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Objectives This article outlines a process for differentiating preeclampsia from other potential causes of end-organ damage in a critically ill patient. Case Presentation A patient in her early 30s, G2P1001 with intrauterine pregnancy at 12 weeks’ gestation was admitted seven months after delivering her first child due to new-onset psychosis and starvation ketosis. She was started on lithium for postpartum psychosis at 20 weeks’ gestation. She subsequently developed respiratory failure at 26 weeks’ gestation due to aspiration pneumonia in the setting of lithium toxicity, requiring admission to the intensive care unit (ICU) and intubation. She received antibiotics and vasopressors for suspected septic shock in addition to dialysis for lithium-induced acute kidney injury. One week after ICU admission, her sepsis resolved, her serum creatinine levels returned to normal, and her respiratory status improved. However, after vasopressors were discontinued, she suddenly developed persistently elevated blood pressures with proteinuria and elevated liver function tests (LFT’s). Due to concern for preeclampsia with severe features and rapidly increasing LFT’s, the patient underwent cesarean delivery at 27 weeks’ gestation. Conclusions In a critically ill patient with multiple comorbidities, it can be difficult to diagnose preeclampsia using the standard criteria. It is important to exclude other potential etiologies, as a misdiagnosis can have potentially devastating consequences.

Placenta accreta spectrum (PAS) refers to the spectrum of diagnoses involving abnormally and morbidly adherent trophoblastic tissue to the gravid uterus. These disorders are associated with significant maternal morbidity and mortality. While race/ethnicity is known to impact pregnancy outcomes, racial disparities have not been previously examined in women with PAS. The objective of current study was to compare patient characteristics and perioperative outcomes of women with PAS who underwent cesarean delivery across race/ethnicity. This is a comparative study that retrospectively queried the National Inpatient Sample, a hospital-based inpatient database in the USA. The study cohort was women diagnosed with PAS who underwent cesarean delivery from 10/2015 to 12/2018. The exposure group was race/ethnicity. Main outcomes were (i) patient/pregnancy characteristics and (ii) surgical morbidity for cesarean delivery, assessed in multivariable analysis. A total of 10,535 women comprised the study cohort (White n = 5,230 [49.6%], Black n = 2,045 [19.4%], Hispanic n = 2,540 [24.1%], and Asian n = 720 [6.8%]). Patient demographics, pregnancy characteristics, and hospital factors for the non-White groups significantly differed compared to the White group. Older age, obesity, diabetes, placenta previa, percreta, non-elective surgery, lower median household income, and Medicaid particularly represented the non-White groups. When perioperative outcomes were compared, non-White women were more likely to have any measured complications, hemorrhage/transfusion, and shock/coagulopathy compared to White women. Various sensitivity analyses redemonstrated the main cohort results. In conclusion, this study suggests that there were significant disparities in patient characteristics and outcomes of women with PAS across race/ethnicity.

Background: Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. Methods: In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 μmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. Findings: The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35–3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04–2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86–1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39–0·91; p=0·016). Interpretation: Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. Funding: Tommy's, the Wellcome Trust, ICP Support, and the National Institute for Health Research.

We evaluated the fracture risk assessment tool (FRAX) without bone mineral density (BMD) in predicting treatment recommendations for patients with a recent low trauma fracture other than hip or vertebral. The concordance, sensitivity, and specificity were 75.6%, 67.3%, and 78.2%, respectively. FRAX without BMD can be used after a fracture to expedite treatment. The objective of this study was to evaluate the performance of the fracture risk assessment tool (FRAX) without bone mineral density (BMD) in predicting treatment recommendations for patients who recently sustained a low trauma fracture other than hip or vertebral. We utilized a clinical database established by the Fracture Liaison Service at the Durham Veterans Affairs Medical Center to identify male and female Veterans age ≥ 50 years who sustained a low trauma non-hip/non-vertebral fracture and underwent dual-energy x-ray absorptiometry (DXA) between October 2013 and April 2018. FRAX without BMD (FRAX-BMI) and FRAX with BMD (FRAX-BMD) were calculated for the 229 patients identified, and whether or not they met the National Osteoporosis Foundation (NOF) guideline treatment thresholds was compared. There were 55 (24.0%) patients that met criteria for treatment based on NOF guideline established FRAX-BMD thresholds including 27 (11.8%) patients with osteoporosis by DXA. The concordance of FRAX-BMI in predicting treatment recommendations was 75.6% with a sensitivity of 67.3% and a specificity of 78.2%. The area under the curve (AUC) of FRAX-BMI hip fracture risk was 0.79. Assessment/treatment thresholds for hip fracture risk of 1%

Current guidelines recommend primary osteoporosis screening for at-risk men to reduce the morbidity, mortality, and cost associated with osteoporotic fractures. However, analyses in a national Veterans Health Administration cohort of over 4,000,000 men demonstrated that primary osteoporosis screening as it is currently operationalized does not benefit most older Veterans due to inefficient targeting and low subsequent treatment and adherence rates. The overall objective of this study is to determine whether a new model of primary osteoporosis screening reduces fracture risk compared to usual care. We are conducting a pragmatic group randomized trial of 38 primary care teams assigned to usual care or a Bone Health Service (BHS) screening model in which screening and adherence activities are managed by a centralized expert team. The study will: 1) compare the impact of the BHS model on patient-level outcomes strongly associated with fracture rates (eligible proportion screened, proportion meeting treatment criteria who receive osteoporosis medications, medication adherence, and femoral neck bone mineral density); 2) quantify the impact on provider and facility-level outcomes including change in DXA volume, change in metabolic bone disease clinic volume, and PACT provider time and satisfaction; and 3) estimate the impact on health system and policy outcomes using Markov models of screening program cost per quality adjusted life year based from health system and societal perspectives.

