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ABSTRACT Some, but not all, prior observational studies have shown that beta blocker (BB) use is associated with lower fracture risk and higher bone mineral density (BMD). Rodent studies show the mechanism to involve the reduction in the effects of beta‐adrenergic signaling on bone remodeling. Because previous studies did not have detailed information on dose, duration, and beta‐1 selectivity, we examined these in a cross‐sectional analysis of the association between BB use and hip and spine BMD using DXA with the Offspring Cohort of the Framingham Heart Study. The sample size was n = 1520, and 397 individuals used BBs. We used propensity score modeling to balance a comprehensive set of covariates using inverse probability of treatment weighting (IPTW) to minimize bias due to treatment indication. We found significant differences in BMD between BB users and non‐users for three of four BMD measurements (femoral neck: 3.1%, 95% CI, 1.1% to 5.0%; total femur: 2.9%, 95% CI, 0.9% to 4.9%; femoral trochanter: 2.4%, 95% CI, −0.1% to 5.0%; and lumbar spine: 2.7%, 95% CI, 0.2% to 5.0%). Results were found to be similar between sexes although the magnitude of association was larger for women. Similar differences were estimated for beta‐1 selective and nonselective BBs compared with no BB use. We modeled dose in categories (no BB use, low‐dose, high‐dose) and as a continuous variable and found an increasing dose response that levels off at higher doses. Finally, associations were similar for short‐term versus long‐term (≤4 years versus >4 years) use. In summary, this large comprehensive study shows that BB use is associated with higher BMD in a dose‐related manner regardless of beta‐1 specificity and duration of use, which supports the conduct of a randomized clinical trial of BBs for achieving improvements in BMD for individuals at risk of bone loss with aging. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Abstract Background Although a majority of patients in the U.S. receive post-acute care in skilled nursing facilities (SNFs) following hip fracture, large-sample observational studies of analgesic prescribing and use in SNFs have not been possible due to limitations in available data sources. We conducted a proof-of-concept federated analysis of electronic health records (EHRs) from 11 SNF chains to describe analgesic use during hip fracture post-acute care. Methods We included residents with a diagnosis of hip fracture between January 1, 2018 and June 30, 2021 who had at least one administration of an analgesic. Use of analgesics was ascertained from EHR medication orders and medication administration records. We quantified the proportion of residents receiving analgesic regimens based on the medications that were administered up to 100 days after hip fracture diagnosis. Plots visualizing trends in analgesic use were stratified by multiple resident characteristics including age and Alzheimer’s Disease and Related Dementias (ADRD) diagnosis. Results The study included 23,706 residents (mean age 80.5 years, 68.6% female, 87.7% White). Most (~ 60%) residents received opioids + APAP. Monotherapy with APAP or opioids was also common. The most prevalent regimens were oxycodone + APAP (20.1%), hydrocodone + APAP (15.8%), APAP only (15.1%), tramadol + APAP (10.4%), and oxycodone only (4.3%). During the study period, use of APAP-only increased, opioids-only decreased, and opioids + APAP remained stable. Use of APAP-only appeared to be more prevalent among individuals aged > 75 years (versus ≤ 75 years) and those with ADRD (versus without). Conclusions We successfully leveraged federated SNF EHR data to describe analgesic use among residents receiving hip fracture post-acute care.

