Treatment patterns and clinical outcomes of palbociclib-based therapy received in US community oncology practices.

Background: Limited studies have evaluated palbociclib-based therapy use in patients with advanced/metastatic breast cancer in the real world. This retrospective study used medical records from US community oncology practices to address the gap. Materials & methods: Eligible patients receiving palbociclib-based therapy per label indication from 3 February 2015 to 31 December 2017 were included. Descriptive analyses were conducted for patient characteristics, treatment patterns and clinical outcomes. Results: The study included 233 patients who received palbociclib + aromatase inhibitor (P+AI) and 48 who received palbociclib + fulvestrant (P+F). Real-world progression-free rate for P+AI was 69.8% (46.8%) at 12 (24) months (P+F: 43.5% [39.9%]) months. Real-world survival rate was 89.8% (71.4%) at 12 (24) months (P+F: 76.3% [65.0%]). Conclusion: The study findings are consistent with previous studies of palbociclib-based therapy.

A prospective study of elderly initiating mirabegron versus antimuscarinics: Patient reported outcomes from the Overactive Bladder Satisfaction Scales and other instruments.

AIMS: To understand differences in patient reported outcomes (PRO) between patients initiating mirabegron or an antimuscarinic using a validated PRO instrument, OAB-Satisfaction (OAB-S). METHODS: This prospective observational study used real-time prescription claims from Humana to identify Medicare patients initiating mirabegron or an antimuscarinic to participate in a series of three phone surveys over ninety days. RESULTS: A total of 1897 mirabegron and 2444 randomly selected antimuscarinic initiators were identified; 174 mirabegron and 193 antimuscarinic initiators completed all three surveys. Among responders, mirabegron initiators were slightly older (76 vs 75 years, P = 0.032), included more males (32% vs 23%, P = 0.044), more likely to have prior OAB treatment (21% vs 13%, P = 0.048), and had greater medication burden (number of unique medications: 10.0 vs 8.7, P = 0.014). There were no between-group differences at any time or on any OAB-S scale. There were significant within-group differences at follow-up compared to baseline for OAB-S scales: "impact on daily living," with improvement over the 90-day survey period for both mirabegron (P = 0.008) and antimuscarinic (P < 0.001); "interruption of day-to-day life," with improvement for both mirabegron (P < 0.001) and antimuscarinic (P < 0.001); and improvement in "OAB control" for mirabegron (P < 0.001) and antimuscarinic (P < 0.001). CONCLUSIONS: Mirabegron initiators tended to be older, had a greater number of unique medications and previously tried prescriptions to treat OAB; nonetheless, mirabegron, and antimuscarinic initiators reported similar trends in improvement in PROs over the first 90 days of treatment. Significant improvement in daily impact of OAB was observed after treatment initiation; however, no significant differences between groups were observed.

Factors influencing enrollment of African Americans in the Look AHEAD trial.

BACKGROUND: Many factors have been identified that influence the recruitment of African Americans into clinical trials; however, the influence of eligibility criteria may not be widely appreciated. We used the experience from the Look AHEAD (Action for Health in Diabetes) trial screening process to examine the differential impact eligibility criteria had on the enrollment of African Americans compared to other volunteers. METHODS: Look AHEAD is a large randomized clinical trial to examine whether assignment to an intensive lifestyle intervention designed to produce and maintain weight loss reduces the long-term risk of major cardiovascular events in adults with type 2 diabetes. Differences in the screening, eligibility, and enrollment rates between African Americans and members of other racial/ethnic groups were examined to identify possible reasons. RESULTS: Look AHEAD screened 28,735 individuals for enrollment, including 6226 (21.7%) who were self-identified African Americans. Of these volunteers, 12.9% of the African Americans compared to 19.3% of all other screenees ultimately enrolled (p < 0.001). African Americans no more often than others were lost to follow-up or refused to attend clinic visits to establish eligibility. Furthermore, the enrollment rates of individuals with histories of cardiovascular disease and diabetes therapy did not markedly differ between the ethnic groups. Higher prevalence of adverse levels of blood pressure, heart rate, HbA1c, and serum creatinine among African American screenees accounted for the greater proportions excluded (all p < 0.001). CONCLUSIONS: Compared to non-African Americans, African American were more often ineligible for the Look AHEAD trial due to comorbid conditions. Monitoring trial eligibility criteria for differential impact, and modifying them when appropriate, may ensure greater enrollment yields.

