Defining Clinically Meaningful Cut Points for Leg Power Impairment Using Physical Performance in Older Adults: A Secondary Analysis From Boston RISE.

OBJECTIVE: To identify clinically meaningful thresholds of leg power impairment identified by the stair climb power test (SCPT). DESIGN: Cross-sectional analysis using the baseline data from an observational cohort study. SETTING: The Boston Rehabilitative Impairment Study of the Elderly. PARTICIPANTS: Community-dwelling older adults (N=413). MAIN OUTCOME MEASURES: SCPT and the Short Physical Performance Battery (SPPB). RESULTS: Using the receiver operating characteristic curves and Youden's J statistics, the optimal threshold for the SCPT associated with mobility limitation as defined by an SPPB score ≤9 was 3.07 Watts/kg for men with a sensitivity of 74%, a specificity of 73% and, an area under the curve (AUC) value of 0.78. For women, the optimal threshold was 2.59 Watts/kg with a sensitivity of 83%, a specificity of 69%, and an AUC value of 0.81. The classification and regression tree sensitivity analysis demonstrated similar thresholds, 2.88 Watts/kg and 2.53 Watts/kg for men and women, respectively. CONCLUSIONS: The study identified clinically meaningful thresholds of impairment for the SCPT for mobility limited older primary care patients. These thresholds may be used to inform rehabilitation care to improve functional mobility of older adults and should be validated in larger more representative clinical trials.

A compressed large language model embedding dataset of ICD 10 CM descriptions.

This paper presents novel datasets providing numerical representations of ICD-10-CM codes by generating description embeddings using a large language model followed by a dimension reduction via autoencoder. The embeddings serve as informative input features for machine learning models by capturing relationships among categories and preserving inherent context information. The model generating the data was validated in two ways. First, the dimension reduction was validated using an autoencoder, and secondly, a supervised model was created to estimate the ICD-10-CM hierarchical categories. Results show that the dimension of the data can be reduced to as few as 10 dimensions while maintaining the ability to reproduce the original embeddings, with the fidelity decreasing as the reduced-dimension representation decreases. Multiple compression levels are provided, allowing users to choose as per their requirements, download and use without any other setup. The readily available datasets of ICD-10-CM codes are anticipated to be highly valuable for researchers in biomedical informatics, enabling more advanced analyses in the field. This approach has the potential to significantly improve the utility of ICD-10-CM codes in the biomedical domain.

A Randomized Trial of a Multifactorial Strategy to Prevent Serious Fall Injuries.

BACKGROUND: Injuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined. METHODS: We conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group. RESULTS: The demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups. CONCLUSIONS: A multifactorial intervention, administered by nurses, did not result in a significantly lower rate of a first adjudicated serious fall injury than enhanced usual care. (Funded by the Patient-Centered Outcomes Research Institute and others; STRIDE ClinicalTrials.gov number, NCT02475850.).

Costs of fall injuries in the STRIDE study: an economic evaluation of healthcare system heterogeneity and heterogeneity of treatment effect.

OBJECTIVES: The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) Study cluster-randomized 86 primary care practices in 10 healthcare systems to a patient-centered multifactorial fall injury prevention intervention or enhanced usual care, enrolling 5451 participants. We estimated total healthcare costs from participant-reported fall injuries receiving medical attention (FIMA) that were averted by the STRIDE intervention and tested for healthcare-system-level heterogeneity and heterogeneity of treatment effect (HTE). METHODS: Participants were community-dwelling adults age ≥ 70 at increased fall injury risk. We estimated practice-level total costs per person-year of follow-up (PYF), assigning unit costs to FIMA with and without an overnight hospital stay. Using independent variables for treatment arm, healthcare system, and their interaction, we fit a generalized linear model with log link, log follow-up time offset, and Tweedie error distribution. RESULTS: Unadjusted total costs per PYF were $2,034 (intervention) and $2,289 (control). The adjusted (intervention minus control) cost difference per PYF was -$167 (95% confidence interval (CI), -$491, $216). Cost heterogeneity by healthcare system was present (p = 0.035), as well as HTE (p = 0.090). Adjusted total costs per PYF in control practices varied from $1,529 to $3,684 for individual healthcare systems; one system with mean intervention minus control costs of -$2092 (95% CI, -$3,686 to -$944) per PYF accounted for HTE, but not healthcare system cost heterogeneity. CONCLUSIONS: We observed substantial heterogeneity of healthcare system costs in the STRIDE study, with small reductions in healthcare costs for FIMA in the STRIDE intervention accounted for by a single healthcare system. TRIAL REGISTRATION: Clinicaltrials.gov (NCT02475850).