Abstract Background Post-acute care (PAC) services after hospitalization for hip fracture are typically provided in skilled nursing facilities (SNFs), inpatient rehabilitation facilities (IRFs), or at home via home health care (HHC). Little is known about the clinical course following PAC for hip fracture. We examined the nationwide burden of adverse outcomes by PAC setting in the year following discharge from PAC for hip fracture. Methods This retrospective cohort included Medicare Fee-for-Service beneficiaries > 65 years who received PAC services in U.S. SNFs, IRFs, or HHC following hip fracture hospitalization between 2012 and 2018. Individuals who had a fall-related injury (FRI) during PAC or received PAC services in multiple settings were excluded. Primary outcomes included FRIs, all-cause hospital readmissions, and death in the year following discharge from PAC. Cumulative incidences and incidence rates for adverse outcomes were reported by PAC setting. Exploratory analyses examined risk ratios and hazard ratios between settings before and after inverse-probability-of-treatment-weighting, which accounted for 43 covariates. Results Among 624,631 participants (SNF, 67.78%; IRF, 16.08%; HHC, 16.15%), the mean (standard deviation) age was 82.70 (8.26) years, 74.96% were female, and 91.30% were non-Hispanic White. Crude incidence rates (95%CLs) per 1000 person-years were highest among individuals receiving SNF care for FRIs (SNF, 123 [121, 123]; IRF, 105 [102, 107]; HHC, 89 [87, 91]), hospital readmission (SNF, 623 [619, 626]; IRF, 538 [532, 544]; HHC, 418 [414, 423]), and death (SNF, 167 [165, 169]; IRF, 47 [46, 49]; HHC, 55 [53, 56]). Overall, rates of adverse outcomes generally remained higher among SNF care recipients after covariate adjustment. However, inferences about the group with greater adverse outcomes differed for FRIs and hospital readmissions based on risk ratio or hazard ratio estimates. Conclusions In this retrospective cohort study of individuals hospitalized for hip fracture, rates of adverse outcomes in the year following PAC were common, especially among SNF care recipients. Understanding risks and rates of adverse events can inform future efforts to improve outcomes for older adults receiving PAC for hip fracture. Future work should consider calculating risk and rate measures to assess the influence of differential time under observation across PAC groups.

Background Dose reduction of direct oral anticoagulant (DOAC) medications is inconsistently applied to older adults with multiple morbidities, potentially due to perceived harms and unknown benefits of standard dosing. Methods and Results Using 2013 to 2017 US Medicare claims linked to Minimum Data Set records, we conducted a retrospective cohort study. We identified DOAC initiators (apixaban, dabigatran, rivaroxaban) aged ≥65 years with nonvalvular atrial fibrillation residing in a nursing home. We estimated inverse‐probability of treatment weights for DOAC dose using propensity scores. We examined safety (hospitalization for major bleeding) and effectiveness outcomes (all‐cause mortality, thrombosis [myocardial infarction, stroke, systemic embolism, venous thromboembolism]). We estimated hazard ratios (HRs) and 95% CIs using cause‐specific hazard‐regression models. Of 21 878 DOAC initiators, 48% received reduced dosing. The mean age of residents was 82.0 years, 66% were female, and 31% had moderate/severe cognitive impairment. After estimating inverse‐probability of treatment weights, standard dosing was associated with a higher rate of bleeding (HR, 1.18 [95% CI, 1.03–1.37]; 9.4 versus 8.0 events per 100 person‐years). Standard‐dose therapy was associated with the highest rates of bleeding among those aged >80 years (9.1 versus 6.7 events per 100 person‐years) and with a body mass index

Abstract Background Deprescribing initiatives in the long-term care (LTC) setting are often unsuccessful or not sustained. Prior research has considered how physicians and pharmacists feel about deprescribing, yet little is known about the perspectives of frontline nursing staff and residents. Our aim was to elicit perspectives from LTC nursing staff, patients, and proxies regarding their experiences and preferences for deprescribing in order to inform future deprescribing efforts in LTC. Methods This study was a qualitative analysis of interviews with nurses, nurse aides, a nurse practitioner, residents, and proxies (family member and/or responsible party) from three LTC facilities. The research team used semi-structured interviews. Guides were designed to inform an injury prevention intervention. Interviews were recorded and transcribed. A qualitative framework analysis was used to summarize themes related to deprescribing. The full study team reviewed the summary to identify actionable, clinical implications. Results Twenty-six interviews with 28 participants were completed, including 11 nurse aides, three residents, seven proxies, one nurse practitioner, and six nurses. Three themes emerged that were consistent across facilities: 1) build trust with team members, including residents and proxies; 2) identify motivating factors that lead to resident, proxy, nurse practitioner, and staff acceptance of deprescribing; 3) standardize supportive processes to encourage deprescribing. These themes suggest several actionable steps to improve deprescribing initiatives including: 1) tell stories about successful deprescribing, 2) provide deprescribing education to frontline staff, 3) align medication risk/benefit discussions with what matters most to the resident, 4) standardize deprescribing monitoring protocols, 5) standardize interprofessional team huddles and care plan meetings to include deprescribing conversations, and 6) strengthen non-pharmacologic treatment programs. Conclusions By interviewing LTC stakeholders, we identified three important themes regarding successful deprescribing: Trust, Motivating Factors, and Supportive Processes. These themes may translate into actionable steps for clinicians and researchers to improve and sustain person-centered deprescribing initiatives. Trial registration NCT04242186