Adiponectin and arterial stiffness in youth with type 1 diabetes: the SEARCH for diabetes in youth study.

Persons with type 1 diabetes are at increased risk of developing vascular disease. Adiponectin concentrations may play an intermediate role in this process. We sought to determine whether adiponectin is correlated with vascular stiffness in adolescents with type 1 diabetes. Plasma adiponectin, pulse wave velocity (PWV), augmentation index (AIx-75), and brachial distensibility (BrachD) were collected in 225 adolescents. Outcomes were evaluated by sex, and regression models were used to determine whether adiponectin was an independent determinant of arterial stiffness. Males had lower adiponectin levels and stiffer vessels (lower BrachD, p < 0.01) than females. Unadjusted correlations revealed that adiponectin was correlated with BrachD (p < 0.01) but not PWV and AIx-75. After adjustment, adiponectin was not a significant predictor of BrachD. The most consistent predictors of increased stiffness were age, male sex, blood pressure, obesity, and total cholesterol (p < 0.05). Adiponectin's contributions to arterial stiffness appear to be masked by other cardiovascular risk factors in persons with type 1 diabetes.

Prevalence of increased arterial stiffness in children with type 1 diabetes mellitus differs by measurement site and sex: the SEARCH for Diabetes in Youth Study.

OBJECTIVE: To discuss vascular stiffness commonly encountered in children with type 1 diabetes mellitus (T1DM). STUDY DESIGN: We examined 535 subjects with T1DM (14.6 years; 53% male, 88% non-Hispanic white) and 241 healthy control subjects (17.8 years; 42% male, 39% non-Hispanic white). Abnormalities in brachial distensibility (BrachD), pulse wave velocity, and augmentation index corrected to a HR of 75 (AIx-75) were examined. RESULTS: Subjects with T1DM had higher body mass index, LDL-cholesterol, fasting glucose, and blood pressure than control subjects. Diabetic subjects had lower BrachD and higher AIx-75 indicating increased stiffness. Age-adjusted pulse wave velocity-trunk (aorto-femoral) was higher in cases (all P

Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth study.

OBJECTIVE: Obesity's association with type 2 diabetes (T2DM) is well established, but is less clear with type 1 diabetes (T1DM). We calculated the prevalence of overweight and obesity among diabetic youth in the USA from a six-center, population-based study of racially and ethnically diverse youth with diabetes, and we compared these rates with estimates among nondiabetic youth. DESIGN/SETTING: Diabetic participants were examined in 2001-2004 for the SEARCH for Diabetes in Youth study (SEARCH) and nondiabetic participants were examined during the same years of the National Health and Nutrition Examination Survey (NHANES). PARTICIPANTS: 3953 diabetic youth and 7666 nondiabetic youth aged 3-19 yr. MAIN OUTCOME MEASURES: Overweight was defined as body mass index (BMI) from the 85th to <95th percentile for age and sex and obesity defined as > or = 95th percentile. Diabetes type was categorized as T1DM or T2DM based on physician diagnosis. RESULTS: Among youth with T2DM, the prevalence of overweight was 10.4% and obesity was 79.4%. Among youth with T1DM, 22.1% were overweight. The prevalence of overweight among youth with T1DM was higher than among those without diabetes overall (22.1% vs. 16.1%) (P <.05). The obesity rate for T1DM was 12.6% overall (range Non-Hispanic White 10.7%-African-American 20.1%). CONCLUSIONS: As expected, most of the youth with T2DM were obese. Youth with T1DM had a higher prevalence of overweight, but not of obesity, than nondiabetic youth. Future studies of obesity among youth with diabetes of all types will further our understanding of the impact of obesity on diabetes both as a risk factor and a comorbidity.

The effect of a quality improvement collaborative to improve antimicrobial prophylaxis in surgical patients: a randomized trial.

