AESurv: autoencoder survival analysis for accurate early prediction of coronary heart disease.

Coronary heart disease (CHD) is one of the leading causes of mortality and morbidity in the United States. Accurate time-to-event CHD prediction models with high-dimensional DNA methylation and clinical features may assist with early prediction and intervention strategies. We developed a state-of-the-art deep learning autoencoder survival analysis model (AESurv) to effectively analyze high-dimensional blood DNA methylation features and traditional clinical risk factors by learning low-dimensional representation of participants for time-to-event CHD prediction. We demonstrated the utility of our model in two cohort studies: the Strong Heart Study cohort (SHS), a prospective cohort studying cardiovascular disease and its risk factors among American Indians adults; the Women's Health Initiative (WHI), a prospective cohort study including randomized clinical trials and observational study to improve postmenopausal women's health with one of the main focuses on cardiovascular disease. Our AESurv model effectively learned participant representations in low-dimensional latent space and achieved better model performance (concordance index-C index of 0.864 ± 0.009 and time-to-event mean area under the receiver operating characteristic curve-AUROC of 0.905 ± 0.009) than other survival analysis models (Cox proportional hazard, Cox proportional hazard deep neural network survival analysis, random survival forest, and gradient boosting survival analysis models) in the SHS. We further validated the AESurv model in WHI and also achieved the best model performance. The AESurv model can be used for accurate CHD prediction and assist health care professionals and patients to perform early intervention strategies. We suggest using AESurv model for future time-to-event CHD prediction based on DNA methylation features.

Hysterectomy, oophorectomy and risk of non-Hodgkin's lymphoma.

Hysterectomy is associated with an increased risk for adverse health outcomes. However, its connection to the risk of non-Hodgkin's lymphoma (NHL) remains unclear. The aims of our study were to investigate the associations between hysterectomy, oophorectomy and risk of NHL and its major subtypes (eg, diffuse large B-cell lymphoma [DLBCL]), and whether these associations were modified by exogenous hormone use. Postmenopausal women (n = 141,621) aged 50-79 years at enrollment (1993-1998) from the Women's Health Initiative were followed for an average of 17.2 years. Hysterectomy and oophorectomy were self-reported at baseline. Incident NHL cases were confirmed by central review of medical records and pathology reports. During the follow-up period, a total of 1719 women were diagnosed with NHL. Hysterectomy, regardless of oophorectomy status, was associated with an increased risk of NHL (hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.05-1.44). Oophorectomy was not independently associated with NHL risk after adjusting for hysterectomy. When stratified by hormone use, the association between hysterectomy and NHL risk was confined to women who had never used hormone therapy (HR = 1.35, 95% CI: 1.06-1.71), especially for DLBCL subtype (P for interaction = .01), and to those who had undergone hysterectomy before the age of 55. Our large prospective study showed that hysterectomy was a risk factor of NHL. Findings varied by hormone use. Future studies incorporating detailed information on the types and indications of hysterectomy may deepen our understanding of the mechanisms underlying DLBCL development and its potential interactions with hormone use.

Infertility and risk of postmenopausal breast cancer in the women's health initiative.

PURPOSE: Although infertility (i.e., failure to conceive after ≥ 12 months of trying) is strongly correlated with established breast cancer risk factors (e.g., nulliparity, number of pregnancies, and age at first pregnancy), its association with breast cancer incidence is not fully understood. Previous studies were primarily small clinic-based or registry studies with short follow-up and predominantly focused on premenopausal breast cancer. The objective of this study was to assess the relationship between infertility and postmenopausal breast cancer risk among participants in the Women's Health Initiative (analytic sample = 131,784; > 25 years of follow-up). METHODS: At study entry, participants were asked about their pregnancy history, infertility history, and diagnosed reasons for infertility. Incident breast cancers were self-reported with adjudication by trained physicians reviewing medical records. Cox proportional hazards models were used to estimate risk of incident postmenopausal breast cancer for women with infertility (overall and specific infertility diagnoses) compared to parous women with no history of infertility. We examined mediation of these associations by parity, age at first term pregnancy, postmenopausal hormone therapy use at baseline, age at menopause, breastfeeding, and oophorectomy. RESULTS: We observed a modest association between infertility (n = 23,406) and risk of postmenopausal breast cancer (HR = 1.07; 95% CI 1.02-1.13). The association was largely mediated by age at first term pregnancy (natural indirect effect: 46.4% mediated, CI 12.2-84.3%). CONCLUSION: These findings suggest that infertility may be modestly associated with future risk of postmenopausal breast cancer due to age at first pregnancy and highlight the importance of incorporating reproductive history across the life course into breast cancer analyses.

