The effect of starting metformin on bone mineral density among women with type 2 diabetes in the Study of Women's Health Across the Nation (SWAN).

We examined longitudinal changes in BMD among women in the mid-life starting metformin. Study subjects were 57 years old (mean), and 36% were White. Women initiating metformin were similar to noninitiators. During the 3-year follow-up, BMD loss at all anatomic areas was similar between groups and in subgroups including baseline fasting blood glucose. PURPOSE/INTRODUCTION: Women with type 2 diabetes have higher bone mineral density (BMD), experience slower BMD loss, but have increased fracture risk. Data regarding the effect of metformin on BMD remain discordant. We examined longitudinal changes in BMD among women in the mid-life starting metformin. METHODS: Participants in the Study of Women's Health Across the Nation (SWAN), a diverse community-based US cohort, with BMD measurements were evaluated. Propensity score matching helped balance baseline characteristics of metformin initiators versus noninitiators. Mixed model regression tested the change in BMD between groups. RESULTS: Subjects (n = 248) were 57.4 years old (mean), and 35.9% were White. Women initiating metformin (n = 124) were similar to noninitiators (n = 124) in age and race/ethnicity. During the median 3-year follow-up, BMD loss at all anatomic areas was similar between the metformin initiators and nonusers (all p > 0.3). Subgroup analyses including baseline fasting blood glucose showed no between-group differences. Initiation of metformin (vs. not) in peri-menopausal women was not associated with BMD changes. CONCLUSIONS: Women in the mid-life starting metformin had longitudinal changes in BMD very similar to other women not starting metformin.

Analysis of narrative assessments of internal medicine resident performance: are there differences associated with gender or race and ethnicity?

BACKGROUND: Equitable assessment is critical in competency-based medical education. This study explores differences in key characteristics of qualitative assessments (i.e., narrative comments or assessment feedback) of internal medicine postgraduate resident performance associated with gender and race and ethnicity. METHODS: Analysis of narrative comments included in faculty assessments of resident performance from six internal medicine residency programs was conducted. Content analysis was used to assess two key characteristics of comments- valence (overall positive or negative orientation) and specificity (detailed nature and actionability of comment) - via a blinded, multi-analyst approach. Differences in comment valence and specificity with gender and race and ethnicity were assessed using multilevel regression, controlling for multiple covariates including quantitative competency ratings. RESULTS: Data included 3,383 evaluations with narrative comments by 597 faculty of 698 residents, including 45% of comments about women residents and 13.2% about residents who identified with race and ethnicities underrepresented in medicine. Most comments were moderately specific and positive. Comments about women residents were more positive (estimate 0.06, p 0.045) but less specific (estimate - 0.07, p 0.002) compared to men. Women residents were more likely to receive non-specific, weakly specific or no comments (adjusted OR 1.29, p 0.012) and less likely to receive highly specific comments (adjusted OR 0.71, p 0.003) or comments with specific examples of things done well or areas for growth (adjusted OR 0.74, p 0.003) than men. Gendered differences in comment specificity and valence were most notable early in training. Comment specificity and valence did not differ with resident race and ethnicity (specificity: estimate 0.03, p 0.32; valence: estimate - 0.05, p 0.26) or faculty gender (specificity: estimate 0.06, p 0.15; valence: estimate 0.02 p 0.54). CONCLUSION: There were significant differences in the specificity and valence of qualitative assessments associated with resident gender with women receiving more praising but less specific and actionable comments. This suggests a lost opportunity for well-rounded assessment feedback to the disadvantage of women.

Psychosocial impacts of the COVID-19 pandemic on women with trauma histories: Study of Women's Health Across the Nation (SWAN).

