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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.

Accurate forecasts can inform response to outbreaks. Most efforts in influenza forecasting have focused on predicting influenza-like activity, but fewer on influenza-related hospitalizations. We conducted a simulation study to evaluate a super learner’s predictions of three 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 to 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.

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.

Background Healthcare utilization during acute medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) episodes remains poorly characterized, particularly among term infants without comorbidities. Describing the care incurred during these episodes may provide important information regarding the impact of MA RSV LRTI. Objective: Estimate the occurrence and average number of outpatient, emergency department (ED), and inpatient visits during infants' first RSV season. Methods Using deidentified insurance claims data (MarketScan Commercial ®, MSC; MarketScan Medicaid ®, MSM; Optum Clinformatics ®, OC), we assembled a cohort of infants born in the United States between April 1, 2016 and February 29, 2020 and identified their first MA RSV LRTI episode during their first RSV season. We defined an RSV episode as the 7 days following an index RSV diagnosis (inclusive of the diagnosis date), allowing for two alternative definitions of the index diagnosis—a specific definition, based on ICD-10 codes explicitly indicating RSV, and a sensitive definition, including codes for unspecified bronchiolitis. We calculated the average number of outpatient, ED, and inpatient visits during this episode, stratifying estimates by gestational age and the presence/absence of comorbidities. We also calculated the proportion of episodes involving a given place of service. Results Using the specific (sensitive) definitions, infants averaged 1.11 (1.19), 0.90 (0.89), and 1.56 (1.39) outpatient visits during their first acute RSV episode, in the MSC, MSM, and OC datasets, respectively (Table). They averaged 0.35 (0.23), 0.51 (0.47), and 0.39 (0.23) visits to the ED and 0.28 (0.14), 0.25 (0.14), and 0.23 (0.11) inpatient stays. While MA RSV LRTI episodes among infants who were preterm and/or had other comorbidities (comorbidity groups B and C) were more likely to involve an ED or inpatient visit, up to 21% (10%) of episodes among otherwise healthy term infants involved an inpatient stay. Conclusion Up to 1 in 5 infants experiencing an MA RSV LRTI episode during their first RSV season visited an inpatient setting, including between 9% and 21% of otherwise healthy term infants. This study was funded by Sanofi and AstraZeneca. Disclosures Jason Gantenberg, PhD, MPH, Sanofi: Grant/Research Support Robertus van Aalst, PhD, MSc, Sanofi: Stocks/Bonds David R. Diakun, BS, Sanofi: Employed by IBM Watson Health which was contracted by Sanofi to perfom outcomes research|Sobi: Employed by IBM Watson Health which was contracted by Sobi to conduct the study Christopher B. Nelson, PhD MPH, Sanofi: employee|Sanofi: Stocks/Bonds David A. Savitz, PhD, Sanofi-Pasteur: Grant/Research Support|Sanofi-Pasteur: Honoraria Andrew R. Zullo, PharmD, PhD, Sanofi: Grant/Research Support.

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.

SummaryBackgroundThroughout the COVID-19 pandemic, human mobility has played a central role in shaping disease transmission. In this study, we develop a mechanistic model to calculate disease incidence from commercially-available US mobility data over the course of 2020. We use it to study, at the US state level, the lag between infection and case report. We examine the evolution of per-contact transmission probability, and its dependence on mean air temperature. Finally, we evaluate the potential of the model to produce short-term incidence forecasts from mobility data.MethodsWe develop a mechanistic model that relates COVID-19 incidence to time series contact index (CCI) data collected by mobility data vendor Cuebiq. From this, we perform maximum-likelihood estimates of the transmission probability per CCI event. Finally, we retrospectively conduct forecasts from multiple dates in 2020 forward.FindingsAcross US states, we find a median lag of 19 days between transmission and case report. We find that the median transmission probability from May onward was about 20% lower than it was during March and April. We find a moderate, statistically significant negative correlation between mean state temperature and transmission probability, r = − .57, N = 49, p = 2 × 10−5. We conclude that for short-range forecasting, CCI data would likely have performed best overall during the first few months of the pandemic.InterpretationOur results are consistent with associations between colder temperatures and stronger COVID-19 burden reported in previous studies, and suggest that changes in the per-contact transmission probability play an important role. Our model displays good potential as a short-range (2 to 3 week) forecasting tool during the early stages of a future pandemic, before non-pharmaceutical interventions (NPIs) that modify per-contact transmission probability, principally face masks, come into widespread use. Hence, future development should also incorporate time series data of NPI use.

