Changes in Physical Function and Physical Therapy Use in Older Veterans Not Infected by CoVID-19 Residing in Community Living Centers During the CoVID-19 Pandemic.

OBJECTIVES: Examine physical function change and physical therapy (PT) use in short-stay and long-stay residents not infected by CoVID-19 within Veterans Affairs (VA) Community Living Centers (CLCs). DESIGN: Retrospective cohort study using Minimum Data Set (MDS) 3.0 assessments. SETTINGS AND PARTICIPANTS: 12,606 Veterans in 133 VA CLCs between September 2019 and September 2020. METHODS: Difference in physical function [MDS Activities of Daily Living Score (MDS-ADL)] and PT use (minutes in past 7 days) from admission to last assessment in a period were compared between the pre-CoVID-19 (September 2019 to February 2020) and early CoVID-19 (April 2020 to September 2020) period using mixed effects regression with multivariable adjustment. Assessments after a positive CoVID-19 test were excluded. Differences were examined in the sample and repeated after stratifying into short- and long-stay stratums. RESULTS: Veterans admitted during early CoVID-19 had more comorbidities, worse MDS-ADL scores, and were more often long-stay residents compared with those admitted during pre-CoVID-19. In comparison to pre-CoVID-19, Veterans in VA CLCs during early CoVID-19 experienced greater improvements in their MDS-ADL (-0.49 points, 95% CI -0.27, -0.71) and received similar minutes of therapy (2.6 minutes, 95% CI -0.8, 6.0). Stratification revealed short-stay residents had relative improvements in their function (-0.69 points, 95% CI -0.44, -0.94) and higher minutes of PT (5.1 minutes, 95% CI 0.9, 9.2) during early CoVID-19 whereas long-stay residents did not see differences in functional change (0.08 points, 95% CI -0.36, 0.51) or PT use (-0.6 minutes, 95% CI -6.1, 4.9). CONCLUSIONS AND IMPLICATIONS: During early CoVID-19, physical function improved while the amount of PT received was maintained compared with pre-CoVID-19 for Veterans in VA CLCs. Short-stay residents experienced greater improvements in physical function and increases in PT use. These findings may be partly due to selection bias relating to Veterans admitted to CLCs during early CoVID-19.

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination.

BACKGROUND: Bivalent SARS-CoV-2 vaccines were developed to counter increasing susceptibility to emerging SARS-CoV-2 variants. We evaluated the durability of immunity and protection following first bivalent vaccination among nursing home residents. METHODS: We evaluated anti-spike and neutralization titers from blood in 653 community nursing home residents before and after each monovalent booster, and a bivalent vaccine. Concurrent clinical outcomes were evaluated using electronic health record data from a separate cohort of 3783 residents of Veterans Affairs (VA) nursing homes who had received at least the primary series monovalent vaccination. Using target trial emulation, we compared VA residents who did and did not receive the bivalent vaccine to measure vaccine effectiveness against infection, hospitalization, and death. FINDINGS: In the community cohort, Omicron BA.5 neutralization activity rose after each monovalent and bivalent booster vaccination regardless of prior infection history. Titers declined over time but six months post-bivalent vaccination, BA.5 neutralization persisted at detectable levels in 75% of infection-naive and 98% of prior-infected individuals. In the VA nursing home cohort, bivalent vaccine added effectiveness to monovalent booster vaccination by 18.5% for infection (95% confidence interval (CI) -5.6, 34.0%), and 29.2% for hospitalization or death (95% CI -14.2, 56.2%) over five months. INTERPRETATION: The level of protection declined after bivalent vaccination over a 6 month period and may open a window of added vulnerability before the next updated vaccine becomes available, suggesting a subset of nursing home residents may benefit from an additional vaccination booster. FUNDING: CDC, NIH, VHA.

Wandering Behavior and SARS-CoV-2 Infection in Veterans Affairs Community Living Center Residents.