Older adults, particularly those with trauma histories, may be vulnerable to adverse psychosocial outcomes during the COVID-19 pandemic. We tested associations between prepandemic childhood abuse or intimate partner violence (IPV) and elevated depressive, anxiety, conflict, and sleep symptoms during the pandemic among aging women. Women (N = 582, age: 65-77 years) from three U.S. sites (Pittsburgh, Boston, Newark) of the longitudinal Study of Women's Health Across the Nation (SWAN) reported pandemic-related psychosocial impacts from June 2020-March 2021. Prepandemic childhood abuse; physical/emotional IPV; social functioning; physical comorbidities; and depressive, anxiety, and sleep symptoms were drawn from SWAN assessments between 2009 and 2017. There were no measures of prepandemic conflict. In total, 47.7% and 35.3% of women, respectively, reported childhood abuse or IPV. Using logistic regression models adjusted for age; race/ethnicity; education; site; prepandemic social functioning and physical comorbidities; and, in respective models, prepandemic depressive, anxiety, or sleep symptoms, childhood abuse predicted elevated anxiety symptoms, OR = 1.67, 95% CI [1.10, 2.54]; household conflict, OR = 2.19, 95% CI [1.32, 3.61]; and nonhousehold family conflict, OR = 2.14, 95% CI [1.29, 3.55]. IPV predicted elevated sleep problems, OR = 1.63, 95% CI [1.07, 2.46], and household conflict, OR = 1.96, 95% CI [1.20, 3.21]. No associations emerged for depressive symptoms after adjusting for prepandemic depression. Aging women with interpersonal trauma histories reported worse anxiety, sleep, and conflict during the COVID-19 pandemic than those without. Women's trauma histories and prepandemic symptoms are critical to understanding the psychosocial impacts of the pandemic.

A Women in Medicine Trainees' Council: a model for women trainee professional development.

Women physicians are promoted less often, more likely to experience harassment and bias, and paid less than their male peers. Although many institutions have developed initiatives to help women physicians overcome these professional hurdles, few are specifically geared toward physicians-in-training. The Women in Medicine Trainees' Council (WIMTC) was created in 2015 to support the professional advancement of women physicians-in-training in the Massachusetts General Hospital Department of Medicine (MGH-DOM). In a 2021 survey, the majority of respondents agreed that the WIMTC ameliorated the challenges of being a woman physician-in-training and contributed positively to overall wellness. Nearly all agreed that they would advise other training programs to implement a similar program. We present our model for women-trainee support to further the collective advancement of women physicians.

Exploring gender and thematic differences in qualitative assessments of internal medicine resident performance.

INTRODUCTION: Evidence suggests gender disparities in medical education assessment, including differences in ratings of competency and narrative comments provided in resident performance assessments. This study explores how gender manifests within the content of qualitative assessments (i.e., narrative comments or performance feedback) of resident performance. METHODS: Qualitative content analysis was used to explore gender-based differences in narrative comments included in faculty assessments of resident performance during inpatient medicine rotations at six Internal Medicine residency programs, 2016-2017. A blinded, multi-analyst approach was employed to identify themes across comments. Patterns in themes with resident gender and post-graduate year (PGY) were explored, focusing on PGY2 and PGY3 when residents are serving in the team leader role. RESULTS: Data included 3,383 evaluations with narrative comments of 385 men (55.2%) and 313 women residents (44.8%). There were thematic differences in narrative comments received by men and women residents and how these themes manifested within comments changed with training time. Compared to men, comments about women had a persistent relationship-orientation and emphasized confidence over training including as interns and in PGY2 and PGY3, when serving as team leader. The relationship-orientation was characterized not only by the residents' communal attributes but also their interpersonal and communication skills, including efforts supporting others and establishing the tone for the team. Comments about women residents often highlighted confidence, including recommendations around behaviors that convey confidence in decision-making and team leadership. DISCUSSION: There were gender-based thematic differences in qualitative assessments. Comments about women resident team leaders highlight relationship building skills and urge confidence and actions that convey confidence as team leader. Persistent attention to communal skills suggests gendered expectations for women resident team leaders and a lost opportunity for well-rounded feedback to the disadvantage of women residents. These findings may inform interventions to promote equitable assessment, such as providing feedback across the competencies.