Vaccination remains the most effective way to prevent influenza infection, albeit vaccine effectiveness (VE) varies by year. Compared to other age groups, children and elderly adults have the highest risk of developing influenza-related complications and requiring hospitalization. During the last years, “test negative design” (TND) studies have been implemented in order to estimate influenza VE. The aim of this systematic review and meta-analysis was to summarize the findings of TND studies reporting influenza VE against laboratory-confirmed influenza-related hospitalization in children aged 6 months to 17 years. We searched the PubMed and Embase databases and identified 2615 non-duplicate studies that required detailed review. Among them, 28 met our inclusion criteria and we performed a random-effects meta-analysis using adjusted VE estimates. In our primary analysis, influenza vaccine offered significant protection against any type influenza-related hospitalization (57.48%; 95% CI 49.46–65.49). When we examined influenza VE per type and strain, VE was higher against H1N1 (74.07%; 95% CI: 54.85–93.30) and influenza B (50.87%; 95% CI: 41.75–59.98), and moderate against H3N2 (40.77%; 95% CI: 25.65–55.89). Notably, influenza vaccination offered higher protection in children who were fully vaccinated (61.79%; 95% CI: 54.45–69.13), compared to those who were partially vaccinated (33.91%; 95% CI: 21.12 – 46.69). Also, influenza VE was high in children less than 5 years old (61.71%; 95% CI: 49.29–74.12) as well as in children 6–17 years old (54.37%; 95% CI: 35.14–73.60). In conclusion, in the pediatric population, influenza vaccination offered significant protection against influenza-related hospitalization and complete annual vaccination should be encouraged.

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 ( 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.

There is large county-level geographic variation in pneumonia and influenza hospitalizations among short-stay and long-stay long-term care facility residents in the United States. Long-term care facilities in counties in the Southern and Midwestern regions had the highest rates of pneumonia and influenza from 2013 to 2015. Future research should identify reasons for these geographic differences.

Background Adults 65 years and older (seniors) experience more complications following influenza infection than younger adults. We estimated the relative vaccine effectiveness (rVE) of a trivalent high dose (HD-IIV3) versus an adjuvanted trivalent influenza vaccine (aIIV3) in seniors for respiratory-related hospitalizations. Methods We conducted a retrospective cohort study using claims data from Optum’s Clinformatics® Data Mart to compare outcome rates between seniors who received HD-IIV3 versus aIIV3 during the 2016/17 and 2017/18, predominantly A/H3N2 respiratory seasons. Rates were adjusted for demographic characteristics, comorbid conditions, previous influenza vaccination, and geography. We used the previous event rate ratio (PERR) approach to address bias by time-fixed unmeasured confounders. Results We identified 842,282 HD-IIV3 and 34,157 aIIV3 recipients for the 2016/17 season and 1,058,638 HD-IIV3 and 189,636 aIIV3 recipients for the 2017/18 season. The pooled rVE of HD-IIV3 versus aIIV3 for respiratory-related hospitalizations over both seasons was 12% (95% confidence interval: 3.3%–20%); 13% (−6.4% to 32%) for the 2016/17 season and 12% (2.1%–21%) for the 2017/18 season. Conclusions Pooled over two predominantly A/H3N2 respiratory seasons, HD-IIV3 was associated with fewer respiratory hospital admissions than aIIV3 in senior members of large national managed health care company in the U.S.

