BRCA testing and outcomes in women with breast cancer.

MAIN PURPOSE: Germline BRCA mutations (BRCAm) strongly influence the risk of developing breast cancer. This study aimed to understand the role of BRCAm testing in affected individuals and to assess its impact on the outcome of BRCAm carriers compared to non-carriers (BRCAwt) with breast cancer. RESEARCH QUESTION: The research question is "Does standard of care testing for BRCAm improve survival outcomes of breast cancer patients?" METHODS: In a single institution observational cohort study, demographic and clinical characteristics were compared between breast cancer patients with and without BRCAm. Frequency of BRCA testing was assessed. Survival outcomes were assessed by initial treatment setting stratified by BRCA status. RESULTS: Of 5712 identified women with breast cancer, 14.6% (n = 835) were tested for a BRCA mutation and had a documented result. The total number and proportion of women tested for a BRCAm increased between 2000 and 2014, resulting in an increased number of BRCAm carriers identified. However, the proportion of women who underwent testing and had a BRCAm decreased during the study period from 27.5% in 2000-2004 to 13.3% in 2010-2014. Disease-free survival was similar in the adjuvant and neoadjuvant treatment settings between BRCAm and BRCAwt patients. Progression-free survival on first line treatment and overall survival for patients with metastatic disease was also similar between BRCAm and BRCAwt patients. CONCLUSIONS: The proportion of women tested and the number of BRCAm identified increased during the study period despite a decreasing proportion of positive results among women tested.

Assessing pharmacy student confidence to answer patient questions regarding herbal medicines and natural product drugs.

BACKGROUND AND PURPOSE: To assess the change in confidence answering questions about herbal medicines and natural product drugs (HMNPD) in third year professional pharmacy students in an HMNPD course. EDUCATIONAL ACTIVITY AND SETTING: A questionnaire was developed to query confidence in responding to patient questions, recommending specific products, and ability to retrieve resources regarding HMNPD. It was administered the first and last week of the semester; responses were evaluated using a Chi-squared test. FINDINGS: At baseline, 46 students (84%) were "very hesitant", "hesitant", or "neither hesitant nor confident" in responding to HMNPD questions; after the course, most students were "confident" or "very confident" (n=30, 54%) (p < .001). Confidence in finding reliable resources increased from the first week (29 students [40%] were "confident" or "very confident") to the last week (51 students [91%] were "confident" or "very confident" [p < .001]). At baseline, five students (9%) were "confident" or "very confident" in ability to recommend a specific product; after the course, 26 students (46%) were "confident" or "very confident" (p < .001). Nine students (16%) felt "very confident" or "confident" in HMNPD safety/effectiveness at baseline; the same proportion felt this way at conclusion (p = .93). Four students (7%) were confident in HMNPD efficacy at baseline and nine (16%) felt the same way at the end (p = .12). DISCUSSION: Significant increases in student confidence answering patient questions, responding to disease-specific queries, and using appropriate resources were found. There was no difference in confidence in HMNPD safety/efficacy. SUMMARY: This study supported continued HMNPD education in the pharmacy program.

Impact of statin guidelines on statin utilization and costs in an employer-based primary care clinic.

