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.

Facilitators and Barriers to Verifying Penicillin Allergies in a Veteran Nursing Home Population.

BACKGROUND: Unconfirmed penicillin allergies are common and may contribute to adverse outcomes, especially in frail older patients. Evidence-based clinical pathways for evaluating penicillin allergies have been effectively and safely applied in selected settings, but not in nursing home populations. OBJECTIVE: To identify potential facilitators and barriers to implementing a strategy to verify penicillin allergies in Veterans Health Administration nursing homes, known as Community Living Centers (CLCs). METHODS: We conducted semistructured interviews with staff, patients, and family members at 1 CLC to assess their understanding of penicillin allergies and receptiveness to verifying the allergy. We also asked staff about the proposed allergy assessment strategy, including willingness to delabel by history and feasibility of performing oral challenges or skin testing on their unit. RESULTS: From 24 interviews (11 front-line staff, 4 leadership, 3 patients, 6 family members), we identified several facilitators or barriers. Staff recognized the importance of allergy verification and were willing to support and assist in implementing verification strategies. The CLC residents were willing to have their allergy status verified. However, some family members expressed reluctance to verifying their relative's allergy status owing to safety concerns. Front-line staff also expressed concern over having the necessary resources, including time and expertise, to implement the strategy. Staff suggested involving clinical pharmacists and educating staff, patients, and family members as ways to overcome these barriers. CONCLUSIONS: Concerns about safety and staff resources are important potential barriers to implementing verification strategies. Involvement of pharmacists and education of both staff and patients and family members will be important components of any successful intervention.

Predicting Seasonal Influenza Hospitalizations Using an Ensemble Super Learner: A Simulation Study.

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.

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.

Class II/III Obesity Prevalence in Residents of US Nursing Homes: Cross-sectional Study and Forecasting 2030 with COVID-19 Perspective.

OBJECTIVES: This study aimed to better understand Class II/III obesity prevalence trends among older adults residing in nursing homes (NH) nationwide. METHODS: Our retrospective cross-sectional study evaluated Class II/III obesity (BMI ≥35 kg/m²) prevalence among NH residents in two independent national NH cohorts. We used databases from Veterans Administration NHs called Community Living Centers (CLCs) covering 7 years to 2022, and Rhode Island Medicare data covering 20 years ending in 2020. We also performed forecasting regression analysis of obesity trends. RESULTS: While VA CLC resident obesity prevalence was less overall and dipped during the COVID-19 pandemic, obesity prevalence increased in NH residents in both cohorts over the last decade and is predicted to do so through 2030. CONCLUSION: Obesity prevalence in NHs is on the rise. It will be important to understand clinical, functional, and financial implications for NHs, particularly if predictions on increases materialize.

SARS-CoV-2 Antibody Responses to the Ancestral SARS-CoV-2 Strain and Omicron BA.1 and BA.4/BA.5 Variants in Nursing Home Residents After Receipt of Bivalent COVID-19 Vaccine - Ohio and Rhode Island, September-November 2022.

Introduction of monovalent COVID-19 mRNA vaccines in late 2020 helped to mitigate disproportionate COVID-19-related morbidity and mortality in U.S. nursing homes (1); however, reduced effectiveness of monovalent vaccines during the period of Omicron variant predominance led to recommendations for booster doses with bivalent COVID-19 mRNA vaccines that include an Omicron BA.4/BA.5 spike protein component to broaden immune response and improve vaccine effectiveness against circulating Omicron variants (2). Recent studies suggest that bivalent booster doses provide substantial additional protection against SARS-CoV-2 infection and severe COVID-19-associated disease among immunocompetent adults who previously received only monovalent vaccines (3).* The immunologic response after receipt of bivalent boosters among nursing home residents, who often mount poor immunologic responses to vaccines, remains unknown. Serial testing of anti-spike protein antibody binding and neutralizing antibody titers in serum collected from 233 long-stay nursing home residents from the time of their primary vaccination series and including any subsequent booster doses, including the bivalent vaccine, was performed. The bivalent COVID-19 mRNA vaccine substantially increased anti-spike and neutralizing antibody titers against Omicron sublineages, including BA.1 and BA.4/BA.5, irrespective of previous SARS-CoV-2 infection or previous receipt of 1 or 2 booster doses. These data, in combination with evidence of low uptake of bivalent booster vaccination among residents and staff members in nursing homes (4), support the recommendation that nursing home residents and staff members receive a bivalent COVID-19 booster dose to reduce associated morbidity and mortality (2).