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.

BackgroundMore 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.MethodsWe 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 groups. We examined three NH-level outcomes: percentage of residents assessed and appropriately provided the influenza vaccine, receiving influenza vaccine, and refusing influenza vaccine.ResultsThere 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). Adjusting for covariates, influenza vaccination rates among long-stay residents were higher in NHs with moderate (1.7%,PPPPPConclusionThe relationship between MA concentration and influenza vaccination measures varied among post-acute and long-term NH residents. As MA takes a larger role in the Medicare program, and more MA beneficiaries enter NHs, there is need to consider how managed care can be leveraged to improve the delivery of preventive services such as influenza vaccinations in NH settings.

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.

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.

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.

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.

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. (C) 2021 The Author(s). Published by Elsevier Ltd.

ObjectiveEstimates of influenza vaccine use are not available at the county level for U.S. nursing home (NH) residents but are critically necessary to guide implementation of quality improvement programs aimed at increasing vaccination rates. Furthermore, estimates that account for differences in resident characteristics between counties are unavailable. We estimated risk-standardized vaccination rates among short- and long-stay NH residents by U.S. county and identified drivers of geographic variation.MethodsWe 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 LTCFocUS. We separately evaluated short-stay (ResultsThe overall study cohort consisted of 2,817,217 residents in 14,658 NHs across 2,798 counties. Short-stay residents had lower RSVRs than long-stay residents (2013-2014: median [IQR], 69.6% [62.8-74.5] vs 84.0% [80.8-86.4]). Counties with the highest vaccination rates were concentrated in the Midwestern, Southern, and Northeast US. 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.ConclusionsSubstantial 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.

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.

Background Complications following influenza infection are a major cause of morbidity and mortality, and the Centers for Disease Control Advisory Committee on Immunization Practices recommends universal annual vaccination. However, vaccination rates have remained significantly lower than the Department of Health and Human Services goal. The aim of this work was to assess the vaccination rate among patients who present to health care providers with influenza-like illness and identify groups with lower vaccination rates. Methods We performed a systematic search of the PubMed and EMBASE databases with a time frame of January 1, 2010, to March 1, 2019 and focused on the vaccination rate among patients seeking care for acute respiratory illness in the United States. A random effects meta-analysis was performed to estimate the pooled seasonal influenza vaccination rate, and we used a time trend analysis to identify differences in annual vaccination over time. Results The overall pooled influenza vaccination rate was 48.61% (whites: 50.87%; blacks: 36.05%; Hispanics: 41.45%). There was no significant difference among gender groups (men: 46.43%; women: 50.11%). Interestingly, the vaccination rate varied by age group and was significantly higher among adults aged >65 (78.04%) and significantly lower among children 9–17 years old (36.45%). Finally, we found a significant upward time trend in the overall influenza vaccination rate among whites (coef. = .0107; P = .027). Conclusions In conclusion, because of the significantly lower influenza vaccination rates in black and Hispanic communities, societal initiatives and community outreach programs should focus on these populations and on children and adolescents aged 9–17 years.

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., The persisting White–Black influenza vaccination gap among nursing home residents continues to occur at the facility level in states with at least 1% Black nursing home residents, particularly in states with the most White–Black racial segregation.

