Long-Term Oral Bisphosphonate Therapy and Fractures in Older Women: The Women's Health Initiative.

OBJECTIVES: To examine the association between long-term bisphosphonate use and fracture in older women at high risk of fracture. DESIGN: Retrospective cohort. SETTING: Women's Health Initiative. PARTICIPANTS: Older women who reported at least 2 years of bisphosphonate use in 2008-09 (N = 5,120). MEASUREMENTS: Exposure data were from a current medications inventory. Outcomes (hip, clinical vertebral, wrist or forearm, any clinical fracture) were ascertained annually. Using multivariate Cox proportional hazards models, the association between duration of bisphosphonate use (3-5, 6-9, 10-13 years) and fracture was estimated, using 2 years as the referent group. RESULTS: On average participants were 80 years old and were followed for 3.7 ± 1.2 years. There were 127 hip, 159 wrist or forearm, 235 clinical vertebral, and 1,313 clinical fractures. In multivariate-adjusted analysis, 10 to 13 years of bisphosphonate use was associated with higher risk of any clinical fracture than 2 years of use (hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.07-1.57). This association persisted in analyses limited to women with a prior fracture (HR = 1.30, 95% CI = 1.01-1.67) and women with no history of cancer (HR = 1.36, 95% CI = 1.10-1.68). The association of 10 to 13 years of use, compared with 2 years of use, was not statistically significant for hip (HR = 1.66, 95% CI = 0.81-3.40), clinical vertebral (HR = 1.65, 95% CI = 0.99-2.76), or wrist fracture (HR = 1.16, 95% CI = 0.67-2.00). CONCLUSION: In older women at high risk of fracture, 10 to 13 years of bisphosphonate use was associated with higher risk of any clinical fracture than 2 years of use. These results add to concerns about the benefit of very long-term bisphosphonate use.

Speaker Introductions at Internal Medicine Grand Rounds: Forms of Address Reveal Gender Bias.

BACKGROUND: Gender bias has been identified as one of the drivers of gender disparity in academic medicine. Bias may be reinforced by gender subordinating language or differential use of formality in forms of address. Professional titles may influence the perceived expertise and authority of the referenced individual. The objective of this study is to examine how professional titles were used in the same and mixed-gender speaker introductions at Internal Medicine Grand Rounds (IMGR). METHODS: A retrospective observational study of video-archived speaker introductions at consecutive IMGR was conducted at two different locations (Arizona, Minnesota) of an academic medical center. Introducers and speakers at IMGR were physician and scientist peers holding MD, PhD, or MD/PhD degrees. The primary outcome was whether or not a speaker's professional title was used during the first form of address during speaker introductions at IMGR. As secondary outcomes, we evaluated whether or not the speakers professional title was used in any form of address during the introduction. RESULTS: Three hundred twenty-one forms of address were analyzed. Female introducers were more likely to use professional titles when introducing any speaker during the first form of address compared with male introducers (96.2% [102/106] vs. 65.6% [141/215]; p < 0.001). Female dyads utilized formal titles during the first form of address 97.8% (45/46) compared with male dyads who utilized a formal title 72.4% (110/152) of the time (p = 0.007). In mixed-gender dyads, where the introducer was female and speaker male, formal titles were used 95.0% (57/60) of the time. Male introducers of female speakers utilized professional titles 49.2% (31/63) of the time (p < 0.001). CONCLUSION: In this study, women introduced by men at IMGR were less likely to be addressed by professional title than were men introduced by men. Differential formality in speaker introductions may amplify isolation, marginalization, and professional discomfiture expressed by women faculty in academic medicine.

Imploding and exploding migraine headaches: comparison of methods to diagnose pain directionality.

