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Background: Respiratory syncytial virus (RSV) is the leading cause of infant hospitalization in the United States. Understanding healthcare utilization associated with medically attended (MA) RSV lower respiratory tract infection (LRTI) might inform research priorities aimed at reducing RSV-associated pediatric morbidity. We described healthcare utilization during acute MA RSV LRTI episodes within a geographically diverse cohort of infants in the United States., Methods: We created retrospective cohorts of infants born in the United States from July 1, 2016 through February 29, 2020 in each of three de-identified insurance claims datasets: Merative MarketScan Commercial Claims and Encounters, Multi-State MarketScan Medicaid, and Optum's de-identified Clinformatics ® Data Mart. We identified infants' first MA RSV LRTI diagnosis during their first RSV season and followed them for 7 subsequent days to record outpatient, emergency department, and inpatient hospital utilization. We calculated the number of outpatient visits, emergency department visits, and inpatient hospital stays occurring during this acute episode and estimated the proportion of episodes involving ≥ 2 visits to a given healthcare setting., Results: In the CCAE database, we identified 25,409 acute MA RSV LRTI episodes under the specific RSV definition and 69,068 under the sensitive definition. In the MDCD database, these totals were 67,357 and 170,744, while in the CDM database, they were 12,402 and 31,363, respectively. Across data sources, 34%-69% of infants' first acute MA RSV LRTI episodes involve 2 or more visits to a healthcare setting within 7 days. The percentage of episodes involving at least 2 visits ranged from 34-62% among healthy term infants, 38-65% for Palivizumab-eligible infants, and 38-69% for infants with other comorbidities., Conclusions: Within a week of their first MA RSV LRTI diagnosis, infants frequently experience at least 2 visits to one or more healthcare settings, regardless of their comorbidity profile. The percentage of MA RSV LRTI episodes involving at least 2 visits to a healthcare setting may vary by insurance claims database, even between commercial payers., Competing Interests: JRG, ARZ, AMB and DAS receive research funding support from Sanofi (awarded to and administered by Brown University). DRD and BLL are employees of Merative, who was contracted by Sanofi to perform analyses included in this paper. CBN and RvA are employees of Sanofi and may hold shares and/or stock options in the company., (Copyright: © 2025 Gantenberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Respiratory syncytial virus (RSV) is the leading cause of hospitalization among US infants. Characterizing service utilization during infant RSV hospitalizations may provide important information for prioritizing resources and interventions., Objective: The objective of this study was to describe the procedures and services received by infants hospitalized during their first RSV episode in their first RSV season, in addition to what proportion of infants died during this hospitalization., Methods: In this retrospective observational study, we analyzed three different administrative claims datasets to examine healthcare service utilization during RSV hospitalizations among infants. The study population included infants born between July 2016 and February 2020 who experienced an RSV episode during their first RSV season and had an associated inpatient hospitalization. We stratified infants into three comorbidity groups: healthy term, palivizumab-eligible, and other comorbidities. Outcomes included extracorporeal membrane oxygenation, supplemental oxygen use (in-hospital and post-discharge), mechanical ventilation (invasive and non-invasive), chest imaging, infant mortality, length of inpatient stay, intensive care unit (ICU) admission, and number of days in the ICU., Results: Chest imaging was the most frequently administered procedure during RSV-associated hospitalizations, with approximately 34-38% of infants receiving it. Around one-quarter of infants were admitted to the ICU during their first RSV hospitalization. Median lengths of stay in the hospital were 3-4 days, extending to 4-6 days in the presence of ICU admission. Palivizumab-eligible infants had higher utilization of healthcare services and spent more time in the hospital or ICU compared to healthy infants or those with other comorbidities., Conclusions: This study provides insights into the utilization of healthcare services during RSV hospitalizations among infants. Understanding service utilization patterns can aid in improved management and resource allocation for infants in the United States, ultimately contributing to better outcomes and reduced healthcare costs overall. However, likely under-ascertainment of ventilation and oxygen-related services in insurance claims remains an impediment to studying these outcomes., Competing Interests: JRG, MRB, AMB, DAS, and ARZ have received salary support paid directly to Brown University by research grants from Sanofi for collaborative epidemiologic research on respiratory syncytial virus infections. RvA, CBN, SSC, WVLV, and CR are employees of Sanofi and may hold shares and/or stock options in the company. DMS and MR are employees of Merative., (Copyright: © 2025 Gantenberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Influenza may contribute to coronary/cerebrovascular events and exacerbate underlying conditions., Methods: We used self-controlled case series (SCCS) design to analyze data from US Veterans ≥18 years with coronary/cerebrovascular or exacerbation event +/-1 year of lab-confirmed influenza (LCI) during 2010-2018. We estimated the incidence ratio (IR) (95% CI) of the event for risk interval (Days 1-7 post-LCI) versus control interval (all other times +/-1 year of LCI) with fixed-effects conditional Poisson regression. We included biomarker data for mediation analysis., Results: We identified 3439 episodes with coronary/cerebrovascular-related hospitalizations. IRs (95% CI) for LCI risk versus control interval were STEMI 0.6 (0.1, 4.4), NSTEMI 7.3 (5.8, 9.2), ischemic stroke 4.0 (3.0, 5.4), hemorrhagic stroke 6.2 (3.4, 11.5), and coronary spasm 1.3 (0.5, 3.0). IR significantly increased for NSTEMI and ischemic stroke among those ≥ 65 years. IR for NSTEMI and ischemic stroke dropped 26% and 10%, respectively, when white blood cell (WBC) and platelet count were considered. LCI was significantly associated with exacerbation of preexisting asthma, chronic obstructive pulmonary disease, and congestive heart failure., Conclusions: We found significant association between LCI and hospitalization for NSTEMI, ischemic stroke, and hemorrhagic stroke, the latter possibly due to unaccounted time-varying confounding in SCCS design., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Accurate forecasts can inform response to outbreaks. Most efforts in influenza forecasting have focused on predicting influenza-like activity, with fewer on influenza-related hospitalizations. We conducted a simulation study to evaluate a super learner's predictions of 3 seasonal measures of influenza hospitalizations in the United States: peak hospitalization rate, peak hospitalization week, and cumulative hospitalization rate. We trained an ensemble machine learning algorithm on 15,000 simulated hospitalization curves and generated weekly predictions. We compared the performance of the ensemble (weighted combination of predictions from multiple prediction algorithms), the best-performing individual prediction algorithm, and a naive prediction (median of a simulated outcome distribution). Ensemble predictions performed similarly to the naive predictions early in the season but consistently improved as the season progressed for all prediction targets. The best-performing prediction algorithm in each week typically had similar predictive accuracy compared with the ensemble, but the specific prediction algorithm selected varied by week. An ensemble super learner improved predictions of influenza-related hospitalizations, relative to a naive prediction. Future work should examine the super learner's performance using additional empirical data on influenza-related predictors (e.g., influenza-like illness). The algorithm should also be tailored to produce prospective probabilistic forecasts of selected prediction targets., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