OBJECTIVE: Wandering behavior in nursing home (NH) residents could increase risk of infection. The objective of this study was to assess the association of wandering behavior with SARS-CoV-2 infection in Veterans Affairs (VA) Community Living Center (CLC) residents. DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Veterans residing in 133 VA CLCs. METHODS: We included residents with SARS-CoV-2 test from March 1, 2020 to December 31, 2020 from VA electronic medical records. We identified CLC residents with wandering on Minimum Data Set 3.0 assessments and compared them with residents without wandering. The outcome was SARS-CoV-2 infection, as tested for surveillance testing, in those with and without wandering. Generalized linear model with Poisson link adjusted for relevant covariates was used. RESULTS: Residents (n = 9995) were included in the analytic cohort mean, (SD) age 73.4 (10.7); 388 (3.9%) women. The mean (SD) activities of daily living score in the overall cohort was 13.6 (8.25). Wandering was noted in 379 (3.8%) (n = 379) of the cohort. The exposure groups differed in prior dementia (92.6% vs 62.1%, standardized mean difference [SMD] = 0.8) and psychoses (41.4% vs 28.1%, SMD = 0.3). Overall, 12.5% (n = 1248) tested positive for SARS-CoV-2 and more residents among the wandering group were SARS-CoV-2 positive as compared with those in the group without wandering (19% [n = 72] vs 12.2% [n = 1176], SMD = 0.19). Adjusting for covariates, residents with wandering had 34% higher relative risk for SARS-CoV-2 infection (adjusted relative risk, 1.34; 95% CI, 1.04-1.69). CONCLUSIONS AND IMPLICATIONS: CLC residents with wandering had a higher risk of SARS-CoV-2 infection. This may inform implementation of infection control and isolation policies as NHs attempt to balance ethical concepts of resident autonomy, proportionality, equity, and utilitarianism.

Longitudinal analysis of nursing home residents' T cell responses after SARS-CoV-2 mRNA vaccinations shows influence of biological sex and SARS-CoV-2 infection history.

BACKGROUND: Vaccines and vaccine boosting have blunted excess morbidity and mortality from SARS-CoV-2 infection suffered by older nursing home residents (NHR). However, the impact of repeated vaccination on the T cell response based on biological sex and prior infection of NHR remain understudied. METHODS: We examined T cell responses to mRNA vaccines to SARS-CoV-2 in a cohort of NHR and healthcare workers (HCW) over 2 years. We used IFN-γ ELIspot and flow cytometry to assess T cell response before, two weeks and 6 months after the initial series and each of two booster vaccines. We analyzed these data longitudinally with mixed-effect modeling and also examined subsets of our cohorts for additional changes in T cell effector function. RESULTS: We show that prior SARS-CoV-2 infection and female sex contribute to higher T cell response in NHR but not HCW. When looking across time points, NHR but not HCW with prior infection had significantly higher T cell responses than infection-naive subjects. These patterns of response were maintained across multiple booster vaccinations and suggest that the age, multimorbidity, and/or frailty of the NHR cohort may accentuate sex and infection status differences in T cell response to mRNA vaccination.

Avidity maturation of humoral response following primary and booster doses of BNT162b2 mRNA vaccine among nursing home residents and healthcare workers.

Infections, despite vaccination, can be clinically consequential for frail nursing home residents (NHR). Poor vaccine-induced antibody quality may add risk for such subsequent infections and more severe disease. We assessed antibody binding avidity, as a surrogate for antibody quality, among NHR and healthcare workers (HCW). We longitudinally sampled 112 NHR and 52 HCWs who received the BNT162b2 mRNA vaccine after each dose up to the Wuhan-BA.4/5-based Omicron bivalent boosters. We quantified anti-spike, anti-receptor binding domain (RBD), and avidity levels to the ancestral Wuhan, Delta, and Omicron BA.1 & 4/5 strains. The primary vaccination series produced substantial anti-spike and RBD levels which were low in avidity against all strains tested. Antibody avidity progressively increased in the 6-8 months that followed. Avidity significantly increased after the 1st booster but not for subsequent boosters. This study underscores the importance of booster vaccination among NHR and HCWs. The 1st booster dose increases avidity, increasing vaccine-induced functional antibody. The higher cross-reactivity of higher avidity antibodies to other SARS-CoV-2 strains should translate to better protection from ever-evolving strains. Higher avidities may help explain how the vaccine's protective effects persist despite waning antibody titers after each vaccine dose.

