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.

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.

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.

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.

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.

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.

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.

Comparing the impact of high-dose versus standard dose influenza vaccines on hospitalization cost for cardiovascular and respiratory diseases: Economic assessment in the US Veteran population during 5 respiratory seasons using an instrumental variable method.

OBJECTIVES: Cost savings associated with high-dose (HD) as compared to standard-dose (SD) influenza vaccination in the United States (US) Veteran's Health Administration (VHA) population have been attributed to better protection against hospitalization for cardiac and respiratory diseases. The relative contribution of each of these disease categories to the reported savings remains to be explored. METHODS: During a recently completed study of HD versus SD vaccine effectiveness (conducted in the VHA over five respiratory seasons from 2010/11 through 2014/15), we collected cost data for all healthcare services provided at both VHA and Medicare-funded facilities. In that analysis, we compared the costs of vaccination and hospital care for patients admitted with either cardiovascular or respiratory disease. Treatment selection bias and other confounding factors were adjusted using an instrumental variable (IV) method. In this brief report we use the same study cohort and methods to stratify the results by patients admitted for cardiovascular disease (CVD) and those admitted for respiratory disease. RESULTS: We analyzed 3.5 million SD and 0.16 million HD person-seasons. The IV-adjusted rVEs were 14% (7-20%) against hospitalizations for CVD and 15% (5-25%) against respiratory hospitalizations. Net cost savings per HD recipient were $138 ($66-$200) for CVD related hospitalizations and $62 ($10-$107) for respiratory disease related hospitalizations. CONCLUSIONS: In the US VHA population, the reduction in hospitalizations for CVD over five respiratory seasons contributed twice the cost savings (per HD recipient) of the reduction in hospitalizations for respiratory disease.

High-dose influenza vaccination and mortality among predominantly male, white, senior veterans, United States, 2012/13 to 2014/15.

IntroductionIt is unclear whether high-dose influenza vaccine (HD) is more effective at reducing mortality among seniors.AimThis study aimed to evaluate the relative vaccine effectiveness (rVE) of HD. MethodsWe linked electronic medical record databases in the Veterans Health Administration (VHA) and Medicare administrative files to examine the rVE of HD vs standard-dose influenza vaccines (SD) in preventing influenza/pneumonia-associated and cardiorespiratory mortality among VHA-enrolled veterans 65 years or older during the 2012/13, 2013/14 and 2014/15 influenza seasons. A multivariable Cox proportional hazards model was performed on matched recipients of HD vs SD, based on vaccination time, location, age, sex, ethnicity and VHA priority level. ResultsAmong 569,552 person-seasons of observation, 207,574 (36%) were HD recipients and 361,978 (64%) were SD recipients, predominantly male (99%) and white (82%). Pooling findings from all three seasons, the adjusted rVE estimate of HD vs SD during the high influenza periods was 42% (95% confidence interval (CI): 24-59) against influenza/pneumonia-associated mortality and 27% (95% CI: 23-32) against cardiorespiratory mortality. Residual confounding was evident in both early and late influenza periods despite matching and multivariable adjustment. Excluding individuals with high 1-year predicted mortality at baseline reduced the residual confounding and yielded rVE of 36% (95% CI: 10-62) and 25% (95% CI: 12-38) against influenza/pneumonia-associated and cardiorespiratory mortality, respectively. These were confirmed by results from two-stage residual inclusion estimations.DiscussionThe HD was associated with a lower risk of influenza/pneumonia-associated and cardiorespiratory death in men during the high influenza period.

Risk factors for pneumonia and influenza hospitalizations in long-term care facility residents: a retrospective cohort study.

