Nilay D. Shah

Exposure to Low-Dose Ionizing Radiation from Medical Imaging Procedures

BACKGROUND The growing use of imaging procedures in the United States has raised concerns about exposure to low-dose ionizing radiation in the general population. METHODS We identified 952,420 nonelderly adults (between 18 and 64 years of age) in five health care markets across the United States between January 1, 2005, and December 31, 2007. Utilization data were used to estimate cumulative effective doses of radiation from imaging procedures and to calculate population-based rates of exposure, with annual effective doses defined as low (< or = 3 mSv), moderate (> 3 to 20 mSv), high (> 20 to 50 mSv), or very high (> 50 mSv). RESULTS During the study period, 655,613 enrollees (68.8%) underwent at least one imaging procedure associated with radiation exposure. The mean (+/-SD) cumulative effective dose from imaging procedures was 2.4+/-6.0 mSv per enrollee per year; however, a wide distribution was noted, with a median effective dose of 0.1 mSv per enrollee per year (interquartile range, 0.0 to 1.7). Overall, moderate effective doses of radiation were incurred in 193.8 enrollees per 1000 per year, whereas high and very high doses were incurred in 18.6 and 1.9 enrollees per 1000 per year, respectively. In general, cumulative effective doses of radiation from imaging procedures increased with advancing age and were higher in women than in men. Computed tomographic and nuclear imaging accounted for 75.4% of the cumulative effective dose, with 81.8% of the total administered in outpatient settings. CONCLUSIONS Imaging procedures are an important source of exposure to ionizing radiation in the United States and can result in high cumulative effective doses of radiation.

Hospitalizations After Heart Failure Diagnosis: A Community Perspective

OBJECTIVES The purpose of this study was to determine the lifetime burden and risk factors for hospitalization after heart failure (HF) diagnosis in the community. BACKGROUND Hospitalizations in patients with HF represent a major public health problem; however, the cumulative burden of hospitalizations after HF diagnosis is unknown, and no consistent risk factors for hospitalization have been identified. METHODS We validated a random sample of all incident HF cases in Olmsted County, Minnesota, from 1987 to 2006 and evaluated all hospitalizations after HF diagnosis through 2007. International Classification of Diseases-9th Revision codes were used to determine the primary reason for hospitalization. To account for repeated events, Andersen-Gill models were used to determine the predictors of hospitalization after HF diagnosis. Patients were censored at death or last follow-up. RESULTS Among 1,077 HF patients (mean age 76.8 years, 582 [54.0%] female), 4,359 hospitalizations occurred over a mean follow-up of 4.7 years. Hospitalizations were common after HF diagnosis, with 895 (83.1%) patients hospitalized at least once, and 721 (66.9%), 577 (53.6%), and 459 (42.6%) hospitalized > or =2, > or =3, and > or =4 times, respectively. The reason for hospitalization was HF in 713 (16.5%) hospitalizations and other cardiovascular in 936 (21.6%), whereas over one-half (n = 2,679, 61.9%) were noncardiovascular. Male sex, diabetes mellitus, chronic obstructive pulmonary disease, anemia, and creatinine clearance <30 ml/min were independent predictors of hospitalization (p < 0.05 for each). CONCLUSIONS Multiple hospitalizations are common after HF diagnosis, though less than one-half are due to cardiovascular causes. Comorbid conditions are strongly associated with hospitalizations, and this information could be used to define effective interventions to prevent hospitalizations in HF patients.

