Risk Assessment and Prevention of Falls in Older Community-Dwelling Adults: A Review.

Importance: Falls are reported by more than 14 million US adults aged 65 years or older annually and can result in substantial morbidity, mortality, and health care expenditures. Observations: Falls result from age-related physiologic changes compounded by multiple intrinsic and extrinsic risk factors. Major modifiable risk factors among community-dwelling older adults include gait and balance disorders, orthostatic hypotension, sensory impairment, medications, and environmental hazards. Guidelines recommend that individuals who report a fall in the prior year, have concerns about falling, or have gait speed less than 0.8 to 1 m/s should receive fall prevention interventions. In a meta-analysis of 59 randomized clinical trials (RCTs) in average-risk to high-risk populations, exercise interventions to reduce falls were associated with 655 falls per 1000 patient-years in intervention groups vs 850 falls per 1000 patient-years in nonexercise control groups (rate ratio [RR] for falls, 0.77; 95% CI, 0.71-0.83; risk ratio for number of people who fall, 0.85; 95% CI, 0.81-0.89; risk difference, 7.2%; 95% CI, 5.2%-9.1%), with most trials assessing balance and functional exercises. In a meta-analysis of 43 RCTs of interventions that systematically assessed and addressed multiple risk factors among individuals at high risk, multifactorial interventions were associated with 1784 falls per 1000 patient-years in intervention groups vs 2317 falls per 1000 patient-years in control groups (RR, 0.77; 95% CI, 0.67-0.87) without a significant difference in the number of individuals who fell. Other interventions associated with decreased falls in meta-analysis of RCTs and quasi-randomized trials include surgery to remove cataracts (8 studies with 1834 patients; risk ratio [RR], 0.68; 95% CI, 0.48-0.96), multicomponent podiatry interventions (3 studies with 1358 patients; RR, 0.77; 95% CI, 0.61-0.99), and environmental modifications for individuals at high risk (12 studies with 5293 patients; RR, 0.74; 95% CI, 0.61-0.91). Meta-analysis of RCTs of programs to stop medications associated with falls have not found a significant reduction, although deprescribing is a component of many successful multifactorial interventions. Conclusions and Relevance: More than 25% of older adults fall each year, and falls are the leading cause of injury-related death in persons aged 65 years or older. Functional exercises to improve leg strength and balance are recommended for fall prevention in average-risk to high-risk populations. Multifactorial risk reduction based on a systematic clinical assessment for modifiable risk factors may reduce fall rates among those at high risk.

Screening for phenotypic outliers identifies an unusually low concentration of a ß-lactoglobulin B protein isoform in bovine milk caused by a synonymous SNP.

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, ß-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 ß-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.

Epigenetic Age Acceleration and Change in Frailty in MOBILIZE Boston.

Age-associated changes in DNA methylation have been implicated as 1 mechanism to explain the development of frailty; however, previous cross-sectional studies of epigenetic age acceleration (eAA) and frailty have had inconsistent findings. Few longitudinal studies have considered the association of eAA with change in frailty. We sought to determine the association between eAA and change in frailty in the MOBILIZE Boston cohort. Participants were assessed at 2 visits 12-18 months apart. Intrinsic, extrinsic, GrimAge, and PhenoAge eAA were assessed from whole-blood DNA methylation at baseline using the Infinium 450k array. Frailty was assessed by a continuous frailty score based on the frailty phenotype and by frailty index (FI). Analysis was by correlation and linear regression with adjustment for age, sex, smoking status, and body mass index. Three hundred and ninety-five participants with a frailty score and 431 with an FI had epigenetic and follow-up frailty measures. Mean (standard deviation) ages were 77.8 (5.49) and 77.9 (5.47) for the frailty score and the FI cohorts respectively, and 232 (58.7%) and 257 (59.6%) were female. All participants with epigenetic data identified as White. Baseline frailty score was not correlated with intrinsic or extrinsic eAA, but was correlated with PhenoAge and, even after adjustment for covariates, GrimAge. Baseline FI was correlated with extrinsic, GrimAge, and PhenoAge eAA with and without adjustment. No eAA measure was associated with change in frailty, with or without adjustment. Our results suggest that no eAA measure was associated with change in frailty. Further studies should consider longer periods of follow-up and repeated eAA measurement.

Discontinuation of beta-blockers among nursing home residents at end of life.