Comparative safety of tramadol and other opioids following total hip and knee arthroplasty.

BACKGROUND: Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA. METHODS: This retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models. RESULTS: The study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons. CONCLUSIONS: Postoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA.

Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.

Background: SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs). However, emerging variants coupled with waning immunity, immunosenescence, and variability of vaccine efficacy undermine vaccine effectiveness. We therefore need to update our understanding of the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Methods: The current study focuses on a subset of participants from a longitudinal study of consented NHRs and HCWs who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine after FDA approval in Fall 2023. NHRs were classified based on whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. Results: The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). Following XBB.1.5 monovalent vaccination, there was a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers of 17.3 (95% confidence interval [CI] 9.3, 32.4) and 11.3 (95% CI 5, 25.4) in NHRs with and without interval infection, respectively. The GMFR in HCWs was 13.6 (95% CI 8.4,22). Similarly, we noted a robust GMFR in JN.1-specific neutralizing antibody titers of 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) among NHRs with and without interval infection, and a GMFR of 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher neutralizing antibody titers across all analyzed strains following XBB.1.5 monovalent vaccination, compared to NHRs without interval infection. Conclusion: The XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs. This response was more pronounced in individuals known to be infected with SARS-CoV-2 since bivalent vaccination. Impact Statement: All authors certify that this work entitled " Broad immunogenicity to prior strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents " is novel. It shows that the XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers in both nursing home residents and healthcare workers to XBB and BA.28.6/JN.1 strains. This work is important since JN.1 increased from less than 0.1% to 94% of COVID-19 cases from October 2023 to February 2024 in the US. This information is timely given the CDC's latest recommendation that adults age 65 and older receive a Spring 2024 XBB booster. Since the XBB.1.5 monovalent vaccine produces compelling immunogenicity to the most prevalent circulating JN.1 strain in nursing home residents, our findings add important support and rationale to encourage vaccine uptake. Key Points: Emerging SARS-CoV-2 variants together with waning immunity, immunosenescence, and variable vaccine efficacy reduce SARS-CoV-2 vaccine effectiveness in nursing home residents.XBB.1.5 monovalent vaccination elicited robust response in both XBB.1.5 and JN.1 neutralizing antibodies in nursing home residents and healthcare workers, although the absolute titers to JN.1 were less than titers to XBB.1.5Why does this paper matter? Among nursing home residents, the XBB.1.5 monovalent SARS-CoV-2 vaccine produces compelling immunogenicity to the JN.1 strain, which represents 94% of all COVID-19 cases in the U.S. as of February 2024.

Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity.

Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains, but novel variants continue to evade updated mRNA vaccines, demonstrating the need for novel approaches to adequately control SARS-CoV-2 transmission.

Early Mortality After the First Dose of COVID-19 Vaccination: A Target Trial Emulation.

BACKGROUND: Vaccine hesitancy persists alongside concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines. We aimed to examine the effect of COVID-19 vaccination on risk of death among US veterans. METHODS: We conducted a target trial emulation to estimate and compare risk of death up to 60 days under two COVID-19 vaccination strategies: vaccination within 7 days of enrollment versus no vaccination through follow-up. The study cohort included individuals aged ≥18 years enrolled in the Veterans Health Administration system and eligible to receive a COVID-19 vaccination according to guideline recommendations from 1 March 2021 through 1 July 2021. The outcomes of interest included deaths from any cause and excluding a COVID-19 diagnosis. Observations were cloned to both treatment strategies, censored, and weighted to estimate per-protocol effects. RESULTS: We included 3 158 507 veterans. Under the vaccination strategy, 364 993 received vaccine within 7 days. At 60 days, there were 156 deaths per 100 000 veterans under the vaccination strategy versus 185 deaths under the no vaccination strategy, corresponding to an absolute risk difference of -25.9 (95% confidence limit [CL], -59.5 to 2.7) and relative risk of 0.86 (95% CL, .7 to 1.0). When those with a COVID-19 infection in the first 60 days were censored, the absolute risk difference was -20.6 (95% CL, -53.4 to 16.0) with a relative risk of 0.88 (95% CL, .7 to 1.1). CONCLUSIONS: Vaccination against COVID-19 was associated with a lower but not statistically significantly different risk of death in the first 60 days. These results agree with prior scientific knowledge suggesting vaccination is safe with the potential for substantial health benefits.