Increased Mortality of Patients With Diabetes Reporting Severe Hypoglycemia

OBJECTIVE Hypoglycemia is a cause of significant morbidity among patients with diabetes and may be associated with greater risk of death. We conducted a retrospective study to determine whether patient self-report of severe hypoglycemia is associated with increased mortality. RESEARCH DESIGN AND METHODS Adult patients (N = 1,020) seen in a specialty diabetes clinic between August 2005 and July 2006 were questioned about frequency of hypoglycemia during a preencounter interview; 7 were lost to follow-up and excluded from analysis. Mild hypoglycemia was defined as symptoms managed without assistance, and severe hypoglycemia was defined as symptoms requiring external assistance. Mortality data, demographics, clinical characteristics, and Charlson comorbidity index (CCI) were obtained from the electronic medical record after 5 years. Patients were stratified by self-report of hypoglycemia at baseline, demographics were compared using the two-sample t test, and risk of death was expressed as odds ratio (95% CI). Associations were controlled for age, sex, diabetes type and duration, CCI, HbA1c, and report of severe hypoglycemia. RESULTS In total, 1,013 patients with type 1 (21.3%) and type 2 (78.7%) diabetes were questioned about hypoglycemia. Among these, 625 (61.7%) reported any hypoglycemia, and 76 (7.5%) reported severe hypoglycemia. After 5 years, patients who reported severe hypoglycemia had 3.4-fold higher mortality (95% CI 1.5–7.4; P = 0.005) compared with those who reported mild/no hypoglycemia. CONCLUSIONS Self-report of severe hypoglycemia is associated with 3.4-fold increased risk of death. Patient-reported outcomes, including patient-reported hypoglycemia, may therefore augment risk stratification and disease management of patients with diabetes.

Cumulative complexity: a functional, patient-centered model of patient complexity can improve research and practice

OBJECTIVE To design a functional, patient-centered model of patient complexity with practical applicability to analytic design and clinical practice. Existing literature on patient complexity has mainly identified its components descriptively and in isolation, lacking clarity as to their combined functions in disrupting care or to how complexity changes over time. STUDY DESIGN AND SETTING The authors developed a cumulative complexity model, which integrates existing literature and emphasizes how clinical and social factors accumulate and interact to complicate patient care. A narrative literature review is used to explicate the model. RESULTS The model emphasizes a core, patient-level mechanism whereby complicating factors impact care and outcomes: the balance between patient workload of demands and patient capacity to address demands. Workload encompasses the demands on the patients time and energy, including demands of treatment, self-care, and life in general. Capacity concerns ability to handle work (e.g., functional morbidity, financial/social resources, literacy). Workload-capacity imbalances comprise the mechanism driving patient complexity. Treatment and illness burdens serve as feedback loops, linking negative outcomes to further imbalances, such that complexity may accumulate over time. CONCLUSION With its components largely supported by existing literature, the model has implications for analytic design, clinical epidemiology, and clinical practice.

The Diabetes Mellitus Medication Choice Decision Aid: A Randomized Trial

BACKGROUND Patient involvement in the choice of antihyperglycemic agents could improve adherence and optimize glycemic control in patients with type 2 diabetes mellitus. METHODS We conducted a pilot, cluster randomized trial of Diabetes Medication Choice, a decision aid that describes 5 antihyperglycemic drugs, their treatment burden (adverse effects, administration, and self-monitoring demands), and impact on hemoglobin A(1c) (HbA(1c)) levels. Twenty-one clinicians were randomized to use the decision aid during the clinical encounter and 19 to dispense usual care and an educational pamphlet. We used surveys and video analysis to assess postvisit decisional outcomes, and medical and pharmacy records to assess 6-month medication adherence and HbA(1c) levels. RESULTS Compared with usual care patients (n = 37), patients receiving the decision aid (n = 48) found the tool more helpful (clustered-adjusted mean difference [AMD] in a 7-point scale, 0.38; 95% confidence interval [CI], 0.04-0.72); had improved knowledge (AMD, 1.10 of 10 questions; 95% CI, 0.11-2.09); and had more involvement in making decisions about diabetes medications (AMD, 21.8 of 100; 95% CI, 13.0-30.5). At 6-month follow-up, both groups had nearly perfect medication use (median, 100% of days covered), with better adherence (AMD, 9% more days covered; 95% CI, 4%-14%) and persistence (AMD, 12 more days covered; 95% CI, 3-21 days) in the usual care group, and no significant impact on HbA(1c) levels (AMD, 0.01; 95% CI, -0.49 to 0.50). CONCLUSION An innovative decision aid effectively involved patients with type 2 diabetes mellitus in decisions about their medications but did not improve adherence or HbA(1c) levels. Trial Registration clinicaltrials.gov Identifier: NCT00388050.