BACKGROUND: Given limited life expectancy of nursing home (NH) residents, harms of continuing beta-blockers (BBs) may outweigh clinical benefits. Our objective was to describe beta-blocker discontinuation for NH residents during the last year of life, and identify characteristics associated with earlier discontinuation. METHODS: This was a retrospective cohort study that included all long-stay residents in fee-for-service Medicare who died in 2016 and were prescribed oral BBs 1 year before death. Beta-blocker discontinuation was defined as a gap in medication on hand for ≥45 days per Medicare Part D claims, measured from the last date drug was on hand. Comorbidities were obtained from Chronic Condition Warehouse, and other characteristics from the Minimum Data Set. Kaplan-Meier curves were used to describe time to first discontinuation. Findings were stratified by cardiac diagnoses, perceived life expectancy of <6 months, or elevated mortality index. RESULTS: Eighty-eight thousand two hundred and eighty-four residents were prescribed ≥1 daily BB 12 months before death. Mean age was 84.1 years and 69.2% were female. Of these, 60,573 residents (68.6%) remained on a BB in the last 45 days of life, and 57,880 residents (65.6%) had ≥1 cardiac diagnosis. Only 5239 residents (5.9%) had elevated mortality index, whereas 16,798 residents (19.0%) had perceived poor prognosis. In the last year of life, there was no difference in beta-blocker discontinuation pattern between residents with and without cardiac diagnoses. Residents with perceived poor prognosis and elevated mortality index discontinued BBs earlier. For example, mean time until discontinuation among residents with poor perceived prognosis was 245 versus 279 days in residents without such prognosis (p < 0.0001). CONCLUSIONS: BBs are commonly prescribed to NH residents in the final year of life. Overall, discontinuation occurs earlier in residents for whom clinicians perceive limited life expectancy, suggesting that improved prognostication may offer an important opportunity to reduce polypharmacy toward end of life.

Risk factors for injuries in New Zealand older adults with complex needs: a national population retrospective study.

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.

Potentially burdensome end-of-life transitions among nursing home residents with poor-prognosis cancer.

BACKGROUND: This study examined factors associated with potentially burdensome end-of-life (EOL) transitions between care settings among older adults with advanced cancer in nursing homes (NHs). METHODS: A retrospective analysis of deceased older NH residents with poor-prognosis solid tumors was conducted with Medicare claims and the Minimum Data Set. A potentially burdensome transition was defined as 2 or more hospitalizations or an intensive care unit admission in the last 90 days of life. RESULTS: Among 34,670 subjects, many had moderate to severe cognitive impairment (53.8%), full dependence in activities of daily living (ADLs; 66.5%), and comorbidities such as congestive heart failure (CHF; 29.3%) and chronic obstructive pulmonary disease (34.1%). Only 56.3% of the patients used hospice at any time in the 90 days before death; 36.0% of the patients experienced a potentially burdensome EOL transition, and this was higher among patients who did not receive hospice (45.4% vs 28.7%; P < .01). In multivariable analyses, full dependence in ADLs (odds ratio [OR], 1.70; P < .01), CHF (OR, 1.48; P < .01), and chronic obstructive pulmonary disease (OR, 1.28; P < .01) were associated with a higher risk of burdensome EOL transitions. Those with do-not-resuscitate directives (OR, 0.60; P < .01) and impaired cognition (OR, 0.89; P < .01) had lower odds of burdensome EOL transitions. CONCLUSIONS: NH residents with advanced cancer have substantial comorbidities and functional impairment, yet more than a third experience potentially burdensome EOL transitions. These findings help to identify a population at risk for poor EOL outcomes in order to target interventions, and they point to the importance of advanced care planning in this population.

Risk factors for hip fracture in New Zealand older adults seeking home care services: a national population cross-sectional study.

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.

Drug Burden Index and Its Association With Hip Fracture Among Older Adults: A National Population-Based Study.

BACKGROUND: The Drug Burden Index (DBI) calculates the total sedative and anticholinergic load of prescribed medications and is associated with functional decline and hip fractures in older adults. However, it is unknown if confounding factors influence the relationship between the DBI and hip fractures. The objective of this study was to evaluate the association between the DBI and hip fractures, after correcting for mortality and multiple potential confounding factors. METHODS: A competing-risks regression analysis conducted on a prospectively recruited New Zealand community-dwelling older population who had a standardized (International Resident Assessment Instrument) assessment between September 1, 2012, and October 31, 2015, the study's end date. Outcome measures were survival status and hip fracture, with time-varying DBI exposure derived from 90-day time intervals. The multivariable competing-risks regression model was adjusted for a large number of medical comorbidities and activities of daily living. RESULTS: Among 70,553 adults assessed, 2,249 (3.2%) experienced at least one hip fracture, 20,194 (28.6%) died without experiencing a fracture, and 48,110 (68.2%) survived without a fracture. The mean follow-up time was 14.9 months (range: 1 day, 37.9 months). The overall DBI distribution was highly skewed, with median time-varying DBI exposure ranging from 0.93 (Q1 = 0.0, Q3 = 1.84) to 0.96 (Q1 = 0.0, Q3 = 1.90). DBI was significantly related to fracture incidence in unadjusted (p < .001) and adjusted (p < .001) analyses. The estimated subhazard ratio was 1.52 (95% confidence interval: 1.28-1.81) for those with DBI > 3 compared with those with DBI = 0 in the adjusted analysis. CONCLUSIONS: In this study, increasing DBI was associated with a higher likelihood of fractures after accounting for the competing risk of mortality and adjusting for confounders. The results of this unique study are important in validating the DBI as a guide for medication management and it could help reduce the risk of hip fractures in older adults.

