Citations

Purpose To describe attitudes of first- and second-year U.S. medical students toward value-added medical education, assess their self-reported desire to participate in value-added activities, and identify potentially modifiable factors influencing their engagement. Method The authors conducted a cross-sectional survey of first- and second-year students at nine U.S. medical schools in 2017. Survey items measured students’ attitudes toward value-added medical education (n = 7), desire to participate in value-added activities (n = 20), and factors influencing potential engagement (n = 18). Results Of 2,670 students invited to participate, 1,372 (51%) responded. Seventy-six percent (1,043/1,368) moderately or strongly agreed they should make meaningful contributions to patient care. Students’ desire to participate was highest for patient care activities approximating those traditionally performed by physicians, followed by systems improvement activities and lowest for activities not typically performed by physicians. Factors increasing desire to participate included opportunities to interact with practicing physicians (1,182/1,244; 95%), patients (1,177/1,246; 95%), and residents or fellows (1,166/1,246; 94%). Factors decreasing desire to participate included making changes to the health care system (365/1,227; 30%), interacting with patients via phone or electronic communication (410/1,243; 33%), and lack of curricular time (634/1,233; 51%). Conclusions First- and second-year medical students agree they should add value to patient care, but their desire to participate in value-added activities varies depending on the nature of the tasks. Medical schools may be able to increase students’ desire to participate by enabling face-to-face interactions with patients, embedding students in health care teams, and providing dedicated curricular time.

Abstract Background Sexual dysfunction is often complex and biopsychosocial. Traditional sexual health care management involves individual providers not in a multi-disciplinary setting. A multi-disciplinary team may consist of a medical provider, pelvic floor physical therapist, and sex therapist. Aim The aim was to explore the patient perceptions of benefit from management of their sexual dysfunction by a biopsychosocial multi-disciplinary team. Methods A survey was e-mailed to women patients seen by multi-disciplinary teams at 2 different settings: San Diego Sexual Medicine or Mayo Clinic Women's Health Clinic during a 27-month period. Data are reported using summary statistics for age and count for remaining survey responses. Cochran-Armitage tests for trend were used to compare pre- and post-comfort levels. Outcomes Main outcome measures included perceived benefit of being managed in a team-based model of care, level of benefit and satisfaction from each provider, and difference from pre-conceived level of comfort to actual comfort after each provider visit. Results 89 of 270 e-mailed surveys were analyzed. Patient populations (mean age 47.6, range 23–77 years) were similar between sites. Overall, 82% of respondents reported moderate/great benefit from the team-based model; 72.1% reported management by all 3 providers valuable/extremely valuable; and 84.3% were somewhat/very satisfied with the model. Women endorsed specific ways in which they benefitted from the team-based model including: improved sexual function (58.1%), feeling validated (72.1%) and listened to (62.8%), that they better understood their health concerns (65.1%), that their partner better understood their health concerns (46.5%), and feeling normal (46.5%). There were no significant differences between the 2 clinics in terms of patient-perceived benefit, value, or satisfaction. Conclusions The team-based model of care for management of sexual dysfunction in women including a medical provider, physical therapist, and sex therapist is associated with patient-perceived benefit, satisfaction, and value.

Gynecologic cancers are common in the United States and represent a significant health burden. Treatment of these cancers often causes premature cessation of ovarian function, with resultant symptoms that are often more severe than those associated with natural menopause. Hormone therapy is the most effective treatment for menopausal symptoms, but the decision-making process about its use can be complex for survivors of gynecologic cancer. In this review, we provide evidence-based recommendations about the use of hormone therapy after gynecologic cancer.

Abstract The objective of The North American Menopause Society (NAMS) and The International Society for the Study of Women's Sexual Health (ISSWSH) Expert Consensus Panel was to create a point of care algorithm for treating genitourinary syndrome of menopause (GSM) in women with or at high risk for breast cancer. The consensus recommendations will assist healthcare providers in managing GSM with a goal of improving the care and quality of life for these women. The Expert Consensus Panel is comprised of a diverse group of 16 multidisciplinary experts well respected in their fields. The panelists individually conducted an evidence-based review of the literature in their respective areas of expertise. They then met to discuss the latest treatment options for genitourinary syndrome of menopause (GSM) in survivors of breast cancer and review management strategies for GSM in women with or at high risk for breast cancer, using a modified Delphi method. This iterative process involved presentations summarizing the current literature, debate, and discussion of divergent opinions concerning GSM assessment and management, leading to the development of consensus recommendations for the clinician. Genitourinary syndrome of menopause is more prevalent in survivors of breast cancer, is commonly undiagnosed and untreated, and may have early onset because of cancer treatments or risk-reducing strategies. The paucity of evidence regarding the safety of vaginal hormone therapies in women with or at high risk for breast cancer has resulted in avoidance of treatment, potentially adversely affecting quality of life and intimate relationships. Factors influencing decision-making regarding treatment for GSM include breast cancer recurrence risk, severity of symptoms, response to prior therapies, and personal preference. We review current evidence for various pharmacologic and nonpharmacologic therapeutic modalities in women with a history of or at high risk for breast cancer and highlight the substantial gaps in the evidence for safe and effective therapies and the need for future research. Treatment of GSM is individualized, with nonhormone treatments generally being first line in this population. The use of local hormone therapies may be an option for some women who fail nonpharmacologic and nonhormone treatments after a discussion of risks and benefits and review with a woman's oncologist. We provide consensus recommendations for an approach to the management of GSM in specific patient populations, including women at high risk for breast cancer, women with estrogen-receptor positive breast cancers, women with triple-negative breast cancers, and women with metastatic disease.