BACKGROUND: Quality improvement collaboratives are used to improve health care quality, but their efficacy remains controversial. OBJECTIVE: To assess the effects of a quality improvement collaborative on preoperative antimicrobial prophylaxis. DESIGN: Longitudinal cluster randomized trial, with the quality improvement collaborative as the intervention. SETTING: United States. PARTICIPANTS: 44 acute care hospitals, each of which randomly sampled approximately 100 selected surgical cases (cardiac, hip or knee replacement, and hysterectomy) at both the baseline and remeasurement phases. INTERVENTION: All hospitals received a comparative feedback report. Hospitals randomly assigned to the intervention group (n = 22) participated in a quality improvement collaborative comprising 2 in-person meetings led by experts, monthly teleconferences, and receipt of supplemental materials over 9 months. MEASUREMENTS: Change in the proportion of patients receiving at least 1 antibiotic dose within 60 minutes of surgery (primary outcome) and change in the proportions of patients given any antibiotics, given antibiotics for 24 hours or less, given an appropriate drug, and given a single preoperative dose and receipt of any of the 5 measures (secondary outcome). RESULTS: The groups did not differ in the change in proportion of patients who received a properly timed antimicrobial prophylaxis dose (-3.8 percentage points [95% CI, -13.9 to 6.2 percentage points]) after adjustment for region, hospital size, and surgery type. Similarly, the groups did not differ in individual measures of antibiotic duration; use of appropriate drug; receipt of a single preoperative dose; or an all-or-none measure combining timing, duration, and selection. LIMITATIONS: Hospitals volunteered for the effort, thereby resulting in selection for participants who were motivated to change. Implementation of the surgical infection prevention measure reporting requirements by the Centers for Medicare & Medicaid Services and The Joint Commission may have motivated improvement in prophylaxis performance. CONCLUSION: At a time of heightened national attention toward measures of antimicrobial prophylaxis performance, the trial did not demonstrate a benefit of participation in a quality improvement collaborative over performance feedback for improvement of these measures.

Control of blood pressure in North Carolina primary care: baseline data from the GLAD Heart Trial.

BACKGROUND: In general, adherence to blood pressure guidelines is low. We assessed whether hypertension recognition and control in North Carolina was consistent with the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) in primary care practices participating in a quality improvement study regarding the implementation of the ATP3 cholesterol management guideline in primary care in North Carolina (GLAD Heart). METHODS: Demographic and clinical data were abstracted from 5,073 charts (patients aged 21-84 years, seen from June 1, 2001 to May 31, 2003) at 60 practices. Sites were non-university based primary care practices from 22 North Carolina counties. A dyslipidemia screening was defined as a lipid profile performed when not on lipid-lowering therapy. Among patients receiving a lipid profile, the proportion with diagnosed, undiagnosed, and controlled hypertension, was calculated according to JNC 7 guidelines. Practice level hypertension control was examined using the median and interquartile range across practices. RESULTS: Among 1,763 patients screened for dyslipidemia, 49.4% had diagnosed hypertension. Only 67 individuals (3.8%) had undiagnosed hypertension. Although 85.8% of hypertensive patients were treated, the median proportions of patients with blood pressure below goal (< 140/90, < 130/80 with diabetes) was 33.3% (21.8%-43.7%), with women more likely to be controlled and individuals treated by a solo provider less likely to be controlled. LIMITATIONS: These data were abstracted from the charts of patients who received a lipid profile; therefore, they are only generalizable to individuals who are screened for hyperlipidemia. CONCLUSIONS: There remains a need to improve hypertension management in North Carolina primary care among patients screened for hyperlipidemia.

Cognitive function, gait speed decline, and comorbidities: the health, aging and body composition study.

