Longitudinal assessment of coagulation potential before, during, and following an in vitro fertilization cycle.

INTRODUCTION: The association between estrogen and hypercoagulability is well-established but little is known about coagulation dynamics during IVF. Our goal was to measure coagulation potential prior to, during, and following an IVF cycle and to investigate differences by conception outcome. MATERIALS AND METHODS: Patients undergoing IVF with fresh embryo transfer at a single academic center using oral contraceptive pills for cycle batching underwent evaluation of thrombin generation using the calibrated automated thrombogram at multiple points during the IVF cycle. Multiple thrombin generation parameters were compared across timepoints and by IVF cycle outcome using ANOVA repeated measures analysis. RESULTS: Of the 17 patients included, 11 conceived. There was a significant increase in peak and total thrombin generation in the entire cohort between the pre-treatment natural follicular phase and following a short course of oral contraceptive pills used for cycle batching. Further increase in these parameters was seen at the time of oocyte retrieval. In the pre-treatment natural follicular phase, patients who conceived had lower peak thrombin generation. There were changes throughout the cycle for factors II, V, VIII, X, XI, XII, antithrombin, and tissue factor pathway inhibitor. Only Factor XI was distinguishable by conception status; values were lower at all visits in patients who conceived. CONCLUSION: Increases in coagulation potential are seen in patients undergoing IVF following a short course of oral contraceptive pills for cycle batching and continue during controlled ovarian hyperstimulation. Those who conceived were seen to have lower peak thrombin generation in the pre-treatment natural follicular phase.

Dilation of Pregnant Rat Uterine Arteries with Phenols from Extra Virgin Olive Oil Is Endothelium-Dependent and Involves Calcium and Potassium Channels.

During pregnancy, uterine vasculature undergoes significant circumferential growth to increase uterine blood flow, vital for the growing feto-placental unit. However, this process is often compromised in conditions like maternal high blood pressure, particularly in preeclampsia (PE), leading to fetal growth impairment. Currently, there is no cure for PE, partly due to the adverse effects of anti-hypertensive drugs on maternal and fetal health. This study aimed to investigate the vasodilator effect of extra virgin olive oil (EVOO) phenols on the reproductive vasculature, potentially benefiting both mother and fetus. Isolated uterine arteries (UAs) from pregnant rats were tested with EVOO phenols in a pressurized myograph. To elucidate the underlying mechanisms, additional experiments were conducted with specific inhibitors: L-NAME/L-NNA (10-4 M) for nitric oxide synthases, ODQ (10-5 M) for guanylate cyclase, Verapamil (10-5 M) for the L-type calcium channel, Ryanodine (10-5 M) + 2-APB (3 × 10-5 M) for ryanodine and the inositol triphosphate receptors, respectively, and Paxilline (10-5 M) for the large-conductance calcium-activated potassium channel. The results indicated that EVOO-phenols activate Ca2+ signaling pathways, generating nitric oxide, inducing vasodilation via cGMP and BKCa2+ signals in smooth muscle cells. This study suggests the potential use of EVOO phenols to prevent utero-placental blood flow restriction, offering a promising avenue for managing PE.

Subclinical Metabolic and Cardiovascular Factors and Brain White Matter Microstructural Integrity in Young Women.

Women who have experienced pregnancy complications, specifically preeclampsia and gestational diabetes, have well documented increased risks of cardiovascular, metabolic, and neurological disease later in life. This study examined how specific cardiovascular and metabolic risk factors for preeclampsia assessed in a non-pregnant state were associated with brain white matter microstructural integrity. This study examined sixty-two healthy women (mean age 31 ± 5 years) who received metabolic and cardiovascular assessments as well as multiple modality MRI imaging. Participants were either nulliparous (n = 31) or had a history of preterm preeclampsia (n = 31). Imaging included acquisition Diffusion Tensor Imaging (DTI) to assess white matter integrity within the brain. We hypothesized that healthy, young, non-pregnant women with cardiovascular and metabolic profiles suggesting elevated risk would have decreased white matter integrity, represented by lower Fractional Anisotropy (FA) and increased Mean Diffusivity (MD) estimates in the posterior cortical areas of the brain. We observed increased white matter degradation (lower FA and increased MD) in posterior and occipital tracts, commissural fibers, and subcortical structures in women with increased adiposity, worse measures of cardiovascular and metabolic function, including greater insulin resistance (HOMA-IR), hyperlipidemia, elevated blood pressure, and increased arterial stiffness. The relationships detected between subclinical cardiovascular and metabolic phenotypes and increased white matter disruption at a young age, outside of pregnancy, are indicative that adverse changes are detectable long before cognitive clinical presentation. This may suggest that many of the long-term cardiovascular and metabolic risks of aging are influenced by physiologic aging trajectories rather than damage caused by pregnancy complications.