We examined the process of obtaining informed consent (IC) for clinical research purposes in long-term care facilities (LTCFs) in Rhode Island (RI), USA. We assessed factors that were associated with resident ability to consent, such as Brief Interview for Mental Status scores. We used a self-administered questionnaire to further understand the effect of LTCF staff evaluation of ability to consent on residents' autonomy and control over their medical decision making.Observational clinical studyLong-term care setting.LTCF personnel provided us with residents' names, as well as their professional assessment of resident ability to consent. We used Brief Interview for Mental Status (BIMS) scores to assess the cognitive capacity of all residents to assess, and compare it to the assessment provided by LTCF personnel. A logistic regression analysis was performed to determine the relationship between LTCF assessment of resident ability to consent and BIMS score or confirmed diagnosis of dementia as seen from residents' medical charts. A self-administered questionnaire was filled out by the personnel of 10 LTCFs across RI, USA.LTCF personnel in 9 out of 10 recruited facilities reported that their assessment of resident ability to consent was based on subjective assessment of the resident as alert and oriented. There was a statistically significant relationship between the LTCF assessment of resident ability to consent and previously diagnosed dementia (OR: 0.211, 95% CI 0.107-0.415). Therefore, as BIMS scores increased, the likelihood that the resident would be deemed able to consent by LTCF personnel also increased. Furthermore, there was a statistically significant relationship between LTCF assessment of resident ability to consent and BIMS scores (OR: 1.430, 95% CI 1.274-1.605).There is no standard on obtaining IC for research studies conducted in LTCFs. We recommend that standardizing the process of obtaining IC in LTCFs can enhance the ability to perform research with LTCF residents.

Introduction It is unclear whether high-dose influenza vaccine (HD) is more effective at reducing mortality among seniors. Aim This study aimed to evaluate the relative vaccine effectiveness (rVE) of HD. Methods We 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. Results Among 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. Discussion The HD was associated with a lower risk of influenza/pneumonia-associated and cardiorespiratory death in men during the high influenza period.

Highlights • Disparities in uptake by ethnicity, varying by age, were evident. • Older adults with higher socioeconomic deprivation were less likely to be vaccinated. • Patients with morbid obesity had the lowest odds of being vaccinated. • Patients who had more annual GP consultations were more likely to be vaccinated., 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.

Adults 65 years and older (hereinafter referred to as seniors) are at greater risk for complications following influenza infection compared with younger adults, due to decreased vaccine efficacy and increased prevalence of chronic medical conditions with increasing age. Currently in the U.S., two influenza vaccines are licensed exclusively for use in seniors: a high-dose influenza vaccine (HD-IIV3) and an adjuvanted influenza vaccine (aIIV3). HD-IIV3 aims to improve protection through quadrupling the antigen dose per influenza strain, whereas aIIV3 is a standard-dose vaccine (SD-IIV3) to which an oil-in-water emulsion of squalene oil is added. HD-IIV3 is often offered at a price premium compared to SD-IIV3 and aIIV3. In this thesis we attempted to answer if this premium is worthwhile. We studied two specific sub-populations in the United States – Veterans receiving care through the Veterans Health Administration (VHA) and members of a large national managed care company affiliated with Optum. For our analyses we used real-word data (RWD): health insurance claims data and electronic medical records from VHA, Medicare and Optum. The availability of large databases with data of millions of people makes affordable retrospective cohort studies possible but introduces unique challenges when trying to find causal relationships. We discuss the causal interpretation of rate-change methods and propose a novel approach to test its sensitivity to violations of underlying assumptions. We conclude that HD-IIV3 is associated with less hospitalizations compared to SD-IIV3 and aIIV3. The avoided hospitalization costs offset HD-IIV3’s higher price and resulted in net cost savings.

Background Pneumococcal infections are an important source of morbidity and mortality in older adults and persons with compromised immune systems. New recommendations from the Advisory Committee on Immunization Practices (ACIP) became available September 2014, which included recommendations for the use of the 13-valent pneumococcal conjugate vaccine (PCV13). A study was conducted to increase the PCV13 vaccination rates of hospitalized patients at the White River Junction Veterans Affairs Medical Center (White River Junction, Vermont) through the use of a resident-driven quality improvement (QI) project. Methods From December 2014 through April 2016, 16 internal medicine inpatient residents addressed inpatient PCV13 vaccination rates by participating in the facility's QI curriculum. Eight Plan-Do-Study-Act cycles were used, including discharge template editing, electronic reminders, and the discovery of a vaccination administration documentation error in the record through data validation. The measure was the monthly percentage of patients who received PCV13 vaccination (vaccination completion rate) of those discharged from the hospital medicine service who were due for PCV13 vaccination. Results The percentage of veterans discharged with an up-to-date PCV13 vaccination on discharge increased from approximately 30% to 87% and was sustained. Conclusion Despite being driven by many different residents, this project demonstrates that continuous improvement can be achieved through a structured and iterative process while providing active learning of core QI concepts to residents. It also displays a method in which new guidelines can be incorporated into practice in an effective manner. Finally, this project is an example of how resident-driven data validation can lead to further improvement.