Clinical Trial Evidence Supporting FDA Approval of Novel Therapeutic Agents, 2005-2012

IMPORTANCE Many patients and physicians assume that the safety and effectiveness of newly approved therapeutic agents is well understood; however, the strength of the clinical trial evidence supporting approval decisions by the US Food and Drug Administration (FDA) has not been evaluated. OBJECTIVES To characterize pivotal efficacy trials (clinical trials that serve as the basis of FDA approval) for newly approved novel therapeutic agents. DESIGN AND SETTING Cross-sectional analysis using publicly available FDA documents for all novel therapeutic agents approved between 2005 and 2012. MAIN OUTCOMES AND MEASURES Pivotal efficacy trials were classified according to the following design features: randomization, blinding, comparator, and trial end point. Surrogate outcomes were defined as any end point using a biomarker expected to predict clinical benefit. The number of patients, trial duration, and trial completion rates were also determined. RESULTS Between 2005 and 2012, the FDA approved 188 novel therapeutic agents for 206 indications on the basis of 448 pivotal efficacy trials. The median number of pivotal trials per indication was 2 (interquartile range, 1-2.5), although 74 indications (36.8%) were approved on the basis of a single pivotal trial. Nearly all trials were randomized (89.3% [95% CI, 86.4%-92.2%]), double-blinded (79.5% [95% CI, 75.7%-83.2%]), and used either an active or placebo comparator (87.1% [95% CI, 83.9%-90.2%]). The median number of patients enrolled per indication among all pivotal trials was 760 (interquartile range, 270-1550). At least 1 pivotal trial with a duration of 6 months or greater supported the approval of 68 indications (33.8% [95% CI, 27.2%-40.4%]). Pivotal trials using surrogate end points as their primary outcome formed the exclusive basis of approval for 91 indications (45.3% [95% CI, 38.3%-52.2%]), clinical outcomes for 67 (33.3% [95% CI, 26.8%-39.9%]), and clinical scales for 36 (17.9% [95% CI, 12.6%-23.3%]). Trial features differed by therapeutic and indication characteristics, such as therapeutic area, expected length of treatment, orphan status, and accelerated approval. CONCLUSIONS AND RELEVANCE The quality of clinical trial evidence used by the FDA as the basis for recent approvals of novel therapeutic agents varied widely across indications. This variation has important implications for patients and physicians as they make decisions about the use of newly approved therapeutic agents.

The Chest Pain Choice Decision Aid A Randomized Trial

Background— Cardiac stress testing in patients at low risk for acute coronary syndrome is associated with increased false-positive test results, unnecessary downstream procedures, and increased cost. We judged it unlikely that patient preferences were driving the decision to obtain stress testing. Methods and Results— The Chest Pain Choice trial was a prospective randomized evaluation involving 204 patients who were randomized to a decision aid or usual care and were followed for 30 days. The decision aid included a 100-person pictograph depicting the pretest probability of acute coronary syndrome and available management options (observation unit admission and stress testing or 24–72 hours outpatient follow-up). The primary outcome was patient knowledge measured by an immediate postvisit survey. Additional outcomes included patient engagement in decision making and the proportion of patients who decided to undergo observation unit admission and cardiac stress testing. Compared with usual care patients (n=103), decision aid patients (n=101) had significantly greater knowledge (3.6 versus 3.0 questions correct; mean difference, 0.67; 95% CI, 0.34–1.0), were more engaged in decision making as indicated by higher OPTION (observing patient involvement) scores (26.6 versus 7.0; mean difference, 19.6; 95% CI, 1.6–21.6), and decided less frequently to be admitted to the observation unit for stress testing (58% versus 77%; absolute difference, 19%; 95% CI, 6%–31%). There were no major adverse cardiac events after discharge in either group. Conclusions— Use of a decision aid in patients with chest pain increased knowledge and engagement in decision making and decreased the rate of observation unit admission for stress testing. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01077037.

Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study.

Objective To determine the real world risk of gastrointestinal bleeding associated with the use of the novel oral anticoagulants dabigatran and rivaroxaban compared with warfarin. Design Retrospective, propensity matched cohort study. Setting: Optum Labs Data Warehouse, a large database including administrative claims data on privately insured and Medicare Advantage enrollees. Participants New users of dabigatran, rivaroxaban, and warfarin from 1 November 2010 to 30 September 2013. Main outcome measures Incidence rates (events/100 patient years) and propensity score matched Cox proportional hazards models were used to estimate rates of total gastrointestinal bleeds, upper gastrointestinal bleeds, and lower gastrointestinal bleeds for the novel oral anticoagulants compared with warfarin in patients with and without atrial fibrillation. Heterogeneity of treatment effect related to age was examined using a marginal effects model. Results The incidence of gastrointestinal bleeding associated with dabigatran was 2.29 (95% confidence interval 1.88 to 2.79) per 100 patient years and that associated with warfarin was 2.87 (2.41 to 3.41) per 100 patient years in patients with atrial fibrillation. In non-atrial fibrillation patients, the incidence of gastrointestinal bleeding was 4.10 (2.47 to 6.80) per 100 patient years with dabigatran and 3.71 (2.16 to 6.40) per 100 patient years with warfarin. With rivaroxaban, 2.84 (2.30 to 3.52) gastrointestinal bleeding events per 100 patient years occurred in atrial fibrillation patients (warfarin 3.06 (2.49 to 3.77)/100 patient years) and 1.66 (1.23 to 2.24) per 100 patient years in non-atrial fibrillation patients (warfarin 1.57 (1.25 to 1.99)/100 patient years). In propensity score matched models, the risk of gastrointestinal bleeding with novel oral anticoagulants was similar to that with warfarin in atrial fibrillation patients (dabigatran v warfarin, hazard ratio 0.79 (0.61 to 1.03); rivaroxaban v warfarin, 0.93 (0.69 to 1.25)) and in non-AF patients (dabigatran v warfarin, hazard ratio 1.14 (0.54 to 2.39); rivaroxaban v warfarin, 0.89 (0.60 to 1.32)). The risk of gastrointestinal bleeding increased after age 65, such that by age 76 the risk exceeded that with warfarin among atrial fibrillation patients taking dabigatran (hazard ratio 2.49 (1.61 to 3.83)) and patients with and without atrial fibrillation taking rivaroxaban (2.91 (1.65 to 4.81) and 4.58 (2.40 to 8.72), respectively). Conclusions: The risk of gastrointestinal bleeding related to novel oral anticoagulants was similar to that for warfarin. Caution should be used when prescribing novel oral anticoagulants to older people, particularly those over 75 years of age.

Potential Overtreatment of Diabetes Mellitus in Older Adults With Tight Glycemic Control