Infections, Hospitalizations, and Deaths Among US Nursing Home Residents With vs Without a SARS-CoV-2 Vaccine Booster.

Importance: A SARS-CoV-2 vaccine booster dose has been recommended for all nursing home residents. However, data on the effectiveness of an mRNA vaccine booster in preventing infection, hospitalization, and death in this vulnerable population are lacking. Objective: To evaluate the association between receipt of a SARS-CoV-2 mRNA vaccine booster and prevention of infection, hospitalization, or death among nursing home residents. Design, Setting, and Participants: This cohort study emulated sequentially nested target trials for vaccination using data from 2 large multistate US nursing home systems: Genesis HealthCare, a community nursing home operator (system 1) and Veterans Health Administration community living centers (VHA CLCs; system 2). The cohort included long-term (≥100 days) nursing home residents (10 949 residents from 202 community nursing homes and 4321 residents from 128 VHA CLCs) who completed a 2-dose series of an mRNA vaccine (either BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) and were eligible for a booster dose between September 22 and November 30, 2021. Residents were followed up until March 8, 2022. Exposures: Receipt of a third mRNA vaccine dose, defined as a booster dose (boosted group), or nonreceipt of a booster dose (unboosted group) on an eligible target trial date. If participants in the unboosted group received a booster dose on a later target trial date, they were included in the booster group for that target trial; thus, participants could be included in both the boosted and unboosted groups. Main Outcomes and Measures: Test-confirmed SARS-CoV-2 infection, hospitalization, or death was followed up to 12 weeks after booster vaccination. The primary measure of estimated vaccine effectiveness was the ratio of cumulative incidences in the boosted group vs the unboosted group at week 12, adjusted with inverse probability weights for treatment and censoring. Results: System 1 included 202 community nursing homes; among 8332 boosted residents (5325 [63.9%] female; 6685 [80.2%] White) vs 10 886 unboosted residents (6865 [63.1%] female; 8651 [79.5%] White), the median age was 78 (IQR, 68-87) years vs 78 (IQR, 68-86) years. System 2 included 128 VHA CLCs; among 3289 boosted residents (3157 [96.0%] male; 1950 [59.3%] White) vs 4317 unboosted residents (4151 [96.2%] male; 2434 [56.4%] White), the median age was 74 (IQR, 70-80) vs 74 (IQR, 69-80) years. Booster vaccination was associated with reductions in SARS-CoV-2 infections of 37.7% (95% CI, 25.4%-44.2%) in system 1 and 57.7% (95% CI, 43.5%-67.8%) in system 2. For hospitalization, reductions of 74.4% (95% CI, 44.6%-86.2%) in system 1 and 64.1% (95% CI, 41.3%-76.0%) in system 2 were observed. Estimated vaccine effectiveness for death associated with SARS-CoV-2 was 87.9% (95% CI, 75.9%-93.9%) in system 1; however, although a reduction in death was observed in system 2 (46.6%; 95% CI, -34.6% to 94.8%), this reduction was not statistically significant. A total of 45 SARS-CoV-2-associated deaths occurred in system 1 and 18 deaths occurred in system 2. For the combined end point of SARS-CoV-2-associated hospitalization or death, boosted residents in system 1 had an 80.3% (95% CI, 65.7%-88.5%) reduction, and boosted residents in system 2 had a 63.8% (95% CI, 41.4%-76.1%) reduction. Conclusions and Relevance: In this study, during a period in which both the Delta and Omicron variants were circulating, SARS-CoV-2 booster vaccination was associated with significant reductions in SARS-CoV-2 infections, hospitalizations, and the combined end point of hospitalization or death among residents of 2 US nursing home systems. These findings suggest that administration of vaccine boosters to nursing home residents may have an important role in preventing COVID-19-associated morbidity and mortality.