Background RSV-associated lower respiratory tract infection (LRTI) is the leading cause of infant hospitalization. Most studies of RSV have focused on infants with underlying comorbidities, including prematurity. The purpose of this analysis is to describe the burden of RSV LRTI across all medical settings and in all infants experiencing their first RSV season. Methods Using de-identified claims data from two commercial (MarketScan Commercial, MSC; Optum Clinformatics, OC) and one public (MarketScan Medicaid, MSM) insurance database, we estimated the prevalence of MA RSV LRTI among infants born between April 1, 2016 and June 30, 2019 in their first RSV season. Estimates were made by gestational age, presence/absence of comorbidities, and setting (inpatient, emergency department and outpatient). Due to limited laboratory testing, we defined MA RSV LRTI using two sets of ICD-10-CM diagnosis codes: a specific definition (identifying RSV explicitly) and a sensitive definition that included unspecified bronchiolitis. The first specific diagnosis triggered a search for another MA RSV LRTI diagnosis (either specific or sensitive) within the next 7 days. In the sensitive analysis, the first diagnosis was allowed to meet the sensitive definition. Setting was recorded as the highest level of care attached to a MA RSV LRTI diagnosis within this 7-day period. Results Using the specific (sensitive) definitions, 4.2% (12.2%), 6.8% (16.8%), and 2.7% (7.2%) of newborns had an MA RSV LRTI diagnosis during their first respiratory season across the MSC, MSM, and OC datasets (Table 1). Term infants without comorbidities accounted for 77% (83%), 79% (86%), and 80 (81%) of all MA RSV LRTI, and 21% (10%), 19% (10%), and 21% (10%) of all infants with MA RSV LRTI had an inpatient hospital stay (Table 2). Term infants without comorbidities accounted for 69% (68%), 67% (79%), and 73% (73%) of all MA RSV LRTI inpatients (Table 2). Conclusion In commercial and public claims data, during their first RSV season, term infants without comorbidities accounted for a sizable majority of inpatient, emergency room, and outpatient encounters for RSV LRTI in the US. To address the burden of RSV LRTI, future RSV prevention efforts should target all infants. Funding Sanofi Pasteur, AstraZeneca Disclosures Jason Gantenberg, MPH, Sanofi Pasteur (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Nicole Zimmerman, MS, IBM Watson Health (Employee, Nicole Zimmerman is an employee of IBM, which was compensated by Sanofi to complete this work.)Sanofi (Other Financial or Material Support, Nicole Zimmerman is an employee of IBM, which was compensated by Sanofi to complete this work.) Andrew R. Zullo, PharmD, PhD, ScM, Sanofi Pasteur (Grant/Research Support, Research Grant or Support) Brendan Limone, PharmD, PharmD, Sanofi Pasteur (Other Financial or Material Support, IBM was contracted by Sanofi to perform analysis) Clarisse Demont, n/a, Sanofi Pasteur (Employee, Shareholder) Sandra S. Chaves, MD, MSc, Sanofi Pasteur (Employee) William V. La Via, MD, AstraZeneca (Shareholder)Sanofi Pasteur (Employee) Christopher Nelson, PhD, Epidemiology, Sanofi Pasteur (Employee) Christopher Rizzo, MD, Sanofi (Employee) David A. Savitz, PhD, Sanofi Pasteur (Grant/Research Support) Robertus Van Aalst, MSc, Sanofi Pasteur (Employee, Shareholder)

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.

