Publications by authors named "Kristine Ruppert"

57 Publications

Association Between Hyperoxemia and Increased Cell-Free Plasma Hemoglobin During Cardiopulmonary Bypass in Infants and Children.

Pediatr Crit Care Med 2021 Sep 24. Epub 2021 Sep 24.

Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA. Department of Pediatrics, Division of Critical Care Medicine, Ochsner Hospital for Children, New Orleans, LA. Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA. Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA. UPMC Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA. Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA.

Objectives: To determine potential risk factors for severe hemolysis during pediatric cardiopulmonary bypass and examine whether supraphysiologic levels of oxygen and cardiopulmonary bypass duration are associated with hemolysis.

Design: Prospective observational study.

Setting: Cardiac ICU in a university-affiliated children's hospital.

Patients: Greater than 1 month to less than 18 years old patients undergoing cardiopulmonary bypass for cardiac surgery.

Interventions: None.

Measurements And Main Results: Plasma samples from 100 patients to assess cell-free plasma hemoglobin levels were obtained at start cardiopulmonary bypass, at the end of cardiopulmonary bypass, and 2 and 24 hours after reperfusion. Arterial blood gas samples were obtained before and every 30 minutes during cardiopulmonary bypass. Patient demographics and laboratory data were collected from the electronic medical record. Plasma hemoglobin levels peaked at the end of cardiopulmonary bypass and haptoglobin levels continued to fall throughout all time points. There were 44 patients with severe hemolysis (change in cell-free plasma hemoglobin > 50 mg/dL). Younger age (odds ratio/SD 0.45 [95% CI, 0.25-0.81]) and higher mean PaO2 × cardiopulmonary bypass duration (31.11 [1.46-664.64]) were identified as risk factors for severe hemolysis in multivariable analysis. Severe hemolysis was associated with longer hospital and ICU lengths of stay as well as acute kidney injury.

Conclusions: We observed younger age and the exposure to both oxygen and duration of cardiopulmonary bypass as risk factors for hemolysis. Oxygen delivery through the cardiopulmonary bypass circuit is an easily modifiable risk factor. Its role in the production of reactive oxygen species that could alter the erythrocyte membrane deserves further examination in larger prospective studies.
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http://dx.doi.org/10.1097/PCC.0000000000002814DOI Listing
September 2021

Associations of age at menopause with postmenopausal bone mineral density and fracture risk in women.

J Clin Endocrinol Metab 2021 Sep 19. Epub 2021 Sep 19.

Division of Geriatrics, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles.

Context: Menopause before age 45 is a risk factor for fractures, but menopause occurs at age 45 or later in ~90% of women.

Objective: To determine, in women with menopause at age 45 or later, whether: 1) years since the FMP is more strongly associated with postmenopausal bone mineral density (BMD) than chronological age; and 2) lower age at FMP is related to more fractures.

Design And Setting: The Study of Women's Health Across the Nation, a longitudinal cohort study of the menopause transition (MT).

Participants: A diverse cohort of ambulatory women (pre- or early perimenopausal at baseline, with 15 near-annual follow-up assessments).

Main Outcome Measures: 1) Postmenopausal lumbar spine (LS) or femoral neck (FN) BMD (N=1,038); 2) Time to fracture (N=1,554).

Results: Adjusted for age, BMI, cigarette use, alcohol intake, baseline LS or FN BMD, baseline MT stage, and study site using multivariable linear regression, each additional year after the FMP was associated with 0.006 (p<0.0001) and 0.004 (p<0.0001) g/cm 2 lower postmenopausal LS and FN BMD, respectively. Age was not related to FN BMD independent of years since FMP. In Cox proportional hazards regression, accounting for race/ethnicity, BMI, cigarette use, alcohol intake, prior fracture, diabetes status, exposure to bone-modifying medications/supplements, and study site, the hazard for incident fracture was 5% greater for each one-year decrement in age at FMP (p=0.02).

Conclusions: Years since the FMP is more strongly associated with postmenopausal BMD than chronological age, and earlier menopause is associated with more fractures.
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http://dx.doi.org/10.1210/clinem/dgab690DOI Listing
September 2021

The relationship between 19-year trends in medication use and changes in physical function among women in the mid-life: A Study of Women's Health Across the Nation pharmacoepidemiology study.

Pharmacoepidemiol Drug Saf 2021 Sep 8. Epub 2021 Sep 8.

Division of Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Purpose: Medication side effects are a major concern in aging adults who report using an increasing number of medications. The relationship between accumulating medication use and physical function has not been examined in a longitudinal cohort.

Methods: We conducted a longitudinal cohort study using prospectively collected data from the Study of Women's Health Across the Nation (SWAN). Community-dwelling women from five US cities were followed for up to 20 years. The exposure of interest was the number of prescription medications. They were examined as a count variable and then for specific categories of medication. The outcome of interest was physical function measured repeatedly using the short form (SF)-36 physical function (PF) scale. Linear mixed models, using repeated measures of sociodemographics and comorbidities were assessed.

Results: 1452 participants qualified for the analyses with a median follow-up of 19.2 years. At baseline, the mean age was 46.5 years and 53.5% reported White race. Fully adjusted models demonstrated a reduction in the SF-36 PF of 0.99 for each additional prescription medication used or a 6.14-point reduction for women reporting more than five medications and an 8.92-point reduction among those reporting more than 10 medications. These results were similar across race and ethnicity. Specific medication categories with a significant and largely negative impact (at least a two-point reduction) on physical component score included beta-blockers, analgesics, glucocorticoids, anticonvulsants, anxiolytics, anticoagulants, and anti-depressants.

Conclusions: There is a moderate association between increasing medication use and decreasing physical function among women transitioning through the mid-life.
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http://dx.doi.org/10.1002/pds.5355DOI Listing
September 2021

Total Vaginal Hysterectomy With Uterosacral Ligament Suspension Compared With Supracervical Hysterectomy With Sacrocervicopexy for Uterovaginal Prolapse.

Obstet Gynecol 2021 09;138(3):435-442

Division of Urogynecology and Reconstructive Pelvic Surgery, Magee-Womens Hospital of UPMC, University of Pittsburgh, the University of Pittsburgh, School of Public Health, and the Division of Female Pelvic Medicine and Reconstructive Surgery, Allegheny Health Network Women's and Children's Institute, Pittsburgh, Pennsylvania.

Objective: To compare prolapse recurrence after total vaginal hysterectomy with uterosacral ligament suspension to recurrence after supracervical hysterectomy with mesh sacrocervicopexy for the primary management of uterovaginal prolapse.

Methods: We conducted a retrospective cohort study of women undergoing uterovaginal prolapse repair at an academic center from 2009 to 2019. Women who underwent vaginal hysterectomy with uterosacral ligament suspension or laparoscopic supracervical hysterectomy with mesh sacrocervicopexy were included. The primary outcome was composite prolapse recurrence (prolapse beyond the hymen or retreatment with pessary or surgery). Secondary outcomes included mesh complications, time to recurrence, and overall reoperation for either prolapse recurrence or mesh complication. We used propensity scoring with a 2:1 ratio of sacrocervicopexy to uterosacral suspension.

Results: The cohort consisted of 654 patients, of whom 228 (34.9%) underwent uterosacral suspension and 426 (65.1%) underwent sacrocervicopexy. The median follow-up was longer for the sacrocervicopexy group (230 vs 126 days, P<.001) and less than 1 year for both groups. The uterosacral group had a greater proportion of composite prolapse recurrence (14.9% [34/228] vs 8.7% [37/426], P=.02) and retreatment for recurrent prolapse (7.5% [17/228] vs 2.8% [12/426], P=.02). The uterosacral group demonstrated a shorter time to prolapse recurrence on multivariable Cox regression (hazard ratio 3.14, 95% CI 1.90-5.16). There were 14 (3.3%) mesh complications in the sacrocervicopexy group. Overall reoperation was similar between groups (4.8% [11/228] vs 3.8% [16/426], P=.51).