Attitudes and Actions Related to Racism: the Anti-RaCism (ARC) Survey Study.

BACKGROUND: Racism negatively impacts health and well-being. Members of the medical community must intervene to address racism. OBJECTIVE: To assess whether attitudes about the impact of racism on health or society are associated with intervening around racism. DESIGN: Cross-sectional survey of a large department of medicine in an urban academic setting. PARTICIPANTS: Interns, residents, fellows, and faculty. MAIN MEASURES: The primary outcome was the likelihood of intervening around an observed racist encounter or a racist policy. Predictor variables included age, gender identity, race/ethnicity, and attitudes about racism. KEY RESULTS: Although the majority of the 948 respondents endorsed the impact of racism on health and other societal effects, levels of endorsement were lower among older individuals, or those reporting male gender identity or selecting other race. Higher endorsement of the impact of racism on health was associated with increased odds of speaking up about a racist encounter or racist policy, with odds ratios from 1.18 to 1.30 across scenarios. Likelihood of speaking up about racism did not differ by racial or ethnic group, but older individuals were generally more likely to speak up and individuals between 20 and 29 years of age were more likely to speak with someone other than leadership or the source of a racist encounter. CONCLUSIONS: Awareness of the effects of racism on health is associated with increased likelihood of intervening when a racist encounter is observed or a racist policy is noted. Including information on the impact of racism on health and creating safe spaces to discuss racism may increase the likelihood of bystander intervention in anti-racism strategies.

Association of Gender and Race/Ethnicity with Internal Medicine In-Training Examination Performance in Graduate Medical Education.

BACKGROUND: Disparities in objective assessments in graduate medical education such as the In-Training Examination (ITE) that disadvantage women and those self-identifying with race/ethnicities underrepresented in medicine (URiM) are of concern. OBJECTIVE: Examine ITE trends longitudinally across post-graduate year (PGY) with gender and race/ethnicity. DESIGN: Longitudinal analysis of resident ITE metrics at 7 internal medicine residency programs, 2014-2019. ITE trends across PGY of women and URiM residents compared to non-URiM men assessed via ANOVA. Those with ITE scores associated with less than 90% probability of passing the American Board of Internal Medicine certification exam (ABIM-CE) were identified and odds of being identified as at-risk between groups were assessed with chi square. PARTICIPANTS: A total of 689 IM residents, including 330 women and URiM residents (48%). MAIN MEASURES: ITE score KEY RESULTS: There was a significant difference in ITE score across PGY for women and URiM residents compared to non-URiM men (F(2, 1321) 4.46, p=0.011). Adjusting for program, calendar year, and baseline ITE, women and URiM residents had smaller ITE score gains (adjusted mean change in score between PGY1 and PGY3 (se), non-URiM men 13.1 (0.25) vs women and URiM residents 11.4 (0.28), p<0.001). Women and URiM residents had greater odds of being at potential risk for not passing the ABIM-CE (OR 1.75, 95% CI 1.10 to 2.78) with greatest odds in PGY3 (OR 3.13, 95% CI 1.54 to 6.37). CONCLUSION: Differences in ITE over training were associated with resident gender and race/ethnicity. Women and URiM residents had smaller ITE score gains across PGY translating into greater odds of potentially being seen as at-risk for not passing the ABIM-CE. Differences in ITE over training may reflect differences in experiences of women and URiM residents during training and may lead to further disparities.

Temporal increases in 25-hydroxyvitamin D in midlife women: Longitudinal results from the Study of Women's Health Across the Nation.