World guidelines for falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. OBJECTIVES: to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. METHODS: a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. RECOMMENDATIONS: all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. CONCLUSIONS: the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.

The Rehabilitation Enhancing Aging Through Connected Health Prehabilitation Trial.

OBJECTIVE: To evaluate the proof of concept of an innovative model of physical therapy Rehabilitation Enhancing Aging through Connected Health (REACH) and evaluated its feasibility and effect on physical function and health care utilization. DESIGN: Quasi-experimental 12-month clinical trial. SETTING: Two outpatient rehabilitation centers. PARTICIPANTS: Community-dwelling older primary care patients with a treatment arm undergoing the intervention (n=75; mean age=77±5.9y; 54% women) and propensity matched controls derived from a longitudinal cohort study (n=430; mean age=71±7.0y; 68% women) using identical recruitment criteria (N=505). INTERVENTION: Combined outpatient and home PT augmented with a commercially available app and computer tablet. MEASUREMENTS: Primary outcomes included a feasibility questionnaire, exercise adherence, self-reported function, and the Short Physical Performance Battery (SPPB). Secondary outcomes included the rates of emergency department (ED) visits and hospitalizations. RESULTS: Among REACH participants, we observed a 9% dropout rate. After accounting for dropouts, with propensity matching, n=68 treatments and n=100 controls were analyzed. Over the 12-month study duration, 85% of participants adhered to the exercise program an average of 2 times a week and evaluated the treatment experience favorably. In comparison to controls, after 1 year of treatment and within multivariable regression models, REACH participants did not manifest a significant difference in patient reported function (group x time effect 1.67 units, P=.10) but did manifest significant differences in SPPB (group x time effect 0.69 units, P=.03) and gait speed (group x time effect .08m/s, P=.02). In comparison to controls, after 1 year, the rate of ED visits (group x time treatment rate=0.27, P<.004) were significantly reduced, but a significant reduction in hospitalizations was not observed. CONCLUSION: The REACH intervention is feasible and has proof of concept in preventing functional decline and favorably affecting health care utilization. Evaluation on a larger scale is warranted.

The rehabilitation enhancing aging through connected health (REACH) study: study protocol for a quasi-experimental clinical trial.

BACKGROUND: Mobility limitations among older adults increase the risk for disability and healthcare utilization. Rehabilitative care is identified as the most efficacious treatment for maintaining physical function. However, there is insufficient evidence identifying a healthcare model that targets prevention of mobility decline among older adults. The objective of this study is to evaluate the preliminary effectiveness of a physical therapy program, augmented with mobile tele-health technology, on mobility function and healthcare utilization among older adults. METHODS: This is a quasi-experimental 12-month clinical trial conducted within a metropolitan-based healthcare system in the northeastern United States. It is in parallel with an existing longitudinal cohort study evaluating mobility decline among community-dwelling older adult primary care patients over one year. Seventy-five older adults (≥ 65-95 years) are being recruited using identical inclusion/exclusion criteria to the cohort study. Three aims will be evaluated: the effect of our program on 1) physical function, 2) healthcare utilization, and 3) healthcare costs. Changes in patient-reported function over 1 year in those receiving the intervention (aim 1) will be compared to propensity score matched controls (N = 150) from the cohort study. For aims 2 and 3, propensity scores, derived from logistic regression model that includes demographic and diagnostic information available through claims and enrollment information, will be used to match treatment and control patients in a ratio of 1:2 or 1:3 from a Medicare Claims Registry derived from the same geographic region. The intervention consists of a one-year physical therapy program that is divided between a combination of outpatient and home visits (6-10 total visits) and is augmented on a computerized tablet using of a commercially available application to deliver a progressive home-based exercise program emphasizing lower-extremity function and a walking program. DISCUSSION: Incorporating mobile health into current healthcare models of rehabilitative care has the potential to decrease hospital visits and provide a longer duration of care. If the hypotheses are supported and demonstrate improved mobility and reduced healthcare utilization, this innovative care model would be applicable for optimizing the maintenance of functional independence among community-dwelling older adults. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT02580409 (Date of registration October 14, 2015).