Conclusion: Total vaginal hysterectomy with uterosacral ligament suspension was associated with higher rate of, and shorter time-to-prolapse recurrence compared with supracervical hysterectomy with mesh sacrocervicopexy.
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http://dx.doi.org/10.1097/AOG.0000000000004484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376791PMC
September 2021

Two-Layer Compared With One-Layer Vaginal Cuff Closure at the Time of Total Laparoscopic Hysterectomy to Reduce Complications.

Obstet Gynecol 2021 07;138(1):59-65

Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital of UPMC, Pittsburgh, Pennsylvania; Obstetrics and Gynecology, Mercy Medical Center, Baltimore, Maryland; IVF and Minimally Invasive Gynecological Surgery, Moulana Hospital, Perinthalmanna, India; the Uniformed Services University, Bethesda, Maryland; and the Clinical and Translational Science Institute, Office of Clinical Research, University of Pittsburgh, Pittsburgh, Pennsylvania.

Objective: To explore whether two-layer laparoscopic vaginal cuff closure at the time of laparoscopic hysterectomy is associated with a lower rate of postoperative complications compared with a standard one-layer cuff closure.

Methods: A retrospective cohort study of total laparoscopic hysterectomies performed by fellowship-trained minimally invasive gynecologic surgeons between 2011 and 2017 was performed. Surgeons sutured the vaginal cuff laparoscopically, either in a two- or one-layer closure. The primary outcome was a composite of total postoperative complications, including all medical and surgical complications within 30 days and vaginal cuff complications within 180 days. Factors known to influence laparoscopic vaginal cuff complications including age, postmenopausal status, body mass index, tobacco use, and immunosuppressant medications were examined and controlled for, while surgeon skill, colpotomy technique, and suture material remained standardized. We conducted statistical analyses including χ2, Fisher exact test, logistic regression, and post hoc power calculations.

Results: Of the 2,973 women who underwent total laparoscopic hysterectomies, 40.8% (n=1,213) of vaginal cuffs were closed with a two-layer closure and 59.2% (n=1,760) with a one-layer technique. Two-layer vaginal cuff closure was associated with decreased numbers of total postoperative complications (3.5% vs 5.7%; P<.01). The primary difference stemmed from lower vaginal cuff complications within 180 days (0.9% vs 2.6%; P<.01); no differences in 30-day medical and surgical postoperative complications were observed between the two groups (2.6% vs 3.1%; P=.77). No patients in the two-layer vaginal cuff closure cohort experienced a vaginal cuff dehiscence or mucosal separation compared with 1.0% in the one-layer group (P<.01). Compared with a one-layer closure, a two-layer closure was protective from postoperative complications (adjusted odds ratio 0.38, 95% CI 0.19-0.74).

Conclusion: Although postoperative complications with laparoscopic hysterectomies are rare, two-layer laparoscopic vaginal cuff closure is associated with lower total postoperative complications compared with a one-layer closure. The difference was primary driven by cuff complications.
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http://dx.doi.org/10.1097/AOG.0000000000004428DOI Listing
July 2021

Race/ethnic difference in trabecular bone score in midlife women: The Study of Women's Health Across the Nation (SWAN).

Arch Osteoporos 2021 06 8;16(1):91. Epub 2021 Jun 8.

Department of Medicine, Division of Geriatrics, UCLA, Los Angeles, CA, USA.

There was no difference in Trabecular Bone Score (TBS) comparing White and Black women after adjusting for body mass index (BMI) and diabetes status. Japanese women had lower TBS than White women. Our results diverge from established differences in fracture rates by race/ethnicity.

Introduction: The TBS was developed as an indirect measure of vertebral bone microarchitecture derived from texture analysis of lumbar spine DXA scans. There is little information on race/ethnic differences in TBS.

Methods: We compared TBS in 656 White, 492 Black, and 268 Japanese pre- and early perimenopausal women. We used a beta version of TBS that accounts for tissue thickness using DXA measured soft tissue thickness rather than BMI. The relation between BMI and tissue thickness corrected TBS differed by BMI; we used a three-segment linear spline to adjust for BMI.

Results: The women were, on average, 46.5 years of age; 50% were premenopausal. In BMI and diabetes adjusted models, there was no difference in TBS between White and Black women. TBS was modestly (2%) lower in the Japanese women compared to White women, p = 0.04. In a sensitivity analysis, restricting the analysis to those with BMI 24-31 kg/m, results were similar.

Conclusions: TBS was similar in Black and White women after accounting for tissue thickness and adjusting for BMI, diabetes, and other covariates. The Japanese women had modestly lower TBS. These results diverge from established race/ethnic differences in fracture rates and areal bone mineral density, underscoring the need for further studies.
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http://dx.doi.org/10.1007/s11657-021-00951-4DOI Listing
June 2021

Effect of a Primary Care-Based Diabetes Education Model on Provider Referrals and Patient Participation.

Sci Diabetes Self Manag Care 2021 Feb;47(1):74-84

University of Pittsburgh, Pittsburgh, Pennsylvania.

Purpose: The purpose of this study was to evaluate the impact of a primary care (PC)-based delivery model on diabetes self-management education and support (DSMES) referrals and participation. Despite evidence that DSMES is a critical component of diabetes care, referrals and participation remain low.

Methods: PC practices were assigned to the intervention (n = 6) or usual care (n = 6). Intervention practices had direct access to a diabetes educator (DE) and applied patient-centered medical home elements to DSMES delivery. Usual care practices referred patients to traditional hospital-based outpatient DSMES programs. DSMES referrals and participation were examined for patients with diabetes, 18 to 75 years old, presenting to PC over 18 months (n = 4,894) and compared between groups.

Results: Compared to the usual care group, a higher percentage of patients in the intervention practices were referred to DSMES (18.4% vs 13.4%; < .0001), and of those referred, a higher percentage of patients in the intervention practices participated in DSMES (34.9% vs 26.1%; = .02). Patient-level factors predicting referrals were obesity (odds ratio [OR] = 1.6), higher A1C (OR = 1.4), female (OR = 1.3), and younger age (OR = 0.98). The only patient-level factor that predicted DSMES participation was lower A1C (OR = 0.9).

Conclusions: This study demonstrates the positive influence of a PC-based intervention on DSMES referral and participation. However, modest improvements in DSMES rates, even with targeted efforts to address reported barriers, raise questions as to what is truly needed to drive meaningful change.
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http://dx.doi.org/10.1177/0145721720981840DOI Listing
February 2021

Prescription medications for sleep disturbances among midlife women during 2 years of follow-up: a SWAN retrospective cohort study.

BMJ Open 2021 05 11;11(5):e045074. Epub 2021 May 11.

Department of Psychiatry, Rush Medical College of Rush University, Chicago, Illinois, USA.

Objective: To examine the effects of prescription sleep medications on patient-reported sleep disturbances.

Design: Retrospective cohort.

Setting: Longitudinal cohort of community-dwelling women in the USA.

Participants: Racially and ethnically diverse middle-aged women who reported a sleep disturbance.

Interventions: New users of prescription sleep medications propensity score matched to women not starting sleep medications.

Main Outcomes And Measures: Self-reported sleep disturbance during the previous 2 weeks-difficulty initiating sleep, waking frequently and early morning awakening-using a 5-point Likert scale, ranging from no difficulty on any night (rating 1) to difficulty on 5 or more nights a week (rating 5). Sleep disturbances were compared at 1 year (primary outcome) and 2 years of follow-up.