BACKGROUND: Emerging evidence indicates an association between cognitive function and physical performance in late life. This study examines the relationship between cognitive function and subsequent gait speed decline among high-functioning older adults. METHODS: Measures of global cognitive function (Modified Mini Mental State Examination [3MS]) and executive control function (ECF) (a clock drawing task [CLOX 1] and the 15-item Executive Interview [EXIT 15]) were obtained in the Health, Aging, and Body Composition Study in 1999-2000. Gait-speed (meters/second) was assessed over 20 meters at usual pace. Using a mixed model, we assessed the relationship between baseline cognitive function and gait-speed change over 3 years. RESULTS: Two thousand, three hundred forty-nine older adults (mean age 75.6 +/- 2.9 years) completed the assessments. After adjustment for baseline gait speed, a 1-standard-deviation (SD) lower performance on each cognitive test was associated with greater gait-speed decline over 3 years: 0.016 m/s for the 3MS (SD = 8.1), 0.009 m/s for CLOX 1 (SD = 2.4), and 0.012 m/s for EXIT 15 (SD = 4.1) (p <.0005 for all). After adjustment for comorbidities, the effect size was attenuated for 3MS and CLOX 1, and the association for EXIT 15 was no longer significant. Depression score was most strongly associated with the EXIT 15 effect reduction. CONCLUSION: Global and executive cognitive functions predict declines in gait speed. The association of ECF with gait speed decline is attenuated by comorbid conditions, particularly depression. Elucidation of the mechanisms underlying these associations may point to new pathways for the treatment of physical decline associated with diminished cognitive function.

Older adults in the rural South are not meeting healthful eating guidelines.

OBJECTIVE: To evaluate diet quality of rural older adults using national dietary guidelines and the Healthy Eating Index (HEI). DESIGN: Five to six 24-hour recalls were conducted at monthly intervals over a 6-month period, using the Nutrition Coordinating Center food grouping system to calculate intake. SUBJECTS: Included in this cross-sectional study were 63 females and 59 males aged 65 to 93 years residing in two rural North Carolina counties; one third of each sex group was African American, Native American, or white. Inclusion criteria included age>65 years, education

Impact of 2015 Update to the Beers Criteria on Estimates of Prevalence and Costs Associated with Potentially Inappropriate Use of Antimuscarinics for Overactive Bladder.

BACKGROUND: Research has demonstrated that the use of potentially inappropriate medication (PIM) is highly prevalent among older individuals and may lead to increased healthcare costs, adverse drug reactions, hospitalizations, and mortality. OBJECTIVES: The purpose of this study was to examine the impact of the 2015 updates to the Beers Criteria on estimates of prevalence and cost associated with potentially inappropriate use of antimuscarinic medications indicated for treatment of overactive bladder (OAB). METHODS: A retrospective database analysis was conducted using a historical cohort design and including data collected between 2007 and 2013. Claims data were used to identify Medicare Advantage patients aged ≥65 years newly initiated on antimuscarinic OAB treatment. Patients were classified with potentially inappropriate use of antimuscarinic OAB drugs based on either the 2012 Beers Criteria or the 2015 Beers Criteria. Prevalence of PIM at the time of antimuscarinic initiation was determined. Bivariate comparisons of healthcare costs and medical condition burden were conducted to compare the marginal groups of patients (who qualified based on the 2012 Beers Criteria only or the 2015 Beers Criteria only). Differences in healthcare costs for patients with and without potentially inappropriate use of urinary antimuscarinics based on the 2012 and 2015 Beers Criteria were also examined. RESULTS: Of 66,275 patients, overall prevalence of potentially inappropriate use of OAB antimuscarinics was higher using 2015 Beers Criteria than when using the 2012 Beers Criteria (25.0 vs. 20.6%). Dementia was the most common PIM-qualifying condition under both versions. The 2015 Beers Criteria identified more females, more White people, and a younger population with PIM. Comorbid medical condition burden was lower using the 2015 Beers Criteria. The 2015 Beers Criteria only group had lower median unadjusted healthcare costs ($7104 vs. 8301; p < 0.001). The incremental net cost associated with potentially inappropriate use of antimuscarinic medication was higher under the 2012 Beers Criteria than under the 2015 Beers Criteria. CONCLUSIONS: In this cohort of patients newly initiated on antimuscarinic OAB treatment, substantial overlap of patients identified with PIM based on the 2015 Beers Criteria compared with the 2012 Beers Criteria was observed. In addition, the findings suggest that, when applied to antimuscarinic initiators, the 2015 Beers Criteria result in a greater prevalence of PIM and the identification of patients with less overall medical morbidity than the 2012 Beers Criteria.

"Act on Threes" Paradigm for Treatment Intensification of Type 2 Diabetes in Managed Care: Results of a Randomized Controlled Study with an Educational Intervention Targeting Improved Glycemic Control.

