlation for those with long-stay residents (r = 0.68, 95%CI: 0.67-0.69). CONCLUSIONS: In LTCFs with inconsistent influenza vaccination across seasons or between populations, targeted vaccination protocols for all residents, regardless of stay type, may improve successful vaccination in this vulnerable patient population.

Medically Attended Illness due to Respiratory Syncytial Virus Infection Among Infants Born in the United States Between 2016 and 2020.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization in the United States. Preterm infants and those with select comorbidities are at highest risk of RSV-related complications. However, morbidity due to RSV infection is not confined to high-risk infants. We estimated the burden of medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) among infants in the United States. METHODS: We analyzed commercial (MarketScan Commercial [MSC], Optum Clinformatics [OC]), and Medicaid (MarketScan Medicaid [MSM]) insurance claims data for infants born between April 2016 and February 2020. Using both specific and sensitive definitions of MA RSV LRTI, we estimated the burden of MA RSV LRTI during infants' first RSV season, stratified by gestational age, comorbidity status, and highest level of medical care associated with the MA RSV LRTI diagnosis. RESULTS: According to the specific definition 75.0% (MSC), 78.6% (MSM), and 79.6% (OC) of MA RSV LRTI events during infants' first RSV season occurred among term infants without known comorbidities. CONCLUSIONS: Term infants without known comorbidities account for up to 80% of the MA RSV LRTI burden in the United States during infants' first RSV season. Future prevention efforts should consider all infants.

Reply to letter to editor by Hadigal et al. regarding the immunogenicity and safety trial of high-dose influenza vaccine in adults aged ≥60 years.

Hadigal et al. argued the recommendation of high-dose influenza vaccine over standard-dose formulation is not supported by comparisons of numbers-needed-to-vaccinate (NNV) nor aligned with the WHO mandate of improving vaccine coverage. However, the authors' NNV calculation was inaccurate. A preferential recommendation for vaccines preventing influenza/complications can increase coverage. Furthermore, the impact of vaccination is a function of efficacy/effectiveness and the vaccine-preventable fraction of disease burden; therefore Hadigal et al. should interpret the absolute risk reduction by vaccination within the context of overall disease burden. To address the threat of COVID-19 pandemic, authorities should implement concomitant influenza/COVID-19 vaccination to reduce the burden of cocirculation of influenza and SARS- CoV- 2 viruses and increase the coverage of proven influenza vaccines as per WHO mandate.

Methods to account for measured and unmeasured confounders in influenza relative vaccine effectiveness studies: A brief review of the literature.

Observational seasonal influenza relative vaccine effectiveness (rVE) studies employ a variety of statistical methods to account for confounding and biases. To better understand the range of methods employed and implications for policy, we conducted a brief literature review. Across 37 included rVE studies, 10 different types of statistical methods were identified, and only eight studies reported methods to detect residual confounding, highlighting the heterogeneous state of the literature. To improve the comparability and credibility of future rVE research, researchers should clearly explain methods and design choices and implement methods to detect and quantify residual confounding.

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.

Variation in influenza vaccine assessment, receipt, and refusal by the concentration of Medicare Advantage enrollees in U.S. nursing homes.

BACKGROUND: More older adults enrolled in Medicare Advantage (MA) are entering nursing homes (NHs), and MA concentration could affect vaccination rates through shifts in resident characteristics and/or payer-related influences on preventive services use. We investigated whether rates of influenza vaccination and refusal differ across NHs with varying concentrations of MA-enrolled residents. METHODS: We analyzed 2014-2015 Medicare enrollment data and Minimum Data Set clinical assessments linked to NH-level characteristics, star ratings, and county-level MA penetration rates. The independent variable was the percentage of residents enrolled in MA at admission and categorized into three equally-sized groups. We examined three NH-level outcomes including the percentages of residents assessed and appropriately considered for influenza vaccination, received influenza vaccination, and refused influenza vaccination. RESULTS: There were 936,513 long-stay residents in 12,384 NHs. Categories for the prevalence of MA enrollment in NHs were low (0% to 3.3%; n = 4131 NHs), moderate (3.4% to 18.6%; n = 4127 NHs) and high (>18.6%; n = 4126 NHs). Overall, 81.3% of long-stay residents received influenza vaccination and 14.3% refused the vaccine when offered. Adjusting for covariates, influenza vaccination rates among long-stay residents were higher in NHs with moderate (1.70 percentage points [pp], 95% confidence limits [CL]: 1.15 pp, 2.24 pp), or high (3.05 pp, 95% CL: 2.45 pp, 3.66 pp) MA versus the lowest prevalence of MA. Influenza vaccine refusal was lower in NHs with moderate (-3.10 pp, 95% CL: -3.53 pp, -2.68 pp), or high (-4.63 pp, 95% CL: -5.11 pp, -4.15 pp) MA compared with NHs with the lowest prevalence of MA. CONCLUSION: A higher concentration of long-stay NH residents enrolled in MA was associated with greater influenza vaccine receipt and lower vaccine refusal. As MA becomes a larger share of the Medicare program, and more MA beneficiaries enter NHs, decisionmakers need to consider how managed care can be leveraged to improve the delivery of preventive services like influenza vaccinations in NH settings.