Results: 238 women who started sleep medications were matched with 447 non-users. Participants had a mean age of 49.5 years and approximately half were white. At baseline, sleep disturbance ratings were similar: medication users had a mean score for difficulty initiating sleep of 2.7 (95% CI 2.5 to 2.9), waking frequently 3.8 (95% CI 3.6 to 3.9) and early morning awakening 2.8 (95% CI 2.6 to 3.0); non-users ratings were 2.6 (95% CI 2.5 to 2.7), 3.7 (95% CI 3.6 to 3.9) and 2.7 (95% CI 2.6 to 2.8), respectively. After 1 year, ratings for medication users were 2.6 (95% CI 2.4 to 2.8) for initiating sleep, 3.6 (95% CI 3.4 to 3.8) for waking frequently and 2.8 (95% CI 2.6 to 3.0) for early morning awakening; for non-users, the mean ratings were 2.3 (95% CI 2.2 to 2.5), 3.5 (95% CI 3.3 to 3.6) and 2.5 (95% CI 2.3 to 2.6), respectively. None of the 1 year changes were statistically significant nor were they different between medication users and non-users. Two-year follow-up results were consistent, without statistically significant reductions in sleep disturbance in medication users compared with non-users.

Conclusions: These analyses suggest that women who initiated sleep medications rated their sleep disturbances similar after 1 and 2 years. The effectiveness of long-term sleep medication use should be re-examined.
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http://dx.doi.org/10.1136/bmjopen-2020-045074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127972PMC
May 2021

Associations between longitudinal trajectories of insomnia symptoms and sleep duration with objective physical function in postmenopausal women: the Study of Women's Health Across the Nation.

Sleep 2021 Aug;44(8)

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Study Objectives: Examine the association between trajectories of self-reported insomnia symptoms and sleep duration over 13 years with objective physical function.

Methods: We utilized data from 1,627 Study of Women's Health Across the Nation participants, aged 61.9 ± 2.7 years at the end of the 13-year follow-up. Latent class growth models identified trajectories of insomnia symptoms (trouble falling asleep, frequent night-time awakenings, and/or early morning awakening) and sleep duration over 13 years. Physical function tests were performed at the end of the 13-year period: 40-ft walk, 4-m walk, repeated chair stand, grip strength, and balance. Multivariable regression analyses examined each physical function measure according to the insomnia symptom or sleep duration trajectory group.

Results: Five insomnia symptom trajectories and two sleep duration trajectories were identified. Women with a consistently high likelihood of insomnia symptoms and women with a decreased likelihood of insomnia symptoms (i.e. improving) had slower gait speed (3.5% slower 40-ft walk [consistently high], 3.7% slower 4-m walk [improving]; each p ≤ .05) than those with a consistently low likelihood of insomnia symptoms. In contrast, women with a steep increase in the likelihood of insomnia symptoms over time and women with persistent insufficient sleep duration had lower odds of having a balance problem (odds ratio [OR] = 0.36 and OR = 0.61, respectively; each p < .02) compared to those with a consistently low likelihood of insomnia symptoms and those with persistent sufficient sleep duration, respectively.

Conclusion: These results suggest that women's sleep during midlife has important implications for maintaining physical function during the transition into older adulthood.
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http://dx.doi.org/10.1093/sleep/zsab059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361301PMC
August 2021

Activity-Based Cost Analysis of Robotic Anatomic Lung Resection During Program Implementation.

Ann Thorac Surg 2021 Feb 16. Epub 2021 Feb 16.

Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address:

Background: While robotic-assisted lung resection has seen a significant rise in adoption, concerns remain regarding initial programmatic outcomes and potential increased costs. We present our initial outcomes and cost analysis since initiation of a robotic lung resection program.

Methods: Patients undergoing either video-assisted thoracoscopic lobectomy or segmentectomy (VATS) or robotic-assisted lobectomy or segmentectomy (RALS) between August of 2014 and January of 2017 underwent retrospective review. Patients underwent 1:1 propensity matching based on preoperative characteristics. Perioperative and 30-day outcomes were compared between groups. Detailed activity-based costing analysis was performed on individual patient encounters taking into effect direct and indirect controllable costs, including robotic operative supplies.

Results: There were no differences in 30-day mortality between RALS (n = 74) and VATS (n = 74) groups (0% vs 1.4%; P = 1). RALS patients had a decreased median length of stay (4 days vs 7 days; P < .001) and decreased median chest tube duration (3 days vs 5 days, P < .001). Total direct costs, including direct supply costs, were not significantly different between RALS and VATS ($6621 vs $6483; P = .784). Median total operating costs and total unit support costs, which are closely correlated to length of stay, were lower in the RALS group. Overall median controllable costs were significantly different between RALS and VATS ($16,352 vs $21,154; P = .025).

Conclusions: A potentially cost-advantageous robotic-assisted pulmonary resection program can be initiated within the context of an existing minimally invasive thoracic surgery program while maintaining good clinical outcomes when compared with traditional VATS. Process-of-care changes associated with RALS may account for decreased costs in this setting.
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http://dx.doi.org/10.1016/j.athoracsur.2021.01.053DOI Listing
February 2021

Intraoperative Remifentanil Infusion and Postoperative Pain Outcomes After Cardiac Surgery-Results from Secondary Analysis of a Randomized, Open-Label Clinical Trial.

J Cardiothorac Vasc Anesth 2021 Feb 2;35(2):458-466. Epub 2020 Sep 2.

Department of Anaesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA.

Design: Report of secondary pain outcomes from a prospective, randomized, open-label clinical trial that compared remifentanil and fentanyl on perioperative hyperglycemic response in cardiac surgery.

Setting: Single institution, tertiary university hospital.

Participants: The study comprised 116 adult elective cardiac surgical patients.

Interventions: Participants were randomly assigned to receive either intermittent fentanyl boluses (F) or continuous remifentanil infusion (R) intraoperatively.

Measurements And Main Results: Postoperative pain was evaluated with pain scores every 6 hours for 48 hours. Pain threshold to mechanical stimuli was measured around the sternotomy incision at 48 and 96 hours. The development of chronic pain was assessed using the numeric rating scale at 1, 3, 6, and 12 months after discharge. The final analysis included 106 patients. Pain scores and wound hyperalgesia were not significantly different postoperatively between the groups. The incidence of chronic pain at 3 months was comparable in both groups (61% in group F v 58% in group R; p = 0.79). Pain of more-than-mild degree was seen in 13 (32%) patients in group F and 8 (19%) in group R (p = 0.25) at 3 months. Median pain scores were not significantly different between the groups at 1, 3, 6, and 12 months after discharge from the hospital.

Conclusions: The present study's findings suggested that intraoperative remifentanil infusion does not significantly worsen pain outcomes in patients undergoing elective cardiac surgery.
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http://dx.doi.org/10.1053/j.jvca.2020.08.064DOI Listing
February 2021

Associations between sleep and cognitive performance in a racially/ethnically diverse cohort: the Study of Women's Health Across the Nation.

Sleep 2021 02;44(2)

Department of Epidemiology, University of Michigan, Ann Arbor, MI.

Study Objectives: To determine whether actigraphy-assessed indices of sleep are associated with cognitive performance in women, and explore whether these associations vary by race/ethnicity.

Methods: Participants were 1,126 postmenopausal community-dwelling females (mean age 65 years) from the observational Study of Women's Health Across the Nation (SWAN); 25% were black, 46% white, 13% Chinese, 11% Japanese, and 5% Hispanic. Actigraphy-assessed sleep measures included total sleep time, wake after sleep onset (WASO), and fragmentation. Cognitive measures included immediate and delayed verbal memory, working memory, and information processing speed. All measures were assessed in conjunction with SWAN annual visit 15.