BACKGROUND: Clinical inertia, which has been defined as the recognition of a problem with a patient's management but failing to act, is a concern in type 2 diabetes (T2D) because it places the patient at risk of diabetes-related complications. Despite managed care organizations making significant investment in this area, little is known about the impact of educational programs aimed at aligning patients and their physicians with diabetes guidelines and thus overcoming clinical inertia. OBJECTIVE: To assess the impact of an educational intervention specifically designed to align patients and their physicians with 2012 American Diabetes Association (ADA) guidelines on glycated hemoglobin (A1c) testing frequency and insulin initiation. METHODS: The "Act on Threes" educational intervention was a 12-month, randomized controlled prospective study that included Medicare Advantage patients aged 18-85 years with T2D, who received ≥ 3 oral antidiabetes drugs (OADs) and/or had A1c not at goal and/or had no recent A1c evaluation over 12 months, as identified through the analysis of administrative claims data (May 1, 2011-April 30, 2013) from the Humana database. Identified patients were randomized 3:1 to receive the Act on Threes educational intervention in conjunction with standard care (intervention group) or standard care alone (control group). For the educational intervention, patients and physicians were simultaneously mailed general and targeted information aimed at aligning them to 3 vital aspects of A1c control: timely measurement of A1c every 3 months; timely treatment intensification to meet A1c goals with treatment intensification every 3 months if A1c is not at goal; and insulin initiation when appropriate, including patients receiving ≥ 3 OADs with A1c not at goal. Control patients were only enrolled if the treating physician was not involved in the care of any patients in the intervention group. The primary outcome measures were A1c testing frequency based on the ADA standard for compliance of ≥ 2 tests per year and insulin initiation in the 12-month postintervention period. A1c levels were evaluated for the subgroup of patients with available A1c measurements in the pre- and postintervention periods. Descriptive statistics were used to analyze differences between the intervention and control groups. Multiple logistic regression analysis was used to identify determinants of insulin initiation in the full study cohort. RESULTS: 6,243 patients (mean age 70 years; 43.5% female) were identified: 4,555 were randomized to the intervention group and 1,688 to the control group. The percentage of patients with ≥ 2 A1c tests per year was not significantly different postintervention for patients in the intervention and control groups (47.7% vs. 46.8%, respectively; P = 0.995). Intriguingly, the frequency of A1c testing increased significantly from pre- to postintervention in the intervention and control groups. Change in A1c level from pre- to postintervention was also similar for the 2 groups (P = 0.240). A similar percentage of patients in the intervention and control groups initiated insulin during the postintervention period (6.3% vs. 7.6%, respectively; P = 0.059). CONCLUSIONS: This randomized controlled study demonstrated that, compared with standard care, the Act on Threes educational intervention combined with standard care did not result in any significant differences in the frequency of A1c testing or in the initiation of insulin in patients with T2D. These findings are in contrast to uncontrolled comparative studies showing significant improvements in outcomes postintervention and reinforce the importance of study design in evaluating the effectiveness of educational programs. DISCLOSURES: This study was funded by Sanofi U.S. Reynolds, Davis, Kamble, and Uribe are employees of Comprehensive Health Insights, which was contracted by Sanofi U.S. to conduct, publish, and present this study. Bieszk and Wei are employees of Sanofi U.S. Reynolds and Uribe provided expertise and key clinical insights for the study design and methodology, provided interpretations of the data, contributed to the discussion, and reviewed the manuscript. Bieszk and Wei codeveloped the study design, researched data, contributed to discussion, and reviewed the manuscript. Davis and Kamble collected the data, provided study design, clinical insights, statistical and analytic reflections of the data, drafted the study reports, and reviewed the manuscript. All authors had full access to all the data in the study. Reynolds is the guarantor of this work and, as such, takes responsibility for the integrity of the data and the accuracy of the data analysis. ACKNOWLEDGMENTS: Writing/editorial support in the preparation of this manuscript, which was funded by Sanofi U.S., was provided by Rosalie Gadiot, PhD, of Excerpta Medica, who wrote the initial draft of the manuscript.

Effect of Potentially Inappropriate Use of Antimuscarinic Medications on Healthcare Use and Cost in Individuals with Overactive Bladder.

