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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. [ABSTRACT FROM AUTHOR]

Aim: High‐dose quadrivalent influenza vaccine (QIV‐HD) has been shown to be more effective than standard‐dose (QIV‐SD) in reducing influenza infection, but whether diabetes status affects relative vaccine effectiveness (rVE) is unknown. We aimed to assess rVE on change in glycated haemoglobin [HbA1c (∆HbA1c)], incident diabetes, total all‐cause hospitalizations (first + recurrent), and a composite of all‐cause mortality and hospitalization for pneumonia or influenza. Methods: DANFLU‐1 was a pragmatic, open‐label trial randomizing adults (65‐79 years) 1:1 to QIV‐HD or QIV‐SD during the 2021/22 influenza season. Cox proportional hazards regression was used to estimate rVE against incident diabetes and the composite endpoint, negative binomial regression to estimate rVE against all‐cause hospitalizations, and ANCOVA when assessing rVE against ∆HbA1c. Results: Of the 12 477 participants, 1162 (9.3%) had diabetes at baseline. QIV‐HD, compared with QIV‐SD, was associated with a reduction in the rate of all‐cause hospitalizations irrespective of diabetes [overall: 647 vs. 742 events, incidence rate ratio (IRR): 0.87, 95% CI (0.76‐0.99); diabetes: 93 vs. 118 events, IRR: 0.80, 95% CI (0.55‐1.15); without diabetes: 554 vs. 624 events, IRR: 0.88, 95% CI (0.76‐1.01), pinteraction = 0.62]. Among those with diabetes, QIV‐HD was associated with a lower risk of the composite outcome [2 vs. 11 events, HR: 0.18, 95% CI (0.04‐0.83)] but had no effect on ∆HbA1c; QIV‐HD adjusted mean difference: ∆ + 0.2 mmol/mol, 95% CI (−0.9 to 1.2). QIV‐HD did not affect the risk of incident diabetes [HR 1.18, 95% CI (0.94‐1.47)]. Conclusions: In this post‐hoc analysis, QIV‐HD versus QIV‐SD was associated with an increased rVE against the composite of all‐cause death and hospitalization for pneumonia/influenza, and the all‐cause hospitalization rate irrespective of diabetes status. [ABSTRACT FROM AUTHOR]

A large Danish clinical trial found that invitation letters designed using behavioral science principles increased influenza vaccination rates among older adults in Denmark. Here, in a preplanned secondary analysis, the investigators report the effects of the electronically delivered "behavioral nudging" letters on clinical outcomes. Visual Abstract. Clinical Outcomes With Electronic Nudges to Increase Influenza Vaccination: A large Danish clinical trial found that invitation letters designed using behavioral science principles increased influenza vaccination rates among older adults in Denmark. Here, in a preplanned secondary analysis, the investigators report the effects of the electronically delivered "behavioral nudging" letters on clinical outcomes. Background: In the NUDGE-FLU (Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake) trial, electronic letters incorporating cardiovascular (CV) gain-framing and repeated messaging increased influenza vaccination by approximately 1 percentage point. Objective: To evaluate the effects of the successful nudging interventions on downstream clinical outcomes. Design: Prespecified exploratory analysis of a nationwide randomized implementation trial. (ClinicalTrials.gov: NCT05542004) Setting: The 2022 to 2023 influenza season. Participants: 964 870 Danish citizens aged 65 years or older. Intervention: Usual care or 9 different electronically delivered behavioral nudging letters. Measurements: Cardiovascular, respiratory, and other clinical end points during follow-up from intervention delivery (16 September 2022) through 31 May 2023. Results: The analysis set included 691 820 participants. Hospitalization for pneumonia or influenza occurred in 3354 of 346 327 (1.0%) participants in the usual care group, 396 of 38 586 (1.0%) in the CV gain-framing group (hazard ratio [HR], 1.06 [95% CI, 0.95 to 1.18]; versus usual care), and 403 of 38 231 (1.1%) in the repeated letter group (HR, 1.09 [CI, 0.98 to 1.21]; versus usual care). In the usual care group, 44 682 (12.9%) participants were hospitalized for any cause, compared with 5002 (13.0%) in the CV gain-framing group (HR, 1.00 [CI, 0.97 to 1.03]; versus usual care) and 4965 (13.0%) in the repeated letter group (HR, 1.01 [CI, 0.98 to 1.04]; versus usual care). A total of 6341 (1.8%) participants died in the usual care group, compared with 721 (1.9%) in the CV gain-framing group (HR, 1.02 [CI, 0.94 to 1.10]; versus usual care) and 646 (1.7%) in the repeated letter group (HR, 0.92 [CI, 0.85 to 1.00]; versus usual care). Limitation: Prespecified but exploratory analysis, potential misclassification of events in routinely collected registry data, and results may not be generalizable to other health systems or countries with other racial compositions and/or cultural or societal norms. Conclusion: In a prespecified exploratory analysis, modest increases in influenza vaccination rates seen with electronic nudges did not translate into observable improvements in clinical outcomes. Seasonal influenza vaccination should remain strongly recommended. Primary Funding Source: Sanofi. [ABSTRACT FROM AUTHOR]