Abstract Background Milk samples from 10,641 dairy cattle were screened by a mass spectrometry method for extreme concentrations of the A or B isoforms of the whey protein, β-lactoglobulin (BLG), to identify causative genetic variation driving changes in BLG concentration. Results A cohort of cows, from a single sire family, was identified that produced milk containing a low concentration of the BLG B protein isoform. A genome-wide association study (GWAS) of BLG B protein isoform concentration in milk from AB heterozygous cows, detected a group of highly significant single nucleotide polymorphisms (SNPs) within or close to the BLG gene. Among these was a synonymous G/A variation at position + 78 bp in exon 1 of the BLG gene (chr11:103256256G > A). The effect of the A allele of this SNP (which we named B’) on BLG expression was evaluated in a luciferase reporter assay in transfected CHO-K1 and MCF-7 cells. In both cell types, the presence of the B’ allele in a plasmid containing the bovine BLG gene from -922 to + 898 bp (relative to the transcription initiation site) resulted in a 60% relative reduction in mRNA expression, compared to the plasmid containing the wild-type B sequence allele. Examination of a mammary RNAseq dataset (n = 391) identified 14 heterozygous carriers of the B’ allele which were homozygous for the BLG B protein isoform (BB’). The level of expression of the BLG B’ allele was 41.9 ± 1.0% of that of the wild-type BLG B allele. Milk samples from three cows, homozygous for the A allele at chr11:103,256,256 (B’B’), were analysed (HPLC) and showed BLG concentrations of 1.04, 1.26 and 1.83 g/L relative to a mean of 4.84 g/L in milk from 16 herd contemporaries of mixed (A and B) BLG genotypes. The mechanism by which B’ downregulates milk BLG concentration remains to be determined. Conclusions High-throughput screening and identification of outliers, enabled the discovery of a synonymous G > A mutation in exon 1 of the B allele of the BLG gene (B’), which reduced the milk concentration of β-lactoglobulin B protein isoform, by more than 50%. Milk from cows carrying the B’ allele is expected to have improved processing characteristics, particularly for cheese-making.

Summary: Background: Nursing home (NH) residents have borne a disproportionate share of SARS-CoV-2 morbidity and mortality. Vaccines have limited hospitalisation and death from earlier variants in this vulnerable population. With the rise of Omicron and future variants, it is vital to sustain and broaden vaccine-induced protection. We examined the effect of boosting with BNT162b2 mRNA vaccine on humoral immunity and Omicron-specific neutralising activity among NH residents and healthcare workers (HCWs). Methods: We longitudinally enrolled 85 NH residents (median age 77) and 48 HCWs (median age 51), and sampled them after the initial vaccination series; and just before and 2 weeks after booster vaccination. Anti-spike, anti-receptor binding domain (RBD) and neutralisation titres to the original Wuhan strain and neutralisation to the Omicron strain were obtained. Findings: Booster vaccination significantly increased vaccine-specific anti-spike, anti-RBD, and neutralisation levels above the pre-booster levels in NH residents and HCWs, both in those with and without prior SARS-CoV-2 infection. Omicron-specific neutralisation activity was low after the initial 2 dose series with only 28% of NH residents’ and 28% HCWs’ titres above the assay's lower limit of detection. Omicron neutralising activity following the booster lifted 86% of NH residents and 93% of HCWs to the detectable range. Interpretation: With boosting, the vast majority of HCWs and NH residents developed detectable Omicron-specific neutralising activity. These data provide immunologic evidence that strongly supports booster vaccination to broaden neutralising activity and counter waning immunity in the hope it will better protect this vulnerable, high-risk population against the Omicron variant. Funding: NIH AI129709-03S1, U01 CA260539-01, CDC 200-2016-91773, and VA BX005507-01.