Preterm Preeclampsia Risk Modelling: Examining Hemodynamic, Biochemical, and Biophysical Markers Prior to Pregnancy.

Preeclampsia (PE) is a leading cause of maternal and perinatal death globally and can lead to unplanned preterm birth. Predicting risk for preterm or early-onset PE, has been investigated primarily after conception, and particularly in the early and mid-gestational periods. However, there is a distinct clinical advantage in identifying individuals at risk for PE prior to conception, when a wider array of preventive interventions are available. In this work, we leverage machine learning techniques to identify potential pre-pregnancy biomarkers of PE in a sample of 80 women, 10 of whom were diagnosed with preterm preeclampsia during their subsequent pregnancy. We explore prospective biomarkers derived from hemodynamic, biophysical, and biochemical measurements and several modeling approaches. A support vector machine (SVM) optimized with stochastic gradient descent yields the highest overall performance with ROC AUC and detection rates up to .88 and .70, respectively on subject-wise cross validation. The best performing models leverage biophysical and hemodynamic biomarkers. While preliminary, these results indicate the promise of a machine learning based approach for detecting individuals who are at risk for developing preterm PE before they become pregnant. These efforts may inform gestational planning and care, reducing risk for adverse PE-related outcomes.Clinical Relevance- This work considers the development and optimization of pre-pregnancy biomarkers for improving the identification of preterm (early-onset) preeclampsia risk prior to conception.

The Quick Inventory of Depressive Symptomatology, Adolescent Version (QIDS-A17): A Psychometric Evaluation.

Objective: The current study aimed to evaluate the psychometric features of the Quick Inventory of Depressive Symptomatology, Adolescent version (QIDS-A17) and the clinician-rated Children's Depression Rating Scale-Revised (CDRS-R). Methods: Altogether, 103 outpatients (8 to 17 years) completed the self-report QIDS-A17-SR. Clinician interviews of adolescents (QIDS-A17-C (Adolescent)) and of parents (QIDS-A17-C (Parent)) were combined to create the QIDS-A17-C(Composite) and the CDRS-R. Results: All QIDS-A17 measures and the CDRS-R evidenced high total score correlations and internal consistency. Factor analysis found all four measures to be unidimensional. Item Response Theory (IRT) analysis found results that complemented the reliability results found in CTT. All four also demonstrated discriminant diagnostic validity based on logistic regression and ANOVA analyses. Conclusion: The psychometric properties of the self-report and composite versions of the QIDS-A17 suggest acceptability as a measure of depression in adolescents either as a measure of depressive symptoms or severity of illness in adolescents. The self-report version may be a helpful tool in busy clinical practices.

Care plan for individuals at risk for preeclampsia: shared approach to education, strategies for prevention, surveillance, and follow-up.