Results: Across the sample, after covariate adjustment, greater WASO and fragmentation were concurrently associated with slower information processing speed. Black participants had significantly worse sleep relative to other race/ethnic groups. Significant race/sleep interactions were observed; in black, but not white, participants, greater fragmentation was concurrently associated with worse verbal memory and slower information processing speed, and greater WASO was concurrently associated with slower information processing speed. Sleep-cognitive performance associations were not different in Chinese and Japanese participants relative to white participants.

Conclusions: Greater wakefulness and fragmentation during sleep are concurrently associated with slower information processing. Sleep continuity impacted concurrent cognitive performance in black, but not white, women. This effect may not have been detected in white women because their sleep was largely within the normal range. Future longitudinal studies in diverse samples are critical to further understand whether race/ethnicity moderates the influence of sleep on cognitive performance.
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http://dx.doi.org/10.1093/sleep/zsaa182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879413PMC
February 2021

Is race or ethnicity associated with under-utilization of statins among women in the United States: The study of women's health across the nation.

Clin Cardiol 2020 Dec 30;43(12):1388-1397. Epub 2020 Aug 30.

Division of Rheumatology, Division of Pharmacoepidemiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: Rates of statin use among minority women are unclear.

Hypothesis: We hypothesized that statin use would vary by race/ethnicity with lower rates among minority women compared with Whites.

Methods: Data from the study of women's health across the nation, a multiethnic cohort of women collected between 2009 to 2011 were used to examine reported statin use by race/ethnicity and risk profile. Multivariable logistic modeling was performed to estimate the odds ratio (OR) of statin treatment.

Results: Of the 2399 women included, 234 had a diagnosis of atherosclerotic disease (ASCVD), 254 were diabetic (without ASCVD), 163 had an LDL ≥190 mg/dL, and 151 had a 10 year ASCVD pooled risk score ≥7.5%. Statins were used by 49.6% of women with CVD; 59.8% of women with diabetes without known ASCVD; 42.3% of women with an LDL ≥190 mg/dL; and 19.9% of women with an ASCVD risk ≥7.5%. Rates of statin use were 43.8% for women with ≥ two prior ASCVD events and 69.4% for women with ≥ one prior ASCVD event plus multiple high-risk conditions. Among women eligible for statins, Black women had a significantly reduced adjusted odds of being on a statin (OR 0.53, 95% confidence interval [CI] 0.36-0.78) compared with White women.

Conclusions: In this cohort of multiethnic women, rates of statin use among women who would benefit were low, with Black women having lower odds of statin use than White women.
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http://dx.doi.org/10.1002/clc.23448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724205PMC
December 2020

Sleep medications and sleep disturbances across middle aged pre- or peri-menopausal women of different race and ethnicities: A SWAN pharmacoepidemiology cohort study.

Pharmacoepidemiol Drug Saf 2020 12 18;29(12):1715-1721. Epub 2020 Aug 18.

Department of Psychiatry and Department of Preventive Medicine, Rush University Medical Center, Chicago, Illinois, USA.

Purpose: Sleep disturbances are common, particularly in middle aged women. Prescription medications for this indication are increasingly used, despite uncertain safety. This study assessed prescription medication use for sleep among a cohort of women with and without sleep disturbances.

Methods: We examined reports of sleep disturbance and sleep medication use among pre- and early peri-menopausal womenassessed annually or biennially since 1996. Women self-reported medications at visits, and we identified medications that have been used primarily for sleep disturbances. They reported on difficulties falling and staying asleep, and early morning wakening. Sleep medication use across 20 years of follow-up was examined for all women and by race/ethnicity. Women who reported data for both sleep disturbance and sleep medication use were included in the analyses..

Results: Among participants in a cohort of 3302 women who were enrolled prior to their menopause transition, 3082 women were included in the analytic sample and 2531 (82%) reported sleep disturbances. They were more likely to endorse higher anxiety and pain scores and more comorbid conditions than women without sleep disturbances. Baseline characteristics were similar among women who did and did not use sleep medications. Among women reporting a sleep disturbance at baseline, 2.5% reported sleep medication use, increasing to 8% over 20 years. However, the proportion of women reporting sleep medication use who did not report a sleep disturbance remained low, approximately 1% to 2% over the entire follow-up. Increases in sleep medication use was observed across women of all race/ethnicities.

Conclusions: The use of sleep medications among women reporting sleep disturbance grew over the last 20 years. Growth was observed across women of all race/ethnicities.
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http://dx.doi.org/10.1002/pds.5102DOI Listing
December 2020

Trajectory analysis of sleep maintenance problems in midlife women before and after surgical menopause: the Study of Women's Health Across the Nation (SWAN).

Menopause 2020 03;27(3):278-288

Department of Preventive Medicine, Rush University Medical Center, Chicago, IL.

Objective: Investigate temporal patterns of sleep maintenance problems in women who became surgically menopausal (hysterectomy with bilateral oophorectomy) before their final menstrual period and examine whether presurgery trajectories of sleep maintenance problems are related to problems staying asleep postsurgery.

Methods: Longitudinal analysis of sleep self-reports collected every 1 to 2 years from 1996 to 2013 from 176 surgically menopausal women in the Study of Women's Health Across the Nation, a seven-site community-based, multiethnic/multiracial, cohort study. Median follow-up was 15.3 years (4.2 years presurgery, 10.2 years postsurgery). Group-based trajectory modeling was used to identify patterns of problems staying asleep, and the presurgery trajectories were used to predict similar postsurgery sleep problems.

Results: Four trajectory patterns of sleep maintenance problems were identified: low (33.5% of women), moderate (33.0%), increasing during presurgery (19.9%), and high (13.6%). One-fifth of women reported a presurgery increase in these problems. Postsurgically, problems staying asleep remained associated with similar levels of presurgical problems, even after adjusting for postsurgical early morning awakening, frequent vasomotor symptoms, and bodily pain score (βlow = -1.716, βmoderate = -1.144, βincreasing = -0.957, βhigh = -1.021; all P values <0.01).

Conclusions: Sleep maintenance problems were relatively stable across time postsurgery. These data are remarkably consistent with our trajectory results across the natural menopause, suggesting that presurgical assessment of sleep concerns could help guide women's expectations postsurgically. Although reassuring that sleep complaints do not worsen postsurgically for most surgically menopausal women, referral to a sleep specialist should be considered if sleep symptoms persist or worsen after surgery.
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http://dx.doi.org/10.1097/GME.0000000000001475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047569PMC
March 2020

30-Day unanticipated healthcare encounters after prolapse surgery: impact of same day discharge.

Am J Obstet Gynecol 2020 05 13;222(5):482.e1-482.e8. Epub 2019 Nov 13.

Department of Obstetrics, Gynecology and Reproductive Sciences of the University of Pittsburgh, Division of Urogynecology and Pelvic Reconstructive Surgery, Magee-Womens Hospital of the University of Pittsburgh Medical Center.

Background: Same-day discharge is becoming increasingly common in gynecologic surgery; however, data are limited for frequency, setting, and severity of unanticipated healthcare visits for women who are discharged on the day of surgery after major prolapse repair.

Objective: The purpose of this study was to evaluate whether discharge on the day of surgery is associated with increased 30-day unanticipated healthcare encounters after major pelvic organ prolapse surgery compared with discharge on or after postoperative day 1.