Adverse pregnancy outcomes and risk of type 2 diabetes in postmenopausal women.

BACKGROUND: Although gestational diabetes mellitus and delivering high-birthweight infants are known to predict a higher risk of future type 2 diabetes mellitus, the association of hypertensive disorders of pregnancy and other adverse pregnancy outcomes with type 2 diabetes mellitus is not well established. OBJECTIVE: This study aimed to examine the associations between different types of adverse pregnancy outcomes and incident type 2 diabetes mellitus among postmenopausal women. STUDY DESIGN: The Women's Health Initiative, a nationwide cohort of postmenopausal women, collected self-reported history of adverse pregnancy outcomes, including gestational diabetes mellitus, hypertensive disorders of pregnancy, preterm birth, and delivering low- birthweight (<2500 g) or high-birthweight (>4500 g) infants. Participants were followed up annually for self-reported incident type 2 diabetes mellitus treated with medication from baseline (1993-1998) to March 2021. This study used logistic regression to examine the associations of any and individual adverse pregnancy outcomes with diabetes mellitus. Stratified analyses were performed to assess effect modification by body mass index, race and ethnicity, education, parity, breastfeeding, and age at first birth. RESULTS: This analysis included 49,717 women without a history of diabetes mellitus at enrollment who had a least 1 pregnancy and responded to the questionnaire about adverse pregnancy outcomes. After adjusting for body mass index, demographic, lifestyle, and reproductive factors, gestational diabetes mellitus (odds ratio, 2.26; 95% confidence interval, 1.94-2.63), high birthweight (odds ratio, 1.30; 95% confidence interval, 1.18-1.44), and hypertensive disorders of pregnancy (odds ratio, 1.18; 95% confidence interval, 1.08-1.30) were independently associated with higher odds of type 2 diabetes mellitus, whereas preterm birth and low birthweight were not associated with diabetes mellitus risk. A history of ≥2 adverse pregnancy outcomes was associated with higher odds of type 2 diabetes mellitus (odds ratio, 1.55; 95% confidence interval, 1.28-1.88). This study further observed higher odds of type 2 diabetes mellitus (odds ratio, 3.69; 95% confidence interval, 2.38-5.70) among women with a history of both gestational diabetes mellitus and hypertensive disorders of pregnancy than those without any adverse pregnancy outcomes. CONCLUSION: Postmenopausal women with a history of gestational diabetes mellitus, those delivering high-birthweight infants, or those with hypertensive disorders of pregnancy are at risk of future type 2 diabetes mellitus. In addition, women with ≥2 conditions had an augmented risk and might be prioritized for screening and prevention efforts for type 2 diabetes mellitus.

Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women with Inflammatory Bowel Disease.

BACKGROUND: Individuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear. METHODS: We conducted a survival analysis of Women's Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.). RESULTS: Of 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73-1.24), VTE (HR 1.11, 95% CI 0.81-1.52) or PAD (HR 0.64, 95% CI 0.28-1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06-1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98-1.76). CONCLUSIONS: Among postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.

Designing heterotropically activated allosteric conformational switches using supercharging.

Heterotropic allosteric activation of protein function, in which binding of one ligand thermodynamically activates the binding of another, different ligand or substrate, is a fundamental control mechanism in metabolism and as such has been a long-aspired capability in protein design. Here we show that greatly increasing the magnitude of a protein's net charge using surface supercharging transforms that protein into an allosteric ligand- and counterion-gated conformational molecular switch. To demonstrate this we first modified the designed helical bundle hemoprotein H4, creating a highly charged protein which both unfolds reversibly at low ionic strength and undergoes the ligand-induced folding transition commonly observed in signal transduction by intrinsically disordered proteins in biology. As a result of the high surface-charge density, ligand binding to this protein is allosterically activated up to 1,300-fold by low concentrations of divalent cations and the polyamine spermine. To extend this process further using a natural protein, we similarly modified Escherichia coli cytochrome b562 and the resulting protein behaves in a like manner. These simple model systems not only establish a set of general engineering principles which can be used to convert natural and designed soluble proteins into allosteric molecular switches useful in biodesign, sensing, and synthetic biology, the behavior we have demonstrated--functional activation of supercharged intrinsically disordered proteins by low concentrations of multivalent ions--may be a control mechanism utilized by Nature which has yet to be appreciated.

