Cardiac valvular abnormalities associated with use and cumulative exposure of cabergoline for hyperprolactinemia: the CATCH study.

BACKGROUND: Whether lower dose cabergoline therapy for hyperprolactinemia increases risk of valvular dysfunction remains controversial. We examined valvular abnormalities among asymptomatic adults with hyperprolactinemia treated with dopamine agonists. METHODS: This cross-sectional study was conducted among adults receiving cabergoline or bromocriptine for > 12 months for hyperprolactinemia and had no cardiac-related symptoms. Cardiac valve morphology and function were assessed from transthoracic echocardiograms at the study visit (except for two participants) with evaluation performed blinded to type and duration of dopamine agonist received. RESULTS: Among 174 participants (mean age 49 ± 13 years, 63% women) without known structural heart disease before starting therapy, 62 received only cabergoline, 63 received only bromocriptine, and 49 received both. Median cabergoline use was 2.8 years in cabergoline only users and 3.2 years for those exposed to both cabergoline and bromocriptine; median bromocriptine use was 5.5 years in bromocriptine only users and 1.1 years for those exposed to both cabergoline and bromocriptine. Compared with bromocriptine only users (17.5%), regurgitation of ≥1 valve was more common for cabergoline only (37.1%, P = 0.02) but not for combined exposure (26.5%, P = 0.26). Compared with bromocriptine only exposure (1.6%), regurgitation of ≥2 valves was more common for cabergoline only (11.3%, P = 0.03) and combined exposure (12.2%, P = 0.04). Cabergoline only users had higher age-sex-adjusted odds for ≥1 valve with grade 2+ regurgitation compared to bromocriptine only users (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI]:1.3-7.5, P = 0.008), but the association for combined exposure to cabergoline and bromocriptine was not significant (aOR 1.7, 95%CI:0.7-4.3, P = 0.26). Compared to bromocriptine only, age-sex-adjusted odds of ≥2 valves with grade 2+ regurgitation were higher for both cabergoline only (aOR 8.4, 95% CI:1.0-72.2, P = 0.05) and combined exposure (aOR 8.8, 95% CI:1.0-75.8, P = 0.05). Cumulative cabergoline exposure > 115 mg was associated with a higher age-sex adjusted odds of ≥2 valves with grade 2+ regurgitation (aOR 9.6, 95%CI:1.1-81.3, P = 0.04) compared to bromocriptine only. CONCLUSIONS: Among community-based adults treated for hyperprolactinemia, cabergoline use and greater cumulative cabergoline exposure were associated with a higher prevalence of primarily mild valvular regurgitation compared with bromocriptine. Research is needed to clarify which patients treated with dopamine agonists may benefit from echocardiographic screening and surveillance.

Evidence-Based Workflows for Thyroid and Parathyroid Surgery.

A need exists to reduce care variations by standardizing the practice of thyroid and parathyroid surgery. During the course of a year, a task force developed algorithms representing decision points and workflows based on American Thyroid Association guidelines and three internal studies of surgical practices in the Northern and Southern California Regions of Kaiser Permanente conducted in collaboration with Health Information Technology Transformation & Analytics (HITTA).

The association of race/ethnicity and risk of atypical femur fracture among older women receiving oral bisphosphonate therapy.

PURPOSE: Several epidemiologic studies suggest that compared to white women, Asians have a greater propensity to suffer an atypical femur fracture (AFF) while taking bisphosphonate therapy. This study examines the relative risk of AFF following bisphosphonate initiation for Asian compared to white women. METHODS: Using data from a large integrated northern California healthcare delivery system, we examined diaphyseal femur fracture outcomes among women age≥50years old who initiated oral bisphosphonate therapy during 2002-2007. An AFF was defined by the 2013 American Society of Bone and Mineral Research Task Force criteria. The risk of radiographically-confirmed AFF was examined for Asian compared to white women, adjusting for differences in bisphosphonate exposure and other potential risk factors. RESULTS: Among 48,390 women (65.3% white, 17.1% Asian) who newly initiated bisphosphonate therapy and were followed for a median of 7.7years, 68 women experienced an AFF. The rate of AFF was 18.7 per 100,000 person-years overall and eight-fold higher among Asian compared to white women (64.2 versus 7.6 per 100,000 person-years). Asians were also more likely to have longer bisphosphonate treatment duration compared to whites (median 3.8 versus 2.7years). The age-adjusted relative hazard for AFF was 8.5 (95% confidence interval 4.9-14.9) comparing Asian to white women, and was only modestly reduced to 6.6 (3.7-11.5) after adjusting for bisphosphonate duration and current use. CONCLUSIONS: Our study confirms marked racial disparity in AFF risk that should be further investigated, particularly the mechanisms accounting for this difference. These findings also underscore the need to further examine the association of bisphosphonate duration and AFF in women of Asian race, as well as differential risk across Asian subgroups. In the interim, counseling of Asian women about osteoporosis drug continuation should include consideration of their potentially higher AFF risk.