Preeclampsia is a multisystemic disorder of pregnancy that affects 250,000 pregnant individuals in the United States and approximately 10 million worldwide per annum. Preeclampsia is associated with substantial immediate morbidity and mortality but also long-term morbidity for both mother and offspring. It is now clearly established that a low dose of aspirin given daily, beginning early in pregnancy modestly reduces the occurrence of preeclampsia. Low-dose aspirin seems safe, but because there is a paucity of information about long-term effects on the infant, it is not recommended for all pregnant individuals. Thus, several expert groups have identified clinical factors that indicate sufficient risk to recommend low-dose aspirin preventive therapy. These risk factors may be complemented by biochemical and/or biophysical tests that either indicate increased probability of preeclampsia in individuals with clinical risk factors, or more importantly, identify increased likelihood in those without other evident risk. In addition, the opportunity exists to provide this population with additional care that may prevent or mitigate the short- and long-term effects of preeclampsia. Patient and provider education, increased surveillance, behavioral modification, and other approaches to improve outcomes in these individuals can improve the chance of a healthy outcome. We assembled a group with diverse, relevant expertise (clinicians, investigators, advocates, and public and private stakeholders) to develop a care plan in which providers and pregnant individuals at risk can work together to reduce the risk of preeclampsia and associated morbidities. The plan is for care of individuals at moderate to high risk for developing preeclampsia, sufficient to receive low-dose aspirin therapy, as identified by clinical and/or laboratory findings. The recommendations are presented using the GRADE methodology with the quality of evidence upon which each is based. In addition, printable appendices with concise summaries of the care plan's recommendations for patients and healthcare providers are provided. We believe that this shared approach to care will facilitate prevention of preeclampsia and its attendant short- and long-term morbidity in patients identified as at risk for development of this disorder.

Preterm Preeclampsia Risk Modelling: Examining Hemodynamic, Biochemical, and Biophysical Markers Prior to Pregnancy.

Preeclampsia (PE) is a leading cause of maternal and perinatal death globally and can lead to unplanned preterm birth. Predicting risk for preterm or early-onset PE, has been investigated primarily after conception, and particularly in the early and mid-gestational periods. However, there is a distinct clinical advantage in identifying individuals at risk for PE prior to conception, when a wider array of preventive interventions are available. In this work, we leverage machine learning techniques to identify potential pre-pregnancy biomarkers of PE in a sample of 80 women, 10 of whom were diagnosed with preterm preeclampsia during their subsequent pregnancy. We explore biomarkers derived from hemodynamic, biophysical, and biochemical measurements and several modeling approaches. A support vector machine (SVM) optimized with stochastic gradient descent yields the highest overall performance with ROC AUC and detection rates up to .88 and .70, respectively on subject-wise cross validation. The best performing models leverage biophysical and hemodynamic biomarkers. While preliminary, these results indicate the promise of a machine learning based approach for detecting individuals who are at risk for developing preterm PE before they become pregnant. These efforts may inform gestational planning and care, reducing risk for adverse PE-related outcomes.

Corrigendum: Preeclampsia and its relationship to pathological brain aging.

[This corrects the article DOI: 10.3389/fphys.2022.979547.].

Preeclampsia and its relationship to pathological brain aging.

The development of preeclampsia during pregnancy may have long-term effects on brain aging in women. Associations between preeclampsia and vascular dementia have been established, however the connection between preeclampsia and Alzheimer's disease has not been as thoroughly explored. Both preeclampsia and Alzheimer's disease have been associated with misfolded amyloid beta proteins and inflammation; due to these similarities, in this minireview, we examined the potential links between a history of preeclampsia and the development of dementia. We also discussed how hypertensive disorders of pregnancy may relate to both normal brain aging and dementia to highlight the need for additional research regarding the long-term cognitive effects of preeclampsia on the brain.

Randomized Controlled Trial Examining the Efficacy of Adding Financial Incentives to Best practices for Smoking Cessation Among pregnant and Newly postpartum Women.

We report results from a single-blinded randomized controlled trial examining financial incentives for smoking cessation among 249 pregnant and newly postpartum women. Participants included 169 women assigned to best practices (BP) or BP plus financial incentives (BP + FI) for smoking cessation available through 12-weeks postpartum. A third condition included 80 never-smokers (NS) sociodemographically-matched to women who smoked. Trial setting was Burlington, Vermont, USA, January, 2014 through January, 2020. Outcomes included 7-day point-prevalence abstinence antepartum and postpartum, and birth and other infant outcomes during 1st year of life. Reliability and external validity of results were assessed using pooled results from the current and four prior controlled trials coupled with data on maternal-smoking status and birth outcomes for all 2019 singleton live births in Vermont. Compared to BP, BP + FI significantly increased abstinence early- (AOR = 9.97; 95%CI, 3.32-29.93) and late-pregnancy (primary outcome, AOR = 5.61; 95%CI, 2.37-13.28) and through 12-weeks postpartum (AOR = 2.46; CI,1.05-5.75) although not 24- (AOR = 1.31; CI,0.54-3.17) or 48-weeks postpartum (AOR = 1.33; CI,0.55-3.25). There was a significant effect of trial condition on small-for-gestational-age (SGA) deliveries (χ2 [2] = 9.01, P = .01), with percent SGA deliveries (+SEM) greatest in BP, intermediate in BP + FI, and lowest in NS (17.65 + 4.13, 10.81 + 3.61, and 2.53 + 1.77, respectively). Reliability analyses supported the efficacy of financial incentives for increasing abstinence antepartum and postpartum and decreasing SGA deliveries; external-validity analyses supported relationships between antepartum cessation and SGA risk. Adding financial incentives to Best Practice increases smoking cessation among antepartum and postpartum women and improves other maternal-infant outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02210832.