Do High Rates of Atypical Glandular Cells Correlate With Higher Incidence of Disease in a Large Safety Net Hospital.

OBJECTIVE: The aim of the study was to describe the incidence and correlates of atypical glandular cell (AGC) Pap tests in a low socioeconomic status, underserved population. MATERIALS AND METHODS: Medical records of patients with AGC Pap tests at a single institution were reviewed from January 2013 to August 2019. Baseline characteristics were extracted including age, body mass index, birth control, abnormal uterine bleeding, and human papillomavirus (HPV). All colposcopy and endometrial biopsies were classified into negative/low-risk (polyps, tubular metaplasia, microglandular hyperplasia, cervical intraepithelial neoplasia 1) and high-risk (HR) lesions (cervical intraepithelial neoplasia 2/3, adenocarcinoma in situ, endometrial hyperplasia, cervical cancer, endometrial cancer). Logistic regression identified significant associations. Sixty-eight randomly selected AGC cytology slides from the cohort and 32 non-AGC slides outside the cohort were blindly reviewed by 6 pathologists. Fleiss κ interrater agreement was assessed. RESULTS: Seven hundred forty patients with AGC Pap tests were identified (0.8% of all Pap tests performed during this time). After excluding for incomplete data, 478 patients were included. Sixty-three patients had HR lesions (13.3%). Patients with HR lesions had increased odds of abnormal uterine bleeding (odds ratio = 4.32, p < .001) and HPV positivity (odds ratio = 10.89, p < .001) when compared with patients with low-risk lesions. The κ agreement was 0.21 for all cases and 0.18 for AGC alone. CONCLUSIONS: This population falls within the national averages for AGC Pap tests. There was an increased risk of HR lesions in patients with abnormal uterine bleeding and HPV positivity. The rate of HR lesions among AGC Pap tests was at the lower end of values in the literature. After blinded pathologist review, interobserver κ agreement was low for AGC Pap tests.

Transvaginal ultrasound training for the obstetrics and gynecology resident: A multisite randomized controlled trial of educational DVD.

PURPOSE: Residents in obstetrics and gynecology are deemed to be proficient in transvaginal ultrasound (TVUS) upon graduation, although TVUS education in residency is not standardized. The objective of this study is to assess for improvement in TVUS knowledge among residents after viewing an educational DVD. METHODS: This is a multisite prospective randomized controlled trial using an educational DVD ("Gynecology: Beginners Only"), compared to routine education. All participants completed a pretest on TVUS images and principles. The intervention group repeated the test after DVD viewing. During the trial, performing and logging TVUS examinations were encouraged. All enrolled residents repeated the test 6-10 months later. RESULTS: Fifty-seven residents completed the study with a mean pretest score of 9.7 (1st year resident 9.8, 2nd year resident 9.6, 3rd year resident 10.1, 4th year resident 9.4, P = .763), with a mean of 31.5 TVUS examinations logged prior to intervention. The mean score in the intervention group (n = 34) improved significantly after viewing (11.2, P < 0.003). This improvement did not persist 6-10 months later on a follow-up quiz (mean 10.7, P = .894). At completion of the study, participants logged an average of 56.7 TVUS examinations. CONCLUSION: An educational DVD is easily implemented and demonstrates short-term benefit. Exploration of different teaching modalities in development of a comprehensive training program may improve long-term retention.

Gynecologic Screening for Men in an OBGYN Resident Community Outreach Clinic: The Transgender Care Experience.