Trends in mortality following hip fracture in older women.

OBJECTIVES: To examine contemporary trends in mortality following hip fracture among older postmenopausal women in an integrated healthcare delivery system. STUDY DESIGN: Retrospective cohort study of 13,550 women aged ≥65 years with hip fracture during 2000 to 2010. METHODS: Demographic factors, comorbidity index score, fracture history, early rehospitalization, and all-cause mortality within 1 year following hip fracture were examined using health plan databases and records. Temporal trends, risk factors, and the association of race/ethnicity and mortality within 1 year post fracture were examined using multivariable logistic regression. RESULTS: Among 13,550 women with hip fracture, 84.6% were aged ≥75 years: 83.6% were white, 2.8% black, 5.6% Hispanic, 4.5% Asian, and 3.5% of other/unknown race. Following hip fracture, 2.4% died during the index hospitalization, while 12.3% were rehospitalized within 30 days of discharge. Infection, pneumonia, and cardiovascular conditions were the most common nonorthopedic indications for readmission. Mortality rates at 6 months (17%) and 1 year (22.8%) following hip fracture were high and increased with age. Greater comorbidity and early rehospitalization were associated with increased mortality risk, while Asian and Hispanic race/ethnicity were associated with lower mortality risk (vs white). Temporal trends demonstrated a small but significant reduction in mortality risk during 2004 to 2010. CONCLUSIONS: While hip fracture morbidity and mortality remain high, temporal trends suggest recent declines in mortality risk, with risk of death following hip fracture lower for Asian and Hispanic women. Future studies should examine potential benefits of targeted interventions within integrated healthcare settings and factors contributing to observed racial/ethnic differences in post fracture survival.

Treatment of vitamin D deficiency within a large integrated health care delivery system.

BACKGROUND: In the past decade, increasing attention has focused on identification and treatment of vitamin D deficiency although repletion outcomes of pharmacologic vitamin D therapy have not been examined at a population level. OBJECTIVE: To investigate population trends and outcomes of pharmacologic treatment of vitamin D deficiency. METHODS: We conducted a retrospective cohort study using data from an integrated health system with approximately 3.2 million members. Automated laboratory and pharmacy databases were used to identify patients aged 18 years or older with hypovitaminosis D (defined as a 25-hydroxy-vitamin D [25(OH)D] serum level < 20 nanograms [ng] per mL) who newly initiated pharmacologic ergocalciferol (50,000 international units [IU] per week) during 2007-2010 and did not have a prescription for ergocalciferol in the prior 12 months. Patients were required to be continuously enrolled for 12 months before and 6 months after ergocalciferol initiation. Age, gender, race/ethnicity, body mass index, and 25(OH)D levels were obtained from health plan electronic medical records and administrative, laboratory, and pharmacy databases. Outcome and predictors of repletion among the subset who received 12 weekly doses of 50,000 IU ergocalciferol (total dose 600,000 IU) were examined using multivariable logistic regression. RESULTS: There were 72,093 vitamin D-deficient patients who newly initiated pharmacologic ergocalciferol. During the study period, the use of ergocalciferol increased nearly 8-fold from 161 per 100,000 adult members in 2007 to 1,241 per 100,000 adult members in 2010. One-fifth (n = 14,727) had severe vitamin D deficiency (25[OH]D level < 10 ng per mL). Among 23,322 patients receiving 50,000 IU ergocalciferol for 12 weeks in whom subsequent 25(OH)D levels were measured between 90 and 365 days after the index ergocalciferol prescription date, 74.0% achieved 25(OH)D of at least 20 ng per mL, and 35.8% achieved 25(OH)D of at least 30 ng per mL. Increasing age (adjusted odds ratio [OR] 1.02, 95% CI 1.02-1.02) and higher baseline 25(OH)D level (OR 1.11, 95% CI 1.10-1.12) were associated with greater odds of successful repletion. Asian race (OR 0.80, 95% CI 0.73-0.88), Hispanic ethnicity (OR 0.71, 95% CI 0.65-0.77), and increasing overweight/obesity (OR 0.78, 95% CI 0.72-0.85 for body mass index [BMI], 25.0-29.9 kg/m²; OR 0.66, 95% CI 0.60-0.71 for BMI 30.0-39.9 kg/m²; OR 0.53, 95% CI 0.48-0.60 for BMI ≥ 40 kg/m²) were associated with lower odds of repletion compared with BMI 18.5-24.9 kg/m². CONCLUSIONS: There is increasing recognition and treatment of vitamin D deficiency within the health care setting. Patients of younger age, Asian and Hispanic race/ethnicity, and those who are obese or with more severe vitamin D deficiency may be at greater risk for incomplete repletion using standard regimens and may require additional treatment to achieve optimal levels.