Assessing the contributions of modifiable risk factors to serious falls and fragility fractures among older persons living with HIV.

BACKGROUND: Although 50 years represents middle age among uninfected individuals, studies have shown that persons living with HIV (PWH) begin to demonstrate elevated risk for serious falls and fragility fractures in the sixth decade; the proportions of these outcomes attributable to modifiable factors are unknown. METHODS: We analyzed 21,041 older PWH on antiretroviral therapy (ART) from the Veterans Aging Cohort Study from 01/01/2010 through 09/30/2015. Serious falls were identified by Ecodes and a machine-learning algorithm applied to radiology reports. Fragility fractures (hip, vertebral, and upper arm) were identified using ICD9 codes. Predictors for both models included a serious fall within the past 12 months, body mass index, physiologic frailty (VACS Index 2.0), illicit substance and alcohol use disorders, and measures of multimorbidity and polypharmacy. We separately fit multivariable logistic models to each outcome using generalized estimating equations. From these models, the longitudinal extensions of average attributable fraction (LE-AAF) for modifiable risk factors were estimated. RESULTS: Key risk factors for both outcomes included physiologic frailty (VACS Index 2.0) (serious falls [15%; 95% CI 14%-15%]; fractures [13%; 95% CI 12%-14%]), a serious fall in the past year (serious falls [7%; 95% CI 7%-7%]; fractures [5%; 95% CI 4%-5%]), polypharmacy (serious falls [5%; 95% CI 4%-5%]; fractures [5%; 95% CI 4%-5%]), an opioid prescription in the past month (serious falls [7%; 95% CI 6%-7%]; fractures [9%; 95% CI 8%-9%]), and diagnosis of alcohol use disorder (serious falls [4%; 95% CI 4%-5%]; fractures [8%; 95% CI 7%-8%]). CONCLUSIONS: This study confirms the contributions of risk factors important in the general population to both serious falls and fragility fractures among older PWH. Successful prevention programs for these outcomes should build on existing prevention efforts while including risk factors specific to PWH.

Predictive Risk Model for Serious Falls Among Older Persons Living With HIV.

BACKGROUND: Older (older than 50 years) persons living with HIV (PWH) are at elevated risk for falls. We explored how well our algorithm for predicting falls in a general population of middle-aged Veterans (age 45-65 years) worked among older PWH who use antiretroviral therapy (ART) and whether model fit improved with inclusion of specific ART classes. METHODS: This analysis included 304,951 six-month person-intervals over a 15-year period (2001-2015) contributed by 26,373 older PWH from the Veterans Aging Cohort Study who were taking ART. Serious falls (those falls warranting a visit to a health care provider) were identified by external cause of injury codes and a machine-learning algorithm applied to radiology reports. Potential predictors included a fall within the past 12 months, demographics, body mass index, Veterans Aging Cohort Study Index 2.0 score, substance use, and measures of multimorbidity and polypharmacy. We assessed discrimination and calibration from application of the original coefficients (model derived from middle-aged Veterans) to older PWH and then reassessed by refitting the model using multivariable logistic regression with generalized estimating equations. We also explored whether model performance improved with indicators of ART classes. RESULTS: With application of the original coefficients, discrimination was good (C-statistic 0.725; 95% CI: 0.719 to 0.730) but calibration was poor. After refitting the model, both discrimination (C-statistic 0.732; 95% CI: 0.727 to 0.734) and calibration were good. Including ART classes did not improve model performance. CONCLUSIONS: After refitting their coefficients, the same variables predicted risk of serious falls among older PWH nearly and they had among middle-aged Veterans.

Brief Report: Are Serious Falls Associated With Subsequent Fragility Fractures Among Veterans Living With HIV?

BACKGROUND: The extensive research on falls and fragility fractures among persons living with HIV (PWH) has not explored the association between serious falls and subsequent fragility fracture. We explored this association. SETTING: Veterans Aging Cohort Study. METHODS: This analysis included 304,951 6-month person- intervals over a 15-year period (2001-2015) contributed by 26,373 PWH who were 50+ years of age (mean age 55 years) and taking antiretroviral therapy (ART). Serious falls (those falls significant enough to result in a visit to a health care provider) were identified by the external cause of injury codes and a machine learning algorithm applied to radiology reports. Fragility fractures were identified using ICD9 codes and included hip fracture, vertebral fractures, and upper arm fracture and were modeled with multivariable logistic regression with generalized estimating equations. RESULTS: After adjustment, serious falls in the previous year were associated with increased risk of fragility fracture [odds ratio (OR) 2.10; 95% confidence interval (CI): 1.83 to 2.41]. The use of integrase inhibitors was the only ART risk factor (OR 1.17; 95% CI: 1.03 to 1.33). Other risk factors included the diagnosis of alcohol use disorder (OR 1.49; 95% CI: 1.31 to 1.70) and having a prescription for an opioid in the previous 6 months (OR 1.40; 95% CI: 1.27 to 1.53). CONCLUSIONS: Serious falls within the past year are strongly associated with fragility fractures among PWH on ART-largely a middle-aged population-much as they are among older adults in the general population.