Placental Maternal Vascular Malperfusion is Associated with Prepregnancy and Early Pregnancy Maternal Cardiovascular and Thrombotic Profiles.

Characteristics of maternal vascular malperfusion (MVM) are frequently observed in placentas from pregnancies impacted by preeclampsia, intrauterine growth restriction, preterm labor, and intrauterine fetal demise. We sought to evaluate the associations of features of MVM with subclinical measures of cardiovascular health and coagulation potential in healthy young women. Sixty-three healthy young women were recruited and assessed prior to pregnancy on cycle day 9 ± 4, at gestational age 90 ± 6 of early pregnancy, and gestational age 216 ± 5 of late pregnancy. Women were assessed for plasma volume, blood pressure, response to volume loading, cardiac output, and uterine hemodynamics. Platelet-poor plasma was collected to assess thrombin generation on a subset of 33 women at all time points. Following delivery, placentas were collected and analyzed for evidence of MVM. Thrombin generation (TG) was evaluated in the presence of tissue factor (TF) with and without recombinant soluble thrombomodulin (TM). For each, we compared TG lagtime, peak level, and endogenous thrombin potential (ETP). Comparisons were made between dichotomized presence and absence of each individual feature of MVM and cardiovascular and coagulation features. Mean ± standard deviation are presented. Women were 31 ± 4 years of age, body mass index of 24 ± 5 kg/m2, 86% white race, and 80% nulliparous. MVM occurred in 70% of placentas, with infarcts and agglutination (44%), decidual arteriopathy (40%), accelerated villous maturation (32%), placental hypoplasia (29%), and distal villous hypoplasia (17%) documented. Decidual arteriopathy and distal villous hypoplasia were associated with prepregnancy maternal physiology, including decreased plasma volume and subclinical cardiovascular variations. All assessed MVM characteristics had identifiable early pregnancy physiologic characteristics consistent with altered cardiovascular function and decreased uterine response to pregnancy when compared with women who did and did not develop MVM. Accelerated villous maturation was the only MVM feature to differ by thrombin generation parameters in early pregnancy. Thrombin generation potential and blood pressure were elevated in late pregnancy in women who developed decidual arteriopathy. Prepregnancy health status and adaptation to pregnancy play important roles in pregnancy outcomes. Both cardiovascular health and thrombin generation potential may influence early placentation. Longitudinal assessment of subclinical maternal factors may allow for better understanding of the etiologies of MVM lesions, as well as allow for identification of a timeline of the origins of placental pathologies.

ß -Glucan Improves Protective Qi Status in Adults with Protective Qi Deficiency-A Randomized, Placebo-Controlled, and Double-Blinded Trial.