BACKGROUND: Older adults who reside in long-term care facilities (LTCFs) are at particularly high risk for infection, morbidity and mortality from pneumonia and influenza (P&I) compared to individuals of younger age and those living outside institutional settings. The risk factors for P&I hospitalizations that are specific to LTCFs remain poorly understood. Our objective was to evaluate the incidence of P&I hospitalization and associated person- and facility-level factors among post-acute (short-stay) and long-term (long-stay) care residents residing in LTCFs from 2013 to 2015. METHODS: In this retrospective cohort study, we used Medicare administrative claims linked to Minimum Data Set and LTCF-level data to identify short-stay (< 100 days, index = admission date) and long-stay (100+ days, index = day 100) residents who were followed from the index date until the first of hospitalization, LTCF discharge, Medicare disenrollment, or death. We measured incidence rates (IRs) for P&I hospitalization per 100,000 person-days, and estimated associations with baseline demographics, geriatric syndromes, clinical characteristics, and medication use using Cox regression models. RESULTS: We analyzed data from 1,118,054 short-stay and 593,443 long-stay residents. The crude 30-day IRs (95% CI) of hospitalizations with P&I in the principal position were 26.0 (25.4, 26.6) and 34.5 (33.6, 35.4) among short- and long-stay residents, respectively. The variables associated with P&I varied between short and long-stay residents, and common risk factors included: advanced age (85+ years), admission from an acute hospital, select cardiovascular and respiratory conditions, impaired functional status, and receipt of antibiotics or Beers criteria medications. Facility staffing and care quality measures were important risk factors among long-stay residents but not in short-stay residents. CONCLUSIONS: Short-stay residents had lower crude 30- and 90-day incidence rates of P&I hospitalizations than long-stay LTCF residents. Differences in risk factors for P&I between short- and long-stay populations suggest the importance of considering distinct profiles of post-acute and long-term care residents in infection prevention and control strategies in LTCFs. These findings can help clinicians target interventions to subgroups of LTCF residents at highest P&I risk.

Patient and practice level factors associated with seasonal influenza vaccine uptake among at-risk adults in England, 2011 to 2016: An age-stratified retrospective cohort study.

We sought to gain insights into the determinants of seasonal influenza vaccine (SIV) uptake by conducting an age-stratified analysis (18-64 and 65+) of factors associated with SIV uptake among at-risk adults registered to English practices. Records for at-risk English adults between 2011 and 2016 were identified using the Clinical Practice Research Datalink database. SIV uptake was assessed annually. The associations of patient, practice, and seasonal characteristics with SIV uptake were assessed via cross-sectional and longitudinal analyses, using mixed-effects and general estimating equation logistic regression models. Overall SIV uptake was 35.3% and 74.0% for adults 18-64 and 65+, respectively. Relative to white patients, black patients were least likely to be vaccinated (OR18-64: 0.82 (95% CI: 0.80, 0.85); OR65+: 0.59 (95% CI: 0.56, 0.62)), while Asian patients among 18-64 year olds were most likely to be vaccinated (OR18-64: 1.10 (95% CI: 1.07, 1.13)). Females were more likely than males to be vaccinated among 18-64 year olds (OR18-64: 1.19 (95% CI: 1.18, 1.20)). Greater socioeconomic deprivation was associated with decreased odds of uptake among older patients (OR65+: 0.74 (95% CI: 0.71, 0.77)). For each additional at-risk condition, odds of uptake increased (OR18-64: 2.33 (95% CI: 2.31, 2.36); OR65+: 1.39 (95% CI: 1.38, 1.39)). Odds of uptake were highest among younger patients with diabetes (OR18-64: 4.25 (95% CI: 4.18, 4.32)) and older patients with chronic respiratory disease (OR65+: 1.60 (95% CI: 1.58, 1.63)), whereas they were lowest among morbidly obese patients of all ages (OR18-64: 0.68 (95% CI: 0.67, 0.70); OR65+: 0.97 (95% CI: 0.94, 0.99)). Prior influenza season severity and vaccine effectiveness were marginally predictive of uptake. Our age-stratified analysis uncovered SIV uptake disparities by ethnicity, sex, age, socioeconomic deprivation, and co-morbidities, warranting further attention by GPs and policymakers alike.