Background: Evidence on the burden of seasonal influenza in Switzerland is scarce, yet it is critical for the design of effective prevention and control measures. The objective of this study was to assess influenza‐related resource utilization, health care expenditures and quality‐adjusted life‐years (QALYs) lost in Switzerland across the 2016/2017–2018/2019 influenza seasons. Methods: We retrospectively analyzed multiple real‐world data sources to calculate epidemiological and health outcomes, QALYs lost, and direct medical costs due to influenza in the Swiss adult population. Subgroups included residents 18–49, 50–64, and 65+ years of age. The observation period was Week 26, 2016, to Week 25, 2019. Results: Across the three seasons, we estimated seasonal averages of 203,090 (se ± 26,717) general practitioner (GP) visits for influenza‐like illness (ILI) 4944 (se ± 785) influenza‐attributable hospitalizations and 1355 (se ± 169) excess deaths attributable to influenza. We estimated a total loss of 8429 (2016/2017), 11,179 (2017/2018), and 7701 (2018/2019) QALYs due to influenza. On average, 88% of the loss in QALYs was attributed to premature deaths due to influenza. The total direct medical costs amounted to 44.4 (2016/2017), 77.3 (2017/2018), and 64.5 (2018/2019) million euros. On average, 79.6% of the total costs arose due to hospitalizations. Conclusions: In Switzerland, the burden of influenza on patients and payers is significant and particularly high in the elderly population. Policy interventions to increase vaccination rates and the uptake of more effective vaccines among the elderly are needed to reduce the burden of influenza. [ABSTRACT FROM AUTHOR]

Background High-dose (HD) influenza vaccine offers improved protection from influenza virus infection among older adults compared with standard-dose (SD) vaccine. Here, we explored whether HD vaccine attenuates disease severity among older adults with breakthrough influenza. Methods This was a retrospective cohort study of US claims data for influenza seasons 2016–2017, 2017–2018, and 2018–2019, defined as 1 October through 30 April, among adults aged ≥65 years. After adjusting the different cohorts for the probability of vaccination conditional on patients' characteristics, we compared 30-day mortality rate post-influenza among older adults who experienced breakthrough infection after receipt of HD or SD influenza vaccines and among those not vaccinated (NV). Results We evaluated 44 456 influenza cases: 23 109 (52%) were unvaccinated, 15 037 (33.8%) received HD vaccine, and 6310 (14.2%) received SD vaccine. Significant reductions in mortality rates among breakthrough cases were observed across all 3 seasons for HD vs NV, ranging from 17% to 29% reductions. A significant mortality reduction of 25% was associated with SD vaccination vs NV in the 2016–2017 season when there was a good match between circulating influenza viruses and selected vaccine strains. When comparing HD vs SD cohorts, mortality reductions were higher among those who received HD in the last 2 seasons when mismatch between vaccine strains and circulating H3N2 viruses was documented, albeit not significant. Conclusions HD vaccination was associated with lower post-influenza mortality among older adults with breakthrough influenza, even during seasons when antigenically drifted H3N2 circulated. Improved understanding of the impact of different vaccines on attenuating disease severity is warranted when assessing vaccine policy recommendations. [ABSTRACT FROM AUTHOR]