Study Design: This is a retrospective analysis of women who underwent pelvic organ prolapse surgery by 8 female pelvic medicine and reconstructive surgery surgeons from January 2016 to October 2017. Unanticipated healthcare encounter was a composite variable of any visit to the office, emergency department, or hospital readmission. Number of visits, visit diagnoses, and complication severity (Clavien-Dindo classification) were compared by day of discharge with the use of χ2 tests. Multivariable analyses were performed.

Results: Of 405 women, 258 (63.7%) were discharged on the day of surgery, and 147 (36.3%) were discharged on postoperative day 1 or later. Mean age was 66±11 years, body mass index was 27.9±4.8 kg/m. Most had stage III prolapse (n=273; 67.4%). Procedures included laparoscopic or robotic sacrocolpopexy, (n=163; 40.2%), vaginal apical suspensions (n=115; 28.4%), obliterative (n=105; 25.9%), and concomitant hysterectomy (n=229; 56.5%). There was no increase in the number of women with at least 1 unanticipated healthcare encounter within 30 days of surgery, based on discharge on the day of surgery compared with postoperative day 1 (24.0% vs 26.5%; P=.572). The majority of visits occurred in the office (17.8% vs 19.0%; P=.760). There was no increase in 30-day readmissions (3.5% vs 4.8%; P=.527). The most common visit diagnosis was pain and accounted for 31.5% of all visits, followed by urologic and gastrointestinal symptoms. Diagnoses and complication severity did not vary by day of discharge, except that women who were discharged on the day of surgery were more likely to have a superficial wound separation (11.3% vs 0%; P=.011) and less likely to experience grade II complications (7.4% vs 15.6%, P=.009). Few women had >1 unscheduled visit, and rates were similar between the 2 groups (6.2% vs 6.8%; P=.810). On multivariable regression, younger women (adjusted odds ratio, 1.03; 95% confidence interval, 1.001-1.05), those with lower body mass index (adjusted odds ratio, 1.07; 95% confidence interval, 1.13-1.01), and higher initial postanesthesia recovery unit pain scores (adjusted odds ratio, 1.11; 95% confidence interval, 1.02-1.21) were more likely to have an unanticipated healthcare encounter. Pain complaints were evaluated most often in the office compared with the emergency department (41.1% vs 13.0%); medical complications such as cardiac (15.6% vs 0%) and respiratory (6.5% vs 0%) were more likely to be evaluated in the emergency department. Higher grade complications (II/III) were more likely to visit the emergence department (78.2% vs 27.1%; P<.0001).

Conclusion: Same-day discharge after prolapse surgery did not result in an increase in 30-day unanticipated healthcare encounters.
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http://dx.doi.org/10.1016/j.ajog.2019.11.1249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347073PMC
May 2020

Blood pressure lowering medication initiation and fracture risk: a SWAN pharmacoepidemiology study.

Arch Osteoporos 2019 06 28;14(1):73. Epub 2019 Jun 28.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

We examined the fracture risk after initiation of blood pressure-lowering drugs compared with initiation of antidepressants. Multivariable regression models demonstrated an increased risk of fracture among women initiating a blood pressure-lowering medication (HR 1.73, 95% CI 1.02-2.95). This is likely related to an increased risk of falls.

Purpose: Initiation of blood pressure-lowering drugs has been associated with fractures in several studies, presumably due to an increase in the risk of falls. However, these studies used self-controlled designs without active comparators. We examined the risk of fractures after initiation of blood pressure lowering drugs compared with initiation of antidepressants.

Methods: Women participants in the Study of Women Across the Nation (SWAN) were potentially eligible if they initiated blood pressure-lowering or antidepressant drugs during follow-up. To reduce the risk of confounding, we estimated a propensity score that included potential confounders including age, menopausal status, osteoporosis, and osteoporosis medication use. The propensity score was used to match subjects in both groups and we then constructed multivariable logistic regression models comparing the risk of any fracture. Sensitivity analyses assessed a limited range of fractures less likely related to trauma.

Results: Among the 3302 potentially eligible women participating in the SWAN cohort, we were able to propensity-score match 289 women who initiated a blood pressure-lowering medication with 289 who initiated an antidepressant. Multivariable logistic regression models demonstrated an increased risk of fracture among women initiating a blood pressure lowering medication (OR 1.74, 95% CI 1.02-2.95). After excluding fractures of the digits and face, the results were similar (OR 1.57, 95% CI 0.88-2.81).

Conclusions: There was evidence of an increased risk in fractures among women initiating blood pressure-lowering medications compared to those initiating antidepressants. This is likely related to an increased risk of falling.
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http://dx.doi.org/10.1007/s11657-019-0618-xDOI Listing
June 2019

Variables associated with an inability to learn clean intermittent self-catheterization after urogynecologic surgery.

Int Urogynecol J 2020 07 23;31(7):1401-1407. Epub 2019 May 23.

Division of Urogynecology, Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh Medical Center, Magee-Womens Hospital, 300 Halket Street, Pittsburgh, PA, 1528, USA.

Introduction And Hypothesis: Post-operative urinary retention is a common problem affecting close to half of all women undergoing pelvic reconstructive surgery. This was an exploratory analysis that was aimed at identifying factors associated with an inability to learn clean intermittent self-catheterization (CISC) after a failed post-operative retrograde voiding trial (RGVT).

Methods: We performed a retrospective case-control study of women who underwent pelvic organ prolapse or urinary incontinence surgery within a single division from 2016 to 2018. We compared women who could learn CISC with those unable to learn and discharged home with an indwelling catheter (IC). Analyses were carried out using Fisher's exact test, the Mann-Whitney U test, the Chi-squared test, and the t test with logistic regression.

Results: Of the 202 women who failed their RGVT, 134 (66.3%) were able to learn CISC and 68 (33.7%) were not. Older age, urinary incontinence, diabetes and colpectomy/colpocleisis were associated with an inability to learn CISC (p < 0.05). Women with an IC were more likely to have an office visit related to catheter care (65.7% vs 5.2%, p < 0.001). A UTI within 30 days of surgery was more common with CISC (16.4% vs 6.0%, p = 0.037). In a multivariate logistic regression model, each increasing year of age was associated with a 1.036-fold decrease in the ability to learn CISC (aOR 1.036, 95% CI 1.002-1.071; p = 0.04).

Conclusions: Increasing age was the only variable identified on multivariate logistic regression as a risk factor for failure to learn CISC. Further studies are needed to identify barriers to learning post-operative self-catheterization.
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http://dx.doi.org/10.1007/s00192-019-03974-1DOI Listing
July 2020

Assessing the Performance of the De Novo Postoperative Stress Urinary Incontinence Calculator.

Female Pelvic Med Reconstr Surg 2021 01;27(1):23-27

Department of Obstetrics, Gynecology and Reproductive Sciences of the University of Pittsburgh, Division of Urogynecology and Reconstructive Surgery, Magee-Womens Hospital of UPMC, Pittsburgh, PA.

Objective: The aim of the study was to determine the performance of a previously published stress urinary incontinence (SUI) risk calculator in women undergoing minimally invasive or transvaginal apical suspensions.

Methods: Using a database of stress-continent women who underwent minimally invasive or transvaginal apical suspensions, we calculated 2 prediction risks for development of SUI within 12 months based on inclusion of a "prophylactic" midurethral sling at the time of prolapse surgery. Observed subjective and objective continence status was abstracted from medical records. Regression models were created for the outcome of de novo SUI to generate receiver operating curves. Concordance (c) indices were estimated for the overall and procedure subgroups to determine the calculator's ability to discriminate between SUI outcomes.

Results: Analyses included 502 women. De novo SUI was observed in 23.5% of women. The mean ± SD calculated risk of de novo SUI if a sling was performed was 18.9% ± 13.9 at 12 months compared with 36.4% ± 8.3 without sling. The calculator's discriminative ability for those with a planned sling was moderate (c-index = 0.55, P = 0.037). The calculator failed to discriminate continence outcomes when a sling was not planned in the overall group (c-index = 0.50, P = 0.799) and individual apical procedures.