OBJECTIVE: To test the hypothesis that ß -glucan enhances protective qi (PQi), an important Chinese medicine (CM) concept which stipulates that a protective force circulates throughout the body surface and works as the first line of defense against "external pernicious influences". METHODS: A total of 138 participants with PQi deficiency (PQD) were randomized to receive ß -glucan (200 mg daily) or placebo for 12 weeks. Participants' PQi status was assessed every 2 weeks via conventional diagnosis and a standardized protocol from which a PQD severity and risk score was derived. Indices of participants' immune and general health status were also monitored, including upper respiratory tract infection (URTI), saliva secretory IgA (sIgA), and self-reported measures of physical and mental health (PROMIS). RESULTS: PQi status was not significantly different between the ß -glucan and placebo treatment groups at baseline but improved significantly in the ß -glucan (vs. placebo) group in a time-dependent manner. The intergroup differences [95% confidence interval (CI)] in severity score (scale: 1-5), risk score (scale: 0-1), and proportion of PQD participants (%) at finish line was 0.49 (0.35-0.62), 0.48 (0.35-0.61), and 0.36 (0.25-0.47), respectively. Additionally, ß -glucan improved URTI symptom (scale: 1-9) and PROMIS physical (scale: 16.2-67.7) and mental (scale: 21.2-67.6) scores by a magnitude (95% CI) of 1.0 (0.21-1.86), 5.7 (2.33-9.07), and 3.0 (20.37-6.37), respectively, over placebo. CONCLUSIONS: ß -glucan ameliorates PQi in PQD individuals. By using stringent evidence-based methodologies, our study demonstrated that Western medicine-derived remedies, such as ß -glucan, can be employed to advance CM therapeutics. (ClinicalTrial.Gov registry: NCT03782974).

Cardiovascular profiles associated with white matter hyperintensities in healthy young women.

Women who experience hypertension in pregnancy have increased risk of both chronic hypertension and dementia. High blood pressure is associated with increased evidence of white matter hyperintensities (WMH) in brain imaging. WMH are disruptions of the white matter of the brain that occur with demyelination and axonal degeneration, are associated with vascular disease, occur more frequently in people with hypertension, and are associated with cognitive impairment. We evaluated the relationship between WMH and subclinical cardiovascular function in healthy young nulliparous women and women with a history of early-onset preeclampsia. Sixty-two reproductive-aged women were assessed during the follicular phase of the menstrual cycle after a 3-day sodium/potassium-controlled diet. Half of participants had a history of early-onset preeclampsia, and half were nulliparous. Blood was drawn to assess inflammatory markers. Cardiovascular assessments included tonometric blood pressure monitoring, volume loading to assess vascular compliance, echocardiography to assess cardiac ejection time, brachial pulse wave velocity of the brachial artery, assessing cardiovascular stiffness, and brachial artery flow mediated vasodilation to assess endothelial mediated dilatory response. T2 fluid-attenuated inversion recovery (FLAIR) MRI imaging was obtained. Two raters, blinded to cardiovascular assessments and pregnancy history, reviewed MRI scans for evidence of WMH using the Fazekas rating scale. WMHs were detected in 17 women; 45 had normal white matter structure. Participants with Fazekas score>0 had exaggerated response to volume loading compared to women with a Fazekas score of 0 and longer cardiac ejection times. Fazekas scores >0 had lower brachial flow-mediated vasodilation and increased white blood count compared to those with no evidence of WMH. Women with WMH had reduced cardiovascular compliance, and a trend towards decreased endothelial responsiveness compared to those without WMH. These data demonstrated that the relationship between cardiovascular and brain health was detectable in young, healthy, reproductive-aged women, and may play a role in later development of clinical disease. These findings may help identify women who are at risk for cognitive decline and pathological aging.

Association of pre-pregnancy subclinical insulin resistance with cardiac dysfunction in healthy nulliparous women.