Aims: Seasonal influenza vaccination is strongly recommended in patients with heart failure (HF). The NUDGE‐FLU trial recently found two electronic behavioural nudging letter strategies – a letter highlighting potential cardiovascular benefits of vaccination and a repeated letter at day 14 –effective in increasing influenza vaccination in Denmark. The aims of this pre‐specified analysis was to further examine vaccination patterns and effects of these behavioural nudges in patients with HF including potential off‐target effects on guideline‐directed medical therapy (GDMT) use. Methods and results: The nationwide NUDGE‐FLU trial randomized 964 870 Danish citizens ≥65 years to usual care or nine different electronic nudging letter strategies. Letters were delivered through the official Danish electronic letter system. The primary endpoint was the receipt of an influenza vaccine; additional outcomes for this analysis included GDMT use. In this analysis, we also assessed influenza vaccination rates in the overall Danish HF population including those <65 years (n = 65 075). During the 2022–2023 season, influenza vaccination uptake was 71.6% in the overall Danish HF population but this varied considerably with only 44.6% uptake in those <65 years. A total of 33 109 NUDGE‐FLU participants had HF at baseline. Vaccination uptake was higher among those on higher levels of baseline GDMT (≥3 classes: 85.3% vs. ≤2 classes: 81.9%; p < 0.001). HF status did not modify the effects of the two overall successful nudging strategies on influenza vaccination uptake (cardiovascular gain‐framed letter: pinteraction = 0.37; repeated letter: pinteraction = 0.55). No effect modification was observed across GDMT use levels for the repeated letter (pinteraction = 0.88), whereas a trend towards attenuated effect among those on low levels of GDMT was observed for the cardiovascular gain‐framed letter (pinteraction = 0.07). The letters had no impact on longitudinal GDMT use. Conclusions: Approximately one in four patients with HF did not receive influenza vaccination with a pronounced implementation gap in those <65 years where less than half were vaccinated. HF status did not modify the effectiveness of cardiovascular gain‐framed and repeated electronic nudging letters in increasing influenza vaccination rates. No unintended negative effects on longitudinal GDMT use were observed. Clinical Trial Registration: ClinicalTrials.gov NCT05542004. [ABSTRACT FROM AUTHOR]

The article discusses a study on the impact of the coronavirus disease 2019 (COVID-19) pandemic on influenza and infection control practices in U.S. nursing homes. Topics covered include the pandemic's enhancement of infection control practices which may be continued, and of the value of masking, and the improvement of healthcare workers' vaccination via a vaccine champion. Also noted are general infection control knowledge and practices.

Self-fertilization can facilitate the colonization of new habitats because it allows a single individual to found a population. Here we investigated the relationship between mating systems and colonization in hay-scented fern (Dennstaedtia punctilobula (Michx.) T.Moore). Throughout eastern North America, this species has been called a 'native invasive' for its tendency to dominate forest understories disturbed by logging, inhibiting tree regeneration. Thus, it is important to understand the mechanisms of its spread. We hypothesized that if populations were founded through selfing, then populations disturbed more recently would retain higher selfing ability; this pattern would demonstrate an important link between mating systems and colonization. For four populations logged at different times in the past, we compared the sporophyte production of gametophytes at different levels of inbreeding (intragametophytic selfing, intergametophytic selfing, and outcrossing) using laboratory crosses. Across all treatments, only 9.8% of gametophytes formed sporophytes (N = 400 gametophytes). Neither inbreeding level nor time since disturbance affected sporophyte production. Selfing ability did not differ across populations logged at different times; there was no interaction between inbreeding level and time since disturbance. The low reproductive success of D. punctilobula, regardless of inbreeding level or time since disturbance, suggests that population establishment and expansion via sexual reproduction may be relatively rare in this clonal species. Key words: inbreeding depression, invasive species, mating systems, reproductive assurance, self-fertilization. L'auto-fertilisation peut faciliter la colonisation de nouveaux habitats car elle permet a un seul individu de fonder une population. Les auteurs ont examine ici la relation entre les systemes de croisement et la colonisation de la fougere odorante (Dennstaedtia punctilobula (Michx.) T.Moore). A travers tout l'est de l'Amerique du Nord, cette espece a ete identifiee comme indigene envahissante a cause de sa tendance a dominer les sous-etages forestiers perturbes par l'exploitation forestiere, inhibant la regeneration des arbres. Il est alors important de comprendre les mecanismes de sa dissemination. Les auteurs ont emis l'hypothese que si des populations etaient fondees par autofecondation, alors les populations perturbees plus recemment pourraient conserver plus longtemps leur capacite d'autofecondation; ce patron demontrerait un lien important entre les systemes de croisement et la colonisation. Les auteurs ont compare chez quatre populations exploitees a differentes periodes dans le passe, la production sporophyte des gametophytes a differents niveaux d'endogamie (autofecondation intragametophyte, autofecondation inter-gametophyte et croisement eloigne) a l'aide de croisements en laboratoire. A travers tous les traitements, 9.8% des gametophytes seulement formaient des sporophytes (N = 400 gametophytes). Aucun niveau d'endogamie, ni le temps ecoule depuis la perturbation n'affectait la production de sporophytes. La capacite d'autofecondation ne differait pas d'une population a l'autre, exploitees a des periodes differentes; il n'y avait pas d'interaction entre le niveau d'endogamie et le temps ecoule depuis la perturbation. Le faible succes reproducteur de D. punctilobula, peu importe le niveau d'endogamie ou le temps ecoule depuis la perturbation, suggere que l'etablissement et l'expansion de la population par la reproduction sexuee peut etre relativement rare chez cette espece clonale. [Traduit par la Redaction] Mots-cles : depression d'endogamie, espece envahissante, systemes de croisement, assurance reproductive, auto-fertilisation., Introduction Self-fertilization should facilitate plant invasions by providing reproductive assurance in new habitats, where mates or pollinators may be scarce (Darwin 1876; Baker 1955). In fact, introduced species often have [...]