BACKGROUND: The study aims to compare methods of determining headache directionality (imploding, exploding, and/or ocular headaches) in women with migraine, investigate the concordance between physician assignment and patient self-assignment of pain directionality, and evaluate whether patients assigned their headaches to the same direction when queried using different methods. Directionality of migraine headache pain (imploding, exploding, or ocular) may reflect differences in the underlying pathogenesis of individual migraine attacks among and within individuals. Emerging evidence suggests that directionality of pain in migraine sufferers may predict response to onabotulinumtoxin A. The best method of determining headache directionality in migraine sufferers has not been systematically explored. METHODS: We conducted a prospective cross-sectional survey study of 198 female patients with migraine presenting to a Women's Health Clinic. Patients determined the directionality (imploding, exploding, and/or ocular) of their own migraine pain by choosing among 3 pictures graphically representing directionality and also by responding to a written question regarding directionality. Clinicians then classified directionality of migraine pain using structured interviews. Concordance between clinician assignment of directionality and patient self-assignment was determined with Kappa coefficients. RESULTS: Subjects were females between the ages of 18 and 77 years (mean 48 years). According to patient selection of representative pictures, 62 (31.6%) had imploding headaches with or without ocular pain, 36 (18.4%) had exploding headaches with or without ocular pain, 78 (39.8%) had ocular pain only, and 20 (10.2%) had imploding and exploding headaches with or without ocular pain. Two subjects did not respond. According to patient responses to a written question, 80 (41.0%) had imploding headaches with or without ocular pain, 53 (27.2%) had exploding headaches with or without ocular pain, 46 (23.6%) had ocular pain only, and 16 (8.2%) had imploding and exploding headaches with or without ocular pain. Three subjects did not respond. For physician assignment, 69 (34.9%) subjects had imploding headaches with or without ocular pain, 89 (45%) had exploding headaches with or without ocular pain, 14 (7.1%) had ocular pain only, and 26 (13.1%) had imploding and exploding headaches with or without ocular pain. The concordance (Kappa coefficient) between physician assignment of headache directionality with patient response to the written question was 0.33 (weak agreement), between physician assignment and patient assignment via selection of representative pictures was 0.35 (weak agreement), and between patient assignment via written question and via selection of representative pictures was 0.35 (weak agreement). CONCLUSIONS: The assignment of headache directionality varied substantially depending upon the method of determination. The concordance between clinician assignment, patient-self assignment via answering a written question, and patient self-assignment via choosing a representative picture was weak. Improved methods of determining pain directionality are needed.

Gender distribution of U.S. medical school faculty by academic track type.

PURPOSE: Over the past 30 years, the number and type of academic faculty tracks have increased, and researchers have found differences in promotion rates between track types. The authors studied the gender distribution of medical school faculty on the traditional tenure track (TTT) and clinician-educator track (CET) types. METHOD: The authors analyzed gender and academic track type distribution data from the March 31, 2011, snapshot of the Association of American Medical Colleges' Faculty Roster. Their final analysis included data from the 123 medical schools offering the TTT type and the 106 offering the CET type, which excluded any schools with 10 or fewer faculty on each track type. RESULTS: The original dataset included 134 medical schools representing 138,508 full-time faculty members, 50,376 (36%) of whom were women. Of the 134 medical schools, 128 reported at least one of four track types: TTT, CET, research track, and other. Of the 83 medical schools offering the CET type, 64 (77%) had a higher proportion of female than male faculty on that track type. Of the 102 medical schools offering the TTT type, only 20 (20%) had a higher proportion of female than male faculty on that track type. CONCLUSIONS: Medical schools offering the CET type reported higher proportions of female faculty on that track type. Given that faculty on the CET type lag behind their TTT colleagues in academic promotion, these findings may contribute to continued challenges in gaining academic and leadership parity for women in academic medicine.

Long-term follow-up of a facilitated peer mentoring program.