OBJECTIVES: To examine potentially inappropriate medication (PIM) use in older adults initiating an antimuscarinic medication for the treatment of overactive bladder (OAB). DESIGN: Retrospective database analysis. SETTING: Medical and pharmacy claims data. PARTICIPANTS: Medicare Advantage Prescription Drug Plan members aged 65 and older newly initiated on an antimuscarinic OAB treatment were identified and assigned to PIM and non-PIM comparison groups based on 2012 American Geriatrics Society Beers Criteria and/or the presence of an anticholinergic medication interaction at the time of initiation of treatment (N = 66,275). MEASUREMENTS: Healthcare costs and OAB medication use. RESULTS: Of members initiated on an antimuscarinic OAB medication, 31.1% had a drug-drug or drug-disease or syndrome interaction. Dementia was the most common disease or syndrome interaction (11.3%), followed by constipation (8.6%) and delirium (2.9%). Paroxetine (2.6%), amitriptyline (2.2%), cyclobenzaprine (1.7%), and meclizine (1.6%) were the most common interacting medications. Subjects in the PIM group had greater healthcare costs over 12 months of follow-up ($12,001) than those in the non-PIM group ($9,373) after controlling for baseline characteristics (P < .001). There was no difference between the PIM and the non-PIM groups in odds of discontinuing OAB treatment at 12 months after controlling for baseline characteristics (odds ratio = 0.98, 95% confidence interval = 0.89-1.07, P = .63). CONCLUSION: Potentially inappropriate medication use was highly prevalent and was associated with greater total healthcare costs. Providers should carefully consider medical history and concurrent medication use when initiating antimuscarinic medication for the treatment of OAB. Development of interventions to reduce potentially inappropriate use of antimuscarinics in individuals with OAB is warranted.

COPD exacerbations associated with the modified Medical Research Council scale and COPD assessment test among Humana Medicare members.

BACKGROUND: The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC) or COPD assessment test (CAT) score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs. METHODS: The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart). The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs. RESULTS: Among a total of 1,159 members who returned the survey, a 66% (765) completion rate was observed. Mean (standard deviation) age among survey completers was 72.0 (8.3), 53.7% female and 91.2% white. Odds ratios for having post-index exacerbations were 3.06, 4.55, and 16.28 times for members with 1, 2, and ≥3 pre-index exacerbations, respectively, relative to members with 0 pre-index exacerbations (P<0.001 for all). The odds ratio for high vs low symptoms using CAT was 2.51 (P<0.001). Similarly, exacerbation-related costs were 73% higher with each incremental pre-index exacerbation, and over four fold higher for high-vs low-symptom patients using CAT (each P<0.001). The symptoms using mMRC were not statistically significant in either model (P>0.10). CONCLUSION: The patient-reported symptoms contribute important information related to future COPD exacerbations and exacerbation-related costs beyond that explained by exacerbation history.

The effects of implementation of the Agency for Health Care Policy and Research urinary incontinence guidelines in primary care practices.

OBJECTIVES: To determine whether a multifaceted intervention based on the Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guidelines for Urinary Incontinence would increase primary care physician screening for and management of urinary incontinence (UI). DESIGN: Group randomized trial, conducted from 1996 to 1997. SETTING: Internal medicine and family medicine community practices. PARTICIPANTS: Forty-one primary care practices, including 57 physicians and their staff and 1,145 patients aged 60 and older. INTERVENTION: Twenty of the 41 primary care practices in North Carolina were randomized to a composite intervention that included a 3-hour continuing medical education accredited course, training in management of UI, patient educational materials, and on-site physician and office support. The remaining 21 practices served as "usual care" controls. Telephone surveys of UI status and quality of life were obtained from 1,145 patients before the intervention. At 1 year, patients and physicians were contacted by telephone and mail to determine the effect of the educational intervention. MEASUREMENTS: Patients completed telephone surveys to assess screening for UI, UI status, treatment interventions, and quality of life. Physicians completed surveys related to UI treatment and practice patterns. RESULTS: Baseline and endpoint telephone surveys were completed by 668 of 1,145 (58%) of patients, who were cared for by 45 physicians (10 internists, 35 family medicine). Physician screening rates for UI were 22% for those patients who did not report UI. UI was reported by 39.5% of patients at baseline, of whom 30% reported being asked about UI by their primary care physician during the study. Rates of assessment and management of existing UI were low in both the control and intervention groups. Additional historical questioning indicated that 54.2% reported that they had ever undergone assessment, including history, urinalysis, or testing, or had had management of their UI by any physician. CONCLUSION: Attempts at increasing screening and management of UI by primary care physicians using the AHCPR standardized guidelines using a multifaceted system of educational and logistical support were not successful. These guidelines may not be the best approach to treating UI in the primary care setting.