Influenza vaccine in chronic obstructive pulmonary disease among elderly male veterans.

BACKGROUND: Prior studies have established those elderly patients with chronic obstructive pulmonary disease (COPD) are at elevated risk for developing influenza-associated complications such as hospitalization, intensive-care admission, and death. This study sought to determine whether influenza vaccination could improve survival among elderly patients with COPD. MATERIALS/METHODS: This study included Veterans (age ≥ 65 years) diagnosed with COPD that received care at the United States Veterans Health Administration (VHA) during four influenza seasons, from 2012-2013 to 2015-2016. We linked VHA electronic medical records and Medicare administrative files to Centers for Disease Control and Prevention National Death Index cause of death records as well as influenza surveillance data. A multivariable time-dependent Cox proportional hazards model was used to compare rates of mortality of recipients of influenza vaccination to those who did not have records of influenza vaccination. We estimated hazard ratios (HRs) adjusted for age, gender, race, socioeconomic status, comorbidities, and healthcare utilization. RESULTS: Over a span of four influenza seasons, we included 1,856,970 person-seasons of observation where 1,199,275 (65%) had a record of influenza vaccination and 657,695 (35%) did not have a record of influenza vaccination. After adjusting for comorbidities, demographic and socioeconomic characteristics, influenza vaccination was associated with reduced risk of death during the most severe periods of influenza seasons: 75% all-cause (HR = 0.25; 95% CI: 0.24-0.26), 76% respiratory causes (HR = 0.24; 95% CI: 0.21-0.26), and 82% pneumonia/influenza cause (HR = 0.18; 95% CI: 0.13-0.26). A significant part of the effect could be attributed to "healthy vaccinee" bias as reduced risk of mortality was also found during the periods when there was no influenza activity and before patients received vaccination: 30% all-cause (HR = 0.70; 95% CI: 0.65-0.75), 32% respiratory causes (HR = 0.68; 95% CI: 0.60-0.78), and 51% pneumonia/influenza cause (HR = 0.49; 95% CI: 0.31-0.78). However, as a falsification study, we found that influenza vaccination had no impact on hospitalization due to urinary tract infection (HR = 0.97; 95% CI: 0.80-1.18). CONCLUSIONS: Among elderly patients with COPD, influenza vaccination was associated with reduced risk for all-cause and cause-specific mortality.

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.

Economic Assessment of High-Dose Versus Adjuvanted Influenza Vaccine: An Evaluation of Hospitalization Costs Based on a Cohort Study.

Two influenza vaccines are licensed in the U.S. exclusively for the 65 years and older population: a trivalent inactivated high-dose influenza vaccine (HD-IIV3) and a trivalent inactivated adjuvanted influenza vaccine (aIIV3). In a recent publication, we estimated a relative vaccine effectiveness (rVE) of HD-IIV3 vs. aIIV3 of 12% (95% CI: 3.3-20%) for influenza-related hospitalizations using a retrospective study design, but did not report the number of prevented hospitalizations nor the associated avoided cost. In this paper we report estimations for both. METHODS: Leveraging the rVE of a cohort study over two influenza seasons (2016/17 and 2017/18), we collected cost data for healthcare provided to the same study population. Vaccine costs were obtained from the Medicare pricing schedule. Our economic assessment compared cost of vaccination and hospital care for patients experiencing acute respiratory or cardiovascular illness. RESULTS: We analyzed 1.9 million HD-IIV3 and 223,793 aIIV3 recipients. Average vaccine list prices were $46.23 for HD-IIV3 and $48.26 for aIIV3. The hospitalization rates for respiratory disease in HD-IIV3 and aIIV3 recipients were 187 (95% CI: 185-189) and 212 (195-231) per 10,000 persons-years, respectively. Attributing the average cost per hospitalization of $12,652 ($12,214-$13,090) to the difference in hospitalization rates, we estimate net savings of HD-IIV3 to be $34 ($10-$62) per recipient. CONCLUSION: Pooled over two predominantly A/H3N2 respiratory seasons, vaccination with HD-IIV3 was associated with lower hospitalization rates and associated costs compared to aIIV3 in senior members of a large national managed health care company in the U.S. Reduced hospitalizations affect healthcare utilization overall, and therefore other costly health outcomes.

