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.

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.

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.

Binge eating and weight loss outcomes in overweight and obese individuals with type 2 diabetes: results from the Look AHEAD trial.

CONTEXT: Binge eating (BE) is common in overweight and obese individuals with type 2 diabetes mellitus, but little is known about how BE affects weight loss in this population. OBJECTIVE: To determine whether BE was related to 1-year weight losses in overweight and obese individuals with type 2 diabetes participating in an ongoing clinical trial. DESIGN, SETTING, AND PARTICIPANTS: The Look AHEAD (Action for Health in Diabetes) trial is a randomized controlled trial examining the long-term effect of intentional weight loss on cardiovascular disease in overweight and obese adults with type 2 diabetes. A total of 5145 overweight and obese individuals aged 45 to 76 years with type 2 diabetes participated in this study. INTERVENTIONS: Participants were randomly assigned to an intensive lifestyle intervention or to enhanced usual care (a diabetes support and education control condition). MAIN OUTCOME MEASURES: At baseline and 1 year, participants had their weight measured and completed a fitness test and self-report measures of BE and dietary intake. Four groups were created based on BE status at baseline and 1 year (yes/yes, no/no, yes/no, and no/yes). Analyses controlled for baseline differences between binge eaters and non-binge eaters. RESULTS: Most individuals (85.4%) did not report BE at baseline or 1 year (no/no), 7.5% reported BE only at baseline (yes/no), 3.7% reported BE at both times (yes/yes), and 3.4% reported BE only at 1 year (no/yes), with no differences between intensive lifestyle intervention and diabetes support and education conditions (P = .14). Across intensive lifestyle intervention and diabetes support and education, greater weight losses were observed in participants who stopped BE at 1 year (mean [SE] weight loss, 5.3 [0.4] kg) and those who reported no BE at either time (mean [SE] weight loss, 4.8 [0.1] kg) than in those who continued BE (mean [SE] weight loss, 3.1 [0.6] kg) and those who began BE at 1 year (mean [SE] weight loss, 3.0 [0.6] kg) (P < .001). Post hoc analyses suggested that these differences were due to changes in caloric intake. CONCLUSION: Overweight and obese individuals with type 2 diabetes who stop BE appear to be just as successful at weight loss as non-binge eaters after 1 year of treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00017953.

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.

Inflammatory markers and physical function among older adults with knee osteoarthritis.

OBJECTIVE: To investigate whether serum concentrations of various inflammatory markers are associated with physical function and disease severity among older obese adults with knee osteoarthritis (OA). METHODS: Data are from baseline assessments in 274 patients with knee OA participating in an exercise and nutrition intervention study. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness. The presence of disability was assessed, walking speed was calculated on the basis of the 6-minute walk test, and knee radiographs determined the radiographic severity of OA. Serum concentration of interleukin 6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and the soluble receptors IL-6sR, IL-2sR, TNF-sR1 and TNF-sR2 were measured by ELISA. RESULTS: In multivariate regression analyses adjusted for age, sex, race, body mass index, comorbid conditions, and use of nonsteroid antiinflammatory drugs, higher serum levels of TNF-sR1 and TNF-sR2 were significantly associated with lower scores on the WOMAC physical function, with more symptoms of pain and stiffness, and with more reported physical disability. In addition, higher serum levels of TNF-sR1 and TNF-sR2 were significantly associated with slower walking speed, and tended to be associated with worse radiographic scores. Higher serum levels of IL-6 tended to be associated with slower walking speed, but no significant associations were observed for CRP, IL-6sR, or IL-2sR. CONCLUSION: Especially high levels of the soluble receptors of TNF-alpha were found to be associated with lower physical function, increased OA symptoms, and worse knee radiographic scores in older obese adults with knee OA.

Genome-wide scan for prostate cancer susceptibility genes using families from the University of Michigan prostate cancer genetics project finds evidence for linkage on chromosome 17 near BRCA1.

BACKGROUND: Previous linkage studies have suggested prostate cancer susceptibility genes located on chromosomes 1, 20, and X. Several putative prostate cancer candidate genes have also been identified including RNASEL, MSR1, and ELAC2. Presently, these linkage regions and candidate genes appear to explain only a small proportion of hereditary prostate cancer cases suggesting the need for additional whole genome analyses. METHODS: A genome-wide mode-of-inheritance-free linkage scan, using 405 genetic markers, was conducted on 175 pedigrees, the majority containing three or more affected individuals diagnosed with prostate cancer. Stratified linkage analyses were performed based on previously established criteria. RESULTS: Results based on the entire set of 175 pedigrees showed strong suggestive evidence for linkage on chromosome 17q (LOD = 2.36), with strongest evidence coming from the subset of pedigrees with four or more affected individuals (LOD = 3.27). Race specific analyses revealed strong suggestive evidence for linkage in our African-American pedigrees on chromosome 22q (LOD = 2.35). CONCLUSIONS: Genome-wide analysis of a large set of prostate cancer families indicates new areas of the genome that may harbor prostate cancer susceptibility genes. Specifically, our linkage results suggest that there is a prostate cancer susceptibility gene on chromosome 17 that is independent of ELAC2. Further research including combined analyses of independent genome-wide scan data may clarify the most important regions for future investigation.

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.