Cardiac Rehabilitation and the COVID-19 Pandemic: Persistent Declines in Cardiac Rehabilitation Participation and Access Among US Medicare Beneficiaries.

BACKGROUND: The impact of the COVID-19 pandemic on participation in and availability of cardiac rehabilitation (CR) is unknown. METHODS: Among eligible Medicare fee-for-service beneficiaries, we evaluated, by month, the number of CR sessions attended per 100 000 beneficiaries, individuals eligible to initiate CR, and centers offering in-person CR between January 2019 and December 2021. We compared these outcomes between 2 periods: December 1, 2019 through February 28, 2020 (period 1, before declaration of the pandemic-related national emergency) and October 1, 2021 through December 31, 2021 (period 2, the latest period for which data are currently available). RESULTS: In period 1, Medicare beneficiaries participated in (mean±SD) 895±84 CR sessions per 100 000 beneficiaries each month. After the national emergency was declared, CR participation sharply declined to 56 CR sessions per 100 000 beneficiaries in April 2020. CR participation recovered gradually through December 2021 but remained lower than prepandemic levels (period 2: 698±29 CR sessions per month per 100 000 beneficiaries, P=0.02). Declines in CR participation were most marked among dual Medicare and Medicaid enrollees and patients residing in rural areas or socially vulnerable communities. There was no statistically significant change in CR eligibility between the 2 periods. Compared with 2618±5 CR centers in period 1, there were 2464±7 in period 2 (P<0.01). Compared with CR centers that survived the pandemic, 220 CR centers that closed were more likely to be affiliated with public hospitals, located in rural areas, and serve the most socially vulnerable communities. CONCLUSIONS: The COVID-19 pandemic was associated with a persistent decline in CR participation and the closure of CR centers, which disproportionately affected rural and low-income patients and the most socially vulnerable communities. Innovation in CR financing and delivery is urgently needed to equitably enhance CR participation among Medicare beneficiaries.

Effectiveness of a Second COVID-19 Vaccine Booster Dose Against Infection, Hospitalization, or Death Among Nursing Home Residents - 19 States, March 29-July 25, 2022.

Nursing home residents continue to experience significant COVID-19 morbidity and mortality (1). On March 29, 2022, the Advisory Committee on Immunization Practices (ACIP) recommended a second mRNA COVID-19 vaccine booster dose for adults aged ≥50 years and all immunocompromised persons who had received a first booster ≥4 months earlier.* On September 1, 2022, ACIP voted to recommend bivalent mRNA COVID-19 vaccine boosters for all persons aged ≥12 years who had completed the primary series using monovalent vaccines ≥2 months earlier (2). Data on COVID-19 booster dose vaccine effectiveness (VE) in the nursing home population are limited (3). For this analysis, academic, federal, and private partners evaluated routine care data collected from 196 U.S. community nursing homes to estimate VE of a second mRNA COVID-19 vaccine booster dose among nursing home residents who had received 3 previous COVID-19 vaccine doses (2 primary series doses and 1 booster dose). Residents who received second mRNA COVID-19 vaccine booster doses during March 29-June 15, 2022, with follow-up through July 25, 2022, were found to have 60-day VE of 25.8% against SARS-CoV-2 (the virus that causes COVID-19 infection), 73.9% against severe COVID-19 outcomes (a combined endpoint of COVID-19-associated hospitalizations or deaths), and 89.6% against COVID-19-associated deaths alone. During this period, subvariants BA.2 and BA.2.12.1 (March-June 2022), and BA.4 and BA.5 (July 2022) of the B.1.1.529 and BA.2 (Omicron) variant were predominant. These findings suggest that among nursing home residents, second mRNA COVID-19 vaccine booster doses provided additional protection over first booster doses against severe COVID-19 outcomes during a time of emerging Omicron variants. Facilities should continue to ensure that nursing home residents remain up to date with COVID-19 vaccination, including bivalent vaccine booster doses, to prevent severe COVID-19 outcomes.