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. Electronic supplementary material The online version of this article (10.1186/s12877-019-1236-6) contains supplementary material, which is available to authorized users.

Background Pneumonia and influenza (P&I) increase morbidity and mortality among older adults, especially those residing in long-term care facilities (LTCFs). Facility-level characteristics may affect the risk of P&I beyond resident-level risk factors. However, the relationship between facility characteristics and P&I is poorly understood. To address this, we identified potentially modifiable facility-level characteristics that influence the incidence of P&I across LTCFs. Methods We conducted a retrospective cohort study using 2013–2015 Medicare claims linked to Minimum Data Set and LTCF-level data. Short-stay ( Results We included 1 767 241 short-stay (13 683 LTCFs) and 922 863 long-stay residents (14 495 LTCFs). LTCFs with lower RSIRs had more licensed independent practitioners (nurse practitioners or physician assistants) among short-stay (44.9% vs 41.6%, P < .001) and long-stay residents (47.4% vs 37.9%, P < .001), higher registered nurse hours/resident/day among short-stay and long-stay residents (mean [SD], 0.5 [0.7] vs 0.4 [0.4], P < .001), and fewer residents for whom antipsychotics were prescribed among short-stay (21.4% [11.6%] vs 23.6% [13.2%], P < .001) and long-stay residents (22.2% [14.3%] vs 25.5% [15.0%], P < .001). Conclusions LTCF characteristics may play an important role in preventing P&I hospitalizations. Hiring more registered nurses and licensed independent practitioners, increasing staffing hours, and higher-quality care practices may be modifiable means of reducing P&I in LTCFs.

Background: Influenza is a major cause of morbidity and mortality in patients diagnosed with heart failure. The aim of this study was to evaluate the effectiveness of influenza vaccination in this population in terms of reduction in all-cause mortality and rate of hospitalization.Methods: We conducted a systematic review and meta-analysis using PubMed and EMBASE entries from January of 2000 through April 2018. Publication bias was examined using the Egger's regression test. Statistical heterogeneity was examined using the Higgins I 2 statistic. Subgroup analyses were performed to examine the effect of vaccination during the influenza and noninfluenza seasons.Results: We identified 8 studies that included a total of 82 354 patients with heart failure. In patients with heart failure who were vaccinated against influenza, we found a reduced risk of all-cause mortality (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.51-0.87). No evidence of publication bias was found, and the effect was more pronounced during influenza season (HR, 0.49; 95% CI, 0.30-0.69), compared with noninfluenza season (HR, 0.79; 95% CI, 0.68-0.89). In terms of heart failure hospitalizations, we did not identify a statistically significant difference between the cohorts (HR, 0.62; 95% CI, 0.00-1.23).Conclusions: Influenza vaccination was associated with a decreased risk of all-cause mortality in patients with heart failure, and this effect was more prominent during the influenza season.

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 (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.

Background Integrating teaching and hands-on experience in quality improvement (QI) may increase the learning and the impact of resident QI work. Objective We sought to determine the clinical and educational impact of an integrated QI curriculum. Methods This clustered, randomized trial with early and late intervention groups used mixed methods evaluation. For almost 2 years, internal medicine residents from Dartmouth-Hitchcock Medical Center on the inpatient teams at the White River Junction VA participated in the QI curriculum. QI project effectiveness was assessed using statistical process control. Learning outcomes were assessed with the Quality Improvement Knowledge Application Tool–Revised (QIKAT-R) and through self-efficacy, interprofessional care attitudes, and satisfaction of learners. Free text responses by residents and a focus group of nurses who worked with the residents provided information about the acceptability of the intervention. Results The QI projects improved many clinical processes and outcomes, but not all led to improvements. Educational outcome response rates were 65% (68 of 105) at baseline, 50% (18 of 36) for the early intervention group at midpoint, 67% (24 of 36) for the control group at midpoint, and 53% (42 of 80) for the late intervention group. Composite QIKAT-R scores (range, 0–27) increased from 13.3 at baseline to 15.3 at end point (P Conclusions Learning and participating in hands-on QI can be integrated into the usual inpatient work of resident physicians.