Background Severe immune thrombocytopenia complicating pregnancy may require treatment beyond first-line medications (intravenous immunoglobulins or corticosteroids), but there is a paucity of literature on the use of such second-line agents in pregnancy. Case The patient is a 29-year-old woman with early-onset severe immune thrombocytopenia at 13 weeks of gestation. Maternal platelet counts reached a nadir of less than 5×10/L. The thrombocytopenia persisted despite first-line medications. Romiplostim, rituximab, and azathioprine were added to the therapeutic regimen. Platelet counts eventually stabilized at greater than 150×10/L before delivery. After delivery at term, the neonate had transient B-cell suppression, which was presumed to be secondary to rituximab, but was otherwise doing well and meeting all milestones at 7 months of age. Conclusion The addition of second-line agents was associated with sustained elevation in maternal platelet counts and may have obviated the need for splenectomy.

To compare the frequency and severity of neonatal hypoglycemia in pregnancies treated with and without late preterm antenatal corticosteroids. We conducted a retrospective cohort study of late preterm deliveries at LAC + USC (2015–2018). Neonatal outcomes were compared between pregnancies treated with and without corticosteroids. 93 pregnancies (39.9%) received corticosteroids and 140 (60.1%) did not. Neonates born to women given corticosteroids were more likely to be hypoglycemic (47.3 vs. 29.3%, ORadj 2.25, padj = 0.01). The mean initial glucose (45.6 mg/dL vs. 51.9 mg/dL, p = 0.01) and glucose nadir (39.1 mg/dL vs. 45.4 mg/dL, p

Acetylcholinesterase inhibitors (AChEIs) have been noted to increase bone density and quality in mice. Human studies are limited but suggest an association with improved bone healing after hip fracture. We examined the relationship between AChEI use and fracture risk in a national cohort of 360,015 male veterans aged 65 to 99 years with dementia but without prior fracture using Veterans Affairs (VA) hospital, Medicare, and pharmacy records from 2000 to 2010. Diagnosis of dementia, any clinical fracture (excluding facial and digital), comorbidities, and medications were identified using ICD-9 and drug class codes. Cox proportional hazard models considering AChEI use as a time-varying covariate and adjusting for fall and fracture risk factors compared the time-to-fracture in AChEI users versus non-AChEI users. Potential confounders included demographics (age, race, body mass index), comorbidities associated with fracture or falls (diabetes, lung disease, stroke, Parkinson's, seizures, etc.) and medications associated with fracture or falls (bisphosphonates, glucocorticoids, androgen deprivation therapy [ADT], proton pump inhibitors [PPIs], selective serotonin receptor inhibitors [SSRIs], etc.). Competing mortality risk was considered using the methods of Fine and Gray. To account for persistent effects on bone density or quality that might confer protection after stopping the medication, we completed a secondary analysis using the medication possession ratio (MPR) as a continuous variable in logistic regression models and also compared MPR increments of 10% to minimal/no use (MPR 0 to

Diabetes mellitus among older men has been associated with increased bone mineral density but paradoxically increased fracture risk. Given the interactions among medication treatment, glycemic control, and diabetes-associated comorbidities, the relative effects of each factor remains unclear. This retrospective study includes 652,901 male veterans aged ≥65 years with diabetes and baseline hemoglobin A1c (HbA1c) value. All subjects received primary care in the Veterans Health Administration (VHA) from 2000 to 2010. Administrative data included ICD9 diagnoses and pharmacy records and was linked to Medicare fee-for-service data. Hazard ratios (HR) for any clinical fracture and hip fracture were calculated using competing risk hazards models, adjusted for fracture risk factors including age, race/ethnicity, body mass index (BMI), alcohol and tobacco use, rheumatoid arthritis, corticosteroid use, as well as diabetes-related comorbidities including cardiovascular disease, chronic kidney disease, and peripheral neuropathy. HbA1c