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.

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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 1 st -March 31 st 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., (© 2022. The Author(s).)

Observational seasonal influenza relative vaccine effectiveness (rVE) studies employ a variety of statistical methods to account for confounding and biases. To better understand the range of methods employed and implications for policy, we conducted a brief literature review. Across 37 included rVE studies, 10 different types of statistical methods were identified, and only eight studies reported methods to detect residual confounding, highlighting the heterogeneous state of the literature. To improve the comparability and credibility of future rVE research, researchers should clearly explain methods and design choices and implement methods to detect and quantify residual confounding., (© 2022 Sanofi. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Pneumonia and sepsis are among the most common causes of hospitalization in the United States and often result in discharges to a skilled nursing facility (SNF) for rehabilitation. We described the timing and most common causes of 30-day unplanned hospital readmission following an index hospitalization for pneumonia or sepsis., Methods and Findings: This national retrospective cohort study included adults ≥65 years who were hospitalized for pneumonia or sepsis and were discharged to a SNF between July 1, 2012 and July 4, 2015. We quantified the ten most common 30-day unplanned readmission diagnoses and estimated the daily risk of first unplanned rehospitalization for four causes of readmission (circulatory, infectious, respiratory, and genitourinary). The index hospitalization was pneumonia for 92,153 SNF stays and sepsis for 452,254 SNF stays. Of these SNF stays, 20.9% and 25.9%, respectively, resulted in a 30-day unplanned readmission. Overall, septicemia was the single most common readmission diagnosis for residents with an index hospitalization for pneumonia (16.7% of 30-day readmissions) and sepsis (22.4% of 30-day readmissions). The mean time to unplanned readmission was approximately 14 days overall. Respiratory causes displayed the highest daily risk of rehospitalization following index hospitalizations for pneumonia, while circulatory and infectious causes had the highest daily risk of rehospitalization following index hospitalizations for sepsis. The day of highest risk for readmission occurred within two weeks of the index hospitalization discharge, but the readmission risk persisted across the 30-day follow-up., Conclusion: Among older adults discharged to SNFs following a hospitalization for pneumonia or sepsis, hospital readmissions for infectious, circulatory, respiratory, and genitourinary causes occurred frequently throughout the 30-day post-discharge period. Our data suggests further study is needed, perhaps on the value of closer monitoring in SNFs post-hospital discharge and improved communication between hospitals and SNFs, to reduce the risk of potentially preventable hospital readmissions., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: R.V.A. and A.C. are employed by Sanofi Pasteur and may hold shares and/or stock options in the company. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Prior studies have established those elderly patients with chronic obstructive pulmonary disease (COPD) are at elevated risk for developing influenza-associated complications such as hospitalization, intensive-care admission, and death. This study sought to determine whether influenza vaccination could improve survival among elderly patients with COPD., Materials/methods: This study included Veterans (age ≥ 65 years) diagnosed with COPD that received care at the United States Veterans Health Administration (VHA) during four influenza seasons, from 2012-2013 to 2015-2016. We linked VHA electronic medical records and Medicare administrative files to Centers for Disease Control and Prevention National Death Index cause of death records as well as influenza surveillance data. A multivariable time-dependent Cox proportional hazards model was used to compare rates of mortality of recipients of influenza vaccination to those who did not have records of influenza vaccination. We estimated hazard ratios (HRs) adjusted for age, gender, race, socioeconomic status, comorbidities, and healthcare utilization., Results: Over a span of four influenza seasons, we included 1,856,970 person-seasons of observation where 1,199,275 (65%) had a record of influenza vaccination and 657,695 (35%) did not have a record of influenza vaccination. After adjusting for comorbidities, demographic and socioeconomic characteristics, influenza vaccination was associated with reduced risk of death during the most severe periods of influenza seasons: 75% all-cause (HR = 0.25; 95% CI: 0.24-0.26), 76% respiratory causes (HR = 0.24; 95% CI: 0.21-0.26), and 82% pneumonia/influenza cause (HR = 0.18; 95% CI: 0.13-0.26). A significant part of the effect could be attributed to "healthy vaccinee" bias as reduced risk of mortality was also found during the periods when there was no influenza activity and before patients received vaccination: 30% all-cause (HR = 0.70; 95% CI: 0.65-0.75), 32% respiratory causes (HR = 0.68; 95% CI: 0.60-0.78), and 51% pneumonia/influenza cause (HR = 0.49; 95% CI: 0.31-0.78). However, as a falsification study, we found that influenza vaccination had no impact on hospitalization due to urinary tract infection (HR = 0.97; 95% CI: 0.80-1.18)., Conclusions: Among elderly patients with COPD, influenza vaccination was associated with reduced risk for all-cause and cause-specific mortality., Competing Interests: Competing Interests Statement: YYX has received research funding from Sanofi Pasteur, Sanofi, Pfizer, Genentech, Janssen, VIR Biotechnology, and the Office of Rural Health Resource Center-Eastern Region. SMM has received research funding from Assurex, GSK, Merck, Pfizer, Roche and Sanofi, and is/was a member of advisory boards for GSK and Sanofi. JN, RVA, JKL, EWT and AC are employees of Sanofi Pasteur. The remaining authors have nothing to disclose. Affiliation with Sanofi Pasteur could be perceived as a potential conflict of interest because Sanofi Pasteur produces influenza vaccines.

