It Is Not Just About Enrollment: Recognizing the Impact of RCT Recruitment Approaches on Prediabetes Awareness, Screening, and Capacity Building in African American Communities

Diabetes is a growing epidemic in the USA. Compared to white Americans, African Americans are 1.8 times more likely to have diabetes [1]. Additionally, African Americans with diabetes experience higher rates of morbidity and mortality than other racial groups. Compared to whites, African Americans are twice as likely to suffer from diabetes-related blindness, 1.5 to 2.5 times more likely to suffer from lower limb amputations and 2.6 to 5.6 times more likely to suffer from kidney disease [1, 2]. Prediabetes is a common precursor to diabetes and characterized by blood glucose levels that are above normal but below the criteria for a diagnosis of diabetes [3]. Approximately 30% or 88 million US adults have prediabetes [4] with African Americans disproportionately affected. During the average 3 years of follow-up of the landmark Diabetes Prevention Program, prediabetes developed into type 2 diabetes in approximately 11% of the subjects who participated in the standard care or control group [5]. Other estimates show that if prevention strategies are not implemented, individuals with prediabetes will be diagnosed with type 2 diabetes within 10 years [6]. While African Americans with prediabetes are at significant risk for developing diabetes, this outcome is not inevitable. Diagnosis of prediabetes is an example of secondary prevention, screening to identify diseases at an early stage, before symptoms begin [7]. The identification of pre-diabetes, and subsequent secondary prevention efforts to thwart or delay transition to diabetes, can reduce morbidity, impaired quality of life, monumental healthcare costs, and mortality rates [1, 2, 8, 9]

Using claims data to predict dependency in activities of daily living as a proxy for frailty

Estimating drug effectiveness and safety among older adults in population-based studies using administrative health care claims can be hampered by unmeasured confounding as a result of frailty. A claims-based algorithm that identifies patients likely to be dependent, a proxy for frailty, may improve confounding control. Our objective was to develop an algorithm to predict dependency in activities of daily living (ADL) in a sample of Medicare beneficiaries. Methods: Community-dwelling respondents to the 2006 Medicare Current Beneficiary Survey, >65years old, with Medicare Part A, B, home health, and hospice claims were included. ADL dependency was defined as needing help with bathing, eating, walking, dressing, toileting, or transferring. Potential predictors were demographics, International Classification of Diseases, Ninth Revision Clinical Modification diagnosis/procedure and durable medical equipment codes for frailty-associated conditions. Multivariable logistic regression was used to predict ADL dependency. Cox models estimated hazard ratios for death as a function of observed and predicted ADL dependency. Results: Of 6391 respondents, 57% were female, 88% white, and 38% were ≥80. The prevalence of ADL dependency was 9.5%. Strong predictors of ADL dependency were charges for a home hospital bed (OR=5.44, 95%CI=3.28-9.03) and wheelchair (OR=3.91, 95%CI=2.78-5.51). The c-statistic of the final model was 0.845. Model-predicted ADL dependency of 20% or greater was associated with a hazard ratio for death of 3.19 (95%CI: 2.78, 3.68). Conclusions: An algorithm for predicting ADL dependency using health care claims was developed to measure some aspects of frailty. Accounting for variation in frailty among older adults could lead to more valid conclusions about treatment use, safety, and effectiveness

Missing data approaches in longitudinal studies of aging: A case example using the National Health and Aging Trends Study

Purpose Missing data is a key methodological consideration in longitudinal studies of aging. We described missing data challenges and potential methodological solutions using a case example describing five-year frailty state transitions in a cohort of older adults. Methods We used longitudinal data from the National Health and Aging Trends Study, a nationally-representative cohort of Medicare beneficiaries. We assessed the five components of the Fried frailty phenotype and classified frailty based on their number of components (robust: 0, prefrail: 1–2, frail: 3–5). One-, two-, and five-year frailty state transitions were defined as movements between frailty states or death. Missing frailty components were imputed using hot deck imputation. Inverse probability weights were used to account for potentially informative loss-to-follow-up. We conducted scenario analyses to test a range of assumptions related to missing data. Results Missing data were common for frailty components measured using physical assessments (walking speed, grip strength). At five years, 36% of individuals were lost-to-follow-up, differentially with respect to baseline frailty status. Assumptions for missing data mechanisms impacted inference regarding individuals improving or worsening in frailty. Conclusions Missing data and loss-to-follow-up are common in longitudinal studies of aging. Robust epidemiologic methods can improve the rigor and interpretability of aging-related research