Placenta accreta spectrum (PAS) refers to the spectrum of diagnoses involving abnormally and morbidly adherent trophoblastic tissue to the gravid uterus. These disorders are associated with significant maternal morbidity and mortality. While race/ethnicity is known to impact pregnancy outcomes, racial disparities have not been previously examined in women with PAS. The objective of current study was to compare patient characteristics and perioperative outcomes of women with PAS who underwent cesarean delivery across race/ethnicity. This is a comparative study that retrospectively queried the National Inpatient Sample, a hospital-based inpatient database in the USA. The study cohort was women diagnosed with PAS who underwent cesarean delivery from 10/2015 to 12/2018. The exposure group was race/ethnicity. Main outcomes were (i) patient/pregnancy characteristics and (ii) surgical morbidity for cesarean delivery, assessed in multivariable analysis. A total of 10,535 women comprised the study cohort (White n = 5,230 [49.6%], Black n = 2,045 [19.4%], Hispanic n = 2,540 [24.1%], and Asian n = 720 [6.8%]). Patient demographics, pregnancy characteristics, and hospital factors for the non-White groups significantly differed compared to the White group. Older age, obesity, diabetes, placenta previa, percreta, non-elective surgery, lower median household income, and Medicaid particularly represented the non-White groups. When perioperative outcomes were compared, non-White women were more likely to have any measured complications, hemorrhage/transfusion, and shock/coagulopathy compared to White women. Various sensitivity analyses redemonstrated the main cohort results. In conclusion, this study suggests that there were significant disparities in patient characteristics and outcomes of women with PAS across race/ethnicity.

This cohort study examines recent US trends in patient characteristics and perioperative morbidity and mortality at time of cesarean delivery.

Hip fractures are a significant burden on the aging population, often resulting in reduced mobility, loss of independence, and elevated risk of mortality. While fracture risk is generally inversely related to bone mineral density (BMD), people with diabetes suffer a higher fracture rate despite having a higher BMD. To better understand the connection between diabetes and fracture risk, we developed a method to measure the minimum moment of inertia (mMOI; a geometric factor associated with fracture risk) from clinical CT scans of the pelvis. Since hip fractures are more prevalent in women, we focused on females in this study. We hypothesized that females with diabetes would have a lower mMOI along the femoral neck than those without diabetes, indicative of a higher fracture risk. Three-dimensional models of each hip were created from clinical CT scans of 40 older women (27 with diabetes: 10 fracture/17 non-fractured; 13 without diabetes: non-fractured controls). The mMOI of each hip (n = 80) was reported as the average from three trials. People with diabetes had an 18% lower mMOI as compared to those without diabetes after adjusting for age and BMI (p = 0.02). No differences in the mMOIs between the fractured and contralateral hips in the diabetic group were observed (p = 0.78). Similarly, no differences were observed between the fractured and non-fractured hips of people with diabetes (p = 0.29) when accounting for age and BMI. This suggests structural differences in the hips of individuals with diabetes (measured by the mMOI) may be associated with their elevated fracture risk.

Intrahepatic cholestasis of pregnancy is a hepatic disorder characterized by pruritus and an elevation in serum bile acid levels. Although intrahepatic cholestasis of pregnancy poses little risk for women, this condition carries a significant risk for the fetus, including complications such as preterm delivery, meconium-stained amniotic fluid, and stillbirth. The purpose of this Consult is to review the current literature on intrahepatic cholestasis of pregnancy and provide recommendations based on the available evidence. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we recommend measurement of serum bile acid and liver transaminase levels in patients with suspected intrahepatic cholestasis of pregnancy (GRADE 1B); (2) we recommend that ursodeoxycholic acid be used as the first-line agent for the treatment of maternal symptoms of intrahepatic cholestasis of pregnancy (GRADE 1A); (3) we suggest that patients with a diagnosis of intrahepatic cholestasis of pregnancy begin antenatal fetal surveillance at a gestational age when delivery would be performed in response to abnormal fetal testing results or at the time of diagnosis if the diagnosis is made later in gestation (GRADE 2C); (4) we recommend that patients with total bile acid levels of ≥100 μmol/L be offered delivery at 36 0/7 weeks of gestation, given that the risk of stillbirth increases substantially around this gestational age (GRADE 1B); (5) we recommend delivery between 36 0/7 and 39 0/7 weeks of gestation for patients with intrahepatic cholestasis of pregnancy and total bile acid levels of100 μmol/L (GRADE 1C); (6) we recommend administration of antenatal corticosteroids for fetal lung maturity for patients delivering before 37 0/7 weeks of gestation if not previously administered (GRADE 1A); (7) we recommend against preterm delivery at37 weeks of gestation in patients with a clinical diagnosis of intrahepatic cholestasis of pregnancy without laboratory confirmation of elevated bile acid levels (GRADE 1B).