OBJECTIVE: The aim of the study was to promote the importance of providing gynecologic screening for transgender men (TGM) who desire to keep their female organs. MATERIALS AND METHODS: In June 2015, the Women's Health Center (WHC) at Reading Hospital was approached to become a resource for transgender (TG) patients in our community. This also presented the opportunity to develop an educational program for OBGYN residents/providers in TG healthcare. From June 2015 to August 2016, we educated ourselves, established standards of care, collaborated with other services, and reached out to the community we represent. We present our experience in creating this specialty clinic as well as our first 16 months of experiential data to help other facilities meet the needs of this community. RESULTS: The primary outcome was the establishment of a comprehensive service for TG patients in our community. From August 2016 to December 2017, a total of 27,516 patient visits were conducted in WHC, 67 (0.2%) were TG patient visits with an average age of 33 years. Of 67, 16 (23.9%) were TGM and 51 (76.1%) were transgender women (TGW) visits, representing a total of 20 new TG patients including 9 (45%) TGM and 11 (55%) TG women. A total of 5 (55.6%) of 9 TGM received vaginal/cervical cytology screening. Sexually transmitted infection screenings were performed in 14 (70%) TG patients versus 6,689 (40.7%) in a non-TG WHC population. CONCLUSIONS: Servicing the transgender community is an important aspect of care for OBGYN providers. Our data suggest that TGM have similar gynecologic needs to the rest of our clinic population.

Long-acting reversible contraception in adolescents in Sub-Saharan Africa: evidence from demographic and health surveys.

OBJECTIVE: To explore (1) long-acting reversible contraception (LARC) use and (2) future contraceptive preferences in Sub-Saharan African adolescents as undesired pregnancies in Sub-Saharan African adolescents are associated with significant maternal/neonatal morbidity. METHODS: Nationally-representative Demographic and Health Surveys (USAID) obtained informed consent and interviewed 45,054 adolescents, including 19,561 (43.4% of total) sexually active adolescents (aged 15-19) from 18 least developed Sub-Saharan African nations regarding contraception (years 2005-2011, response rate 89.8-99.1% for all women interviewed). Frequencies and percentages of contraceptive use, prior pregnancies, and unwanted births were reported. Categorical variables were analyzed through χ2 and unadjusted and binary logistic regression, adjusted for confounders, evaluated LARC use. RESULTS: A majority of sexually active adolescents were not using contraception (n = 16,165 non-users; 82.6% of all sexually active adolescents). Many (n = 8465, 43.3% of sexually active adolescents) interviewed already had at least one child, with 31.5% (n = 2646) of those with previous children reporting the pregnancy was not wanted at the time it occurred. Sexually active adolescents using contraception (n = 3384) used LARCs (injectable contraception, implants, or intrauterine devices; 29.8%, n = 1007) barrier contraceptives (31.9%), oral contraceptives (10.9%), and other methods (27.4%). Adolescents using LARCs were more likely to be urban [OR 1.76 (95% CI 1.39-2.22)], to have been visited by a family planning worker in the last 12 months [OR1.62 (95% CI 1.24-2.11)], and to have visited a health facility in the past 12 months [OR1.84 (95% CI 1.53-2.21)]. Injectable contraception was the most preferred (39.9%, n = 3036) future method by sexually-active non-contracepting adolescents who were asked about future methods (n = 7605) compared to other methods. An unfortunate percentage of adolescents surveyed cannot read (35.7%, n = 16,084). CONCLUSION: A majority of sexually-active adolescents in Sub-Saharan Africa are not using contraception and are desirous of doing so. Offering LARCs during post-abortive or postpartum care with particular focus on rural adolescents may reduce undesired pregnancy and subsequent morbidity/mortality. Educational materials should limit printed information as many teens are unable to read.

High-risk HPV testing in the management of atypical glandular cells: A systematic review and meta-analysis.