Conclusions: The SUI risk calculator is significantly limited in its ability to predict de novo SUI in our population of women planning minimally invasive apical suspensions. Refinements to the calculator model are needed to improve its utility in clinical practice.
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http://dx.doi.org/10.1097/SPV.0000000000000717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764919PMC
January 2021

Changes in body composition and weight during the menopause transition.

JCI Insight 2019 03 7;4(5). Epub 2019 Mar 7.

Department of Medicine, Division of Geriatrics, UCLA, Los Angeles, California, USA.

Background: The relation between the menopause transition (MT) and changes in body composition or weight remains uncertain. We hypothesized that, independent of chronological aging, the MT would have a detrimental influence on body composition.

Methods: Participants were from the longitudinal Study of Women's Health Across the Nation (SWAN) cohort. We assessed body composition by dual energy x-ray absorptiometry. Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of outcomes as a function of time before or after the final menstrual period (FMP). Covariates were age at FMP, race, study site, and hormone therapy.

Results: Fat and lean mass increased prior to the MT. At the start of the MT, rate of fat gain doubled, and lean mass declined; gains and losses continued until 2 years after the FMP. After that, the trajectories of fat and lean mass decelerated to zero slope. Weight climbed linearly during premenopause without acceleration at the MT. Its trajectory became flat after the MT.

Conclusion: Accelerated gains in fat mass and losses of lean mass are MT-related phenomena. The rate of increase in the sum of fat mass and lean mass does not differ between premenopause and the MT; thus, there is no discernable change in rate of weight gain at the start of the MT.

Funding: NIH, Department of Health and Human Services (DHHS), through the National Institute on Aging, National Institute of Nursing Research, and NIH Office of Research on Women's Health (U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495).
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http://dx.doi.org/10.1172/jci.insight.124865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483504PMC
March 2019

Serum Sex Hormones and the Risk of Fracture Across the Menopausal Transition: Study of Women's Health Across the Nation.

J Clin Endocrinol Metab 2019 06;104(6):2412-2418

University of California, Los Angeles, Los Angeles, California.

Context: Sex steroid hormones have been linked to fractures in older women.

Objective: To test the hypothesis that hormones measured over the menopausal transition predict fractures.

Setting: Seven US clinical centers.

Subjects And Measurements: Two thousand nine hundred sixty women (average age, 46.4 ± 2.7 years) who had at least two repeat hormone measures and prospective information on fractures. Fasting serum was collected annually for hormone assays. Estradiol (E2) was measured with a modified direct immunoassay. FSH and SHBG were measured with two-site chemiluminescence immunoassays. Hormones were lagged (visit year -1) and transformed using log base 2. Incident fractures were ascertained at each annual visit. All medications including hormone therapy were time varying covariates. Discrete survival methods were used.

Results: Five hundred eight (17.2%) women experienced an incident fracture over an average follow up of 8.8 ± 4.4 years. Women who experienced an incident fracture were more likely to be white, report high alcohol intake and diabetes, and less likely to report premenopausal status at baseline. A woman whose log E2 was twice that of another had a 10% lower risk of fracture independent of covariates, relative risk (95% CI) = 0.90 (0.82, 0.98). Neither FSH nor SHBG were associated with fractures.

Conclusions: Serum E2 levels may help to identify women at higher risk of fractures over the menopausal transition. However, hormone assays must be standardized across laboratories for clinical implementation and further work is needed to define E2 thresholds.
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http://dx.doi.org/10.1210/jc.2018-02047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505454PMC
June 2019

Implementation of a urogynecology-specific enhanced recovery after surgery (ERAS) pathway.

Am J Obstet Gynecol 2018 11 18;219(5):495.e1-495.e10. Epub 2018 Jun 18.

Department of Obstetrics, Gynecology and Reproductive Sciences of the University of Pittsburgh, Division of Urogynecology and Pelvic Reconstructive Surgery, Magee-Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA.

Objective: Enhanced recovery after surgery protocols were developed for colorectal surgery to hasten postoperative recovery. Variations of the protocol are being adopted for gynecological procedures despite limited population and procedure-specific outcome data. Our objective was to evaluate whether implementation of an enhanced recovery after surgery pathway would facilitate reduced length of admission in a urogynecology population.

Materials And Methods: In this retrospective analysis of patients undergoing pelvic floor reconstructive surgery by 7 female pelvic medicine and reconstructive surgeons, we compared same-day discharge, length of admission and postoperative complications before and after implementation of an enhanced recovery after surgery pathway at a tertiary care hospital. Groups were compared using χ and Student t tests. Candidate variables that could have an impact on patient outcomes with P < .2 were included in multivariable logistic regression models. Satisfaction with surgical experience was assessed using a phone-administered questionnaire the day after discharge.

Results: Mean age and body mass index of 258 women (137 before enhanced recovery after surgery and 121 enhanced recovery after surgery) were 65.5 ± 11.3 years and 28.2 ± 5.0 kg/m. The most common diagnosis was pelvic organ prolapse (n = 242, 93.8%) including stage III pelvic organ prolapse (n = 61, 65.1%). Apical suspension procedures included 58 transvaginal (25.1%), 112 laparoscopic/robotic (48.8%), and 61 obliterative (26.4%). Hysterectomy was performed in 57.4% of women. Demographic and surgical procedures were similar in both groups. Compared with before enhanced recovery after surgery, the enhanced recovery after surgery group had a higher proportion of same-day discharge (25.9% vs 91.7%, P < .001) and a 13.8 hour shorter duration of stay (25.9 ± 13.5 vs 12.1 ± 11.2 hours, P <.001). Operative and postsurgical recovery room times were similar (2.6 ± 0.8 vs 2.6 ± 0.9 hours, P =.955; 3.7 ± 2.1 vs 3.6 ± 2.2 hours, P = .879). Women in the enhanced recovery after surgery group were more likely to be discharged using a urethral catheter (57.9% enhanced recovery after surgery vs 25.4% before enhanced recovery after surgery, P = .005). There were no group differences in total 30 day postoperative complications overall and for the following categories: urinary tract infections, emergency room visits, unanticipated office visits, and return to the operating room. However, enhanced recovery after surgery patients had higher 30 day hospital readmission rates (n = 8, 6.7% vs n = 2, 1.5%, P = .048). Patients before enhanced recovery after surgery were readmitted for myocardial infarction and chest pain. Enhanced recovery after surgery patients were admitted for weakness, chest pain, hyponatremia, wound complications, nausea/ileus, and ureteral obstruction. Three enhanced recovery after surgery patients returned to the operating room for ureteral obstruction (n = 1), incisional hernia (n = 1), and vaginal cuff bleeding (n = 1). Enhanced recovery after surgery patients also had more postoperative nursing phone notes (2.6 ± 1.7 vs 2.1 ± 1.4, P = .030). On multivariable logistic regressions adjusting for age and operative time, same-day discharge was more likely in the enhanced recovery after surgery group (odds ratio, 32.73, 95% confidence interval [15.23-70.12]), while the odds of postoperative complications and emergency room visits were no different. After adjusting for age, operative time, and type of prolapse surgery, readmission was more likely in the enhanced recovery after surgery group (odds ratio, 32.5, 95% confidence interval [1.1-28.1]). In the enhanced recovery after surgery group, patient satisfaction (n = 77 of 121) was reported as very good or excellent by 86.7% for pain control, 89.6% for surgery preparedness, and 93.5% for overall surgical experience; 89.6% did not recall any postoperative nausea during recovery.