We determined the extent of and reasons for non-adherence to oral bisphosphonates among veterans and conducted a pilot text message reminder application aimed at the most commonly cited reason for non-adherence. The intervention was found to be acceptable and feasible. To evaluate the extent of and reasons for non-adherence to oral bisphosphonates among veterans and to assess the acceptability and feasibility of a pilot text message reminder application. We surveyed 105 veterans initiating oral bisphosphonates for osteoporosis/osteopenia within the prior 18 months utilizing a validated self-report measure adapted for osteoporosis. Additionally, we conducted a pilot text message reminder to determine feasibility in 12 veterans who were initiating or were currently non-adherent to oral bisphosphonates. Of the 43 (40.9% response rate) completed surveys, the most common reasons for non-adherence were “I forgot” (37.5%), “I had other medications to take” (20.5%), “my bones are not weak” (18.4%), “I felt well” (18.4%), and “I worried about taking them for the rest of my life” (17.9%). Median MPR for the 49 (46.7%) non-adherent (MPR < 0.80) veterans was 0.35 (IQR 0.21–0.64). Of veterans offered a weekly automated text message reminder, 12 (50%) accepted. Nine of these 12 veterans reported that the text message reminders did “very well” at reminding them to take their medication and would recommend the application to other patients/family/friends. The median 6-month MPR for the reminder group was 0.96 (IQR 0.54–1.00). Half the veterans in our sample were taking insufficient doses of oral bisphosphonates to attain the full benefit of fracture risk reduction. Reasons for poor adherence included forgetfulness, polypharmacy, and misconceptions about osteoporosis. A pilot text message reminder intervention targeted to one of the most commonly cited reasons was found to be acceptable and feasible among veterans.

Background: Intrahepatic cholestasis of pregnancy (ICP) is characterized by the elevation of total bile acids (TBAs). The primary concern in women with ICP is the increased risk of stillbirth. ICP is generally considered as “mild” when TBA levels range from 10 to 39 µmol/L and “severe” with levels greater than 40 µmol/L, although levels of TBA ≥100 µmol/L have been also considered as a further threshold of severity. Objective: To quantify the association between different severities of ICP (TBA 10–39, 40–99, and ≥100 µmol/L) and perinatal death. Data sources: Medline, Embase, Scopus, Web of Sciences, and ClinicalTrial.gov were searched from the inception of each database to February 2019. Methods of study selection: Randomized, cohort, case-control, or case series studies reporting maternal and perinatal outcomes on women with ICP by the three prespecified TBA levels (10–39, 40–99, and ≥100 µmol/L) were included. We excluded multiple gestations and trials which included an intervention. The analysis was performed with Pearson chi-square and Fisher’s exact test as appropriate. Continuous outcomes were compared using metaregression with inverse variance weighting using reported sample sizes and standard deviations. Pairwise comparisons used a Bonferroni correction to control for multiple testing. Tabulation, integration, and results: Six articles including 1280 singleton pregnancies affected by ICP were included in the systematic review. Out of the 1280 singleton pregnancies affected by ICP included, 118 had ICP with TBA ≥100 µmol/L. Perinatal death was more common in women with TBA ≥100 µmol/L (0.4% for TBA 10-39 μmol/L versus 0.3% for TBA 40-99 μmol/L versus 6.8% for TBA ≥ 100 μmol/L, p

To compare the frequency and severity of neonatal hypoglycemia in pregnancies treated with and without late preterm antenatal corticosteroids.We conducted a retrospective cohort study of late preterm deliveries at LAC + USC (2015-2018). Neonatal outcomes were compared between pregnancies treated with and without corticosteroids.93 pregnancies (39.9%) received corticosteroids and 140 (60.1%) did not. Neonates born to women given corticosteroids were more likely to be hypoglycemic (47.3 vs. 29.3%, ORAdministration of late preterm corticosteroids was associated with an increased incidence and severity of neonatal hypoglycemia.

Hyperthyroidism has important implications for pregnancy, affecting both mother and fetus. Appropriate maternal and fetal management iscritical to avoiding adverse pregnancy outcomes and requires a multidisciplinary approach.To describe maternal diagnosis and management of hyperthyroidism, across all stages of pregnancy. In addition, to review clinical signs of fetal thyroid dysfunction due to maternal Graves disease and discuss management considerations.Review of published articles on PubMed and guidelines by recognized governing organizations regarding the diagnostic and management considerations for hyperthyroidism in pregnancy, from preconception to the postpartum period.Diagnosis of maternal hyperthyroidism involves both clinical symptoms and laboratory findings. Antithyroid medications are the mainstay of therapy, with trimester-specific pregnancy goals. Hyperthyroidism due to Graves disease has important diagnostic and management considerations for the fetus and neonate.Hyperthyroidism in pregnancy affects mother, fetus, and neonate. Interpretation of thyroid tests and understanding the appropriate use of antithyroid drugs are fundamental. Proper education of physicians providing care to women with hyperthyroidism is essential and starts before pregnancy. Postpartum follow-up is an essential part of the care. A systematic approach to management will ensure optimal pregnancy outcomes.

Objective Obstetrical and medical complications in pregnancy may necessitate delivery between 34 and 37 weeks' gestation. To assist decision making and patient counseling, we sought to determine the prevalence of neonatal morbidities between 34 and 37 weeks' gestation. Study design Retrospective cohort study of live births was conducted at our institution over a seven year period. Multiple gestations and congenital anomalies were excluded. The prevalence of neonatal morbidities between 34 and 37 were calculated. Results 1060 births between weeks 34–36 and 975 births occurred during week 37. Gestational age was inversely related to NICU admission, days in NICU, intubation, poor feeding, hyperbilirubinemia, and respiratory distress (p Conclusion There is decreased neonatal morbidity for each week gained between 34 and 37 weeks' gestation.