Serious Falls in Middle-Aged Veterans: Development and Validation of a Predictive Risk Model.

BACKGROUND/OBJECTIVES: Due to high rates of multimorbidity, polypharmacy, and hazardous alcohol and opioid use, middle-aged Veterans are at risk for serious falls (those prompting a visit with a healthcare provider), posing significant risk to their forthcoming geriatric health and quality of life. We developed and validated a predictive model of the 6-month risk of serious falls among middle-aged Veterans. DESIGN: Cohort study. SETTING: Veterans Health Administration (VA). PARTICIPANTS: Veterans, aged 45 to 65 years, who presented for care within the VA between 2012 and 2015 (N = 275,940). EXPOSURES: The exposures of primary interest were substance use (including alcohol and prescription opioid use), multimorbidity, and polypharmacy. Hazardous alcohol use was defined as an Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) score of 3 or greater for women and 4 or greater for men. We used International Classification of Diseases, Ninth Revision (ICD-9), codes to identify alcohol and illicit substance use disorders and identified prescription opioid use from pharmacy fill-refill data. We included counts of chronic medications and of physical and mental health comorbidities. MEASUREMENTS: We identified serious falls using external cause of injury codes and a machine-learning algorithm that identified serious falls in radiology reports. We used multivariable logistic regression with general estimating equations to calculate risk. We used an integrated predictiveness curve to identify intervention thresholds. RESULTS: Most of our sample (54%) was aged 60 years or younger. Duration of follow-up was up to 4 years. Veterans who fell were more likely to be female (11% vs 7%) and White (72% vs 68%). They experienced 43,641 serious falls during follow-up. We identified 16 key predictors of serious falls and five interaction terms. Model performance was enhanced by addition of opioid use, as evidenced by overall category-free net reclassification improvement of 0.32 (P < .001). Discrimination (C-statistic = 0.76) and calibration were excellent for both development and validation data sets. CONCLUSION: We developed and internally validated a model to predict 6-month risk of serious falls among middle-aged Veterans with excellent discrimination and calibration.

Polypharmacy, Hazardous Alcohol and Illicit Substance Use, and Serious Falls Among PLWH and Uninfected Comparators.

BACKGROUND: Medication classes, polypharmacy, and hazardous alcohol and illicit substance abuse may exhibit stronger associations with serious falls among persons living with HIV (PLWH) than with uninfected comparators. We investigated whether these associations differed by HIV status. SETTING: Veterans Aging Cohort Study. METHODS: We used a nested case-control design. Cases (N = 13,530) were those who fell. Falls were identified by external cause of injury codes and a machine-learning algorithm applied to radiology reports. Cases were matched to controls (N = 67,060) by age, race, sex, HIV status, duration of observation, and baseline date. Risk factors included medication classes, count of unique non-antiretroviral therapy (non-ART) medications, and hazardous alcohol and illicit substance use. We used unconditional logistic regression to evaluate associations. RESULTS: Among PLWH, benzodiazepines [odds ratio (OR) 1.24; 95% confidence interval (CI) 1.08 to 1.40] and muscle relaxants (OR 1.29; 95% CI: 1.08 to 1.46) were associated with serious falls but not among uninfected (P > 0.05). In both groups, key risk factors included non-ART medications (per 5 medications) (OR 1.20, 95% CI: 1.17 to 1.23), illicit substance use/abuse (OR 1.44; 95% CI: 1.34 to 1.55), hazardous alcohol use (OR 1.30; 95% CI: 1.23 to 1.37), and an opioid prescription (OR 1.35; 95% CI: 1.29 to 1.41). CONCLUSION: Benzodiazepines and muscle relaxants were associated with serious falls among PLWH. Non-ART medication count, hazardous alcohol and illicit substance use, and opioid prescriptions were associated with serious falls in both groups. Prevention of serious falls should focus on reducing specific classes and absolute number of medications and both alcohol and illicit substance use.