Background Previous studies established an association between laboratory-confirmed influenza infection (LCI) and hospitalization for acute myocardial infarction (AMI) but not causality. We aimed to explore the underlying mechanisms by adding biological mediators to an established study design used by earlier studies. Methods With data on biomarkers, we used a self-controlled case-series design to evaluate the effect of LCI on hospitalization for AMI among Veterans Health Administration (VHA) patients. We included senior Veterans (age 65 years and older) with LCI between 2010 through 2015. Patient-level data from VHA electronic medical records were used to capture laboratory results, hospitalizations, and baseline patient characteristics. We defined the “risk interval” as the first 7 days after specimen collection and the “control interval” as 1 year before and 1 year after the risk interval. More importantly, using mediation analysis, we examined the role of abnormal white blood cell (WBC) and platelet count in the relationship between LCI and AMI to explore the thrombogenic nature of this association, thus potential causality. Results We identified 391 hospitalizations for AMI that occurred within +/-1 year of a positive influenza test, of which 31 (31.1 admissions/week) occurred during the risk interval and 360 (3.5/per week) during the control interval, resulting in an incidence ratio (IR) for AMI admission of 8.89 (95% confidence interval [CI]: 6.16–12.84). In stratified analyses, AMI risk was significantly elevated among patients with high WBC count (IR, 12.43; 95% CI: 6.99–22.10) and high platelet count (IR, 15.89; 95% CI: 3.59–70.41). Conclusion We confirmed a significant association between LCI and AMI. The risk was elevated among those with high WBC or platelet count, suggesting a potential role for inflammation and platelet activation in the underlying mechanism.

Background Despite universal recommendation of the 3 + 1 diphtheria, tetanus, and pertussis (DTaP) vaccine series in infants and toddlers, adherence (i.e. coverage and timeliness) remain suboptimal in the US. DTaP-containing combination vaccines are presumed to improve vaccine coverage rates and timeliness, but research on this topic is limited. The purpose of this study was to compare adherence to the recommended infant-toddler vaccination series between recipients of DTaP-containing combination vaccines (i.e. quadrivalent/pentavalent) and stand-alone vaccines (i.e. trivalent). Methods We used the Optum de-identified Clinformatics Data Mart database to create a cohort of children born between 2009 and 2016 with > 24 months of continuous enrollment from birth, and records of > 1 DTaP vaccine receipt. Patients were classified by DTaP-containing vaccine receipt: combination vaccines only, stand-alone vaccines only, or a mixture of both. The primary adherence outcome was completion of the 4-dose series within 20 months of life. We adjusted outcomes for gender, birth year, race, and socioeconomic status via a logistic regression model. Results The cohort contained 200,568 female (48.6%) and 211,882 male (51.4%) children. Of these children, 167,091 received combination vaccines only (40.5%), 61,342 received stand-alone vaccines only (14.9%), and 184,017 received a mixture of both (44.6%). Completion of the 4-dose series was highest among children who received combination vaccines only (75.5%), followed by those who received a mixture of vaccines (72.7%) and those who received stand-alone vaccines only (54.5%). Relative to those who received stand-alone vaccines only, adjusted odds of completion were approximately 2.9 times higher among combination vaccine recipients (odds ratio, OR = 2.93 [95% CI: 2.87, 2.98]) and 2.5 times higher among those who received a mixture of vaccines (OR = 2.54 [2.49, 2.59]). Conclusion DTaP-containing combination vaccine use was associated with significantly greater adherence. Although these results warrant further investigation to better understand the determinants of infant vaccination adherence, such evidence may further support preferential recommendations for combination vaccine use. Disclosures Matthew M. Loiacono, MSc, Sanofi Pasteur (Employee) Vitali Pool, MD, Sanofi Pasteur (Employee) Robertus Van Aalst, MSc, Sanofi Pasteur (Employee)