Association of Clinical Outcomes With Surgical Repair of Hip Fracture vs Nonsurgical Management in Nursing Home Residents With Advanced Dementia.

Importance: The decision whether to surgically repair a hip fracture in nursing home (NH) residents with advanced dementia can be challenging. Objective: To compare outcomes, including survival, among NH residents with advanced dementia and hip fracture according to whether they underwent surgical hip fracture repair. Design, Setting, and Participants: We conducted a retrospective cohort study of 3083 NH residents with advanced dementia and hip fracture, but not enrolled in hospice care, using nationwide Medicare claims data linked with Minimum Data Set (MDS) assessments from January 1, 2008, through December 31, 2013. Methods: Residents with advanced dementia were identified using the MDS. Medicare claims were used to identify hip fracture and to determine whether the fracture was managed surgically. Survival between surgical and nonsurgical residents was compared using multivariable Cox proportional hazards with inverse probability of treatment weighting (IPTW). All analyses took place between November 2015 and January 2018. Among 6-month survivors, documented pain, antipsychotic drug use, physical restraint use, pressure ulcers, and ambulatory status were compared between surgical and nonsurgical groups. Results: Among 3083 residents with advanced dementia and hip fracture (mean age, 84.2 years; 79.2% female [n = 2441], 28.5% ambulatory [n = 879]), 2615 (84.8%) underwent surgical repair. By 6-month follow-up, 31.5% (n = 824) and 53.8% (n = 252) of surgically and nonsurgically managed residents died, respectively. After IPTW modeling, surgically managed residents were less likely to die than residents without surgery (adjusted hazard ratio [aHR], 0.88; 95% CI, 0.79-0.98). Among 2007 residents who survived 6 months, residents with surgical vs nonsurgical management had less docmented pain (29.0% [n = 465] vs 30.9% [n = 59]) and fewer pressure ulcers (11.2% [n = 200] vs 19.0% [n = 41]). In IPTW models, surgically managed residents reported less pain (aHR, 0.78; 95% CI, 0.61-0.99) and pressure ulcers (aHR, 0.64; 95% CI, 0.47-0.86). There was no difference between antipsychotic drug use and physical restraint use between the groups. Few survivors remained ambulatory (10.7% [n = 55] of surgically managed vs 4.8% [n = 1] without surgery). Conclusions and Relevance: Surgical repair of a hip fracture was associated with lower mortality among NH residents with advanced dementia and should be considered together with the residents' goals of care in management decisions. Pain and other adverse outcomes were common regardless of surgical management, suggesting the need for broad improvements in the quality of care provided to NH residents with advanced dementia and hip fracture.

Repeat bone mineral density screening and prediction of hip and major osteoporotic fracture.

IMPORTANCE: Screening for osteoporosis with bone mineral density (BMD) is recommended for older adults. It is unclear whether repeating a BMD screening test improves fracture risk assessment. OBJECTIVES: To determine whether changes in BMD after 4 years provide additional information on fracture risk beyond baseline BMD and to quantify the change in fracture risk classification after a second BMD measure. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study involving 310 men and 492 women from the Framingham Osteoporosis Study with 2 measures of femoral neck BMD taken from 1987 through 1999. MAIN OUTCOMES AND MEASURES: Risk of hip or major osteoporotic fracture through 2009 or 12 years following the second BMD measure. RESULTS: Mean age was 74.8 years. The mean (SD) BMD change was -0.6% per year (1.8%). Throughout a median follow-up of 9.6 years, 76 participants experienced an incident hip fracture and 113 participants experienced a major osteoporotic fracture. Annual percent BMD change per SD decrease was associated with risk of hip fracture (hazard ratio [HR], 1.43 [95% CI, 1.16 to 1.78]) and major osteoporotic fracture (HR, 1.21 [95% CI, 1.01 to 1.45]) after adjusting for baseline BMD. At 10 years' follow-up, 1 SD decrease in annual percent BMD change compared with the mean BMD change was associated with 3.9 excess hip fractures per 100 persons. In receiver operating characteristic (ROC) curve analyses, the addition of BMD change to a model with baseline BMD did not meaningfully improve performance. The area under the curve (AUC) was 0.71 (95% CI, 0.65 to 0.78) for the baseline BMD model compared with 0.68 (95% CI, 0.62 to 0.75) for the BMD percent change model. Moreover, the addition of BMD change to a model with baseline BMD did not meaningfully improve performance (AUC, 0.72 [95% CI, 0.66 to 0.79]). Using the net reclassification index, a second BMD measure increased the proportion of participants reclassified as high risk of hip fracture by 3.9% (95% CI, -2.2% to 9.9%), whereas it decreased the proportion classified as low risk by -2.2% (95% CI, -4.5% to 0.1%). CONCLUSIONS AND RELEVANCE: In untreated men and women of mean age 75 years, a second BMD measure after 4 years did not meaningfully improve the prediction of hip or major osteoporotic fracture. Repeating a BMD measure within 4 years to improve fracture risk stratification may not be necessary in adults this age untreated for osteoporosis.