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.

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.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

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., Competing Interests: YYX has received research funding from Sanofi Pasteur, Sanofi, Pfizer, Genentech, Janssen, VIR Biotechnology, and the Office of Rural Health Resource Center- Eastern Region. SMM has received research funding from Assurex, GSK, Merck, Pfizer, Roche and Sanofi, and is/was a member of advisory boards for GSK and Sanofi. RVA, JKL, EWT and AC are employees of Sanofi Pasteur. The remaining authors have nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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: 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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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.

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.

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.

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 (OR 18-64 : 0.82 (95% CI: 0.80, 0.85); OR 65+ : 0.59 (95% CI: 0.56, 0.62)), while Asian patients among 18-64 year olds were most likely to be vaccinated (OR 18-64 : 1.10 (95% CI: 1.07, 1.13)). Females were more likely than males to be vaccinated among 18-64 year olds (OR 18-64 : 1.19 (95% CI: 1.18, 1.20)). Greater socioeconomic deprivation was associated with decreased odds of uptake among older patients (OR 65+ : 0.74 (95% CI: 0.71, 0.77)). For each additional at-risk condition, odds of uptake increased (OR 18-64 : 2.33 (95% CI: 2.31, 2.36); OR 65+ : 1.39 (95% CI: 1.38, 1.39)). Odds of uptake were highest among younger patients with diabetes (OR 18-64 : 4.25 (95% CI: 4.18, 4.32)) and older patients with chronic respiratory disease (OR 65+ : 1.60 (95% CI: 1.58, 1.63)), whereas they were lowest among morbidly obese patients of all ages (OR 18-64 : 0.68 (95% CI: 0.67, 0.70); OR 65+ : 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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MML reports financial and non-financial support from Sanofi Pasteur and University of Toronto. HB, AC, LS, ET, and RA are full-time employee of Sanofi Pasteur. SMM has received research grants and/or consulting fees from GlaxoSmithKline, Merck, Sanofi Pasteur, Pfizer and Roche-Assurex. SMM’s work is supported, in part, by funding from the Canada Research Chair Program., (© 2020 The Author(s).)

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.

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 (<100 days) and long-stay (100+ days) LTCF residents were followed for the first occurrence of hospitalization, LTCF discharge, Medicare disenrollment, or death. We calculated LTCF risk-standardized incidence rates (RSIRs) per 100 person-years for P&I hospitalizations by adjusting for over 30 resident-level demographic and clinical covariates using hierarchical logistic regression., 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.

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., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: AC and JL are employees of Sanofi Pasteur. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. AC has performed duties as a peer reviewer for PLOS ONE, this does not alter AC’s adherence to PLOS ONE Editorial policies and criteria.

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  < .01), as did the self-efficacy composite score ( P  < .05). Satisfaction with the curriculum was rated highly by all participants., Conclusions: Learning and participating in hands-on QI can be integrated into the usual inpatient work of resident physicians., Competing Interests: The authors declare they have no competing interests.