Whereas the utility of high-risk HPV (hrHPV) testing is widely accepted in triage of women with atypical squamous lesions, its role in managing atypical glandular cells (AGC) is not fully elucidated. A systematic review and meta-analysis were performed to evaluate the accuracy of hrHPV testing in the management of women with AGC to detect underlying high-grade intraepithelial neoplasia or worse, and adenocarcinoma in situ or worse (AIS+). Additionally, the diagnosis of extra-cervical cancer was considered as an outcome in this review. A bibliographic database search (PubMed, EMBASE, CENTRAL) identified twelve eligible studies. The occurrence of cervical intraepithelial neoplasia grade two or worse including AIS+ (CIN2+/AIS+), was 19.8% among women with AGC, and 55.7% among women with AGC and concurrent squamous lesions (atypical squamous cells of undetermined significance or worse, ASC-US+). The pooled sensitivity and specificity of hrHPV-testing with Hybrid Capture 2 (HC2) to detect CIN2+/AIS+ in women with AGC was 90.0% (95% CI = 85.1-93.4%) and 75.1% (95% CI = 64.8-83.2%), respectively. Women who were hrHPV-negative, demonstrated an increased risk for extra-cervical malignancy (endometrium, fallopian tube, ovary). In women of 50y and older, a hrHPV-negative result was linked with a 18.0% chance of extra-cervical malignancy, while the chance of cervical pre-cancer and cancer was 0.4 and 0.0%, respectively. In conclusion, given the high risk of underlying CIN2+/AIS+, women with AGC should be referred directly to colposcopy. However, hrHPV test results in combination with the age, appears to improve the diagnostic process by distinguishing the risk for cervical versus non-cervical lesions.

Vitamin D heritability and effect of pregnancy status in Vervet monkeys (Chlorocebus aethiops sabaeus) under conditions of modest and high dietary supplementation.

OBJECTIVES: The two objectives of the current study were to: 1) investigate the genetic contributions to variations in serum vitamin D concentrations under two dietary conditions (a standard monkey biscuit diet vs. a diet designed to model typical American consumption); and 2) explore the interaction of vitamin D with pregnancy status using a cohort of pedigreed female vervet/African green monkeys. METHODS: This study includes 185 female (≥3.5 years) vervet/African green monkeys (Chlorocebus aethiops sabaeus) from a multi-generational, pedigreed breeding colony. The 25(OH)D3 concentrations were first measured seven to eight weeks after consuming a "typical American" diet (TAD), deriving 37, 18, and 45% of calories from fat, protein sources, and carbohydrates, and supplemented with vitamin D to a human equivalent of 1,000 IU/day. Vitamin D concentrations were assessed again when animals were switched to a low-fat, standard biscuit diet (LabDiet 5038) for 8 months, which provided a human equivalent of approximately 4,000 IU/day of vitamin D. All statistical analyses were implemented in SOLAR. RESULTS: Pregnancy was associated with reduced 25(OH)D3 concentrations. Heritability analyses indicated a significant genetic contribution to 25(OH)D3 concentrations in the same monkeys consuming the biscuit diet (h(2) =0.66, P=0.0004) and TAD (h(2) =0.67, P=0.0078) diets, with higher 25(OH)D3 concentrations in animals consuming the biscuit diet. Additionally, there was a significant genotype-by-pregnancy status interaction on 25(OH)D3 concentrations (P<0.05) only among animals consuming the TAD diet. DISCUSSION: These results support the existence of a genetic contribution to differences in serum 25(OH)D3 concentrations by pregnancy status and emphasize the role of diet (including vitamin D supplementation) in modifying genetic signals as well as vitamin D concentrations.

Risk Assessment Tools for Osteoporosis-Related Fractures.

Osteoporosis is a prevalent and po- tential debilitating disease. Characterized by archi- tectural modifications in bone matrix, osteoporosis ultimatelyincreases the propensity forbones to frac- ture, especially at the hip and spine. Fortunately, osteoporosis can be treated effectively if detected at an early stage. While recognizing an increased risk offracture inwomen with osteoporosis, mostcases of fracture occur in women with osteopenia orlowbone mass. A good fracture risk assessment tool would be more clinically meaningful than an accurate osteo-. porosis screening or diagnostic tool. Here we present a concise review ofthe existing modalities which may be utilized to screen for osteoporosis or predict risk of oteonorotic fractures.

Management of "Atypical Endocervical Cells" Compared to "Atypical Glandular Cells".