Neuromuscular Impairments Contributing to Persistently Poor and Declining Lower-Extremity Mobility Among Older Adults: New Findings Informing Geriatric Rehabilitation.

OBJECTIVE: To identify neuromuscular impairments most predictive of unfavorable mobility outcomes in late life. DESIGN: Longitudinal cohort study. SETTING: Research clinic. PARTICIPANTS: Community-dwelling primary care patients aged ≥65 years (N=391) with self-reported mobility modifications, randomly selected from a research registry. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Categories of decline in and persistently poor mobility across baseline, 1 and 2 years of follow-up in the Lower-Extremity Function scales of the Late-Life Function and Disability Instrument. The following categories of impairment were assessed as potential predictors of mobility change: strength (leg strength), speed of movement (leg velocity, reaction time, rapid leg coordination), range of motion (ROM) (knee flexion/knee extension/ankle ROM), asymmetry (asymmetry of leg strength and knee flexion/extension ROM measures), and trunk stability (trunk extensor endurance, kyphosis). RESULTS: The largest effect sizes were found for baseline weaker leg strength (odds ratio [95% confidence interval]: 3.45 [1.72-6.95]), trunk extensor endurance (2.98 [1.56-5.70]), and slower leg velocity (2.35 [1.21-4.58]) predicting a greater likelihood of persistently poor function over 2 years. Baseline weaker leg strength, trunk extensor endurance, and restricted knee flexion motion also predicted a greater likelihood of decline in function (1.72 [1.10-2.70], 1.83 [1.13-2.95], and 2.03 [1.24-3.35], respectively). CONCLUSIONS: Older adults exhibiting poor mobility may be prime candidates for rehabilitation focused on improving these impairments. These findings lay the groundwork for developing interventions aimed at optimizing rehabilitative care and disability prevention, and highlight the importance of both well-recognized (leg strength) and novel impairments (leg velocity, trunk extensor muscle endurance).

Does self-efficacy mediate functional change in older adults participating in an exercise program after hip fracture? A randomized controlled trial.

OBJECTIVES: To examine whether self-efficacy mediated the effect of the Home-based Post-Hip Fracture Rehabilitation program on activity limitations in older adults after hip fracture and whether the mediating effect was different between sex and age groups. DESIGN: Randomized controlled trial. SETTING: Community. PARTICIPANTS: Participants with hip fracture (N=232; mean age ± SD, 79±9.4y) were randomly assigned to intervention (n=120, 51.7%) and attention control (n=112, 48.3%) groups. INTERVENTIONS: The 6-month intervention, the Home-based Post-Hip Fracture Rehabilitation, is a functionally oriented, home-based exercise program. Data were collected at baseline, postintervention (6mo), and follow-up (9mo). MAIN OUTCOME MEASURES: Activity Measure for Post-Acute Care. RESULTS: The mediating effect of the Home-based Post-Hip Fracture Rehabilitation program on Basic Mobility function through self-efficacy for exercise was significant at 9 months (ßindirect=.21). Similarly, the mediating effect of the intervention on Daily Activity function through self-efficacy for exercise was significant at 9 months (ßindirect=.49). In subgroup analyses, the mediating effect was significant at 9 months in the younger group (age, ≤79y) in comparison to the older group and was significant in women in comparison to men. CONCLUSIONS: Self-efficacy may play a partial mediating role in the effect on some longer-term functional outcomes in the Home-based Post-Hip Fracture Rehabilitation intervention. The results suggest that program components that target self-efficacy should be incorporated in future hip fracture rehabilitation interventions. Age and sex of the targeted participants may also need to be considered when developing interventions.