OBJECTIVES: The purpose of this study was to describe statin utilization and costs in an employer-based patient cohort by comparing actual practice and assumed adoption of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) or 2016 US Preventive Services Task Force (USPSTF) statin recommendations versus the guidelines described in 2001 (and supplemented in 2004) in the Third Report of the National Cholesterol Education Program's Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (ATPIII). STUDY DESIGN: Descriptive cohort analysis included patients treated in an employer-based primary care clinic between January 2012 and April 2014. METHODS: ATPIII, ACC/AHA, and USPSTF recommendations were retrospectively applied at the patient level based on lipid levels and statin prescribing data collected from a health risk assessment and electronic health record. Actual statin prescribing was compared with prescribing predicted by guideline recommendations. Costs for each strategy were estimated using employer pharmacy claims data. RESULTS: The study included 555 patients, of whom 112 (20.2%) were treated with a statin at baseline. ATPIII and ACC/AHA recommended statin use in 284 (51.2%) and 279 (50.3%) patients, respectively. Within the subgroup of 479 primary prevention patients, ACC/AHA recommended statin use in 203 (42.4%) versus USPSTF, which recommended statin use in 91 (19.0%). The 90-day cost per patient was similar to baseline with implementation of ATPIII or ACC/AHA recommendations, excluding use of brand name-only high-intensity statins, and costs could be reduced slightly with implementation of USPSTF guidelines. CONCLUSIONS: Despite differences in ATPIII, ACC/AHA, and USPSTF guidelines, application of any of these statin recommendations would result in optimized statin utilization and fairly neutral effects on cost in this real-world employer-based population.

Glycemic Control and Weight Outcomes for Exenatide Once Weekly Versus Liraglutide in Patients with Type 2 Diabetes: A 1-Year Retrospective Cohort Analysis.

PURPOSE: Data comparing real-world effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once weekly (QW) and liraglutide in the treatment of type 2 diabetes (T2D) are limited. Furthermore, there is limited information on exenatide QW or liraglutide response by glycemic control and insulin use status. This study identifies 1-year glycosylated hemoglobin (HbA1c) and weight outcomes with exenatide QW and liraglutide in the real-world setting overall and in insulin-naive patients with uncontrolled T2D. METHODS: This retrospective cohort study using national electronic medical record data compared 1-year HbA1c and weight outcomes in patients with T2D prescribed exenatide QW or liraglutide. Included patients were adults (≥18 years old) with T2D who were GLP-1RA naive when newly prescribed exenatide QW or liraglutide between January 1, 2012, and March 31, 2013 (index date). Outcomes were reported descriptively overall and in subsets of insulin-naive patients with baseline HbA1c ≥7.0% or ≥9.0%. Multivariable linear regression analyses were performed to estimate adjusted change in HbA1c and weight. FINDINGS: The study included 808 exenatide QW and 4333 liraglutide patients. Mean (SD) age was 57 (11) years in both groups. Mean baseline HbA1c was 8.3% (1.5%) in exenatide QW patients and 8.4% (1.6%) in liraglutide patients (P = 0.66); 16 (2%) of the exenatide QW and 1099 (25.4%) of the liraglutide patients were newly prescribed insulin on the index date (P < 0.001). Adjusted mean HbA1c change at 1 year was -0.37% (95% CI, -0.53% to -0.21%) for exenatide QW and -0.37% (95% CI, -0.55% to -0.18%) for liraglutide. Adjusted HbA1c reduction was more pronounced in insulin-naive patients with baseline HbA1c ≥7.0% (-0.71% and -0.80% for the exenatide QW and liraglutide patients, respectively, P > 0.05) and ≥9.0% (-1.73% and -1.57% for exenatide QW and liraglutide patients, respectively, P > 0.05). Mean (adjusted) weight loss was -2.22 kg (95% CI, -3.06 to -1.37 kg) with exenatide QW and -2.21 kg (95% CI, -3.18 to -1.23 kg) with liraglutide. IMPLICATIONS: Exenatide QW and liraglutide lead to similar HbA1c and weight reductions at 1 year in the real-world setting. Greater HbA1c reductions occurred in insulin-naive patients with baseline HbA1c ≥7.0%. Both agents are appropriate options for patients needing antidiabetes therapy to lower HbA1c while promoting weight loss.

BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer - an observational cohort study.