OBJECTIVE: To assess adherence to management guidelines based on the terminology used to describe atypical glandular cells (AGC) on cytology reports. MATERIALS AND METHODS: We analyzed AGC pathology reports from Hartford Hospital, 2004-2007, and identified cases of AGC with the terminology atypical glandular cells or atypical endocervical cells (AEC). We calculated rates of clinical evaluations based on the terminology used to describe the AGC. Statistical analysis was performed using the χ test. RESULTS: Seventy-eight reports contained the terminology AEC and 97 reports contained the terminology AGC. The rate of histologic sampling in women with AEC was lower than in women with AGC (52.6% vs 83.5%; p < .01). Similarly, the rate of comprehensive evaluations was lower (33.3% vs 71.1%; p < .01). Fewer endocervical curettages (47.4% vs 77.3%; p < .01) and fewer endometrial biopsies in women 35 years or older were performed (26.9% vs 69.1%; p < .01) in women with AEC than in women with AGC. CONCLUSIONS: Women with AGC reports containing the term AEC were managed less optimally than those with AGC. These results suggest that the terminology used to describe the finding of atypical glandular cells may influence the clinical evaluation. Clinicians may not recognize AEC as AGCs. Ours results suggest that the terminology atypical endocervical cells should be avoided or accompanied by the terminology atypical glandular cells.

Atypical Glandular Cells of Endometrial Origin and the Risk of Endometrial Cancer.

OBJECTIVES: To assess the risk of endometrial cancer (EC) associated with atypical glandular cells of endometrial origin (AGC-EM) in 2 age groups (age younger than 51 vs 51 years or older). METHODS: A retrospective case series was assembled identifying AGC from a pathology database between January 1, 2005 and January 1, 2009. Demographics, cervical cytology results, and final diagnoses (including clinically significant diseases and cancers) were recorded from the initial AGC diagnosis until August 30, 2011. Data were analyzed using the χ test to compare rates of disease between age groups. RESULTS: Among the 444 patients with AGC, 41% (183/444) had AGC-EM. Women younger than 51 years, compared to those 51 years or older, had significantly lower rates of AGC-EM (35% [105/296] vs 53% [78/148]; p < .001; odds ratio, 0.49; 95% confidence interval, 0.33-0.74). The rate of EC was significantly lower in those younger than 51 years, compared to those aged 51 or older (5% [8/158] vs 19% [18/95]; p < .001; odds ratio, 0.23; 95% confidence interval, 0.09-0.55) in women who underwent endometrial biopsy. In women younger than 51 years who underwent an endometrial biopsy, the rate of EC had a stepwise increase across 3 subclasses of AGC (from AGC of endocervical origin [AGC-EC] to AGC not otherwise specified to AGC-EM) (p = .04). CONCLUSIONS: Women aged 51 years or older who have AGC are more likely to have AGC-EM and EC than women younger than 51 years. In women younger than age 51, AGC-EM is the subclass most associated with EC while compared to 2 other subclasses (AGC not otherwise specified and AGC-EC).

Vitamin D and cardiovascular disease: an appraisal of the evidence.

BACKGROUND: Supplementation with vitamin D has received attention as a potential cardioprotective strategy. Biologically plausible mechanisms have been proposed to link vitamin D to coronary heart disease (CHD) prevention, and observational studies suggest an inverse association between serum 25-hydroxyvitamin D (25OHD) concentrations and CHD. Few randomized clinical trials of vitamin D supplementation and CHD have been conducted, however, and no trial with CHD as the primary prespecified outcome has been completed. CONTENT: A search was conducted in PubMed to find prospective studies of the use of vitamin D supplementation and its relationship to cardiovascular risk factors (RFs) and/or cardiovascular disease (CVD). The exact search query was: ((vitamin D supplement*[Title/Abstract]) AND cardiovascular [Title/Abstract]) AND prospective [Title/Abstract]. This query yielded 42 results. "Randomized Controlled Trial" (article type) was used as a filter in a subsequent query with the same search terms. We review the evidence that vitamin D supplementation modifies coronary RFs, such as blood pressure, lipids, glucose tolerance, and/or affects the development of clinical CHD events. We address potential sources of confounding in observational epidemiologic studies of the relationship between serum 25OHD and CHD. We also address laboratory assay issues relevant to the reliable measurement of 25OHD. SUMMARY: Most vitamin D supplementation trials have not demonstrated improvement in CVD, but they have tested relatively low vitamin D doses. Thus, the evidence remains inconclusive, highlighting the need for rigorous randomized trials of higher vitamin D doses with cardiovascular events as prespecified outcomes. While we await the results of ongoing trials, the recommended dietary allowances from the Institute of Medicine remain the best guidepost for nutritional requirements.