The cluster-randomized BRIGHT trial: Proactive case finding for community-dwelling older adults.

PURPOSE: People are now living longer, but disability may affect the quality of those additional years of life. We undertook a trial to assess whether case finding reduces disability among older primary care patients. METHODS: We conducted a cluster-randomized trial of the Brief Risk Identification Geriatric Health Tool (BRIGHT) among 60 primary care practices in New Zealand, assigning them to an intervention or control group. Intervention practices sent a BRIGHT screening tool to older adults every birthday; those with a score of 3 or higher were referred to regional geriatric services for assessment and, if needed, service provision. Control practices provided usual care. Main outcomes, assessed in blinded fashion, were residential care placement and hospitalization, and secondary outcomes were disability, assessed with Nottingham Extended Activities of Daily Living Scale (NEADL), and quality of life, assessed with the World Health Organization Quality of Life scale, abbreviated version (WHOQOL-BREF). RESULTS: All 8,308 community-dwelling patients aged 75 years and older were approached; 3,893 (47%) participated, of whom 3,010 (77%) completed the trial. Their mean age was 80.3 (SD 4.5) years, and 55% were women. Overall, 88% of the intervention group returned a BRIGHT tool; 549 patients were referred. After 36 months, patients in the intervention group were more likely than those in the control group to have been placed in residential care: 8.4% vs 6.2% (hazard ratio = 1.32; 95% CI, 1.04-1.68; P = .02). Intervention patients had smaller declines in mean scores for physical health-related quality of life (1.6 vs 2.9 points, P = .007) and psychological health-related quality of life (1.1 vs 2.4 points, P = .005). Hospitalization, disability, and use of services did not differ between groups, however. CONCLUSIONS: Our case-finding strategy was effective in increasing identification of older adults with disability, but there was little evidence of improved outcomes. Further research could trial stronger primary care integration strategies.

Computer-adaptive balance testing improves discrimination between community-dwelling elderly fallers and nonfallers.

OBJECTIVES: To build an item response theory-based computer adaptive test (CAT) for balance from 3 traditional, fixed-form balance measures: Berg Balance Scale (BBS), Performance-Oriented Mobility Assessment (POMA), and dynamic gait index (DGI); and to examine whether the CAT's psychometric performance exceeded that of individual measures. DESIGN: Secondary analysis combining 2 existing datasets. SETTING: Community based. PARTICIPANTS: Community-dwelling older adults (N=187) who were aged ≥65 years (mean age, 75.2±6.8y, 69% women). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The BBS, POMA, and DGI items were compiled into an initial 38-item bank. The Rasch partial credit model was used for final item bank calibration. CAT simulations were conducted to identify the ideal CAT. CAT score accuracy, reliability, floor and ceiling effects, and validity were examined. Floor and ceiling effects and validity of the CAT and individual measures were compared. RESULTS: A 23-item bank met model expectations. A 10-item CAT was selected, showing a very strong association with full item bank scores (r=.97) and good overall reliability (.78). Reliability was better in low- to midbalance ranges as a result of better item targeting to balance ability when compared with the highest balance ranges. No floor effect was noted. The CAT ceiling effect (11.2%) was significantly lower than the POMA (40.1%) and DGI (40.3%) ceiling effects (P<.001 per comparison). The CAT outperformed individual measures, being the only test to discriminate between fallers and nonfallers (P=.007), and being the strongest predictor of self-reported function. CONCLUSIONS: The balance CAT showed excellent accuracy, good overall reliability, and excellent validity compared with individual measures, being the only measure to discriminate between fallers and nonfallers. Prospective examination, particularly in low-functioning older adults and clinical populations with balance deficits, is recommended. Development of an improved CAT based on an expanded item bank containing higher difficulty items is also recommended.

Effect of a home-based exercise program on functional recovery following rehabilitation after hip fracture: a randomized clinical trial.