Conclusion: Enhanced recovery after surgery implementation in a urogynecology population resulted in a greater proportion of same-day discharge and high patient satisfaction but with slightly increased hospital readmissions within 30 days.
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http://dx.doi.org/10.1016/j.ajog.2018.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212495PMC
November 2018

Optimal Oblique Radiographs to Identify Fifth Carpometacarpal Dorsal Subluxations: A Cadaveric Study.

J Hand Surg Am 2018 Dec 22;43(12):1139.e1-1139.e5. Epub 2018 May 22.

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA. Electronic address:

Purpose: Carpometacarpal (CMC) joint subluxations of the fifth finger are rare injuries and are notoriously difficult to diagnose due to severe swelling and overlapping of bones on radiographs. Various radiographic studies have been suggested to identify these injuries. We hypothesize that there will be no difference between various oblique radiographs for detection of a fifth finger CMC subluxation.

Methods: Using 4 cadaveric specimens, we took radiographs at various angles (0°, 30°, 45°, and 60°) with the fifth metacarpal in anatomic position, subluxated 25% and 50% dorsally. Radiology and orthopedic residents, fellows, and attending physicians viewed each image to determine whether a subluxation was present. Data were analyzed using area under the receiver operating curve, sensitivity, and specificity.

Results: A total of 36 responses were obtained from 9 radiologists (4 residents, 3 fellows, 2 attendings) and 27 orthopedic surgeons (16 residents, 8 fellows, 3 attendings). Radiographs taken at 60° were more sensitive and specific (Sn 85, Sp 60) than at 0° (Sn 64, Sp 33), 30° (Sn 84, Sp 47), or 45° (Sn 80, Sp 49). Area under the receiver operating curve was also higher for 60° (0.87) than 0° (0.59), 30° (0.75), and 45° (0.75).

Conclusions: Sensitivity, specificity, and area under the receiver operating curve were highest for 60° radiographs. We recommend obtaining radiographs of the hand in 60° of pronation from the lateral if there is suspicion for a fifth CMC subluxation or dislocation.

Clinical Relevance: This study suggests a simple radiographic view to enhance the diagnosis of fifth CMC subluxations.
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http://dx.doi.org/10.1016/j.jhsa.2018.04.012DOI Listing
December 2018

Cyclophosphamide for Refractory Acute Cellular Rejection After Lung Transplantation.

Transplant Direct 2018 May 26;4(5):e350. Epub 2018 Apr 26.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA.

Background: Acute cellular rejection (ACR) is a major risk factor for chronic lung allograft dysfunction after lung transplantation. Acute cellular rejection can persist or recur despite augmentation of immunosuppression by conventional methods. There are limited therapeutic options in treating these recurrent and refractory ACRs. We describe our experience with cyclophosphamide therapy for recurrent and refractory ACR in lung transplant recipients.

Methods: Six consecutive patients who were treated with cyclophosphamide for recurrent or refractory ACR were included in the series. The primary outcome measures were improvement in ACR score and forced expiratory volume at 1 second. Secondary outcome measures included adverse drug events including bone marrow suppression, gastrointestinal side effects, and infections.

Results: Five of the 6 patients treated demonstrated complete resolution of ACR on follow-up biopsies. Acute cellular rejection score improved after cyclophosphamide treatment ( = 0.03). None of the patients had high grade (≥A3) ACR in the 3 months after cyclophosphamide administration. Cyclophosphamide had no effect on forced expiratory volume at 1 second trend or bronchiolitis obliterans score. All patients tolerated cyclophosphamide with minor gastrointestinal side effects, mild bone marrow suppression, and nonfatal infections that were amenable to treatment.

Conclusions: Cyclophosphamide therapy is an option in treating recurrent and refractory ACR in patients who have failed conventional treatments. Cyclophosphamide is tolerated well without serious adverse drug events (ADE).
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http://dx.doi.org/10.1097/TXD.0000000000000790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959344PMC
May 2018

Global quality assessment of liver allograft C4d staining during acute antibody-mediated rejection in formalin-fixed, paraffin-embedded tissue.

Hum Pathol 2018 03 27;73:144-155. Epub 2017 Dec 27.

Department of Pathology, University of Pittsburgh Medical Center, UPMC Montefiore University Hospital, Pittsburgh, PA 15213, USA. Electronic address:

Discussion of liver antibody-mediated rejection during the 2011, 2013, and 2015 Banff liver sessions raised concerns over reliability of complement fragment 4d (C4d) staining, precipitating a global survey followed by a tissue microarray staining quality assessment study among centers on formalin-fixed, paraffin-embedded tissue. Tissue microarray sections containing tissue plugs of resected native and allograft (with acute antibody-mediated rejection) liver, heart, and kidney (n = 33 total cores) were sent to 31 centers for C4d staining using local method(s) and pathologist scoring. Digital whole-slide images (n = 40) were then semiquantitatively scored by 7 experts for background, distribution, and intensity of portal vein and capillary, hepatic artery, sinusoidal, and central vein endothelia and portal and central stromal staining. Results showed that strong and diffuse portal vein and capillary C4d staining, as determined by both local and central pathologists, clearly distinguished allografts showing acute antibody-mediated rejection from native livers and from those with evidence of weaker donor-specific antibody. Downstream vascular endothelial cell C4d staining and assessment were more variable and difficult to identify. C4d staining in the majority of laboratories reliably detects acute liver allograft antibody-mediated rejection in formalin-fixed, paraffin-embedded tissues. Assessment should focus on portal veins and capillaries, sinusoids, and central veins present in peripheral core needle biopsies. C4d staining in one organ does not always translate to staining in another.
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http://dx.doi.org/10.1016/j.humpath.2017.12.007DOI Listing
March 2018

Effects of analgesics on bone mineral density: A longitudinal analysis of the prospective SWAN cohort with three-group matching weights.

Pharmacoepidemiol Drug Saf 2018 02 12;27(2):182-190. Epub 2017 Dec 12.

Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, USA.

Purpose: To examine the effects of analgesics on bone mineral density (BMD), which have not been examined in a longitudinal study with multiple measurements.

Methods: We investigated changes in BMD associated with new use of analgesics in a prospective longitudinal cohort of mid-life women. BMD and medication use were measured annually. We compared BMD among new users of acetaminophen, NSAIDs, and opioids. Adjustment for baseline covariates was conducted through propensity score matching weights. On-treatment analysis was conducted with inverse probability of censoring weights. Analysis based on the initial treatment group was also conducted to provide insights into selection bias. Repeated BMD measurements were examined with generalized estimating equations.

Results: We identified 71 acetaminophen new users, 659 NSAID new users, and 84 opioid new users among 2365 participants. In the on-treatment analysis, the opioid group in comparison to the acetaminophen group had an additional average BMD decline of -0.06% [-1.24, 1.11] per year in the spine and -0.45% [-1.51, 0.61] per year in the femoral neck. BMD mean trajectories over time suggested a fifth-year decline in the opioid persistent users compared with other 2 groups. In the initial treatment group analysis, all 3 groups showed similar trajectories.

Conclusion: The BMD decline over time was similar among the 3 groups. However, 5 years of continuous opioid use may be associated with a greater BMD decline than 5 years on other analgesics. Further studies examining the relationship between very long-term persistent opioid use and BMD are warranted.
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http://dx.doi.org/10.1002/pds.4362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799005PMC
February 2018

Prospective Study of the Impact of Liver Biopsy Core Size on Specimen Adequacy and Procedural Complications.

AJR Am J Roentgenol 2018 Jan 1;210(1):183-188. Epub 2017 Nov 1.