OBJECTIVE: 25-hydroxyvitamin D (25(OH)D) is critical for bone mineralization and may prevent fractures. Understanding vitamin D deficiency trends in midlife women is particularly important given their concurrent menopausal changes that increase risk for fracture. We aimed to evaluate changes in mean 25(OH)D over time and their determinants in a racially, ethnically and socioeconomically diverse cohort of midlife women. DESIGN: A multi-centre prospective cohort study. PATIENTS: 1585 women ages 42-52 years at baseline. MEASUREMENTS: We measured serum 25(OH)D at 2 time points (1998-2000 and 2009-2011). Between-visit change was assessed in the whole cohort and in socioeconomic and demographic subgroups. Among those with vitamin D deficiency (25(OH)D <30 nmol/L) at baseline, we evaluated determinants of persistent deficiency at follow-up. RESULTS: Mean 25(OH)D increased from 53.8 to 70.0 nmol/L (P < 0.001), and the prevalence of deficiency decreased from 20.4% to 9.7% (P < 0.001). While baseline 25(OH)D differed among subgroups, the changes in 25(OH)D were similar among groups. The proportion of women reporting dietary supplement use increased from 40.8% to 67.1% (P < 0.001), and the increase in 25(OH)D was significantly higher in supplement users. Among women with vitamin D deficiency at baseline, White women and supplement users were less likely to remain deficient at follow-up. CONCLUSIONS: Among midlife women, temporal increases in 25(OH)D concentrations are driven largely by increases in supplement use. The proportion of women with 25(OH)D <30 nmol/L and thus at high risk for skeletal consequences remains substantial. Targeted screening for vitamin D deficiency in populations at risk for fragility fracture may be advisable.

Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial.

BACKGROUND: Unlike most chronic diseases, osteoporosis treatments are generally limited to a single drug at a fixed dose and frequency. Nonetheless, no approved therapy is able to restore skeletal integrity in most osteoporotic patients and the long-term use of osteoporosis drugs is controversial. Thus, many patients are treated with the sequential use of two or more therapies. The DATA study showed that combined teriparatide and denosumab increased bone mineral density more than either drug alone. Discontinuing teriparatide and denosumab, however, results in rapidly declining bone mineral density. In this DATA-Switch study, we aimed to assess the changes in bone mineral density in postmenopausal osteoporotic women who transitioned between treatments. METHODS: This randomised controlled trial (DATA-Switch) is a preplanned extension of the denosumab and teriparatide administration study (DATA), in which 94 postmenopausal osteoporotic women were randomly assigned to receive 24 months of teriparatide (20 mg daily), denosumab (60 mg every 6 months), or both drugs. In DATA-Switch, women originally assigned to teriparatide received denosumab (teriparatide to denosumab group), those originally assigned to denosumab received teriparatide (denosumab to teriparatide group), and those originally assigned to both received an additional 24 months of denosumab alone (combination to denosumab group). Bone mineral density at the spine, hip, and wrist were measured 6 months, 12 months, 18 months, and 24 months after the drug transitions as were biochemical markers of bone turnover. The primary endpoint was the percent change in posterior-anterior spine bone mineral density over 4 years. Between-group changes were assessed by one-way analysis of variance in our modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00926380. FINDINGS: Between Sept 27, 2011, and Jan 28, 2013, eligible women from the DATA study were enrolled into DATA-Switch. Of 83 potential enrollees from the DATA study, 77 completed at least one post-baseline visit. After 48 months, the primary outcome of mean spine bone mineral density increased by 18·3% (95% CI 14·9-21·8) in 27 women in the teriparatide to denosumab group, 14·0% (10·9-17·2) in 27 women the denosumab to teriparatide group, and 16·0% (14·0-18·0) in 23 women in the combination to denosumab group, although this increase did not differ significantly between groups (for between-group comparisons, p=0·13 for the teriparatide to denosumab group vs the denosumab to teriparatide group, p=0·30 for the teriparatide to denosumab group vs the combination to denosumab group, and p=0·41 for the denosumab to teriparatide group vs the combination to denosumab group). For the bone mineral density secondary outcomes, total hip bone mineral density increased more in the teriparatide to denosumab group (6·6% [95% CI 5·3-7·9]) than in the denosumab to teriparatide group (2·8% [1·3-4·2], p=0·0002), but had the greatest increase in the combination to denosumab group (8·6% [7·1-10·0]; p=0·0446 vs the teriparatide to denosumab group, p<0·0001 vs the denosumab to teriparatide group). Similarly, femoral neck bone mineral density increased more in the teriparatide to denosumab group (8·3% [95% CI 6·1-10·5]) and the combination to denosumab group (9·1% [6·1-12·0]) than in the denosumab to teriparatide group (4·9% [2·2-7·5]; p=0·0447 for teriparatide to denosumab vs denosumab to teriparatide, p=0·0336 for combination to denosumab vs denosumab to teriparatide). Differences between the combination to denosumab group and the teriparatide to denosumab group did not differ significantly (p=0·67). After 48 months, radius bone mineral density was unchanged in the teriparatide to denosumab group (0·0% [95% CI -1·3 to 1·4]), whereas it decreased by -1·8% (-5·0 to 1·3) in the denosumab to teriparatide group, and increased by 2·8% (1·2-4·4) in the combination to denosumab group (p=0·0075 for the teriparatide to denosumab group vs the combination to denosumab group; p=0·0099 for the denosumab to teriparatide group vs the combination to denosumab group). One participant in the denosumab to teriparatide group had nephrolithiasis, classified as being possibly related to treatment. INTERPRETATION: In postmenopausal osteoporotic women switching from teriparatide to denosumab, bone mineral density continued to increase, whereas switching from denosumab to teriparatide results in progressive or transient bone loss. These results should be considered when choosing the initial and subsequent management of postmenopausal osteoporotic patients. FUNDING: Amgen, Eli Lilly, and National Institutes of Health.