Abstract Objective: Frequency of vasomotor symptoms (VMS) in older women and the contributing factors are largely undefined. We measured the frequency of moderate-to-severe vasomotor symptoms (msVMS) in women ≥60 years of age and examined their characteristics to determine factors that may associate with VMS in older women. Methods: A cross-sectional survey was completed using the Menopause Health Questionnaire from the Data Registry on Experiences of Aging, Menopause, and Sexuality. Data were collected from women presenting for menopause consultation to Mayo Clinic, Rochester, MN, from January 1, 2006 to October 7, 2014. We created a binary variable where women were classified as having msVMS bother if they reported “quite a bit” or “extremely” compared with women reporting “not at all” or “a little bit.” Women with and without msVMS were evaluated by menopause type, self-rated heath, current tobacco, caffeine, and alcohol use, as well as pertinent medication use. Associations between participant characteristics and msVMS were evaluated using logistic regression and a multivariable model with age as a covariate. Interactions between participant characteristics and age were also assessed. Results: Of the 4,956 women presenting for menopause consultation, 921 (18%) were ≥60 years old. Of these, 379 (41.2%) reported msVMS bother. Women with msVMS were more likely to have a history of nonspontaneous menopause and report their health as fair, versus good or excellent. Women reporting current use of hormone therapy (HT) (21%) were less likely to report msVMS compared with those not taking HT (P < 0.001). Conclusions: A substantial number of women seen in a specialty menopause clinic were over age 60 years and reported msVMS, highlighting that VMS may be disruptive in women over a decade past the natural age of menopause.

Abstract Objective: Response to menopausal hormone therapy (MHT) shows individual variation. SLCO1B1 encodes the OATP1B1 transporter expressed in the liver that transports many endogenous substances, including estrone sulfate, from the blood into hepatocytes. This study evaluated the relationship between genetic variation in SLCO1B1 and response to MHT in women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic, Rochester, MN. Methods: KEEPS participants were randomized to oral conjugated equine estrogen (n = 33, oCEE), transdermal 17β-estradiol (n = 33, tE2), or placebo (n = 34) for 48 months. Menopausal symptoms (hot flashes, night sweats, insomnia, palpitations) were self-reported before treatment and at 48 months. Estrone (E1), E2, and sulfated conjugates (E1S, E2S) were measured using high-performance liquid chromatography-tandem mass spectrometry. SLCO1B1 rs4149056 (c.521T>C, p.Val174Ala) was genotyped using a TaqMan assay. Results: After adjusting for treatment, there was a significant association between the SLCO1B1 rs4149056 TT genotype (encoding normal function transporter) and lower E1S, E1S/E1, and E2S (P = 0.032, 0.010, and 0.008, respectively) compared with women who were heterozygous (TC) or homozygous (CC) for the reduced function allele. The interactions between genotype, treatment, and E2S concentration were stronger in women assigned to tE2 (P = 0.013) than the women taking oCEE (P = 0.056). Among women assigned to active treatment, women with the CT genotype showed a significantly greater decrease in night sweats (P = 0.041) than those with the TT genotype. Conclusions: Individual variation in sulfated estrogens is explained, in part, by genetic variation in SLCO1B1. Bioavailability of sulfated estrogens may contribute to relief of night sweats.

Abstract A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend &lt; 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.

AbstractCopy number variation (CNV) is a common form of structural variation detected in human genomes, occurring as both constitutional and somatic events. Cytogenetic techniques like chromosomal microarray (CMA) are widely used in analyzing CNVs. However, CMA techniques cannot resolve the full nature of these structural variations (i.e. the orientation and location of associated breakpoint junctions) and must be combined with other cytogenetic techniques, such as karyotyping or FISH, to do so. This makes the development of a next‐generation sequencing (NGS) approach capable of resolving both CNVs and breakpoint junctions desirable. Mate‐pair sequencing (MPseq) is a NGS technology designed to find large structural rearrangements across the entire genome. Here we present an algorithm capable of performing copy number analysis from mate‐pair sequencing data. The algorithm uses a step‐wise procedure involving normalization, segmentation, and classification of the sequencing data. The segmentation technique combines both read depth and discordant mate‐pair reads to increase the sensitivity and resolution of CNV calls. The method is particularly suited to MPseq, which is designed to detect breakpoint junctions at high resolution. This allows for the classification step to accurately calculate copy number levels at the relatively low read depth of MPseq. Here we compare results for a series of hematological cancer samples that were tested with CMA and MPseq. We demonstrate comparable sensitivity to the state‐of‐the‐art CMA technology, with the benefit of improved breakpoint resolution. The algorithm provides a powerful analytical tool for the analysis of MPseq results in cancer.