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% CI, $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.

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.

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.

DTaP combination vaccine use and adherence: A retrospective cohort study.

Despite universal recommendation of the 4-dose diphtheria, tetanus, and pertussis (DTaP) vaccine series, coverage and timeliness in the US remain suboptimal. DTaP-containing combination vaccines (i.e. quadrivalent and pentavalent) are presumed to improve vaccine coverage rates and timeliness, but research supporting this claim is limited. We sought to investigate the associations between DTaP-containing vaccine use and adherence to the recommended DTaP immunization schedule among children in the US. Using a large claims database, we identified privately insured children born between 2009 and 2016 that received ≥1 DTaP-containing vaccine and had ≥24 months of enrollment from birth, excluding those with DTaP vaccinations not aligned with approved dose indications. Children were classified by DTaP-containing vaccine receipt: combination vaccines only, stand-alone vaccines only, or a mixture of both. Outcome measures included: 1) completion of the 4-dose series and 2) timely receipt of doses. Outcomes were adjusted for gender, birth year, race, and socioeconomic status. The study cohort contained 412,441 children. Of these, 40.5% (167,084) received combination vaccines only, 14.9% (61,342) received stand-alone vaccines only, and 44.6% (184,015) received a mixture of both. Combination vaccine recipients were nearly 3 times as likely to complete the 4-dose series (OR 2.93 (95% CI: 2.88, 2.99)) and for all doses received, more than 4 times as likely to receive doses on time (OR 4.12 (4.04, 4.21), relative to stand-alone vaccine recipients. Significance disparities in adherence were also observed, where minorities were up to 30% less likely (OR 0.70 (0.68, 0.71)) to complete the 4-dose series and up to 27% less likely (OR 0.73 (0.72, 0.75)) to receive doses on time, relative to white children. Our findings demonstrated that adherence to the recommended DTaP immunization schedule was significantly greater among combination vaccine recipients, relative to stand-alone recipients. Further research is needed to investigate underlying causes of disparities in adherence.

Persistence of Racial Inequities in Receipt of Influenza Vaccination Among Nursing Home Residents in the United States.

BACKGROUND: We sought to determine if racial differences in influenza vaccination among nursing home (NH) residents during the 2008-2009 influenza season persisted in 2018-2019. METHODS: We conducted a cross-sectional study of NHs certified by the Centers for Medicare & Medicaid Services during the 2018-2019 influenza season in US states with ≥1% Black NH residents and a White-Black gap in influenza vaccination of NH residents (N = 2 233 392) of at least 1 percentage point (N = 40 states). NH residents during 1 October 2018 through 31 March 2019 aged ≥18 years and self-identified as being of Black or White race were included. Residents' influenza vaccination status (vaccinated, refused, and not offered) was assessed. Multilevel modeling was used to estimate facility-level vaccination status and inequities by state. RESULTS: The White-Black gap in influenza vaccination was 9.9 percentage points. In adjusted analyses, racial inequities in vaccination were more prominent at the facility level than at the state level. Black residents disproportionately lived in NHs that had a majority of Blacks residents, which generally had the lowest vaccination. Inequities were most concentrated in the Midwestern region, also the most segregated. Not being offered the vaccine was negligible in absolute percentage points between White residents (2.6%) and Black residents (4.8%), whereas refusals were higher among Black (28.7%) than White residents (21.0%). CONCLUSIONS: The increase in the White-Black vaccination gap among NH residents is occurring at the facility level in more states, especially those with the most segregation.

On the Causal Interpretation of Rate-Change Methods: The Prior Event Rate Ratio and Rate Difference.

A growing number of studies use data before and after treatment initiation in groups exposed to different treatment strategies to estimate "causal effects" using a ratio measure called the prior event rate ratio (PERR). Here, we offer a causal interpretation for PERR and its additive scale analog, the prior event rate difference (PERD). We show that causal interpretation of these measures requires untestable rate-change assumptions about the relationship between 1) the change of the counterfactual rate before and after treatment initiation in the treated group under hypothetical intervention to implement the control strategy; and 2) the change of the factual rate before and after treatment initiation in the control group. The rate-change assumption is on the multiplicative scale for PERR but on the additive scale for PERD; the 2 assumptions hold simultaneously under testable, but unlikely, conditions. Even if investigators can pick the most appropriate scale, the relevant rate-change assumption might not hold exactly, so we describe sensitivity analysis methods to examine how assumption violations of different magnitudes would affect study results. We illustrate the methods using data from a published study of proton pump inhibitors and pneumonia.