Dementia prevalence, a contextual factor associated with SARS-CoV-2 in veterans affairs community living centers.

BACKGROUND: Alzheimer's disease and related dementias (ADRD) impact the diagnosis and infection control of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in nursing homes (NH) by influencing the behavior of residents and their caregivers. Health system data show an association between ADRD and SARS-CoV-2. Whether this association is present in NH populations remains unknown. How increased SARS-CoV-2 risk among residents with ADRD impacts the greater NH population also remains unknown. METHODS: This retrospective cohort study used electronic health record data on Veterans residing in 133 Veterans Affairs Community Living Centers (CLC) and 15 spinal cord injury units from March 1, 2020 to December 13, 2020. We measured ADRD using diagnostic codes 12 months before an index SARS-CoV-2 test date for each resident. We used Poisson regression to determine the relative risk of SARS-CoV-2 for the highest quartile of facility ADRD prevalence versus the lowest, stratifying by individual ADRD status, and adjusting for covariates, with and without a random intercept to account for facility clustering. RESULTS: Across the study period, 15,043 residents resided in CLCs, 1952 (13.0%) had SARS-CoV-2, and 8067 (53.6%) had ADRD. There was an estimated 60% increased risk of SARS-CoV-2 in facilities with highest dementia prevalence versus lowest (relative risk, 1.6 [95% confidence interval 0.95, 2.7]). CONCLUSIONS: CLC residents had a greater likelihood of SARS-CoV-2 infection in facilities with greater ADRD prevalence. Facility characteristics other than ADRD prevalence may account for this association.

US nursing home residents receiving PCV13 in the SNF by recorded pneumococcal vaccination up-to-date status, 2014-2018.

BACKGROUND: Since PCV13 was recommended in 2014, the characteristics of nursing home (NH) residents (and their facilities) recorded by facilities as not up-to-date with pneumococcal vaccination upon admission were unknown, and it is unknown if they received PCV13 in the NH. METHODS: We conducted a retrospective cohort of NH residents of Centers for Medicare and Medicaid (CMS)-certified skilled nursing facilities from October 1, 2014, through September 22, 2018. CMS' Minimum Data Set (MDS) was linked to Medicare Part B Carrier claims to corroborate pneumococcal vaccination up-to-date status in the MDS with pneumococcal vaccination claims. The primary outcome of interest was vaccination with PCV13 versus nonreceipt among those identified as "not up to date" according to facility MDS records. We estimated generalized estimating equation (GEE) models. RESULTS: Of the 1,459,814 residents recorded not up-to-date, (78.2%) had no Part B claims for PCV13 before or in the NH, the majority of whom (71.5%) were reported to have refused the vaccine when offered. Only 1.3% subsequently received PCV13 within 99 days after NH admission. In adjusted analyses, residents less likely to receive PCV13 in the NH than those who did included: residence in a for-profit facility (OR: 0.94 [95% CI: 0.89, 0.99]); male (OR: 0.92 [95% CI:0.89, 0.95]); black race (OR: 0.71 (95%CI: 0.66, 0.77); Hispanic ethnicity (OR: 0.69 [95%CI: 0.59, 0.75]); severely cognitively impaired compared with any lesser degree of impairment; had diabetes (OR: 0.93 [95%CI: 0.89, 0.97]); long-stay (≥100 days) compared with short-stay residents (OR: 0.17 (95%CI: 0.15, 0.20); and did not receive the influenza vaccine (OR: 0.74 (95%CI: 0.71, 0.77). CONCLUSIONS: Due to refusals, few NH residents recorded not up-to-date on pneumococcal vaccinations from 2014 to 2018 received PCV13 within three months of admission. Strategies to promote newly recommended PCV15 or PCV20 vaccination upon NH admission may be needed.