Gonadal steroids and body composition, strength, and sexual function in men.

BACKGROUND: Current approaches to diagnosing testosterone deficiency do not consider the physiological consequences of various testosterone levels or whether deficiencies of testosterone, estradiol, or both account for clinical manifestations. METHODS: We provided 198 healthy men 20 to 50 years of age with goserelin acetate (to suppress endogenous testosterone and estradiol) and randomly assigned them to receive a placebo gel or 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel daily for 16 weeks. Another 202 healthy men received goserelin acetate, placebo gel or testosterone gel, and anastrozole (to suppress the conversion of testosterone to estradiol). Changes in the percentage of body fat and in lean mass were the primary outcomes. Subcutaneous- and intraabdominal-fat areas, thigh-muscle area and strength, and sexual function were also assessed. RESULTS: The percentage of body fat increased in groups receiving placebo or 1.25 g or 2.5 g of testosterone daily without anastrozole (mean testosterone level, 44±13 ng per deciliter, 191±78 ng per deciliter, and 337±173 ng per deciliter, respectively). Lean mass and thigh-muscle area decreased in men receiving placebo and in those receiving 1.25 g of testosterone daily without anastrozole. Leg-press strength fell only with placebo administration. In general, sexual desire declined as the testosterone dose was reduced. CONCLUSIONS: The amount of testosterone required to maintain lean mass, fat mass, strength, and sexual function varied widely in men. Androgen deficiency accounted for decreases in lean mass, muscle size, and strength; estrogen deficiency primarily accounted for increases in body fat; and both contributed to the decline in sexual function. Our findings support changes in the approach to evaluation and management of hypogonadism in men. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00114114.).

Response to Therapy With Teriparatide, Denosumab, or Both in Postmenopausal Women in the DATA (Denosumab and Teriparatide Administration) Study Randomized Controlled Trial.