To examine non-specific red cell reactivity (NSR) on antibody (Ab) screening of obstetric inpatients.Observational study of 5438 obstetric inpatients (2009-2013). Ab-positive patients were identified and their records reviewed for NSR, other antibodies, transfusion reactions or hemolytic disease of the fetus/newborn (HDFN). Evaluation of NSR frequency by test era assessed the impact of an institutional change to solid-phase screening in 2011.Of obstetric inpatients, 5.3% had at least one positive Ab screen; 1.6% had NSR. Of NSR-positive patients, 16.7% had identifiable Abs that pre-dated NSR; 25% had concurrent Abs and 8.5% had subsequent Ab identification. In 49.1%, NSR resolved during follow-up. The frequency of NSR was higher after the change to solid-phase Ab screening, but specific Ab frequency was similar in both testing periods. No transfusion reactions or cases of HDFN were noted in this cohort.NSR is found in 1-2% of obstetrical inpatients at our institution, and has more than doubled since the initiation of solid-phase screening. Although likely clinically insignificant by itself, NSR is commonly found in relation to other red cell Abs and may precede their development.

Objective We set out to test the hypothesis that infants born vaginally at ≤ 30 weeks gestation have less respiratory distress syndrome (RDS) than those born by cesarean delivery. Study Design We conducted a retrospective cohort study of 652 infants born between 24 and 30 6/7 weeks gestation from March 31, 1996 to May 31, 2014. Comparisons of neonatal outcomes by intended and actual mode of delivery were made using chi-square and t-tests (α = 0.05). Multiple logistic regression was performed to control for confounding variables. Results Neonates born by cesarean delivery were more likely to have RDS (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.10–2.90), require intubation (OR, 1.80; 95% CI, 1.12–2.88), and have longer neonatal intensive care unit stay (70.0 ± 37.1 vs. 57.3 ± 40.1 days, p = 0.02). Conclusion Compared with cesarean delivery, vaginal delivery is associated with a significant reduction in RDS among infants born at ≤ 30 weeks gestation.

Objective To determine whether risk-factor-based screening for thyroid dysfunction in pregnancy performs well for detecting thyroid peroxidase antibodies (TPOAb), a marker for autoimmune thyroid disease. Study design We prospectively evaluated pregnant women for thyroid dysfunction using The Endocrine Society's eleven screening questions. Serum was analysed for TPOAb. Result We enrolled 546 women. TPOAb positivity was higher in women with a personal (odds ratio (OR) = 8·0; 95% confidence interval (CI) = 1·7-37·4; P = 0·02) or family history of thyroid disease (OR = 2·7; 95% CI = 1·3-5·7; P = 0·02). There was no association between the number of positive responses and TPOAb positivity (P = 0·41). Risk-factor-based screening missed 18 women (33%) with TPOAb. Conclusion One-third of women with TPOAb were missed by the case-finding method. A personal or family history of thyroid disease was most strongly associated with TPOAb positivity.

Introduction Type 2 diabetes mellitus among older women has been associated with increased bone mineral density, but paradoxically with increased fracture risk. Findings among older men have varied, and potential mechanisms have not been fully elucidated. Methods A retrospective study of male veterans 65 to 99 years of age who received primary care in the Veterans Health Administration from 2000 to 2010, using administrative data from all 146 Veterans Health Administration medical centers linked to Centers for Medicare and Medicaid Services Medicare fee-for-service data. Potential mediating factors of the diabetes-associated risk were evaluated using negative binomial regression models with the outcomes of any clinical fracture and hip fracture. Results Of 2,798,309 Veterans included in the cohort, 900,402 (32.3%) had a diagnosis of diabetes. After adjusting for age, race, ethnicity, body mass index, alcohol and tobacco use, rheumatoid arthritis, and corticosteroid use, the risk of any clinical fracture associated with diabetes was 1.22 (95% confidence interval, 1.21 to 1.23) and that of hip fracture was 1.21 (95% confidence interval, 1.19 to 1.23). Significant mediating factors included peripheral neuropathy, cardiovascular disease, and congestive heart failure, with 45.5% of the diabetes-associated fracture risk explained by these diagnoses. Conclusions Older male Veterans with diabetes have a 22% increased risk of incident clinical fracture compared with those without. A significant portion of this risk is explained by diabetes-related comorbidities, specifically peripheral neuropathy and congestive heart failure. Identification of these mediating factors suggests possible mechanisms, as well as potential interventions.

Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal morbidity and mortality. Early suppression of B-cell lymphopoiesis is necessary for a normal pregnancy. Dysregulation of factors critical to B-cell survival may result in pregnancy complications, including hypertension. In this prospective observational study at a single medical center, serum levels of BAFF (B-cell activating factor) were measured in pregnant participants at each trimester, at delivery, and postpartum and in nonpregnant controls at a single time point. Comparisons were made between nonpregnant and pregnant subjects and between time periods of pregnancy. First-trimester serum BAFF levels were further tested for association with hypertensive disorders of pregnancy. The study included 149 healthy pregnant women, 25 pregnant women with chronic hypertension, and 48 nonpregnant controls. Median first-trimester serum BAFF level (ng/mL) for healthy women (0.90) was lower than median serum BAFF levels for women with chronic hypertension (0.96; P =0.013) and controls (1.00; P =0.002). Serum BAFF levels steadily declined throughout pregnancy, with the median second-trimester level lower than the corresponding first-trimester level (0.77; P =0.003) and the median third-trimester level lower than the corresponding second-trimester level (0.72; P =0.025). The median first-trimester serum BAFF level was elevated in women who subsequently developed hypertension compared with women who remained normotensive (1.02 versus 0.85; P =0.012), with the area under the receiver operating characteristic curve being 0.709. First-trimester serum BAFF level may be an early and clinically useful predictor of hypertensive disorders of pregnancy.

WOS: 000477016300004, Intrahepatic cholestasis of pregnancy (ICP) affects less than 0.1% to 0.2% of pregnant women. It is diagnosed in women with gestational pruritus and increased serum bile acids and can be complicated by preterm labor, fetal asphyxia, meconium-stained amniotic fluid, and stillbirth.

Objective: To compare the incidence of histopathological features in placentas from women with cholestasis of pregnancy to healthy individuals without ICP. Methods: Placentas from mothers with and without cholestasis of pregnancy were reviewed by a pathologist masked to the study group. Subjects were excluded if they had medical problems already associated with placental histopathology. Results: Twenty-four cases and 30 controls placentas were reviewed. Seventeen placental histopathological features were found. There was no statistically significant difference between the groups. Amongst patients with cholestasis, there was a decrease in villitis of unknown etiology in those treated with ursodeoxycholic acid. Conclusion: There is no difference in the placental histopathology in cholestasis of pregnancy compared to normal pregnancies, but treatment of patients with cholestasis of pregnancy with ursodeoxycholic acid may decrease findings of villitis of unknown etiology.

To compare the cost-effectiveness of population screening for vitamin D insufficiency with that of universal vitamin D supplementation in community-dwelling older adults.A Markov decision model simulating follow-up over a 36-month period. Published data were used to estimate values for the model, including costs (measured in 2011 U.S. dollars), utilities (measured in quality-adjusted life years (QALYs)), and probabilities.Decision analysis simulation from a societal perspective.Hypothetical cohort of community-dwelling women and men aged 65 to 80.Net monetary benefit (NMB) was calculated by subtracting the incremental cost of the strategy from the product of incremental QALYs and willingness-to-pay threshold. A higher NMB indicates greater cost-effectiveness.In women aged 65 to 80, population screening was slightly more cost-effective than universal supplementation, with an incremental NMB of $224 compared with $189 (P.001). Population screening in men was also more cost-effective than universal supplementation (incremental NMB $298 vs $260, P.001). Results differed according to age group. In those aged 65, population screening had cost-effectiveness similar to that of universal supplementation in women ($59 vs $71) and men ($114 vs $120), whereas in those aged 80, population screening was substantially more cost-effective than universal supplementation in women ($563 vs $428) and men ($703 vs $571).Population screening and universal supplementation for vitamin D insufficiency are cost-effective strategies in community-dwelling older women and men. In the oldest old, population screening may be more cost-effective than universal supplementation.

Background Bladder exstrophy is a rare congenital anomaly affecting the lower abdominal wall, pelvis, and genitourinary structures. Pregnant women with bladder exstrophy present a unique challenge to the obstetrician. Case The patient is a 35-year old pregnant woman with bladder exstrophy, an extensive surgical history, and uterine prolapse with an abnormal, rubbery consistency to her cervix. Prenatally, she was counseled on the potential use of Duhrssen incisions to facilitate vaginal delivery. Labor was induced at 36 4/7 weeks of gestation after her pregnancy was complicated by recurrent pyelonephritis. Vaginal delivery was achieved 8 minutes after the creation of Duhrssen incisions. Conclusion The care of pregnant women with bladder exstrophy requires multidisciplinary management and careful delivery planning. Successful vaginal delivery can be attained in these patients.

Current recommendations for timing of blood pressure measurement in ambulatory pregnant women vary and are based on studies in the nonpregnant population. The objective of this study was to determine if there is a difference in systolic blood pressure (SBP) and diastolic blood pressure (DBP) between minute-5 and minute-10.A prospective study was conducted at our prenatal care clinics. Participants had their blood pressure measured upon sitting and every 5 minutes for 15 minutes. Initial SBP and DBP were compared to measurements at each time point. Additionally, the SBP and DBP at minute-5 were compared to minute-10. All statistical tests were two-sided.Data from 400 patients were analyzed. Of these, 34.0% were in the first, 30.7% were in the second trimester, and 35.2% were in the third trimester. In each trimester, there was a significant difference in the SBP and DBP at minute-5 compared to minute-0. At minute-10 compared to minute-5, there was no further drop for all trimesters, except for a small drop in DBP in the second trimester (-1.3 ± 6.0, p = 0.012).In an ambulatory setting, 5 minutes after sitting appears to be an appropriate time point to measure blood pressure in pregnancy.