Assessing the prior event rate ratio method via probabilistic bias analysis on a Bayesian network.

BACKGROUND: Unmeasured confounders are commonplace in observational studies conducted using real-world data. Prior event rate ratio (PERR) adjustment is a technique shown to perform well in addressing such confounding. However, it has been demonstrated that, in some circumstances, the PERR method actually increases rather than decreases bias. In this work, we seek to better understand the robustness of PERR adjustment. METHODS: We begin with a Bayesian network representation of a generalized observational study, which is subject to unmeasured confounding. Previous work evaluating PERR performance used Monte Carlo simulation to calculate joint probabilities of interest within the study population. Here, we instead use a Bayesian networks framework. RESULTS: Using this streamlined analytic approach, we are able to conduct probabilistic bias analysis (PBA) using large numbers of combinations of parameters and thus obtain a comprehensive picture of PERR performance. We apply our methodology to a recent study that used the PERR in evaluating elderly-specific high-dose (HD) influenza vaccine in the US Veterans Affairs population. That study obtained an HD relative effectiveness of 25% (95% CI: 2%-43%) against influenza- and pneumonia-associated hospitalization, relative to standard-dose influenza vaccine. In this instance, we find that the PERR-adjusted result is more like to underestimate rather than to overestimate the relative effectiveness of the intervention. CONCLUSIONS: Although the PERR is a powerful tool for mitigating the effects of unmeasured confounders, it is not infallible. Here, we develop some general guidance for when a PERR approach is appropriate and when PBA is a safer option.

The burden of respiratory infections among older adults in long-term care: a systematic review.

BACKGROUND: Respiratory infections among older adults in long-term care facilities (LTCFs) are a major global concern, yet a rigorous systematic synthesis of the literature on the burden of respiratory infections in the LTCF setting is lacking. To address the critical need for evidence regarding the global burden of respiratory infections in LTCFs, we assessed the burden of respiratory infections in LTCFs through a systematic review of the published literature. METHODS: We identified articles published between April 1964 and March 2019 through searches of PubMed (MEDLINE), EMBASE, and the Cochrane Library. Experimental and observational studies published in English that included adults aged ≥60 residing in LTCFs who were unvaccinated (to identify the natural infection burden), and that reported measures of occurrence for influenza, respiratory syncytial virus (RSV), or pneumonia were included. Disagreements about article inclusion were discussed and articles were included based on consensus. Data on study design, population, and findings were extracted from each article. Findings were synthesized qualitatively. RESULTS: A total of 1451 articles were screened for eligibility, 345 were selected for full-text review, and 26 were included. Study population mean ages ranged from 70.8 to 90.1 years. Three (12%) studies reported influenza estimates, 7 (27%) RSV, and 16 (62%) pneumonia. Eighteen (69%) studies reported incidence estimates, 7 (27%) prevalence estimates, and 1 (4%) both. Seven (27%) studies reported outbreaks. Respiratory infection incidence estimates ranged from 1.1 to 85.2% and prevalence estimates ranging from 1.4 to 55.8%. Influenza incidences ranged from 5.9 to 85.2%. RSV incidence proportions ranged from 1.1 to 13.5%. Pneumonia prevalence proportions ranged from 1.4 to 55.8% while incidence proportions ranged from 4.8 to 41.2%. CONCLUSIONS: The reported incidence and prevalence estimates of respiratory infections among older LTCF residents varied widely between published studies. The wide range of estimates offers little useful guidance for decision-making to decrease respiratory infection burden. Large, well-designed epidemiologic studies are therefore still necessary to credibly quantify the burden of respiratory infections among older adults in LTCFs, which will ultimately help inform future surveillance and intervention efforts.

Economic assessment of a high-dose versus a standard-dose influenza vaccine in the US Veteran population: Estimating the impact on hospitalization cost for cardio-respiratory disease.