BACKGROUND: Mentoring plays an important role in career success of academic medical faculty. New mentoring models such as peer mentoring have emerged. AIM: To evaluate the long-term impact of a facilitated peer mentoring program on academic achievements. METHOD: Women faculty at the instructor or assistant professor rank were recruited to voluntarily participate in a facilitated peer mentoring program. Recruitment occurred over 3.8 years between 2005 and 2009. A 26-item questionnaire to assess academic skill, career satisfaction, and self-efficacy was administered before program participation and again with seven additional questions in 2011. Curriculum vitae were reviewed retrospectively to tally peer-reviewed publications, other academic activities, and promotions. RESULTS: Participants had long-term improvement in their perceived mastery of academic skills. Peer-reviewed publications, book chapters, abstracts, posters, and other academic activities increased when activities before the program were compared to those in the five years after program enrollment. At follow-up, participants reported positive perceptions of the program and 44% continued to work with their original peer mentor groups. CONCLUSIONS: Involvement in the facilitated peer mentoring program was associated with increased skills and academic activities for most participants. Future studies are needed to assess its applicability and success among various demographic groups in academic medicine.

Does the presence of mediastinal adenopathy confer a risk for disseminated infection in immunocompetent persons with pulmonary coccidioidomycosis?

Pulmonary coccidioidomycosis is caused by inhaling airborne arthroconidia of Coccidioides, a soil-dwelling fungus endemic to the desert southwestern United States. Although uncommon, disseminated coccidioidal infection can be associated with well-defined risk factors, such as cell-mediated immunodeficiency, certain racial heritages (e.g. African or Filipino), male sex, or pregnancy. Before widespread use of computed tomography (CT), the presence or persistence of mediastinal lymphadenopathy was postulated to be a risk factor for disseminated coccidioidal infection. To investigate the use of CT scanning to identify the presence of mediastinal lymphadenopathy in patients with pulmonary coccidioidomycosis, and to correlate such lymphadenopathy with disseminated coccidioidal infection, we performed a retrospective review of patients with pulmonary coccidioidomycosis who were evaluated by chest CT. Two radiologists independently interpreted 150 CT scans from patients with pulmonary coccidioidomycosis. Forty-nine patients met CT criteria for mediastinal lymphadenopathy, whereas 101 patients did not. Disseminated coccidioidal infection was observed in 5 (10%) of the 49 patients with mediastinal lymphadenopathy and in 6 of the 101 (6%; P = .34) without such adenopathy. Among patients with coccidioidomycosis, patients with mediastinal lymphadenopathy, as assessed by CT, had a higher rate of disseminated infection, but the difference was not statistically significant.

Bioidentical hormone therapy.

The change in hormonal milieu associated with perimenopause and menopause can lead to a variety of symptoms that can affect a woman's quality of life. Postmenopausal hormone therapy (HT) is an effective, well-tolerated treatment for these symptoms. However, combined HT consisting of conjugated equine estrogen and medroxyprogesterone acetate has been associated with an increased number of health risks when compared with conjugated equine estrogen alone or placebo. As a result, some women are turning to alternative hormonal formulations known as compounded bioidentical HT because they perceive them to be a safer alternative. This article defines compounded bioidentical HT and explores the similarities and differences between it and US Food and Drug Administration-approved HT. We will examine the major claims made by proponents of compounded bioidentical HT and recommend strategies for management of patients who request bioidentical HT from physicians.

Coccidioidomycosis in African Americans.

Coccidioidomycosis is caused by Coccidioides species, a fungus endemic to the desert regions of the southwestern United States, and is of particular concern for African Americans. We performed a PubMed search of the English-language medical literature on coccidioidomycosis in African Americans and summarized the pertinent literature. Search terms were coccidioidomycosis, Coccidioides, race, ethnicity, African, black, and Negro. The proceedings of the national and international coccidioidomycosis symposia were searched. All relevant articles and their cited references were reviewed; those with epidemiological, immunologic, clinical, and therapeutic data pertaining to coccidioidomycosis in African Americans were included in the review. Numerous studies documented an increased predilection for severe coccidioidal infections, coccidioidomycosis-related hospitalizations, and extrapulmonary dissemination in persons of African descent; however, most of the published studies are variably problematic. The immunologic mechanism for this predilection is unclear. The clinical features and treatment recommendations are summarized. Medical practitioners need to be alert to the possibility of coccidioidomycosis in persons with recent travel to or residence in an area where the disease is endemic.