The total bile acid (TBA) concentration criterion for diagnosing intrahepatic cholestasis of pregnancy varies in the published literature. The purpose of this study was to establish pregnancy-specific reference ranges for the TBA concentration among Latina women.Self-identified Latina women (n = 211) over 18 years of age with a singleton pregnancy were recruited and had random serum samples drawn during the second and third trimesters. The total and fractionated bile acid concentrations were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and reference ranges were calculated. Laboratory-provided general reference ranges from a general population of adult men and nonpregnant women were used for comparison.The TBA reference range for our Latina pregnant population (8.5 µmol/L) was markedly lower than the laboratory-provided reference range (4.5 to 19.2 µmol/L).These data suggest that the upper TBA concentration reference range in our Latina pregnant population is 8.5 µmol/L, based on LC-MS/MS measurements.

Despite the increasing number of treatment options for osteoporosis, healthcare providers continue to face clinical conundrums when deciding if and how to treat frail, older adults. The under-representation of this population in randomized controlled trials makes evidence-based decision-making difficult. Furthermore, frail, older adults have multiple medical comorbidities and other competing factors that impact fracture risk prediction. For clinicians to fully assess the potential risks and benefits of treatment, further studies that include frail, older adults are necessary. However, significant feasibility and ethical considerations may complicate trials in this population. Other complementary methodological approaches have been and will need to be utilized. With further understanding of treatment interactions with comorbidities and improvements in risk prediction models, treatment decisions may be better individualized and treatment rates improved in this population at high risk of fracture.

Previous studies have shown an association between the use of traditional anticonvulsants (e.g. phenytoin, carbamazepine, valproate) and decreased bone mineral density (BMD). However, there are limited data regarding the effects of newer anticonvulsants (e.g. gabapentin, levetiracetam, topiramate) on BMD. The aim of this study was to examine the association between the duration of anticonvulsant exposure and BMD, focusing on newer anticonvulsants.This is a retrospective cohort study of patients at a single Veterans Affairs (VA) Medical Center. Longitudinal prescription histories, medical comorbidities, vital statistics, and BMD assessments by dual-energy X-ray absorptiometry (DXA), were abstracted from the computerized medical record. Among 1779 individuals with a DXA scan within the study period, 560 were prescribed at least one anticonvulsant.After adjusting for multiple confounders (including age, gender, body mass index, medical comorbidities, and other medication use), higher duration of use of newer, nonenzyme-inducing anticonvulsants was associated with a higher T-score at the total hip (0.05 standard deviations [SD], p = 0.02) and lumbar (0.10 SD, p0.01), compared to non-users referred for BMD assessment. In contrast, higher duration of use of traditional anticonvulsants had a lower total hip T-score. Furthermore, patients prescribed newer, nonenzyme-inducing anticonvulsants were less likely to have a diagnosis of osteoporosis at the lumbar spine (OR 0.80, 95% CI: 0.68 - 0.95), femoral neck (OR 0.82, 95% CI: 0.69 - 0.98), and total hip (OR 0.74, 95% CI: 0.56 - 0.98).The results suggest that newer anticonvulsant medications are not associated with lower BMD.

We assessed the rate of uterine rupture in patients undergoing labor induction for attempted vaginal birth after cesarean (VBAC). A retrospective study was performed of data from a computerized database. Deliveries from January 1, 1998, to June 30, 2001, in the Southern California Kaiser Permanente system were reviewed and various perinatal characteristics analyzed. A total of 16,218 patients had a prior low transverse cesarean section. Of these, 6832 (42.1%) had a trial of labor. Successful VBAC occurred in 86% of patients with spontaneous onset of labor and 66% of patients with labor induction ( p < 0.001). The uterine rupture rate was not different between patients with spontaneous or induced labor (1.0% versus 1.2%, p = 0.51). Similarly, there was no significant difference between oxytocin or prostaglandin E2 induction (1.4% versus 1.0%, p = 0.59). In our study, labor induction did not appear to increase the risk of uterine rupture in women attempting VBAC.

The purpose of this study was to analyze the relationship of 1-h post-glucola (PG) screening results and the need for insulin therapy in women with gestational diabetes (GDM).The study group was comprised of women with GDM treated at a single institution during calendar years 2000-2004. Women with singleton, term (≥ 37 weeks gestation), liveborn fetuses were included. The association of 1-h PG results and other perinatal risk factors to the need for subsequent insulin therapy was analyzed using multivariable logistic regression models.Of the 1451 women were included in the analysis, 18.1% required insulin treatment. The mean 1-h PG result was 170.0 ± 26.1 mg/dl (range 140-414 mg/dl). We determined that a 1-h PG ≥ 190 mg/dl (p0.0001), an obese body mass index (BMI) (p0.0001), an overweight BMI (p = 0.0019), prior GDM (p = 0.0019), and prior macrosomia (p = 0.0210) were each highly associated with the need for subsequent insulin therapy during the pregnancy.A 1-h PG ≥ 190 mg/dl was strongly associated with the need for insulin therapy in women with GDM. These data may be helpful in counseling and managing women with GDM.