Controlling for frailty in pharmacoepidemiologic studies of older adults

Background: Frailty is a geriatric syndrome characterized by weakness and weight loss and is associated with adverse health outcomes. It is often an unmeasured confounder in pharmacoepidemiologic and comparative effectiveness studies using administrative claims data. Methods: Among the Atherosclerosis Risk in Communities (ARIC) Study Visit 5 participants (2011-2013; n = 3,146), we conducted a validation study to compare a Medicare claims-based algorithm of dependency in activities of daily living (or dependency) developed as a proxy for frailty with a reference standard measure of phenotypic frailty. We applied the algorithm to the ARIC participants' claims data to generate a predicted probability of dependency. Using the claims-based algorithm, we estimated the C-statistic for predicting phenotypic frailty. We further categorized participants by their predicted probability of dependency (<5%, 5% to <20%, and ≥20%) and estimated associations with difficulties in physical abilities, falls, and mortality. Results: The claims-based algorithm showed good discrimination of phenotypic frailty (C-statistic = 0.71; 95% confidence interval [CI] = 0.67, 0.74). Participants classified with a high predicted probability of dependency (≥20%) had higher prevalence of falls and difficulty in physical ability, and a greater risk of 1-year all-cause mortality (hazard ratio = 5.7 [95% CI = 2.5, 13]) than participants classified with a low predicted probability (<5%). Sensitivity and specificity varied across predicted probability of dependency thresholds. Conclusions: The Medicare claims-based algorithm showed good discrimination of phenotypic frailty and high predictive ability with adverse health outcomes. This algorithm can be used in future Medicare claims analyses to reduce confounding by frailty and improve study validity

Comparison of Medicare Claims-based Proxy Measures of Poor Function and Associations With Treatment Receipt and Mortality in Older Colon Cancer Patients

Background: Multiple claims-based proxy measures of poor function have been developed to address confounding in observational studies of drug effects in older adults. We evaluated agreement between these measures and their associations with treatment receipt and mortality in a cohort of older colon cancer patients. Methods: Medicare beneficiaries age 66+ diagnosed with stage II-III colon cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare database (2004-2011). Poor function was operationalized by: (1) summing the total poor function indicators for each model; and (2) estimating predicted probabilities of poor function at diagnosis. Agreement was evaluated using Fleiss' κ and Spearman's correlation. Associations between proxy measures and: (1) laparoscopic versus open surgery; (2) chemotherapy versus none; (3) 5-fluorouracil (5FU)+oxaliplatin (FOLFOX) versus 5FU monotherapy; and (4) 1-year mortality were estimated using log-binomial regression, controlling for age, sex, stage, and comorbidity. Survival estimates were stratified by functional group, age, and comorbidity. Results: Among 29,687 eligible colon cancer patients, 67% were 75+ years and 45% had stage III disease. Concordance across the poor function indicator counts was moderate (κ: 0.64) and correlation of predicted probability measures varied (ρ: 0.21-0.74). Worse function was associated with lower chemotherapy and FOLFOX receipt, and higher 1-year mortality. Within age and comorbidity strata, poor function remained associated with mortality. Conclusions: While agreement varied across the claims-based proxy measures, each demonstrated anticipated associations with treatment receipt and mortality independent of comorbidity. Claims-based comparative effectiveness studies in older populations should consider applying one of these models to improve confounding control

A sixteen-week three-armed, randomized, controlled trial investigating clinical and biochemical effects of targeted alterations in dietary linoleic acid and n-3 EPA+DHA in adults with episodic migraine: Study protocol

Migraine is a prevalent neurological disorder, affecting over 16% of adult women and 7% of adult men in the U.S., causing significant pain, disability, and medical expense, with incomplete benefits from conventional medical management. Migraine, as a chronic pain syndrome, provides a practical model for investigating the impact of dietary modifications in omega-3 (n-3) and omega-6 (n-6) fatty acids. This paper reports the protocol of a trial to assess whether targeted dietary modifications designed to increase n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with or without concurrent reduction in n-6 linoleic acid (LA), will alter nociceptive lipid mediators and mediate decreases in frequency and severity of migraine. This prospective, randomized, controlled trial in 153 male and female adult subjects, ages 18–99, with diagnosed and actively managed episodic migraine tests the efficacy, safety, and biochemical effects of targeted, controlled alterations in dietary omega-3 and omega-6 fatty acids. Participants are masked to diet hypotheses and all assessors are masked to treatment assignment. Following a four-week baseline period, participants with migraine headache frequency of 5–20 per month are randomized to one of three intensive dietary regimens for 16 additional weeks followed by a less intensive observation period. Dietary intervention arms include: 1) increased n-3 EPA+DHA with low n-6 linoleic acid (H3 L6); 2) increased n-3 EPA+DHA with usual US dietary intake of n-6 linoleic acid (H3 H6); and 3) usual US dietary content of n-3 and n-6 fatty acids (L3 H6). During the actual intervention, subjects receive content-specific study oils and foods sufficient for two meals and two snacks per day, as well as dietary counseling. Biochemical and clinical outcome measures are performed at intervals throughout this period. This randomized controlled trial is designed to determine whether targeted alterations in dietary n-3 and n-6 fatty acids can alter nociceptive lipid mediators in a manner that decreases headache pain and enhances quality of life and function in adults with frequent migraines. Trial registration NCT0201279