Postinterview communication with residency applicants: a call for clarity!

The residency match is an increasingly competitive process. Communication from medical student applicants to programs varies, and the effect this has on their rank status is unclear. We assessed how obstetrics and gynecology program directors interpret and act on postinterview communication initiated by applicants by conducting an anonymous cross-sectional web-based survey of allopathic obstetrics and gynecology program directors. One hundred thirty-seven program directors (55%) responded to the survey. Twenty-nine percent would consider ranking an applicant more favorably if the applicant expressed interest (beyond a routine thank you) or if a faculty mentor personally known to the program director stated that the applicant was ranking the program first. Fifty-two percent indicated that they would rank an applicant more favorably if a mentor known to them endorsed the applicant as outstanding. Approximately 30% responded that applicants who did not communicate with their program were disadvantaged compared with those who did. Approximately 17% stated it was desirable to create additional specialty-specific guidelines regarding postinterview contact between programs and applications. Based on the wide variation in how program directors interpret and act on postinterview communication from applicants, residency programs should formulate and communicate a clear policy about whether they request and how they respond to postinterview communication from applicants and their mentors. This will establish a more level playing field and eliminate potential inequities resulting from inconsistent communication practices.

Contraceptive use in adolescents in Sub-Saharan Africa: evidence from Demographic and Health Surveys.

OBJECTIVE: Failure to use contraceptives contributes to an unacceptably high rate of undesired pregnancy in Sub-Saharan adolescents with associated maternal and neonatal mortality/morbidity. Evidence-based research is needed to understand contraceptive usage in Sub-Saharan adolescents and to enable appropriate allocation of donor resources. DESIGN: Nationally-representative USAID (U.S. Agency for International Development) Demographic and Health Surveys from 18 least developed Sub-Saharan African nations. POPULATION: 212,819 Sub-Saharan African women (45,054 were 15-19 years old). METHODS: The percentages of adolescents using contraception, as well as their preferred contraceptive methods and desired family size, were reported. MAIN OUTCOME MEASURES: Contraceptive Use, Neonatal Mortality, Undesired Pregnancy, Pregnancy Terminations. RESULTS: Most adolescents (92.4%) surveyed reported no contraceptive use, although 21.6% reported recent sexual activity. A current pregnancy was reported in 6.6% (n = 2,951) of adolescents with 29.9% of these pregnancies being unwanted. Many surveyed adolescents (18.8%) had at least one prior birth. A death of the previous child was reported in 6.6% (n = 560) with half of these deaths (n = 276) occurring within the first month of life. Many adolescents planned to delay childbearing for at least two years (37.1%) or were unsure about future timing (33.3%), and 2.2% reported a history of at least one pregnancy termination. Most adolescents (73.1%) felt it would be a problem if they became pregnant. Adolescents indicated injectable medications and contraceptive pills were the preferred future contraceptives at 39.9% and 31.4% respectively. CONCLUSIONS: Sub-Saharan African adolescents report a mismatch between desire for contraception and use; preferred methods are oral and injectable contraceptives.

Cohen versus Pfannenstiel Cesarean Skin Incision for BMI =35 kg/m2: a Randomized Controlled Trial.