COVID-19 and Influenza Vaccine Coadministration Among Older U.S. Adults.

INTRODUCTION: Coadministering COVID-19 and influenza vaccines is recommended by public health authorities and intended to improve uptake and convenience; however, the extent of vaccine coadministration is largely unknown. Investigations into COVID-19 and influenza vaccine coadministration are needed to describe compliance with newer recommendations and to identify potential gaps in the implementation of coadministration. METHODS: A descriptive, repeated cross-sectional study between September 1, 2021 to November 30, 2021 (Period 1) and September 1, 2022 to November 30, 2022 (Period 2) was conducted. This study included community-dwelling Medicare beneficiaries ≥ 66 years who received an mRNA COVID-19 booster vaccine in Periods 1 and 2. The outcome was an influenza vaccine administered on the same day as the COVID-19 vaccine. Adjusted ORs and 99% CIs were estimated using logistic regression to describe the association between beneficiaries' characteristics and vaccine coadministration. Statistical analysis was performed in 2023. RESULTS: Among beneficiaries who received a COVID-19 vaccine, 78.8% in Period 1 (N=6,292,777) and 89.1% in Period 2 (N=4,757,501), received an influenza vaccine at some point during the study period (i.e., before, after, or on the same day as their COVID-19 vaccine), though rates were lower in non-White and rural individuals. Vaccine coadministration increased from 11.1% to 36.5% between periods. Beneficiaries with dementia (aORPeriod 2=1.31; 99%CI=1.29-1.32) and in rural counties (aORPeriod 2=1.19; 99%CI=1.17-1.20) were more likely to receive coadministered vaccines, while those with cancer (aORPeriod 2=0.90; 99%CI=0.89-0.91) were less likely. CONCLUSIONS: Among Medicare beneficiaries vaccinated against COVID-19, influenza vaccination was high, but coadministration of the 2 vaccines was low. Future work should explore which factors explain variation in the decision to receive coadministered vaccines.

Comparative Effectiveness of Bivalent (Original/Omicron BA.4/BA.5) COVID-19 Vaccines in Adults.

The emergence of Omicron variants coincided with declining vaccine-induced protection against SARS-CoV-2. Two bivalent mRNA vaccines, mRNA-1273.222 (Moderna) and BNT162b2 Bivalent (Pfizer-BioNTech), were developed to provide greater protection against the predominate circulating variants by including mRNA that encodes both the ancestral (original) strain and BA.4/BA.5. We estimated their relative vaccine effectiveness (rVE) in preventing COVID-19-related outcomes in the US using a nationwide dataset linking primary care electronic health records and pharmacy/medical claims data. The study population (aged ≥18 years) received either vaccine between 31 August 2022 and 28 February 2023. We used propensity score weighting to adjust for baseline differences between groups. We estimated the rVE against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary) for 1,034,538 mRNA-1273.222 and 1,670,666 BNT162b2 Bivalent vaccine recipients, with an adjusted rVE of 9.8% (95% confidence interval: 2.6-16.4%) and 5.1% (95% CI: 3.2-6.9%), respectively, for mRNA-1273.222 versus BNT162b2 Bivalent. The incremental relative effectiveness was greater among adults ≥ 65; the rVE against COVID-19-related hospitalizations and outpatient visits in these patients was 13.5% (95% CI: 5.5-20.8%) and 10.7% (8.2-13.1%), respectively. Overall, we found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 Bivalent vaccine in preventing COVID-19-related hospitalizations and outpatient visits, with increased benefits in older adults.

Identifying strategies that promote staff and resident influenza and COVID-19 vaccination in nursing homes: Perspectives from nursing home staff.