Age-stratified heritability estimation in the Framingham Heart Study families.

The Framingham Heart Study provides a unique source of longitudinal family data related to CVD risk factors. Age-stratified heritability estimates were obtained over three age groups (31-49 years, 50-60 years, and 61-79 years), reflecting the longitudinal nature of the data, for four quantitative traits. Age-adjusted heritability estimates were obtained at a single common time point for the same four quantitative traits. The importance of these groups is that they consist of the same individuals. The highest age-stratified heritability estimate (h2 = 0.88 (+/- 0.06)) was for height in the model adjusting for gender over all three age groups. SBP gave the lowest heritability estimate (h2 = 0.15 (+/- 0.11)) for the 70 age group in the model adjusting for gender, height, BMI, smoker, and drinker. BMI had slightly higher estimates (h2 = 0.64 (+/- 0.11)) in the 40 age group than previously published. The highest age-adjusted heritability estimate (h2 = 0.90 (+/- 0.06)) was for height in the model adjusting for gender. SBP gave the lowest heritability estimate (h2 = 0.38 (+/- 0.09)) for unadjusted model. These results indicate that some common, complex traits may vary little in their genetic architecture over time and suggest that a common set of genes may be contributing to observed variation for these longitudinally collected phenotypes.

Association of out-of-pocket pharmacy costs with adherence to varenicline.

BACKGROUND: Varenicline, a nicotinic acetylcholine receptor partial agonist, is a pharmacotherapy indicated for smoking cessation treatment. To date, no research has examined the relationship between out-of-pocket (OOP) expense and varenicline adherence among Medicare beneficiaries. OBJECTIVES: To (a) characterize medication utilization patterns of varenicline among Medicare members newly initiated on varenicline and (b) examine the relationship between member OOP expense and varenicline medication adherence. METHODS: In this retrospective cohort study, pharmacy claims data were used to identify Medicare Advantage Prescription Drug Plan (MAPD) members newly initiated on varenicline. Demographic and clinical characteristics, varenicline medication utilization patterns, and pharmacy costs (total and varenicline-specific) were determined for members included in the study. Varenicline adherence was measured by calculating the proportion of days covered (PDC) over a period of 84 days (12 weeks) after initiation. Multiple regression analysis was used to examine the relationship between varenicline OOP cost and varenicline medication utilization, while controlling for sociodemographic characteristics, clinical factors, and nonvarenicline pharmacy costs. RESULTS: A total of 15,452 MAPD members were included in the analysis. Mean (SD) subject age was 62.6 (10.0) years; 21.1% (n = 3,256) were dual eligible; and 33.0% (n = 5,106) received a low-income subsidy. Mean (SD) initial varenicline treatment episode duration was 50.8 (37.8) days, with a mean (SD) varenicline days' supply of 47.8 (32.6) obtained by members during the initial treatment episode. Mean (SD) PDC was 0.51 (0.24), and 14.9% (n = 2,302) of members were classified as adherent to treatment (PDC ≥ 0.80). Greater varenicline OOP expense was significantly associated with lower PDC (regression coefficient = -0.058, P less than 0.001) and significantly associated with lower odds of receiving a refill for varenicline (odds ratio 0.594, 95% CI: 0.540-0.655, P less than 0.001). CONCLUSIONS: Among Medicare beneficiaries newly initiated on varenicline, medication adherence was suboptimal, and greater OOP cost was associated with lower adherence and lower odds of refilling varenicline.

Household members of persons with Alzheimer's disease: health conditions, healthcare resource use, and healthcare costs.