BACKGROUND: Maternal obesity is recognized as a significant risk factor for adverse pregnancy outcomes, including increased cesarean delivery rates and heightened surgical complications. It is unclear if the Cohen or Pfannenstiel skin incisions at cesarean delivery are associated with different outcomes. OBJECTIVE: To evaluate the impact of either Cohen or Pfannenstiel cesarean skin incision type on maternal morbidity. STUDY DESIGN: Pregnant individuals with a BMI of ≥35 kg/m2, carrying either singleton or multiple gestations, were consented prenatally and in labor. Eligible participants who underwent a cesarean delivery between 24 and 41 weeks of gestation were randomized to either Pfannenstiel or Cohen skin incisions at Thomas Jefferson University Hospital from October 2016 to March 2020. The study aimed to recruit 284 participants based on a sample size calculation assuming a 50% reduction in wound complications with Cohen versus Pfannenstiel incisions (80% power, α=0.05), but recruitment was terminated early after 72 participants were randomized. The primary outcome was a composite maternal morbidity within six weeks, which consisted of the following: wound infection, hematoma, seroma, separation of skin ≥1 cm, readmission for wound complications, endometritis, and postpartum hemorrhage. Statistical analyses included bivariate tests, t-tests, and non-parametric analyses. RESULTS: Of 331 pregnant individuals consented prenatally and in labor, 72 eventually underwent cesarean delivery and were randomized, 34 to Cohen and 38 to Pfannenstiel skin incisions. The mean BMI was >42 kg/m2, about two thirds of the patients had a pannus, 56% were Black, 47% had diabetes, and 56% hypertensive disorders. The primary outcome of composite maternal morbidity occurred in 47.1% in the Cohen and 36.8% in the Pfannenstiel groups (RR 1.24, 95% CI 0.71-2.08), and was also similar regardless of the presence of a pannus, or by degree of obesity. Surgical site infection, hematoma, seroma, wound separation/dehiscence, endometritis, and postpartum hemorrhage were each similar between Cohen and Pfannenstiel participants. Neonatal outcomes were also similar between the Cohen and Pfannenstiel groups, except that the Cohen group was found to have statistically significant lower Apgar score at 5 minutes and higher need for respiratory support compared to the Pfannenstiel group, possibly related to the trend for a longer time from skin incision to delivery. Physicians were found to be significantly less satisfied with the Cohen compared to the Pfannenstiel incision. CONCLUSION: In pregnant patients with BMI of ≥35 kg/m2, obstetrical providers can chose from either a Cohen or an Pfannenstiel skin incision, as they are associated in general with similar outcomes, except for lower Apgar scores and lower physician satisfaction associated with the Cohen incision. The findings of this study are limited by its early cessation for logistical reasons, leading to an underpowered analysis. It is crucial to acknowledge that these results must be interpreted cautiously due to the reduced sample size and the circumstances surrounding the study's termination. These data can inform future trial design and implementation as well as fuel individual patient level meta-analyses on this topic.

Association of Diet Quality With Risk of Incident Rheumatoid Arthritis in the Women's Health Initiative.

BACKGROUND: Various foods and nutrients are linked with higher or lower risk of rheumatoid arthritis (RA), yet these associations are inconsistent across studies. Limited research has been done evaluating the association between diet quality and RA in a larger-scale prospective study on postmenopausal women. OBJECTIVE: The objective of this study was to evaluate the association between dietary quality and risk of incident RA in postmenopausal women. DESIGN: This was a prospective cohort study as part of the Women's Health Initiative (WHI), with an average follow-up time of 8.1 years. Baseline diet was measured using a food frequency questionnaire (FFQ). Diet quality was evaluated by the Healthy Eating Index (HEI)-2015 total score. In addition, intake of food groups and nutrients that align with HEI-2015 components was assessed. PARTICIPANTS/SETTING: Postmenopausal women (N = 109 591) were included in this study, which was conducted at various clinical centers across the United States with recruitment from 1993 to 1998. Women's Health Initiative participants who were missing outcome data, had unreliable/missing FFQ data, or had RA at baseline were excluded. MAIN OUTCOME MEASURES: The primary outcome measure was incident RA. Statistical analyses performed Multivariable Cox proportional regression analysis was performed evaluating the association of diet quality with self-reported physician-diagnosed RA after adjusting for age, race, ethnicity, education status, income, and body mass index (BMI). RESULTS: During 857 517 person-years of follow-up, 5823 incident RA cases were identified. After adjustment for multiple comparisons, compared with quartile 1, quartiles 2, 3, and 4 of the HEI-2015 total scores were associated with lower RA risks of 1%, 10%, and 19%, respectively (P-trend < .001). Greater consumption of total fruits (P-trend = .014), whole fruits (P-trend < .0002), total vegetables (P-trend = .008), greens and beans (P-trend < .0002), whole grains (P-trend = .008), and dairy (P-trend = .018) were significantly associated with lower rates of incident RA. Conversely, higher consumption of saturated fat (P-trend = .002) was significantly associated with higher rates of incident RA. CONCLUSION: A higher-quality diet reflected by higher HEI-2015 total scores was inversely associated with incident RA in postmenopausal women.