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. [ABSTRACT FROM AUTHOR]

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

Background: The objective of this study was to test a novel household‐based approach to improve late‐season influenza vaccine uptake during the 2020–2021 season, using Epic's MyChart patient portal messages and/or interactive voice response telephone calls. Methods: This study was a non‐blinded, quality improvement program using a block randomized design conducted among patients from Reliant Medical Group clinics residing in a traditional household (≥2 individuals clinically active in the Reliant system living at the same address). Households were randomized 1:1:1 into intervention arms: non‐tailored communication (messaging based on CDC's seasonal influenza vaccination campaign), tailored communication (comprehensive communication including reinforcement of the importance of influenza vaccination for high‐risk individuals), and standard‐of‐care control. Influenza vaccination during the program was captured via medical records, and the odds of vaccination among communication arms versus the control arm were assessed. A survey assessing influenza vaccination drivers was administered using MyChart. Results: Influenza vaccination increased by 3.3% during the program period, and no significant differences in vaccination were observed in intervention arms relative to the control arm. Study operationalization faced substantial challenges related to the concurrent COVID‐19 pandemic. Compared with vaccinated survey respondents, unvaccinated respondents less frequently reported receiving a recommendation for influenza vaccination from their healthcare provider (15.8% vs. 42.3%, p < 0.001) or awareness that vaccination could protect themselves and higher risk contacts (82.3% vs. 92.6%, p < 0.001). Conclusions: No significant effects of the interventions were observed. Survey results highlighted the importance of healthcare provider recommendations and the need for increased education around the benefits of vaccination. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The impact of influenza and pneumonia on individuals in clinical risk groups in England has not previously been well characterized. Using nationally representative linked databases (Clinical Practice Research Database (CPRD), Hospital Episode Statistics (HES) and Office for National Statistics (ONS)), we conducted a retrospective cohort study among adults (≥ 18 years) during the 2010/2011–2019/2020 influenza seasons to estimate the incidence of influenza- and pneumonia-diagnosed medical events (general practitioner (GP) diagnoses, hospitalisations and deaths), stratified by age and risk conditions. The study population included a seasonal average of 7.2 million individuals; approximately 32% had ≥1 risk condition, 42% of whom received seasonal influenza vaccines. Medical event incidence rates increased with age, with ~1% of adults aged ≥75 years hospitalized for influenza/pneumonia annually. Among individuals with vs. without risk conditions, GP diagnoses occurred 2–5-fold more frequently and hospitalisations were 7–10-fold more common. Among those with obesity, respiratory, kidney or cardiovascular disorders, hospitalisation were 5–40-fold more common than in individuals with no risk conditions. Though these findings likely underestimate the full burden of influenza, they emphasize the concentration of disease burden in specific age and risk groups and support existing recommendations for influenza vaccination. [ABSTRACT FROM AUTHOR]

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

• DTaP combination vaccine receipt was associated with significantly greater adherence. • Adherence to the 4-dose DTaP series was significantly lower among minority children. • Children of lower socioeconomic status were less likely to be vaccinated on time. 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. [ABSTRACT FROM AUTHOR]