OBJECTIVES: To compare medical condition burden, healthcare resource use, and healthcare costs of household members (HHMs) of individuals diagnosed with Alzheimer's disease (AD) with those of HHMs of matched individuals without AD. DESIGN: Retrospective cohort study based on administrative claims data collected between January 1, 2007, and December 31, 2011. SETTING: Medicare Advantage Prescription Drug (MAPD) plan. PARTICIPANTS: MAPD plan members with a diagnosis of AD (International Classification of Disease Ninth Revision, Clinical Modification, code 331.0) were selected and linked to a HHM to form patient-HHM dyads. AD dyads were matched to non-AD dyads. MEASUREMENTS: Health-related endpoints, including medical condition burden, healthcare resource use, and direct healthcare costs, were measured during 36 months of continuous health plan enrollment. RESULTS: Individuals with AD (n = 1,861) were linked to HHMs (n = 1,861), and these AD dyads were matched to 1,861 non-AD patient-HHM dyads. AD HHMs had greater medical condition burden scores than non-AD HHMs, with mood disorders, anxiety disorders, insomnia, substance abuse or dependence, cardiovascular disease, and rheumatoid arthritis being more prevalent in AD HHMs. Emergency department and outpatient service use were more common in AD HHMs than in non-AD HHMs, and AD HHMs had greater healthcare costs. CONCLUSION: HHMs of individuals diagnosed with AD demonstrated greater medical condition burden, healthcare resource use, and direct healthcare costs than non-AD HHMs. These findings demonstrate the significant clinical and financial impact of AD on HHMs of individuals with AD.

The Look AHEAD Trial: bone loss at 4-year follow-up in type 2 diabetes.

OBJECTIVE: To determine whether an intensive lifestyle intervention (ILI) designed to sustain weight loss and improve physical fitness in overweight or obese persons with type 2 diabetes was associated with bone loss after 4 years of follow-up. RESEARCH DESIGN AND METHODS: This randomized controlled trial of intensive weight loss compared an ILI with a diabetes support and education (DSE) group among 1,309 overweight or obese subjects. Bone mineral density was assessed at baseline and after 1 year and 4 years of intervention. RESULTS: ILI was effective in producing significant weight loss (5.3% vs. 1.8% in ILI and DSE, respectively; P < 0.01) and increased fitness (6.4% vs. -0.8%) at year 4. In men, ILI participants had a greater rate of bone loss during the first year (-1.66% vs. -0.09% per year in ILI and DSE, respectively). Differences between groups were diminished by one-half after 4 years (-0.88% vs. -0.05% per year in ILI and DSE, respectively) but remained significant (P < 0.01). The difference in rate of hip bone loss between groups over 4 years was related to increased weight loss in ILI. Among women, the rate of bone loss did not differ between ILI and DSE after 4 years. CONCLUSIONS: A 4-year weight loss intervention was significantly associated with a modest increase in bone loss at the hip in men but not in women.

Physical activity and physical function in older adults with knee osteoarthritis.

PURPOSE: To assess correlates of physical activity, and to examine the relationship between physical activity and physical functioning, in 160 older (66 ± 6 years old), overweight/obese (mean body mass index = 33.5 ± 3.8 kg/m2), sedentary (less than 30 mins of activity, 3 days a week) individuals with knee osteoarthritis. METHODS: Physical activity was measured with accelerometers and by self-report. Physical function was assessed by 6-min walk distance, knee strength, and the Short Physical Performance Battery. Pain and perceived function were measured by questionnaires. Pearson correlations and general linear models were used to analyze the relationships. RESULTS: The mean number of steps taken per day was 6209 and the average PAEE was 237 ± 124 kcal/day. Participants engaged in 131 ± 39 minutes of light physical activity (LPA) and 10.6 ± 8.9 minutes of moderate-vigorous physical activity (MPA/VPA). Total steps/day, PAEE, and minutes of MPA/VPA were all negatively correlated with age. The 6-min walk distance and lower extremity function were better in those who had higher total steps/day, higher PAEE, higher minutes of MPA/VPA, and a higher PASE score. CONCLUSIONS: This study demonstrates that a population who has higher levels of spontaneous activity have better overall physical function than those who engage in less activity.