Lessons for deprescribing from a nonessential medication hold policy in US nursing homes.

BACKGROUND: At the height of the COVID-19 pandemic, a large nursing home chain implemented a policy to temporarily hold potentially unnecessary medications. We describe rates of held and discontinued medications after a temporary hold policy of potentially unnecessary or nonessential medications. METHODS: This retrospective cohort study uses electronic health record (EHR) data on 3247 residents of 64 nursing homes operated by a multistate long-term care provider. Medications were documented in the electronic medication administration record. Overall medication held and discontinued incidences are reported. Hierarchical Bayesian modeling is used to determine individual probabilities for medication discontinuation within each facility. RESULTS: In total, 3247 residents had 5297 nonessential medications held. Multivitamins were most likely to be held, followed by histamine-2 receptor antagonists, antihistamines, and statins. At the end of the hold policy, 2897 of 5297 (54%) were permanently discontinued, including probiotics (73%), histamine-2 receptor antagonists (66%), antihistamines (64%), and statins (45%). Demographics, cognitive and functional impairment were similar between residents with medications who were discontinued versus continued. For most medications, more than 50% of the variance in whether medications were discontinued was explained by facility rather than resident-level factors. CONCLUSION: A temporary medication hold policy implemented during the CoVID-19 pandemic led to the deprescribing of a plurality of 'nonessential' medications. This type of organization-wide initiative may be an effective mechanism for altering future prescribing behaviors to reduce the use of unnecessary medications.

Impact of STAR-VA on Staff Injury and Disruptive Behavior Reports in VA Nursing Homes.

OBJECTIVES: Workplace disruptive behavior incidents can be costly for organizations, employees, and customers. Persons with dementia living in long-term care settings have a high risk of exhibiting distressed behaviors. We examined whether a resident-centered, behavioral intervention for residents with dementia led to a reduction in reported workplace disruptive behaviors and staff injury rate due to assault. Impactful interventions are important for quality of care. DESIGN: We examined whether a team-based behavioral program in community living centers (CLCs), where a nurse champion and behavioral coordinator were trained to work with the clinical team to understand and manage distressed behaviors commonly associated with dementia, was associated with reductions in behavior incidents. SETTING AND PARTICIPANTS: The setting was Veterans Health Administration CLCs. The sample consisted of 120 aggregated CLCs operating between 2012 and 2017 with 62 completing training. CLCs were distributed across the United States. METHODS: Outcomes included CLC-level rates of staff injury and number of workplace disruptive behavior incidents. Outcomes were regressed on measures of intervention completion, time since intervention, and several CLC characteristics. RESULTS: The intervention was significantly associated with lower incidence of assault with staff injury rates overall, particularly following the first year of training, but not with other reported workplace disruptive behavior incident rates. CONCLUSIONS AND IMPLICATIONS: A team-based behavioral intervention was associated with reduction of employee assaults, a critical repercussion of distressed behavior in dementia. Given rapid growth in patients with dementia in nursing homes, effective treatment practices, such as interdisciplinary behavioral management approaches may be impactful and valuable to implement.

Impact of an interdisciplinary intervention for distress behaviors in dementia on psychotropic drug use in Veterans Health Administration Community Living Centers: STAR-VA impact on psychotropic drug utilization.

STAR-VA is an interdisciplinary behavioral approach for managing distress behaviors in residents with dementia, implemented at Veterans Health Administration nursing homes. This study evaluated the impact of STAR-VA implementation on psychotropic drug use. The study design is a retrospective, quasi-experimental cohort analysis of residents enrolled as STAR-VA training cases compared with eligible residents at untrained sites to evaluate treatment effects on psychotropic medication use. We matched 229 STAR-VA cases with 1,163 comparisons. STAR-VA cases experienced an average reduction of 0.92 "as-needed" doses per month (95% confidence interval [CI] -1.82, -0.02) compared with controls. No significant effect on non-STAR-VA cases in trained facilities was detected. STAR-VA programs are an important option for reducing potentially inappropriate psychotropic use.