Abstract Background Hip fractures are a common injury in older people. Many studies worldwide have identified various risk factors for hip fracture. However, risk factors for hip fracture have not been studied extensively in New Zealand. The interRAI home care assessment consists of 236 health questions and some of these may be related to hip fracture risk. Methods The cohort consisted of 45,046 home care clients aged 65 years and older, in New Zealand. Assessments ranged from September 2012 to October 2015. Hip fracture diagnosis was identified by linking ICD (International Classification of Diseases) codes from hospital admissions data (September 2012 to December 2015) to the interRAI home care data. Unadjusted and adjusted competing risk regressions, using the Fine and Gray method were used to identify risk factors for hip fracture. Mortality was the competing event. Results The cohort consisted of 61% female with a mean age of 82.7 years. A total of 3010 (6.7%) of the cohort sustained a hip fracture after assessment. After adjusting for sociodemographic and potentially confounding variables falls (SHR (Subhazard Ratio) = 1.17, 95% CI (Confidence interval): 1.05–1.31), previous hip fracture (SHR = 4.16, 95% CI: 2.93–5.89), female gender (SHR = 1.38, 95% CI: 1.22–1.55), underweight (SHR = 1.67, 95% CI = 1.39–2.02), tobacco use (SHR = 1.56, 95% CI = 1.25–1.96), Parkinson’s disease (SHR = 1.45, 95% CI: 1.14–1.84), and Wandering (SHR = 1.36, 95% CI: 1.07–1.72) were identified as risk factors for hip fracture. Shortness of breath (SHR = 0.80, 95% CI: 0.71–0.90), was identified as being protective against hip fracture risk. Males and females had different significant risk factors. Conclusions Risk factors for hip fracture similar to international work on risk factors for hip fracture, can be identified using the New Zealand version of the interRAI home care assessment.

Abstract Background Falls and falls-related injuries are common among older adults. Injuries in older adults lead to poor outcomes and lower quality of life. The objective of our study was to identify factors associated with fall-related injuries among home care clients in New Zealand. Methods The study cohort consisted of 75,484 community-dwelling people aged 65 years or older who underwent an interRAI home care assessment between June 2012 and June 2018 in New Zealand. The injuries included for analysis were fracture of the distal radius, hip fracture, pelvic fracture, proximal humerus fracture, subarachnoid haemorrhage, traumatic subdural haematoma, and vertebral fracture. Unadjusted and adjusted competing risk regression models were used to identify factors associated with fall-related injuries. Results A total of 7414 (9.8%) people sustained a falls-related injury over the 6-year period, and most injuries sustained were hip fractures (4735 63.9%). The rate of injurious falls was 47 per 1000 person-years. The factors associated with injury were female sex, older age, living alone, Parkinson’s disease, stroke/CVA, falls, unsteady gait, tobacco use, and being underweight. Cancer, dyspnoea, high BMI, and a decrease in the amount of food or fluid usually consumed, were associated with a reduced risk of sustaining an injury. After censoring hip fractures the risks associated with other types of injury were sex, age, previous falls, dyspnoea, tobacco use, and BMI. Conclusions While it is important to reduce the risk of falls, it is especially important to reduce the risk of falls-related injuries. Knowledge of risk factors associated with these types of injuries can help to develop focused intervention programmes and development of a predictive model to identify those who would benefit from intervention programmes.