Resident and staff influenza and COVID-19 vaccination are critical components of infection prevention in nursing homes. Our study sought to characterize strategies that nursing home staff use to promote vaccination. Twenty-six telephone/videoconference interviews were conducted with administrators, directors of nursing, infection preventionists, and Minimum Data Set coordinators at 14 nursing homes across the US. Transcripts were analyzed using content analysis and a detailed audit trail was maintained. Staff described resident and staff influenza and COVID-19 vaccine hesitancy and confidence as well as varying approaches to promote vaccination. These included incentives, education efforts, and having a "vaccine champion" responsible for vaccine promotion. While many strategies had been in place prior to COVID-19 in support of improving influenza vaccination, participants reported implementing additional approaches to promote COVID-19 vaccination. Findings may inform future efforts to promote vaccination, which will be critical to mitigate the burden of influenza and COVID-19 in nursing homes.

Racial and ethnic disparities in COVID-19 booster vaccination among U.S. older adults differ by geographic region and Medicare enrollment.

Introduction: COVID-19 booster vaccines are highly effective at reducing severe illness and death from COVID-19. Research is needed to identify whether racial and ethnic disparities observed for the primary series of the COVID-19 vaccines persist for booster vaccinations and how those disparities may vary by other characteristics. We aimed to measure racial and ethnic differences in booster vaccine receipt among U.S. Medicare beneficiaries and characterize potential variation by demographic characteristics. Methods: We conducted a cohort study using CVS Health and Walgreens pharmacy data linked to Medicare claims. We included community-dwelling Medicare beneficiaries aged ≥66 years who received two mRNA vaccine doses (BNT162b2 and mRNA-1273) as of 8/1/2021. We followed beneficiaries from 8/1/2021 until booster vaccine receipt, death, Medicare disenrollment, or end of follow-up (12/31/2021). Adjusted Poisson regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) comparing vaccine uptake between groups. Results: We identified 11,339,103 eligible beneficiaries (mean age 76 years, 60% female, 78% White). Overall, 67% received a booster vaccine (White = 68.5%; Asian = 67.0%; Black = 57.0%; Hispanic = 53.3%). Compared to White individuals, Black (RR = 0.78 [95%CI = 0.78-0.78]) and Hispanic individuals (RR = 0.72 [95% = CI 0.72-0.72]) had lower rates of booster vaccination. Disparities varied by geographic region, urbanicity, and Medicare plan/Medicaid eligibility. The relative magnitude of disparities was lesser in areas where vaccine uptake was lower in White individuals. Discussion: Racial and ethnic disparities in COVID-19 vaccination have persisted for booster vaccines. These findings highlight that interventions to improve vaccine uptake should be designed at the intersection of race and ethnicity and geographic location.

Comparative Risks of Potential Adverse Events Following COVID-19 mRNA Vaccination Among Older US Adults.