IMPORTANCE: For many older people, long-term functional limitations persist after a hip fracture. The efficacy of a home exercise program with minimal supervision after formal hip fracture rehabilitation ends has not been established. OBJECTIVE: To determine whether a home exercise program with minimal contact with a physical therapist improved function after formal hip fracture rehabilitation ended. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted from September 2008 to October 2012 in the homes of 232 functionally limited older adults who had completed traditional rehabilitation after a hip fracture. INTERVENTIONS: The intervention group (n = 120) received functionally oriented exercises (such as standing from a chair, climbing a step) taught by a physical therapist and performed independently by the participants in their homes for 6 months. The attention control group (n = 112) received in-home and telephone-based cardiovascular nutrition education. MAIN OUTCOMES AND MEASURES: Physical function assessed at baseline, 6 months (ie, at completion of the intervention), and 9 months by blinded assessors. The primary outcome was change in function at 6 months measured by the Short Physical Performance Battery (SPPB; range 0-12, higher score indicates better function) and the Activity Measure for Post-Acute Care (AM-PAC) mobility and daily activity (range, 23-85 and 9-101, higher score indicates better function). RESULTS: Among the 232 randomized patients, 195 were followed up at 6 months and included in the primary analysis. The intervention group (n=100) showed significant improvement relative to the control group (n=95) in functional mobility (mean SPPB scores for intervention group: 6.2 [SD, 2.7] at baseline, 7.2 [SD, 3] at 6 months; control group: 6.0 [SD, 2.8] at baseline, 6.2 [SD, 3] at 6 months; and between-group differences: 0.8 [95% CI, 0.4 to 1.2], P < .001; mean AM-PAC mobility scores for intervention group: 56.2 [SD, 7.3] at baseline, 58.1 [SD, 7.9] at 6 months; control group: 56 [SD, 7.1] at baseline, 56.6 [SD, 8.1] at 6 months; and between-group difference, 1.3 [95% CI, 0.2 to 2.4], P = .03; and mean AM-PAC daily activity scores for intervention group: 57.4 [SD, 13.7] at baseline, 61.3 [SD, 15.7] at 6 months; control group: 58.2 [SD, 15.2] at baseline, 58.6 [SD, 15.3] at 6 months; and between-group difference, 3.5 [95% CI, 0.9 to 6.0], P = .03). In multiple imputation analyses, between-group differences remained significant for SPPB and AM-PAC daily activity, but not for mobility. Significant between-group differences persisted at 9 months for all functional measures with and without imputation. CONCLUSIONS AND RELEVANCE: Among patients who had completed standard rehabilitation after hip fracture, the use of a home-based functionally oriented exercise program resulted in modest improvement in physical function at 6 months after randomization. The clinical importance of these findings remains to be determined. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00592813.

Human-Centered Design and Development of a Fall Prevention Exercise App for Older Adults in Primary Care Settings.

BACKGROUND: Falls in older adults are a serious public health problem that can lead to reduced quality of life or death. Patients often do not receive fall prevention guidance from primary care providers (PCPs), despite evidence that falls can be prevented. Mobile health technologies may help to address this disparity and promote evidence-based fall prevention. OBJECTIVE: Our main objective was to use human-centered design to develop a user-friendly, fall prevention exercise app using validated user requirements. The app features evidence-based behavior change strategies and exercise content to support older people initiating and adhering to a progressive fall prevention exercise program. METHODS: We organized our multistage, iterative design process into three phases: gathering user requirements, usability evaluation, and refining app features. Our methods include focus groups, usability testing, and subject-matter expert meetings. RESULTS: Focus groups (total n = 6), usability testing (n = 30) including a posttest questionnaire [Health-ITUES score: mean (standard deviation [SD]) = 4.2 (0.9)], and subject-matter expert meetings demonstrate participant satisfaction with the app concept and design. Overall, participants saw value in receiving exercise prescriptions from the app that would be recommended by their PCP and reported satisfaction with the content of the app. CONCLUSION: This study demonstrates the development, refinement, and usability testing of a fall prevention exercise app and corresponding tools that PCPs may use to prescribe tailored exercise recommendations to their older patients as an evidence-based fall prevention strategy accessible in the context of busy clinical workflows.

Development of an exercise therapy referral clinical support tool for patients with osteoporosis at risk for falls.