Background: The relative vaccine effectiveness (rVE) of high-dose quadrivalent influenza vaccines (QIV-HD) versus standard-dose quadrivalent influenza vaccines (QIV-SD) against hospitalizations and mortality in the general older population has not been evaluated in an individually randomized trial. Because of the large sample size required, such a trial will need to incorporate innovative, pragmatic elements. Methods: We conducted a pragmatic, open-label, active-controlled, randomized feasibility trial in Danish citizens aged 65 to 79 years during the 2021-2022 influenza season. Participants were randomly assigned 1:1 to receive QIV-HD or QIV-SD. Randomization was integrated into routine vaccination practice, and the trial relied solely on nationwide administrative health registries for data collection. Outcomes consisted of a feasibility assessment and descriptive rVE estimates. Results: We invited 34,000 persons to participate. A total of 12,477 randomly assigned participants were included in the final analyses. Mean (±SD) age was 71.7±3.9 years, and 5877 (47.1%) were women. Registry-based data collection was feasible, with complete follow-up data for 99.9% of participants. Baseline characteristics were comparable to those of the overall Danish population aged 65 to 79 years. The incidence of hospitalization for influenza or pneumonia was 10 (0.2%) of 6245 in the QIV-HD group and 28 (0.4%) of 6232 in the QIV-SD group (rVE, 64.4%; 95% confidence interval, 24.4 to 84.6). All-cause death occurred in 21 (0.3%) and 41 (0.7%) participants in the QIV-HD and QIV-SD groups, respectively (rVE, 48.9%; 95% confidence interval, 11.5 to 71.3). Conclusions: Conducting a pragmatic randomized trial of QIV-HD versus QIV-SD using existing infrastructure and registry-based data collection was feasible. The findings of lower incidence of hospitalization for influenza or pneumonia and all-cause mortality in the QIV-HD group compared with the QIV-SD group require replication in a future, fully powered trial. (Funded by Sanofi; ClinicalTrials.gov number, NCT05048589.) [ABSTRACT FROM AUTHOR]

Background: Seasonal influenza vaccine (SIV) uptake in the United States remains suboptimal, requiring new and innovative strategies.Objective: To evaluate the impact of a behavioral peer comparison (PC) intervention on SIV uptake in community pharmacies across the United States.Methods: A cluster randomized study was conducted across a national network of Walmart community pharmacies (> 4500 sites) during the 2019-2020 influenza season. The clusters consisted of 416 markets, each containing an average of 11 pharmacies. All pharmacies in a market were randomly assigned to either no intervention or the PC intervention, a software-delivered communication informing on-site staff, including pharmacists and pharmacy technicians, of their pharmacy's weekly performance, measured as SIV doses administered, compared with that of peer pharmacies within their market. The outcome was the pharmacy-level cumulative SIV doses administered during the intervention period (September 1, 2019,-February 29, 2020). Linear regression models were used to estimate the PC impact, with multiway cluster-robust SEs estimated by market and state.Results: A total of 4589 pharmacies were enrolled in the study, with 2297 (50.1%) randomized to the control group and 2292 (49.9%) randomized to the PC intervention group. Overall, compared with the control pharmacies, the PC pharmacies administered 3.7% (95% CI -0.3% to 7.9%) additional SIV doses. Among large-format pharmacies, the PC pharmacies administered 4.1% (95% CI 0.1%-8.3%) additional SIV doses compared with the controls. Historically low-performing large-format PC pharmacies administered 6.1% (95% CI 0.5%-11.9%) additional SIV doses compared with the controls. No statistically significant treatment effects were observed among small-format pharmacies.Conclusion: Our findings demonstrate that PCs can improve SIV uptake among large-format community pharmacies, with historically low-performing pharmacies potentially exhibiting the greatest relative impact. Wide-scale implementation of PCs in community pharmacies may help to further improve SIV uptake in these settings. [ABSTRACT FROM AUTHOR]

We investigated the role of individual, community and vaccinator characteristics in mediating racial/ethnic disparities in the uptake of differentiated influenza vaccines (DIVs; including high-dose, adjuvanted, recombinant and cell-based vaccines). We included privately-insured (commercial and Medicare Advantage) ≥65 years-old community-dwelling health plan beneficiaries in the US with >1 year of continuous coverage and who received ≥1 influenza vaccine during the study period (July 2014–June 2018). Of 2.8 million distinct vaccination claims, 60% were for DIVs; lower if received in physician offices (49%) compared to pharmacies/facilities (74%). Among those vaccinated in physician offices, non-whites had lower odds of receiving a DIV if they lived in a non-minority county (0.77;95%CI 0.75–0.80) and even lower odds if they lived in a minority county (0.62;0.60–0.63). Differences in education, household income, medical history, community and vaccinator characteristics did not fully explain the disparities. Similar patterns emerged for vaccinations in pharmacies/facilities, although disparities disappeared altogether after controlling for socio-economic and vaccinator characteristics. When vaccinated in physician offices, minority county residents were less likely to receive a DIV, especially for non-whites (0.72;0.67–0.78). These disparities disappeared for whites, but not for non-whites, after controlling for community and vaccinator characteristics. We found an alarming level of inequity in DIV vaccine uptake among fully insured older adults that could not be fully explained by differences in sociodemographic, medical, community, and vaccinator characteristics. New strategies are urgently needed to address these inequities. [ABSTRACT FROM AUTHOR]

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