Importance: Head-to-head safety comparisons of the mRNA vaccines for SARS-CoV-2 are needed for decision making; however, current evidence generalizes poorly to older adults, lacks sufficient adjustment, and inadequately captures events shortly after vaccination. Additionally, no studies to date have explored potential variation in comparative vaccine safety across subgroups with frailty or an increased risk of adverse events, information that would be useful for tailoring clinical decisions. Objective: To compare the risk of adverse events between mRNA vaccines for COVID-19 (mRNA-1273 and BNT162b2) overall, by frailty level, and by prior history of the adverse events of interest. Design, Setting, and Participants: This retrospective cohort study was conducted between December 11, 2020, and July 11, 2021, with 28 days of follow-up following the week of vaccination. A novel linked database of community pharmacy and Medicare claims data was used, representing more than 50% of the US Medicare population. Community-dwelling, fee-for-service beneficiaries aged 66 years or older who received mRNA-1273 vs BNT162b2 as their first COVID-19 vaccine were identified. Data analysis began on October 18, 2022. Exposure: Dose 1 of mRNA-1273 vs BNT162b2 vaccine. Main Outcomes and Measures: Twelve potential adverse events (eg, pulmonary embolism, thrombocytopenia purpura, and myocarditis) were assessed individually. Frailty was measured using a claims-based frailty index, with beneficiaries being categorized as nonfrail, prefrail, and frail. The risk of diagnosed COVID-19 was assessed as a secondary outcome. Generalized linear models estimated covariate-adjusted risk ratios (RRs) and risk differences (RDs) with 95% CIs. Results: This study included 6 388 196 eligible individuals who received the mRNA-1273 or BNT162b2 vaccine. Their mean (SD) age was 76.3 (7.5) years, 59.4% were women, and 86.5% were White. A total of 38.1% of individuals were categorized as prefrail and 6.0% as frail. The risk of all outcomes was low in both vaccine groups. In adjusted models, the mRNA-1273 vaccine was associated with a lower risk of pulmonary embolism (RR, 0.96 [95% CI, 0.93-1.00]; RD, 9 [95% CI, 1-16] events per 100 000 persons) and other adverse events in subgroup analyses (eg, 11.0% lower risk of thrombocytopenia purpura among individuals categorized as nonfrail). The mRNA-1273 vaccine was also associated with a lower risk of diagnosed COVID-19 (RR, 0.86 [95% CI, 0.83-0.87]), a benefit that was attenuated by frailty level (frail: RR, 0.94 [95% CI, 0.89-0.99]). Conclusions and Relevance: In this cohort study of older US adults, the mRNA-1273 vaccine was associated with a slightly lower risk of several adverse events compared with BNT162b2, possibly due to greater protection against COVID-19. Future research should seek to formally disentangle differences in vaccine safety and effectiveness and consider the role of frailty in assessments of COVID-19 vaccine performance.

Incidence of New Dementia Diagnosis in Veterans Admitted to Nursing Homes After Heart Failure Hospitalization.

BACKGROUND: Hospitalization with heart failure (HF) may signal an increased risk of Alzheimer's disease and related dementias (ADRD). Nursing homes routinely assess cognition but the association of these results with new ADRD diagnosis in a population at high risk of ADRD is not known. OBJECTIVE: To determine the association between nursing home cognitive assessment results and new diagnosis of dementia after heart failure hospitalization. METHODS: This retrospective cohort study included Veterans hospitalized for HF and discharged to nursing homes, from 2010 to 2015, without a prior diagnosis of ADRD. We determined mild, moderate, or severe cognitive impairment using multiple items of the nursing home admission assessment. We used Cox regression to determine the association of cognitive impairment with new ADRD diagnosis during 365 days of follow-up. RESULTS: The cohort included 7,472 residents, new diagnosis of ADRD occurred in 4,182 (56%). The adjusted hazard ratio of ADRD diagnosis was 4.5 (95% CI 4.2, 4.8) for the mild impairment group, 5.4 (95% CI 4.8, 5.9) for moderate impairment, and 4.0 (95% CI 3.2, 5.0) for severe impairment compared to the cognitively intact group. CONCLUSION: New ADRD diagnoses occurred in more than half of Veterans with HF admitted to nursing homes for post-acute care.

Assessing the representativeness of cluster randomized trials: Evidence from two large pragmatic trials in United States nursing homes.