BACKGROUND: The purpose of this study was to develop a clinical support tool for osteoporosis clinic providers to support risk assessment and referrals for evidence-based exercise therapy programs. METHODS: A sequential Delphi method was used with a multidisciplinary group of national falls experts, to provide consensus on referral to exercise therapy for patients at risk for falls. The Delphi study included a primary research team, expert panel, and clinical partners to answer the questions: (1) "What patient characteristics are needed to develop a clinical support tool?"; (2) "What are the recommended exercise referrals for patients with osteoporosis at risk for falls?" The consensus process consisted of two rounds with 8 weeks between meetings. Two qualitative researchers analyzed the data using a modified version of a matrix analysis approach. RESULTS: The following were the most important variables to include when determining exercise therapy referrals for patients with osteoporosis: Patient history and demographics, falls history over the last year, current physical function and balance, caregiver and transportation status, socioeconomic and insurance status, and patient preference. Potential exercise therapy referrals included one-on-one physical therapy, group physical therapy, home health, community-based exercise programs, and not acceptable for exercise therapy. CONCLUSIONS: Patient characteristics including patient history, physical function and balance performance, socioeconomic and insurance status, and patient preference for exercise therapy are important to inform both the medical provider and patient with osteoporosis to choose the most appropriate exercise therapy referral. Adoption of the algorithmic suggestions may have a significant impact on uptake and adherence to exercise therapy, ultimately improving patient physical function and reducing falls risk.

Validation of a Rule-Based ICD-10-CM Algorithm to Detect Fall Injuries in Medicare Data.

BACKGROUND: Diagnosis-code-based algorithms to identify fall injuries in Medicare data are useful for ascertaining outcomes in interventional and observational studies. However, these algorithms have not been validated against a fully external reference standard, in ICD-10-CM, or in Medicare Advantage (MA) data. METHODS: We linked self-reported fall injuries leading to medical attention (FIMA) from the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial (reference standard) to Medicare fee-for-service (FFS) and MA data from 2015-19. We measured the area under the receiver operating characteristic curve (AUC) based on sensitivity and specificity of a diagnosis-code-based algorithm against the reference standard for presence or absence of ≥1 FIMA within a specified window of dates, varying the window size to obtain points on the curve. We stratified results by source (FFS vs MA), trial arm (intervention vs control), and STRIDE's 10 participating health care systems. RESULTS: Both reference standard data and Medicare data were available for 4 941 (of 5 451) participants. The reference standard and algorithm identified 2 054 and 2 067 FIMA, respectively. The algorithm had 45% sensitivity (95% confidence interval [CI]: 43%-47%) and 99% specificity (95% CI: 99%-99%) to identify reference standard FIMA within the same calendar month. The AUC was 0.79 (95% CI: 0.78-0.81) and was similar by FFS or MA data source and by trial arm but showed variation among STRIDE health care systems (AUC range by health care system, 0.71 to 0.84). CONCLUSIONS: An ICD-10-CM algorithm to identify fall injuries demonstrated acceptable performance against an external reference standard, in both MA and FFS data.

Assessing readiness to use electronic health record data for outcome ascertainment in clinical trials - A case study.

BACKGROUND: Variable data quality poses a challenge to using electronic health record (EHR) data to ascertain acute clinical outcomes in multi-site clinical trials. Differing EHR platforms and data comprehensiveness across clinical trial sites, especially if patients received care outside of the clinical site's network, can also affect validity of results. Overcoming these challenges requires a structured approach. METHODS: We propose a framework and create a checklist to assess the readiness of clinical sites to contribute EHR data to a clinical trial for the purpose of outcome ascertainment, based on our experience with the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, which enrolled 5451 participants in 86 primary care practices across 10 healthcare systems (sites). RESULTS: The site readiness checklist includes assessment of the infrastructure (i.e., size and structure of the site's healthcare system or clinical network), data procurement (i.e., quality of the data), and cost of obtaining study data. The checklist emphasizes the importance of understanding how data are captured and integrated across a site's catchment area and having a protocol in place for data procurement to ensure consistent and uniform extraction across each site. CONCLUSIONS: We suggest rigorous, prospective vetting of the data quality and infrastructure of each clinical site before launching a multi-site trial dependent on EHR data. The proposed checklist serves as a guiding tool to help investigators ensure robust and unbiased data capture for their clinical trials. ORIGINAL TRIAL REGISTRATION NUMBER: NCT02475850.