IMPORTANCE In older adults with multiple serious comorbidities and functional limitations, the harms of intensive glycemic control likely exceed the benefits. OBJECTIVES To examine glycemic control levels among older adults with diabetes mellitus by health status and to estimate the prevalence of potential overtreatment of diabetes. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of the data on 1288 older adults (≥65 years) with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 2001 through 2010 who had a hemoglobin A1c (HbA1c) measurement. All analyses incorporated complex survey design to produce nationally representative estimates. EXPOSURES Health status categories: very complex/poor, based on difficulty with 2 or more activities of daily living or dialysis dependence; complex/intermediate, based on difficulty with 2 or more instrumental activities of daily living or presence of 3 or more chronic conditions; and relatively healthy if none of these were present. MAIN OUTCOMES AND MEASURES Tight glycemic control (HbA1c level, <7%) and use of diabetes medications likely to result in hypoglycemia (insulin or sulfonylureas). RESULTS Of 1288 older adults with diabetes, 50.7% (95% CI, 46.6%-54.8%), representing 3.1 million (95% CI, 2.7-3.5), were relatively healthy, 28.1% (95% CI, 24.8%-31.5%), representing 1.7 million (95% CI, 1.4-2.0), had complex/intermediate health, and 21.2% (95% CI, 18.3%-24.4%), representing 1.3 million (95% CI, 1.1-1.5), had very complex/poor health. Overall, 61.5% (95% CI, 57.5%-65.3%), representing 3.8 million (95% CI, 3.4-4.2), had an HbA1c level of less than 7%; this proportion did not differ across health status categories (62.8% [95% CI, 56.9%-68.3%]) were relatively healthy, 63.0% (95% CI, 57.0%-68.6%) had complex/intermediate health, and 56.4% (95% CI, 49.7%-62.9%) had very complex/poor health (P = .26). Of the older adults with an HbA1c level of less than 7%, 54.9% (95% CI, 50.4%-59.3%) were treated with either insulin or sulfonylureas; this proportion was similar across health status categories (50.8% [95% CI, 45.1%-56.5%] were relatively healthy, 58.7% [95% CI, 49.4%-67.5%] had complex/intermediate health, and 60.0% [95% CI, 51.4%-68.1%] had very complex/poor health; P = .14). During the 10 study years, there were no significant changes in the proportion of older adults with an HbA1c level of less than 7% (P = .34), the proportion with an HbA1c level of less than 7% who had complex/intermediate or very complex/poor health (P = .27), or the proportion with an HbA1c level of less than 7% who were treated with insulin or sulfonylureas despite having complex/intermediate or very complex/poor health (P = .65). CONCLUSIONS AND RELEVANCE Although the harms of intensive treatment likely exceed the benefits for older patients with complex/intermediate or very complex/poor health status, most of these adults reached tight glycemic targets between 2001 and 2010. Most of them were treated with insulin or sulfonylureas, which may lead to severe hypoglycemia. Our findings suggest that a substantial proportion of older adults with diabetes were potentially overtreated.

A Randomized Controlled Trial of Telemonitoring in Older Adults With Multiple Health Issues to Prevent Hospitalizations and Emergency Department Visits

BACKGROUND Efficiently caring for frail older adults will become an increasingly important part of health care reform;telemonitoring within homes may be an answer to improve outcomes. This study sought to assess differences in hospitalizations and emergency department (ED) visits among older adults using telemonitoring vs usual care. METHODS A randomized controlled trial was performed among adults older than 60 years at high risk for rehospitalization. Participants were randomized to telemonitoring (with daily input) or to patient-driven usual care. Telemonitoring was accomplished by daily biometrics,symptom reporting, and videoconference. The primary outcome was a composite end point of hospitalizations and ED visits in the 12 months following enrollment. Secondary end points included hospitalizations,ED visits, and total hospital days. Intent-to-treat analysis was performed. RESULTS Two hundred five participants were enrolled,with a mean age of 80.3 years. The primary outcome of hospitalizations and ED visits did not differ between the telemonitoring group (63.7%) and the usual care group(57.3%) (P=.35). No differences were observed in secondary end points, including hospitalizations, ED visits,and total hospital days. No significant group differences in hospitalizations and ED visits were found between the pre-enrollment period vs the post-enrollment period. Mortality was higher in the telemonitoring group (14.7%)than in the usual care group (3.9%) (P=.008). CONCLUSIONS Among older patients, telemonitoring did not result in fewer hospitalizations or ED visits. Secondary outcomes demonstrated no significant differences between the telemonitoring group and the usual care group.The cause of greater mortality in the telemonitoring group is unknown.