Major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review.

BACKGROUND: Major adverse cardiovascular events (MACE) are increasingly used as composite outcomes in randomized controlled trials (RCTs) and observational studies. However, it is unclear how observational studies most commonly define MACE in the literature when using administrative data. METHODS: We identified peer-reviewed articles published in MEDLINE and EMBASE between January 1, 2010 to October 9, 2020. Studies utilizing administrative data to assess the MACE composite outcome using International Classification of Diseases 9th or 10th Revision diagnosis codes were included. Reviews, abstracts, and studies not providing outcome code definitions were excluded. Data extracted included data source, timeframe, MACE components, code definitions, code positions, and outcome validation. RESULTS: A total of 920 articles were screened, 412 were retained for full-text review, and 58 were included. Only 8.6% (n = 5/58) matched the traditional three-point MACE RCT definition of acute myocardial infarction (AMI), stroke, or cardiovascular death. None matched four-point (+unstable angina) or five-point MACE (+unstable angina and heart failure). The most common MACE components were: AMI and stroke, 15.5% (n = 9/58); AMI, stroke, and all-cause death, 13.8% (n = 8/58); and AMI, stroke and cardiovascular death 8.6% (n = 5/58). Further, 67% (n = 39/58) did not validate outcomes or cite validation studies. Additionally, 70.7% (n = 41/58) did not report code positions of endpoints, 20.7% (n = 12/58) used the primary position, and 8.6% (n = 5/58) used any position. CONCLUSIONS: Components of MACE endpoints and diagnostic codes used varied widely across observational studies. Variability in the MACE definitions used and information reported across observational studies prohibit the comparison, replication, and aggregation of findings. Studies should transparently report the administrative codes used and code positions, as well as utilize validated outcome definitions when possible.

Estimated Cardiorespiratory Hospitalizations Attributable to Influenza and Respiratory Syncytial Virus Among Long-term Care Facility Residents.

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.

Geographic variation in influenza vaccination among U.S. nursing home residents: A national study.

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.

Short-term impact of nursing home SARS-CoV-2 vaccinations on new infections, hospitalizations, and deaths.

OBJECTIVE: To compare rates of incident SARS-CoV-2 infection and 30-day hospitalization or death among residents with confirmed infection in nursing homes with earlier versus later SARS-CoV-2 vaccine clinics. DESIGN: Matched pairs analysis of nursing homes that had their initial vaccine clinics between December 18, 2020, and January 2, 2021, versus between January 3, 2021, and January 18, 2021. Matched facilities had their initial vaccine clinics between 12 and 16 days apart. SETTING AND PARTICIPANTS: Two hundred and eighty nursing homes in 21 states owned and operated by the largest long-term care provider in the United States. MEASUREMENTS: Incident SARS-CoV-2 infections per 100 at-risk residents per week; hospital transfers and/or deaths per 100 residents with confirmed SARS-CoV-2 infection per day, averaged over a week. RESULTS: The early vaccinated group included 136 facilities with 12,157 residents; the late vaccinated group included 144 facilities with 13,221 residents. After 1 week, early vaccinated facilities had a predicted 2.5 fewer incident SARS-CoV-2 infections per 100 at-risk residents per week (95% CI: 1.2-4.0) compared with what would have been expected based on the experience of the late vaccinated facilities. The rates remained significantly lower for several weeks. Cumulatively over 5 weeks, the predicted reduction in new infections was 5.2 cases per 100 at-risk residents (95% CI: 3.2-7.3). By 5 to 8 weeks post-vaccine clinic, early vaccinated facilities had a predicted 1.1 to 3.8 fewer hospitalizations and/or deaths per 100 infected residents per day, averaged by week than expected based on late vaccinated facilities' experience for a cumulative on average difference of 5 events per 100 infected residents per day. CONCLUSIONS: The SARS-CoV-2 vaccines seem to have accelerated the rate of decline of incident infections, morbidity, and mortality in this large multi-state nursing home population.