Dysregulated nicotinamide adenine dinucleotide metabolome in patients hospitalized with COVID-19.

Nicotinamide adenine dinucleotide (NAD+) depletion has been postulated as a contributor to the severity of COVID-19; however, no study has prospectively characterized NAD+ and its metabolites in relation to disease severity in patients with COVID-19. We measured NAD+ and its metabolites in 56 hospitalized patients with COVID-19 and in two control groups without COVID-19: (1) 31 age- and sex-matched adults with comorbidities, and (2) 30 adults without comorbidities. Blood NAD+ concentrations in COVID-19 group were only slightly lower than in the control groups (p < 0.05); however, plasma 1-methylnicotinamide concentrations were significantly higher in patients with COVID-19 (439.7 ng/mL, 95% CI: 234.0, 645.4 ng/mL) than in age- and sex-matched controls (44.5 ng/mL, 95% CI: 15.6, 73.4) and in healthy controls (18.1 ng/mL, 95% CI 15.4, 20.8; p < 0.001 for each comparison). Plasma nicotinamide concentrations were also higher in COVID-19 group and in controls with comorbidities than in healthy control group. Plasma concentrations of 2-methyl-2-pyridone-5-carboxamide (2-PY), but not NAD+, were significantly associated with increased risk of death (HR = 3.65; 95% CI 1.09, 12.2; p = 0.036) and escalation in level of care (HR = 2.90, 95% CI 1.01, 8.38, p = 0.049). RNAseq and RTqPCR analyses of PBMC mRNA found upregulation of multiple genes involved in NAD+ synthesis as well as degradation, and dysregulation of NAD+-dependent processes including immune response, DNA repair, metabolism, apoptosis/autophagy, redox reactions, and mitochondrial function. Blood NAD+ concentrations are modestly reduced in COVID-19; however, NAD+ turnover is substantially increased with upregulation of genes involved in both NAD+ biosynthesis and degradation, supporting the rationale for NAD+ augmentation to attenuate disease severity.

Improved accuracy and efficiency of primary care fall risk screening of older adults using a machine learning approach.

BACKGROUND: While many falls are preventable, they remain a leading cause of injury and death in older adults. Primary care clinics largely rely on screening questionnaires to identify people at risk of falls. Limitations of standard fall risk screening questionnaires include suboptimal accuracy, missing data, and non-standard formats, which hinder early identification of risk and prevention of fall injury. We used machine learning methods to develop and evaluate electronic health record (EHR)-based tools to identify older adults at risk of fall-related injuries in a primary care population and compared this approach to standard fall screening questionnaires. METHODS: Using patient-level clinical data from an integrated healthcare system consisting of 16-member institutions, we conducted a case-control study to develop and evaluate prediction models for fall-related injuries in older adults. Questionnaire-derived prediction with three questions from a commonly used fall risk screening tool was evaluated. We then developed four temporal machine learning models using routinely available longitudinal EHR data to predict the future risk of fall injury. We also developed a fall injury-prevention clinical decision support (CDS) implementation prototype to link preventative interventions to patient-specific fall injury risk factors. RESULTS: Questionnaire-based risk screening achieved area under the receiver operating characteristic curve (AUC) up to 0.59 with 23% to 33% similarity for each pair of three fall injury screening questions. EHR-based machine learning risk screening showed significantly improved performance (best AUROC = 0.76), with similar prediction performance between 6-month and one-year prediction models. CONCLUSIONS: The current method of questionnaire-based fall risk screening of older adults is suboptimal with redundant items, inadequate precision, and no linkage to prevention. A machine learning fall injury prediction method can accurately predict risk with superior sensitivity while freeing up clinical time for initiating personalized fall prevention interventions. The developed algorithm and data science pipeline can impact routine primary care fall prevention practice.