Both antiresorptive and anabolic osteoporosis medications increase bone mineral density (BMD), but no single agent can restore normal bone strength in most osteoporotic patients. Moreover, the magnitude and consistency of the patient response to each individual agent vary depending on the anatomic site. In the DATA study, we reported that in postmenopausal osteoporotic women, 2 years of combined denosumab and teriparatide increase mean BMD at the hip and spine more than either drug alone. In the current analysis, we wished to determine if the individual rates of BMD response were also greater among women treated with both drugs. In DATA, 94 postmenopausal osteoporotic women (ages 51-91) were randomized to receive teriparatide (20 mcg subcutaneously daily), denosumab (60 mg subcutaneously every 6 mo), or both medications for 24 mo. The BMD of the total hip (TH), femoral neck (FN), and lumbar spine (LS) were assessed by dual-energy X-ray absorptiometry. The 82 subjects who completed all 2-yr treatments were analyzed. Responders were defined as experiencing BMD increases of >3%. An "excellent response" was defined as an increase of >6%. Over 24 mo, TH BMD increased by >3% in 36%, 53%, and 92% of women in the teriparatide, denosumab, and combination groups, respectively, and by >6% in 11%, 17%, and 50% in the teriparatide, denosumab, and combination groups, respectively (p < 0.01 for all comparisons vs combination). FN response rates were similar to TH. In the LS, BMD increased by >3% in 85%, 93%, and 100% of women in the teriparatide, denosumab, and combination groups, respectively (p = nonsignificant for all comparisons) and by >6% in 63%, 78%, and 100% of women in the teriparatide, denosumab, and combination groups, respectively (combination vs teriparatide, p = 0.001; combination vs denosumab, p = 0.016). In summary, more women treated with 24 mo of combined denosumab and teriparatide achieved a significant response at the TH and FN than those treated with either drug alone. All women treated with both agents together experienced an excellent response at the LS. These results support the continued investigation of combined denosumab and teriparatide therapy in postmenopausal osteoporotic women utilizing clinical endpoints such as fracture reduction.

Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial.

BACKGROUND: Osteoporosis medications increase bone-mineral density (BMD) and lower but do not eliminate fracture risk. The combining of anabolic agents with bisphosphonates has not improved efficacy. We compared combined teriparatide and denosumab with both agents alone. METHODS: From September, 2009, to January, 2011, we enrolled postmenopausal women with osteoporosis into this randomised, controlled trial. Patients were assigned in a 1:1:1 ratio to receive 20 µg teriparatide daily, 60 mg denosumab every 6 months, or both. BMD was measured at 0, 3, 6, and 12 months. Women who completed at least one study visit after baseline were assessed in a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00926380. FINDINGS: 94 (94%) of 100 eligible women completed at least one study visit after baseline. At 12 months, posterior-anterior lumbar spine BMD increased more in the combination group (9·1%, [SD 3·9]) than in the teriparatide (6·2% [4·6], p=0·0139) or denosumab (5·5% [3·3], p=0·0005) groups. Femoral-neck BMD also increased more in the combination group (4·2% [3·0]) than in the teriparatide (0·8% [4·1], p=0·0007) and denosumab (2·1% [3·8], p=0·0238) groups, as did total-hip BMD (combination, 4·9% [2·9]; teriparatide, 0·7% [2·7], p<0·0001; denosumab 2·5% [2·6], p=0·0011). INTERPRETATION: Combined teriparatide and denosumab increased BMD more than either agent alone and more than has been reported with approved therapies. Combination treatment might, therefore, be useful to treat patients at high risk of fracture. FUNDING: Amgen, Eli Lilly, National Center for Research Resources.

Experiences of bias in a multidisciplinary hospital medicine group.

ABSTRACT: Clinicians report experiencing bias at work. Although previous studies have characterized these experiences among trainees and clinical faculty, ours is the first to describe experiences of bias within a multidisciplinary hospital medicine group. In our study, 82.5% of surveyed nurse practitioners (NPs), physician assistants (PAs), and physicians reported experiencing gender, racial, or other forms of bias in the workplace. In addition to women reporting higher rates of gender bias and Asian/Black/Latinx/multiracial/other race respondents reporting higher rates of racial bias, half of participants reported experiencing other forms of bias related to gender expression, perceived sexual orientation, body habitus, age, accent, country of origin, or perceived socioeconomic status. Respondents infrequently addressed bias with the person expressing it. Our study expands on the existing literature about experiences of bias by studying a large, multidisciplinary, academic hospital medicine group. With the increasing inclusion of NPs and PAs in hospital medicine, understanding their experiences will enable development of tailored interventions to reduce harm from experiences of bias.