4 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objective: An American Association for the Study of Liver Diseases (AASLD) consensus document stressed the importance of obtaining sufficient liver biopsy specimens to minimize sampling errors. Many centers continue to use smaller-diameter core systems to minimize perceived complication risks. The objective of this study was to assess the impact of core gauge (18- vs 16-gauge) on specimen adequacy and procedural complications.

Subjects And Methods: One hundred fifty patients referred for liver biopsy were randomized to undergo 16- or 18-gauge ultrasound (US)-guided core biopsy. Hemorrhage was qualitatively evaluated, and pain was assessed using a 10-point rating scale. The length and number of portal tracts per specimen were assessed. On the basis of the AASLD guidelines, specimen adequacy was defined as 11 or more portal tracts. Differences in pathology metrics and pain scoring were assessed using chi-square and linear regression models.

Results: No significant hemorrhage occurred in either group, and there was no difference in postbiopsy pain scores. The mean specimen length obtained with 16-gauge needles was less than that obtained with 18-gauge needles (1.7 vs 1.9 cm, p = 0.03). The mean number of portal tracts obtained with 16-gauge biopsies was greater than obtained with 18-gauge systems (14 vs 13, p = 0.03); 85% of 16-gauge biopsy specimens and 80% of 18-gauge biopsy specimens were adequate on the basis of the AASLD criteria, although this difference was not statistically significant.

Conclusion: US-guided 18- and 16-gauge core biopsies are similarly safe. A large percentage of 18- or 16-gauge specimens are inadequate when AASLD quality control adequacy thresholds are applied, and specimen adequacy is not significantly affected by biopsy gauge.
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http://dx.doi.org/10.2214/AJR.17.17792DOI Listing
January 2018

Sleep Trajectories Before and After the Final Menstrual Period in The Study of Women's Health Across the Nation (SWAN).

Curr Sleep Med Rep 2017 Sep 5;3(3):235-250. Epub 2017 Aug 5.

Department of Psychiatry, Brigham and Women's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA.

Purpose Of Review: Longitudinal studies show that the menopausal transition (MT) is associated with poorer self-reported sleep. Increases in sleep disturbances across and beyond the MT are strongly associated with vasomotor symptoms (VMS) but occur even without VMS. We analyzed data from baseline through 13 annual or biennial follow-up assessments from SWAN's multi-racial/ethnic cohort of midlife women, specifically focusing on patterns of sleep problems in the years preceding and following the final menstrual period (FMP). The FMP demarcated the MT and the postmenopausal period. We addressed the following questions: (1) are there distinct trajectory patterns of sleep problems across the MT, and (2) do pre-FMP sleep trajectories predict sleep problems around the time of FMP (trans-FMP) and post-FMP? Group-based trajectory modeling using repeated measures log-binomial regression with generalized estimating equation methods was used to describe trajectory patterns of the most prevalent sleep problem, waking several times at least 3 nights weekly during the previous 2 weeks, in 1,285 naturally menopausal women.

Recent Findings: We found (1) 4 distinct trajectories for waking several times per night across the MT [low prevalence (n=487; 37.9%), moderate prevalence (n=365; 28.4%), increasing prevalence (n=197; 15.3%), and high prevalence (n=236; 18.4%)], (2) the prevalence of sleep problems increased overall, but in one trajectory group (increasing prevalence) more than in the other three, and (3) trouble falling asleep, early morning awakening, and frequent VMS were strongly associated with problems waking several times that persist into postmenopause.

Summary: Using trajectory analysis, we showed that, in general, awakenings were stable from pre-FMP to post-FMP.
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http://dx.doi.org/10.1007/s40675-017-0084-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604858PMC
September 2017

Effect of Race and Ethnicity on Antihypertensive Medication Utilization Among Women in the United States: Study of Women's Health Across the Nation (SWAN).

J Am Heart Assoc 2017 Feb 23;6(3). Epub 2017 Feb 23.

Division of Rheumatology, Division of Pharmacoepidemiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Background: Antihypertensive medication use may vary by race and ethnicity. Longitudinal antihypertensive medication use patterns are not well described in women.

Methods And Results: Participants from the Study of Women's Health Across the Nation (SWAN), a prospective cohort of women (n=3302, aged 42-52), who reported a diagnosis of hypertension or antihypertensive medication use at any annual visit were included. Antihypertensive medications were grouped by class and examined by race/ethnicity adjusting for potential confounders in logistic regression models. A total of 1707 (51.7%) women, mean age 50.6 years, reported hypertension or used antihypertensive medications at baseline or during follow-up (mean 9.1 years). Compared with whites, blacks were almost 3 times as likely to receive a calcium channel blocker (odds ratio, 2.92; 95% CI, 2.24-3.82) and twice as likely to receive a thiazide diuretic (odds ratio, 2.38; 95% CI, 1.93-2.94). Blacks also had a higher probability of reporting use of ≥2 antihypertensive medications (odds ratio, 1.95; 95% CI, 1.55-2.45) compared with whites. Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and thiazide diuretics increased over time for all racial/ethnic groups. Contrary to our hypothesis, rates of β-blocker usage did not decrease over time.

Conclusions: Among this large cohort of multiethnic midlife women, use of antihypertensive medications increased over time, with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers becoming the most commonly used antihypertensive medication, even for blacks. Thiazide diuretic utilization increased over time for all race/ethnic groups as did use of calcium channel blockers among blacks; both patterns are in line with guideline recommendations for the management of hypertension.
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http://dx.doi.org/10.1161/JAHA.116.004758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524010PMC
February 2017

Characterizing the trajectories of vasomotor symptoms across the menopausal transition.

Menopause 2016 10;23(10):1067-74

1Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 2Division of Reproductive Endocrinology and Infertility, University of Michigan Health System, Ann Arbor, MI 3Department of Medicine, University of Massachusetts Medical School, Worcester, MA 4Department of Public Health Sciences, University of California Davis School of Medicine, Davis, CA 5Department of Population Health & Reproduction, University of California, Davis, CA 6Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 7Women's Hormones and Aging Research Program, Brigham and Women's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 8Department of Population Health Sciences, Univerisity of Utah, Salt Lake City, UT 9Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC 10Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI.

Objective: The aim of the study was to investigate the heterogeneity of temporal patterns of vasomotor symptoms (VMS) over the menopausal transition and identify factors associated with these patterns in a diverse sample of women.

Methods: The Study of Women's Health Across the Nation is a multisite longitudinal study of women from five racial/ethnic groups transitioning through the menopause. The analytic sample included 1,455 women with nonsurgical menopause and a median follow-up of 15.4 years. Temporal patterns of VMS and associations with serum estradiol and follicle-stimulating hormone, race/ethnicity, body mass index, and demographic and psychosocial factors were examined using group-based trajectory modeling.

Results: Four distinct trajectories of VMS were found: onset early (11 years before the final menstrual period) with decline after menopause (early onset, 18.4%), onset near the final menstrual period with later decline (late onset, 29.0%), onset early with persistently high frequency (high, 25.6%), and persistently low frequency (low, 27.0%). Relative to women with persistently low frequency of VMS, women with persistently high and early onset VMS had a more adverse psychosocial and health profile. Black women were overrepresented in the late onset and high VMS subgroups relative to white women. Obese women were underrepresented in the late onset subgroup. In multivariable models, the pattern of estradiol over the menopause was significantly associated with the VMS trajectory.

Conclusions: These data distinctly demonstrate heterogeneous patterns of menopausal symptoms that are associated with race/ethnicity, reproductive hormones, premenopause body mass index, and psychosocial characteristics. Early targeted intervention may have a meaningful impact on long-term VMS.
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http://dx.doi.org/10.1097/GME.0000000000000676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028150PMC
October 2016
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