Managing aromatase inhibitors in breast cancer survivors: not just for oncologists.

The role of the general internist in the care of breast cancer survivors is increasing as the number of women living with breast cancer continues to rise. Most breast cancers occurring in women older than 50 years are estrogen receptor- and/or progesterone receptor-positive, and adjuvant endocrine therapy plays an important role in the treatment plan. Aromatase inhibitors are becoming the preferred endocrine therapy, and general internists caring for breast cancer survivors need to be familiar with their use and adverse effect profile. This article reviews the use of aromatase inhibitors, the frequency of common adverse effects, and strategies for their management.

Another treatment gap: restarting secondary prevention medications: the Women's Health Initiative.

BACKGROUND: Women's long-term patterns of evidence-based preventive medication utilization following a coronary heart disease (CHD) diagnosis have not been sufficiently studied. METHODS: Postmenopausal women 50-79 years were eligible for randomization in the Women's Health Initiative's (WHI) hormone trials if they met inclusion and exclusion criteria and were >80% adherent during a placebo-lead-in period and in the dietary modification trial if they were willing to follow a 20% fat diet. Those with adjudicated myocardial infarction or coronary revascularization after the baseline visit were included in the analysis (n=2627). Baseline visits occurred between 1993 and 1998, then annually until the trials ended in 2002 through 2005; medication inventories were obtained at baseline and years 1, 3, 6 and 9. RESULTS: Utilization at the first WHI visit following a CHD diagnosis increased over time for statins (49% to 72%; p<0.0001), beta-blockers (49% to 62%; p=0.003), and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers (ACEI/ARBs ) [26 to 43%; p<0.0001]. Aspirin use remained stable at 76% (p=0.09). Once women reported using a statin, aspirin, or beta-blocker, 84-89% reported use at 1 or more subsequent visits, with slightly lower rates for ACEI/ARBS (76%). Statin, aspirin, beta-blocker, or ACEI/ARB use was reported at 2 or more consecutive visits by 57%, 66%, 48%, and 28% respectively. These drugs were initiated or resumed at a later visit by 24%, 17%, 15%, and 17%, respectively, and were never used during the period of follow-up by 19%, 10%, 33%, and 49% respectively. CONCLUSIONS: Efforts to improve secondary prevention medication utilization should target both drug initiation and restarting drugs in patients who have discontinued them.

Methicillin-resistant Staphylococcus aureus sepsis after elective vaginal prolapse surgery.

Colonization with the virulent pathogen methicillin-resistant Staphylococcus aureus (MRSA) is becoming more prevalent and can result in serious consequences for surgical patients. A 75-year-old woman with diabetes mellitus underwent elective uterovaginal prolapse surgery after an unsuccessful pessary trial. She was noted preoperatively to have MRSA colonization of the urine, and received 10 days of oral linezolid prior to surgery. Four weeks following surgery, the patient was hospitalized for MRSA sepsis. Numerous questions remain regarding the optimal approach to the prevention of MRSA infections in surgical patients. With the increased prevalence of community-acquired MRSA infections, further management strategies and identification of colonization status are necessary to circumvent potentially serious outcomes.

A longitudinal study of the metabolic syndrome and risk of postmenopausal breast cancer.