OBJECTIVE: To compare the economic impact of high-dose trivalent (HD) versus standard-dose trivalent (SD) influenza vaccination on direct medical costs for cardio-respiratory hospitalizations in adults aged 65 years or older enrolled in the United States (US) Veteran's Health Administration (VHA). METHODS: Leveraging a relative vaccine effectiveness study of HD versus SD over five respiratory seasons (2010/11 through 2014/15), we collected cost data for healthcare provided to the same study population both at VHA and through Medicare services. Our economic assessment compared the costs of vaccination and hospital care for patients experiencing acute cardio-vascular or respiratory illness. RESULTS: We analyzed 3.5 million SD and 158,636 HD person-seasons. The average cost of HD and SD vaccination was $23.48 (95% CI: $21.29 - $25.85) and $12.21 (95% CI: $11.49 - $13.00) per recipient, respectively, while the hospitalization rates for cardio-respiratory disease in HD and SD recipients were 0.114 (95% CI: 0.108-0.121) and 0.132 (95% CI: 0.132-0.133) per person-season, respectively. Attributing the average cost per hospitalization of $11,796 (95% CI: $11,685 - $11,907) to the difference in hospitalization rates, we estimated savings attributable to HD to be $202 (95% CI: $115 - $280) per vaccinated recipient. CONCLUSIONS: For the five-season period of 2010/11 through 2014/15, HD influenza vaccination was associated with net cost savings due to fewer hospitalizations, and therefore lower direct medical costs, for cardio-respiratory disease as compared to SD influenza vaccination in the senior US VHA population.

The Annual Burden of Seasonal Influenza in the US Veterans Affairs Population.

Seasonal influenza epidemics have a substantial public health and economic burden in the United States (US). On average, over 200,000 people are hospitalized and an estimated 23,000 people die from respiratory and circulatory complications associated with seasonal influenza virus infections each year. Annual direct medical costs and indirect productivity costs across the US have been found to average respectively at $10.4 billion and $16.3 billion. The objective of this study was to estimate the economic impact of severe influenza-induced illness on the US Veterans Affairs population. The five-year study period included 2010 through 2014. Influenza-attributed outcomes were estimated with a statistical regression model using observed emergency department (ED) visits, hospitalizations, and deaths from the Veterans Health Administration of the Department of Veterans Affairs (VA) electronic medical records and respiratory viral surveillance data from the Centers for Disease Control and Prevention (CDC). Data from VA's Managerial Cost Accounting system were used to estimate the costs of the emergency department and hospital visits. Data from the Bureau of Labor Statistics were used to estimate the costs of lost productivity; data on age at death, life expectancy and economic valuations for a statistical life year were used to estimate the costs of a premature death. An estimated 10,674 (95% CI 8,661-12,687) VA ED visits, 2,538 (95% CI 2,112-2,964) VA hospitalizations, 5,522 (95% CI 4,834-6,210) all-cause deaths, and 3,793 (95% CI 3,375-4,211) underlying respiratory or circulatory deaths (inside and outside VA) among adult Veterans were attributable to influenza each year from 2010 through 2014. The annual value of lost productivity amounted to $27 (95% CI $24-31) million and the annual costs for ED visits were $6.2 (95% CI $5.1-7.4) million. Ninety-six percent of VA hospitalizations resulted in either death or a discharge to home, with annual costs totaling $36 (95% CI $30-43) million. The remaining 4% of hospitalizations were followed by extended care at rehabilitation and skilled nursing facilities with annual costs totaling $5.5 (95% CI $4.4-6.8) million. The annual monetary value of quality-adjusted life years (QALYs) lost amounted to $1.1 (95% CI $1.0-1.2) billion. In total, the estimated annual economic burden was $1.2 (95% CI $1.0-1.3) billion, indicating the substantial burden of seasonal influenza epidemics on the US Veterans Affairs population. Premature death was found to be the largest driver of these costs, followed by hospitalization.