Adjuvanted Influenza Vaccine and Influenza Outbreaks in US Nursing Homes: Results From a Pragmatic Cluster-Randomized Clinical Trial.

BACKGROUND: Influenza outbreaks in nursing homes pose a threat to frail residents and occur even in vaccinated populations. We conducted a pragmatic cluster-randomized trial comparing adjuvanted trivalent influenza vaccine (aTIV) versus trivalent influenza vaccine (TIV). We report an exploratory analysis to compare the effect of aTIV versus TIV on facility-reported influenza outbreaks. METHODS: We evaluated the impact of the intent-to-treat vaccine assignment on outbreaks reported from November 2016 to March 2017. We collected data according to standard CDC definitions for both suspected outbreaks and those with a laboratory-confirmed case and adjusted for facility-level vaccination rates and resident characteristics in nursing homes. RESULTS: Of 823 randomized nursing homes, 777 (aTIV, n = 387; TIV, n = 390) reported information on influenza outbreaks. Treatment groups had similar characteristics at baseline except for race/ethnicity: homes assigned to TIV had a higher percentage of African-American residents (18.0% vs 13.7%). There were 133 versus 162 facility-reported suspected influenza outbreaks in aTIV versus TIV facilities, respectively; of these, 115 versus 140 were laboratory confirmed. The aTIV group experienced a 17% reduction in suspected (rate ratio, .83; 95% confidence interval, .65-1.05) and laboratory-confirmed (.83; .63-1.06) influenza outbreaks. Covariate adjustment increased the estimated reduction for suspected outbreaks to 21% (.79; .61-.99) and 22% for laboratory-confirmed outbreaks (.78; .60-1.02). CONCLUSIONS: In an exploratory analysis of a cluster-randomized trial we observed 17-21% fewer outbreaks with aTIV than TIV. Clinical Trials Registration. (NCT02882100).

Cluster-randomized Trial of Adjuvanted Versus Nonadjuvanted Trivalent Influenza Vaccine in 823 US Nursing Homes.

BACKGROUND: Influenza leads in preventable infection-related hospitalization in nursing home (NH) residents. The adjuvanted trivalent influenza vaccine (aTIV) is more immunogenic than similarly dosed nonadjuvanted trivalent influenza vaccine (TIV), and observational studies suggest aTIV better prevents hospitalizations in older adults. We prospectively tested this in an NH setting. METHODS: NHs with ≥50 long-stay residents aged ≥65 years were randomized to offer aTIV or TIV for residents for the 2016-2017 influenza season. Using intent-to-treat resident-level analysis with Cox proportional hazards regression models adjusted for clustering by facility and a priori baseline covariates (eg, age, heart failure, and facility-level characteristics), we assessed relative aTIV:TIV effectiveness for hospitalization (ie, all-cause, respiratory, and pneumonia and influenza [P&I]). RESULTS: We randomized 823 NHs, housing 50 012 eligible residents, to aTIV or TIV. Residents were similar between groups by age (mean, ~79 years), heart failure, lung disease, and influenza and pneumococcal vaccine uptake, except aTIV homes housed fewer Black residents (14.5 vs 18.9%). Staff vaccine uptake was similar (~55%). P&I and all-cause resident hospitalization rates were lower (adjusted HR [aHR], .80 [95% CI, .66-.98; P = .03] and .94 [.89-.99; P = .02], respectively) for aTIV versus TIV, while the respiratory hospitalization rate was similar, in a season where vaccine effectiveness was considered poor. CONCLUSIONS: aTIV was more effective than TIV in preventing all-cause and P&I hospitalization from NHs during an A/H3N2-predominant season when TIV was relatively ineffective. CLINICAL TRIALS REGISTRATION: NCT02882100.