BACKGROUND: Breast cancer associated (BRCA) genes are critical for DNA repair. Mutations in BRCA1 and BRCA2 (BRCAm) result in loss of these repair mechanisms and potential carcinogenesis. Germline BRCAm are common in ovarian carcinomas, particularly in platinum-sensitive disease. The increased prevalence of BRCAm in platinum-sensitive disease is likely due to enhanced responsiveness to platinum chemotherapy from homologous recombination repair deficiency. The purpose of this study was to explore BRCA testing, treatment patterns and survival in platinum-sensitive recurrent (PSR) ovarian cancer. METHODS: This was an observational cohort analysis of PSR ovarian cancer treated at the Huntsman Cancer Institute from 1995 to 2012. Germline BRCA status was ascertained through chart review and categorized as BRCAm (BRCA1/2 positive), BRCAwt (BRCA wild type or variant of uncertain significance), and untested. Treatment patterns and survival were assessed from recurrence until death or last follow-up. The Kaplan-Meier method was used to evaluate survival from recurrence by BRCA status. Logistic regression and COX proportional hazard model was used to estimate predictors of BRCA testing and survival, respectively. RESULTS: Of the 168 PSR patients, 15 (9 %) were BRCAm, 25 (15 %) were BRCAwt, and 128 (76 %) were untested. Median age at PSR was 56 years for BRCAm and BRCAwt (p = 0.90) and 63 years for those untested (p = 0.033 vs BRCAm). Overall survival was similar between BRCAm and BRCAwt (median 50.4 vs 67.5 months, p = 0.86) and was 24.9 months in untested patients. Significant predictors for the likelihood of BRCA testing were age (OR = 0.93, 95 % CI 0.89, 0.97, p = 0.002), family history of breast or ovarian cancer (OR = 8.33, 95 % CI: 3.08, 22.59, p < 0.001), and cancer diagnosis year (OR = 10.02, 95 % CI: 3.22, 31.21, p < 0.001). BRCA-tested patients had a lower risk of death versus untested (HR 0.35, 95 % CI 0.17, 0.68, p = 0.001). CONCLUSIONS: BRCAwt patients had similar outcomes to BRCAm patients, potentially owing to similar age at diagnosis, representing a BRCA testing channeling bias. Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested. BRCA tested patients had a lower risk of death.

Once-weekly exenatide as a treatment for Type 2 diabetes.

Type 2 diabetes mellitus is a progressive disease that requires pharmacologic treatment to prevent microvascular and macrovascular complications. As the disease progresses, most patients require combination therapy to achieve glucose control targets. Exenatide once weekly (EQW) is a glucagon-like peptide-1 receptor agonist approved in the United States in 2012 for use as a second-line agent to treat Type 2 diabetes mellitus. EQW has shown reductions in HbA1c and weight without causing an increased risk of hypoglycemia. This review will summarize the current clinical trial, observational study, and pharmacoeconomic analyses evaluating EQW and its impact on HbA1c and weight.

A review of the clinical utility of duloxetine in the treatment of diabetic peripheral neuropathic pain.

Diabetes mellitus is a world-wide epidemic with many long-term complications, with neuropathy being the most common. In particular, diabetic peripheral neuropathic pain (DPNP), can be one of the most distressing complications associated with diabetes, leading to decreases in physical and mental quality of life. Despite the availability of many efficient medications, DPNP remains a challenge to treat, and the optimal sequencing of pharmacotherapy remains unknown. Currently, there are only three medications approved by the US Food and Drug Administration specifically for the management of DPNP. Duloxetine (DUL), a selective serotonin-norepinephrine reuptake inhibitor, is one of these. With the goal of optimizing pharmacotherapy use in DPNP population, a review of current literature was conducted, and the clinical utility of DUL described. Along with early clinical trials, recently published observational studies and pharmacoeconomic models may be useful in guiding decision making by clinicians and managed care organizations. In real-world practice settings, DUL is associated with decreased or similar opioid utilization, increased medication adherence, and similar health care costs compared with current standard of care. DUL has consistently been found to be a cost-effective option over short time-horizons. Currently, the long-term cost-effectiveness of DUL is unknown. Evidence derived from randomized clinical trials, real-world observations, and economic models support the use of DUL as a first-line treatment option from the perspective of the patient, clinician, and managed care payer.