BACKGROUND/AIMS: When the randomized clusters in a cluster randomized trial are selected based on characteristics that influence treatment effectiveness, results from the trial may not be directly applicable to the target population. We used data from two large nursing home-based pragmatic cluster randomized trials to compare nursing home and resident characteristics in randomized facilities to eligible non-randomized and ineligible facilities. METHODS: We linked data from the high-dose influenza vaccine trial and the Music & Memory Pragmatic TRIal for Nursing Home Residents with ALzheimer's Disease (METRICaL) to nursing home assessments and Medicare fee-for-service claims. The target population for the high-dose trial comprised Medicare-certified nursing homes; the target population for the METRICaL trial comprised nursing homes in one of four US-based nursing home chains. We used standardized mean differences to compare facility and individual characteristics across the three groups and logistic regression to model the probability of nursing home trial participation. RESULTS: In the high-dose trial, 4476 (29%) of the 15,502 nursing homes in the target population were eligible for the trial, of which 818 (18%) were randomized. Of the 1,361,122 residents, 91,179 (6.7%) were residents of randomized facilities, 463,703 (34.0%) of eligible non-randomized facilities, and 806,205 (59.3%) of ineligible facilities. In the METRICaL trial, 160 (59%) of the 270 nursing homes in the target population were eligible for the trial, of which 80 (50%) were randomized. Of the 20,262 residents, 973 (34.4%) were residents of randomized facilities, 7431 (36.7%) of eligible non-randomized facilities, and 5858 (28.9%) of ineligible facilities. In the high-dose trial, randomized facilities differed from eligible non-randomized and ineligible facilities by the number of beds (132.5 vs 145.9 and 91.9, respectively), for-profit status (91.8% vs 66.8% and 68.8%), belonging to a nursing home chain (85.8% vs 49.9% and 54.7%), and presence of a special care unit (19.8% vs 25.9% and 14.4%). In the METRICaL trial randomized facilities differed from eligible non-randomized and ineligible facilities by the number of beds (103.7 vs 110.5 and 67.0), resource-poor status (4.6% vs 10.0% and 18.8%), and presence of a special care unit (26.3% vs 33.8% and 10.9%). In both trials, the characteristics of residents in randomized facilities were similar across the three groups. CONCLUSION: In both trials, facility-level characteristics of randomized nursing homes differed considerably from those of eligible non-randomized and ineligible facilities, while there was little difference in resident-level characteristics across the three groups. Investigators should assess the characteristics of clusters that participate in cluster randomized trials, not just the individuals within the clusters, when examining the applicability of trial results beyond participating clusters.

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination.

Background: Vaccines have substantially mitigated the disproportional impact of SARS-CoV-2 on the high morbidity and mortality experienced by nursing home residents. However, variation in vaccine efficacy, immune senescence and waning immunity all undermine vaccine effectiveness over time. The introduction of the bivalent vaccine in September 2022 aimed to counter this increasing susceptibility and consequences of breakthrough infection, however data on the durability and protection of the vaccine are limited. We evaluated the durability of immunity and protection after the first bivalent vaccination to SARS-CoV-2 in nursing home residents. Methods: For the immunologic evaluation, community nursing home volunteers agreed to serial blood sampling before, at two weeks, three and six months after each vaccination for antibodies to spike protein and pseudovirus neutralization activity over time. Concurrent clinical outcomes were evaluated by reviewing electronic health record data from residents living in Veterans Administration managed nursing home units. Residents without recent infection but prior vaccination to SARS-CoV-2 were followed over time beginning with administration of the newly available bivalent vaccine using a target trial emulation (TTE) approach; TTE compared time to breakthrough infection, hospitalization and death between those who did and did not receive the bivalent vaccine. Results: We evaluated antibodies in 650 nursing home residents; 452 had data available following a first monovalent booster, 257 following a second monovalent booster and 321 following a bivalent vaccine. We found a rise in BA.5 neutralization activity from the first and second monovalent boosters through the bivalent vaccination regardless of prior SARS-CoV-2 history. Titers declined at three and six months after the bivalent vaccination but generally exceeded those at three months compared to either prior boost. BA.5 neutralization titers six months after the bivalent vaccination were diminished but had detectable levels in 80% of infection-naive and 100% of prior infected individuals. TTE evaluated 5903 unique subjects, of whom 2235 received the bivalent boost. TTE demonstrated 39% or greater reduction in risk of infection, hospitalization or death at four months following the bivalent boost. Conclusion: Immunologic results mirrored those of the TTE and suggest bivalent vaccination added substantial protection for up to six months after bivalent vaccination with notable exceptions. However, the level of protection declined over this period, and by six months may open a window of added vulnerability to infection before the next updated vaccine becomes available. We strongly agree with the CDC recommendation that those who have not received a bivalent vaccination receive that now and these results support a second bivalent booster for those at greatest risk which includes many nursing home residents.

Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers.

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 376 NH residents and 63 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain, Omicron BA.1 and BA.5 variants. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over 3-6 months. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 8.1 (95% CI 4.4, 14.8) and 7.8 (95% CI 4.8, 12.9) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p < 0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up-to-date on recommended SARS-CoV-2 vaccine booster doses.