The metabolic syndrome, characterized by abdominal obesity, high blood glucose levels, impaired glucose tolerance, dyslipidemia, and hypertension, is associated with increased risk of type 2 diabetes and coronary heart disease. Several studies have examined the association of the individual components of the metabolic syndrome with breast cancer; to date, however, no study has assessed the metabolic syndrome per se in relation to breast cancer risk. Furthermore, previous studies have relied only on baseline assessment of components of the syndrome. Therefore, we assessed the association of the metabolic syndrome with the risk of postmenopausal breast cancer among women in the 6% sample of subjects in the Women's Health Initiative clinical trial and the 1% sample of women in the observational study who had repeated measurements of the components of the syndrome during follow-up. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association of breast cancer risk with the presence of the metabolic syndrome, as well as its components, at baseline and in time-dependent analyses. After exclusion of women with diabetes, among 4,888 women with baseline measurements, 165 incident cases of breast cancer were ascertained over a median of 8 years of follow-up. The presence of the metabolic syndrome at baseline was not associated with altered risk. Of the individual components measured at baseline, diastolic blood pressure showed a borderline positive association with breast cancer. In time-dependent covariate analyses, however, certain scenarios indicated a positive association between the metabolic syndrome and breast cancer, due primarily to positive associations with serum glucose, serum triglycerides, and diastolic blood pressure.

The academic quilting bee.

In medicine, the challenges faced by female faculty members who are attempting to achieve academic advancement have been well described. Various strategies have been proposed to increase academic productivity to aid the promotion of women in medicine. We propose an innovative collaboration strategy that encourages completion of an academic writing project. This strategy acknowledges the challenges inherent in achieving work-life balance and utilizes a collaborative work style with a group of peer physicians. The model is designed to encourage the completion and collation of independently prepared sections of an academic paper within a setting that emphasizes social networking and collaboration. This approach has many similarities to the construction of a quilt during a "quilting bee."

Cardiovascular risk in women with non-specific chest pain (from the Women's Health Initiative Hormone Trials).

Women discharged with diagnoses of nonspecific chest pain (NSCP) may be at increased risk for subsequent coronary artery disease (CAD) events. The influence of hormone therapy on NSCP is unknown. The Women's Health Initiative (WHI) enrolled postmenopausal women aged 50 to 79 years. The duration of follow-up was 7.1 years in the WHI Estrogen-Alone trial (E-Alone) and 5.6 years in the WHI Estrogen Plus Progestin trial (E+P). After excluding women with previous cardiovascular disease, 9,427 women in E-Alone and 15,105 women in E+P were included in this analysis. NSCP, defined as having a primary hospital discharge diagnosis of NSCP by International Classification of Diseases, Ninth Revision, code, was reported in 322 women in E-Alone and 249 in E+P. Risks for subsequent CAD events were estimated using intent-to-treat Cox proportional-hazards models stratified by clinic and adjusted for age and other risk factors. In the fully adjusted models of the combined trials, women with NSCP had a twofold greater risk for subsequent nonfatal CAD events, including nonfatal myocardial infarction (2.3% vs 1.7%, hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.11 to 3.98), revascularization (3.5% vs 2.6%, HR 1.99, 95% CI 1.20 to 3.30), and hospitalized angina (3.7% vs 2.3%, HR 2.39, 95% CI 1.46 to 3.92). Hormone therapy did not appear to have a significant effect on either the incidence of NSCP hospitalizations (E-Alone: HR 1.04, 95% CI 0.81 to 1.32; E+P: HR 0.78, 95% CI 0.59 to 1.02) or the risk for a subsequent CAD event. In conclusion, a hospitalization for NSCP doubles the risk for a subsequent CAD event in postmenopausal women over the next 5 to 7 years and identifies them as candidates for aggressive risk factor treatment.

Facilitated peer mentorship: a pilot program for academic advancement of female medical faculty.

BACKGROUND: In the United States, female physicians working in academic medical practices are less likely to achieve the academic rank of associate professor or professor than are male physicians of comparable seniority. Lack of mentoring has been suggested as a possible contributor to this difference. METHODS: In this paper, we describe a facilitated peer mentorship pilot program that was developed to meet the unique needs of women faculty. Experienced female physicians acted as facilitators to a group of junior women who served as their own peer mentors. Outcome measures for the program included comparison of a pretest and a posttest completed by the peer mentor participants, a skills acquisition survey, published papers, and academic advancement of participants. RESULTS: All the peer participants realized increased academic activity in the form of published papers and promotion in academic rank, skills acquisition, and enthusiasm for continuance of the program. CONCLUSIONS: This new model of facilitated peer mentorship demonstrated success in a small-scale pilot program. Expansion of this program and other creative solutions to the lack of mentoring for women may result in greater numbers of women achieving academic advancement.

Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: results from the women's health initiative randomized trial.

UNLABELLED: Further analyses from the Women's Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture. INTRODUCTION: The Women's Health Initiative provided evidence that conjugated equine estrogen (CEE) can significantly reduce fracture risk in postmenopausal women. Additional analysis of the effects of CEE on BMD and fracture are presented. MATERIALS AND METHODS: Postmenopausal women 50-79 years of age with hysterectomy were randomized to CEE 0.625 mg daily (n = 5310) or placebo (n = 5429) and followed for an average 7.1 years. Fracture incidence was assessed by semiannual questionnaire and verified by adjudication of radiology reports. BMD was measured in a subset of women (N = 938) at baseline and years 1, 3, and 6. A global index was used to examine whether the balance of risks and benefits differed by baseline fracture risk. RESULTS: CEE reduced the risk of hip (hazard ratio [HR], 0.65; 95% CI, 0.45-0.94), clinical vertebral (HR, 0.64; 95% CI, 0.44-0.93), wrist/lower arm (HR, 0.58; 95% CI, 0.47-0.72), and total fracture (HR, 0.71; 95% CI, 0.64-0.80). This effect did not differ among strata according to age, oophorectomy status, past hormone use, race/ethnicity, fall frequency, physical activity, or fracture history. Total fracture reduction was less in women at the lowest predicted fracture risk in both absolute and relative terms (HR, 0.86; 95% CI, 0.68-1.08). CEE also provided modest but consistent positive effects on BMD. The HRs of the global index for CEE were relatively balanced across tertiles of summary fracture risk (lowest risk: HR, 0.81; 95% CI, 0.62-1.05; mid risk: HR, 1.09; 95% CI, 0.92-1.30; highest risk: HR, 1.04; 95% CI, 0.88-1.23; interaction, p = 0.42). CONCLUSIONS: CEE reduces the risk of fracture and increases BMD in hysterectomized postmenopausal women. Even among the women with the highest risk for fractures, when considering the effects of estrogen on other important health outcomes, a summary of the burden of monitored effects does not indicate a significant net benefit.

Elderly women diagnosed with nonspecific chest pain may be at increased cardiovascular risk.

BACKGROUND: Women are more likely than men to have nonspecific chest pain (NSCP) symptoms. The long-term outcomes in women discharged with a diagnosis of NSCP are unknown. METHODS: The Women's Health Initiative Observational Study enrolled postmenopausal women aged 50-79 years. After excluding those with prior cardiovascular disease (CVD), 83,622 women were studied. NSCP cases were defined as having an initial primary hospital discharge diagnosis of NSCP (ICD-9 codes 786.50, 786.51, 786.59) without a prior diagnosis of coronary heart disease (CHD). Risks of subsequent CHD events were estimated from Cox proportional hazard ratio (HR) models stratified by clinic and adjusted for baseline age, cardiovascular risk factors, and hormone use. RESULTS: Over an average of 8 years of follow-up, 11% (230 of 2,092) of women with NSCP experienced a cardiovascular event compared with 9.5% (7,724 of 81,530) who did not. Compared with women without a hospitalization for NSCP during follow-up, those with NSCP had a greater than 2-fold higher risk of a subsequent hospitalization for clinically diagnosed angina (HR 2.18, 95% CI 1.66-2.86) and at least a 1.5-fold higher risk of nonfatal myocardial infarction (MI) (HR 1.59, 1.10-2.31), revascularization (HR 1.67, 1.28-2.20), and congestive heart failure (HR 1.75, 1.27-2.41). Women with NSCP who subsequently experienced a CHD event were more likely to be over age 65 or to have cardiovascular risk factors. CONCLUSIONS: Older women discharged with a diagnosis of NSCP may be at increased risk of CHD morbidity. Further research is needed to replicate these findings in other populations.