Intrahepatic cholestasis (ICP) of pregnancy is a disease that is likely multifactorial in etiology and has a prevalence that varies by geography and ethnicity. The diagnosis is made when patients have a combination of pruritus and abnormal liver-function tests. It is associated with a high risk for adverse perinatal outcome, including preterm birth, meconium passage, and fetal death. As of yet, the cause for fetal death is unknown. Because fetal deaths caused by ICP appear to occur predominantly after 37 weeks, it is suggested to offer delivery at approximately 37 weeks. Ursodeoxycholic acid appears to be the most effective medication to improve maternal pruritus and liver-function tests; however, there is no medication to date that has been shown to reduce the risk for fetal death.

To determine whether 17-alpha hydroxyprogesterone (17-OHPC) alters tumor necrosis factor-alpha (TNF-alpha) production and the expression of cyclooxygenase type 2 (COX-2) in myometrium exposed to lipopolysaccharide (LPS).Lower segment myometrial biopsies were obtained from non-laboring patients at term. Tissues were cultured in serum-free media with 17-OHPC (1 microM) and LPS (1 microg/ml), either alone or in combination. At 24 h, the production of tumor necrosis factor-alpha (TNF-alpha) and the expression of COX-2 was determined using enzyme linked immunosorbent assay and real-time (RT-PCR). Statistical analysis was performed using non-parametric testing. A P-value of0.05 was considered significant.17-OHPC had no effect on TNF-alpha production and COX-2 expression when compared with untreated myometrial explants (P=0.61 and P=0.95). LPS induced production of TNF-alpha (P=0.03) and expression of COX-2 (P=0.02). Treatment with 17-OHPC did not block LPS-induced TNF-alpha production (P=0.37) or COX-2 expression (P=0.12).In this pilot study, 17-OHPC did not affect the production of TNF-alpha or COX-2 expression in human myometrium.

Background Osteoporosis and seizure disorders are common diagnoses in older adults and often occur concomitantly. Objective The goal of this review was to discuss the current hypothesis for the pathogenesis of anticonvulsant-induced bone density loss and the evidence regarding the risk for osteoporosis and fractures in older individuals. Methods A review of the literature was performed, searching in MEDLINE and CINAHL for articles published between 1990 and October 2009 with the following search terms: anticonvulsant OR antiepileptic; AND osteoporosis OR bone density OR fracture OR absorptiometry, photon. Studies within the pediatric population, cross-sectional studies, and studies whose results were published in a language other than English were excluded. Results A search of the published literature yielded >300 results, of which 24 met the inclusion and exclusion criteria and were included in this review. Hepatic enzyme induction by certain anticonvulsant medications appears to contribute to increased metabolism of 25-hydroxyvitamin D to inactive metabolites, which results in metabolic bone disease. There is increasing evidence that anticonvulsant use is associated with a higher risk of osteoporosis and clinical fractures, especially among older agents such as phenobarbital, carbamazepine, phenytoin, and valproate. Several observational studies suggest a class effect among anticonvulsant agents, associated with clinically significant reductions in bone mineral density and fracture risk. The use of anticonvulsant medications increases the odds of fracture by 1.2 to 2.4 times. However, only 2 large-scale observational studies have specifically examined the risk among those aged >65 years. This review also identified a randomized controlled trial whose results suggest that supplementation with high-dose vitamin D may be associated with increased bone mineral density in patients taking anticonvulsant medications. However, no randomized controlled trials investigating therapeutic agents to prevent fracture in this population were identified. Consequently, there are no formal practice guidelines for the monitoring, prevention, and management of bone disease among those taking anticonvulsants. Conclusions Observational studies suggest an association between use of anticonvulsant medications, reduced bone mineral density, and increased fracture risk. Randomized clinical trials are needed to guide the management of bone disease among those who use anticonvulsants.

Ab initio electronic structure calculations were carried out to achieve a qualitative description of the charge redistribution that takes place in the enzymatic conversion of CO2 to HCO3-. The electronic effect produced by each of the active site species which act on CO2 (a zinc ion ( + 2) bound into the enzyme by three His residues, two water molecules, His 64, Glu 106, and Thr 199) has been assigned. Zinc is found to be five-coordinate, and force optimization leads to a six-membered ring transition state, one side of which is a hydrogen bond to an oxygen of CO2. The proposed reaction mechanism is compatible with all contemporary experimental measurements. The well-known sulfonamide inhibitors of carbonic anhydrase are shown to partially mimic the geometry of the transition state. A schematic for a superior transition state analog is presented; the development of such inhibitors may be useful in the improved treatment of glaucoma. (His)3Zn is replaced by (H3N)3Zn, and zinc is represented by a d-orbital containing 12-electron pseudopotential. For calculations on the transition state, (H3N)3Zn is further replaced by an eight-electron model: two electrons for each ligand's donor pair plus the two outer zinc electrons. This model is calibrated by matching proton affinities and the zinc-water separation in the (H3N)3ZnOH22+ pseudopotential representation.