We examine the relationship between dementia and psychiatric disorder diagnoses among long-term care residents in nursing homes across the state of Rhode Island (RI), USA.Observational clinical study.Two hundred fifty-five residents with and without the diagnosis of dementia were included in this study.Prevalence analysis was used to elucidate information on psychiatric disorders in the overall cohort, and among residents with dementia. Questions from the quality of life questionnaire (EQ-5D-3L) that provides information on self-care, anxiety/depression, and resident's view of how healthy they are, were used to evaluate their association with dementia and psychiatric disorders. A logistic regression analysis was conducted to understand the relationship between dementia and mental illness diagnoses in long-term care facilities. Finally, a subgroup logistic regression analysis was performed for residents with Alzheimer disease.65.1% of all residents suffered from at least 1 psychiatric disorder. Anxiety was the most common diagnosis (36.5%), followed by depression (28.6%), and insomnia (14.9%). There was a positive and statistically significant association between any mental illness diagnosis and dementia (adjusted OR: 3.73; 95% CI: 1.34-10.41). Bipolar disorder and insomnia were negatively and statistically significantly associated with dementia (adjusted OR: 0.17; 95% CI: 0.03-0.89 AND adjusted OR: 0.39; 95% CI: 0.16-0.96 respectively). Age and COPD were also statistically associated with dementia (adjusted OR: 1.07; 95% CI: 1.03-1.11 AND adjusted OR: 0.28, 95% CI: 0.12-0.66). Alzheimer disease was positively and significantly associated with the diagnosis of any mental illness (adjusted OR: 3.77; 95% CI: 1.17-12.20).We studied the relationship between dementia and diagnoses of psychiatric disorders present in long-term care residents. We found that residents with a diagnosis of dementia were more likely to suffer from at least 1 psychiatric disorder. Further work is needed to establish the neuropathophysiological relationship between psychiatric disorders and dementia.

Background Observational studies of the relative effectiveness of influenza vaccines are essential for public health decision making. Their estimates, however, are subject to bias due to unmeasured confounders. Instrumental variable (IV) methods can control for observed and unobserved confounders. Methods We used linked electronic medical record databases in the Veterans Health Administration (VHA) as well as Medicare administrative files to examine the relative vaccine effectiveness (rVE) of high-dose influenza vaccine (HD) versus standard-dose influenza vaccines (SD) in preventing hospitalizations among VHA-enrolled Veterans ≥65 years of age during 5 influenza seasons (2010–2011 through 2014–2015). Using multivariable IV Poisson regression modeling to address unmeasured confounding and bias, we analyzed the data by each season and through longitudinal analysis of all five seasons. Findings We included 3,638,924 person–influenza seasons of observation where 158,636 (4%) were among HD vaccine recipients and 3,480,288 (96%) were among SD vaccine recipients. Of the 1,728,562 Veterans, 1,702,824 (98.5%) were male and 1,299,412 (75%) were non-Hispanic white. Based on the longitudinal analysis of all five seasons, the IV-adjusted rVE estimate of HD vs. SD was 10% (95% CI, 8–12%) against all-cause hospitalization; 18% (95% CI, 15–21%) against cardiorespiratory-associated hospitalization; and 14% (95% CI, 6–22%) against influenza/pneumonia-associated hospitalization. The findings by season were similar. Interpretation Our analysis of VHA clinical data collected from approximately 1.7 million Veterans 65 years and older during five seasons demonstrates that high-dose influenza vaccine is more effective than standard-dose influenza vaccines in preventing influenza- or pneumonia-associated hospitalizations, cardiorespiratory hospitalizations, and all-cause hospitalizations.