OBJECTIVES: To investigate the association between pre-pregnancy subclinical insulin resistance and cardiovascular dysfunction in healthy nulliparous women, and with hypertension in subsequent pregnancy. STUDY DESIGN: Secondary analysis of a single center prospective observational study conducted November 2011-June 2014. Healthy nulliparous women underwent detailed cardiovascular and metabolic assessment. Insulin resistance was determined by homeostasis model assessment (HOMA-IR). Associations of HOMA-IR with metabolic and cardiovascular measurements were assessed with Spearman correlations. Charts were reviewed in women who conceived singleton pregnancies. MAIN OUTCOME MEASURES: Metabolic measurements included serum glucose, insulin, creatinine, CRP, and lipids. HOMA-IR was calculated using fasting serum insulin and glucose. Indices of cardiovascular stiffness were determined from pulse wave velocity and response to volume challenge. Pregnancy outcomes included delivery mode and gestational age, birthweight, and hypertension. RESULTS: HOMA-IR was positively associated with BMI (r = 0.462, p < 0.001), body fat percentile (r = 0.463, p < 0.001), CRP (r = 0.364, p = 0.003), and negatively associated with serum HDL (r = -0.38, p = 0.002) and creatinine (r = -0.242, p = 0.049). HOMA-IR was positively associated with blood pressure (r = 0.347, p = 0.004), resting heart rate (r = 0.433, p = <0.001), response to volume challenge (r = 0.325, p < 0.01). Increased HOMA-IR was associated with a faster cardiac ejection time in response to volume challenge (r = -0.415, p < 0.001), which is a marker of decreased cardiac compliance to volume increase, or cardiac stiffness. CONCLUSION: HOMA-IR is associated with pre-pregnancy cardiac stiffness. Cholesterol was not associated with cardiovascular dysfunction. A non-significant trend was observed between HOMA-IR and hypertension in subsequent pregnancy.

Proof-of-Concept and Feasibility Study to Evaluate the Effect of ß-Glucan on Protective Qi Deficiency in Adults.

OBJECTIVE: To preliminarily explore the potential effect of ß-glucan on Chinese medicine (CM) concept protective qi deficiency (PQD), and the methodology for future definitive studies. METHODS: To have a standardized assessment of PQD, a list of 13 potentially PQD-relevant parameters were firstly created, each with defined quantitative or categorial scales. Using the data from 37 participants with (21 cases) or without (16 cases) PQD, multivariate logistic modeling was conducted to create a preliminary diagnostic PQD risk score. Subsequently, 21 participants diagnosed with PQD were treated with ß-glucan in a dose of 200 mg/day for 8 weeks. Data were collected for trial acceptability measures (rate of recruitment, withdrawal, and compliance), and the participants were assessed for PQD status at baseline and every 2 weeks thereafter. RESULTS: The preliminary logistic model consisted of 3 parameters (low voice and apathy, aversion to wind and cold, and Cun pulse). The resulting risk score demonstrated a degree of PQD-predicting accuracy that, as evaluated by statistical (discrimination and classification) methods, was higher than those obtained from any of the individual candidate parameters. The 21 PQD participants treated with ß-glucan demonstrated good receptibility and a time-dependent improvement in PQD status as evidenced by the decrease of PQD participant to 9.5% at the end of study. CONCLUSIONS: This study demonstrated the effect of proof-of-concept of ß-glucan on improving PQD and the proof-of-concept of a multivariate-model-derived diagnostic PQD risk score. It also indicated feasibility for future definitive studies. Studies like this embody an innovative approach that uses therapies derived from the mainstream biomedicine to enrich therapeutics guided by CM principle. (Trial registration No. NCT03829228).

Measures of adiposity correlate with renal filtration in young nulliparous women: An observational cohort study.

OBJECTIVE: Renal hyperfiltration, which has been documented in severe obesity and obesity-associated hypertension, can occur with hypertensive disorders of pregnancy. Identification of prepregnancy risk factors for unrecognized renal hyperfiltration could inform screening and intervention strategies to protect against pregnancy complications. In young, healthy, nulliparous women, associations between associations between measures of adiposity, insulin resistance, and renal vascular resistance were thus evaluated. METHODS: This is a secondary analysis of a prospective observational trial characterizing associations of prepregnancy and late-pregnancy maternal physiology. Seventy-nine nulligravid women aged 18-42 years without major medical conditions were assessed for percent android body fat using dual-energy X-ray absorption. Renal cortical vessel blood flow resistance index (CVRI) was determined using Doppler ultrasonography. Creatinine clearance was calculated from 24-hour urine collection. RESULTS: Renal CVRI inversely correlates with body mass index (r = -0.23, p = 0.047), percent android fat (r = -0.30, p = 0.008), and supine pulse (r = -0.44, p < 0.001). Creatinine clearance is positively associated with BMI and HOMA-IR.In regression modeling, supine pulse (r2 = 0.22, p < 0.001) and cardiac index (r2 = 0.05, p = 0.045) predict renal CVRI, whereas HOMA-IR (r2 = 0.11, p = 0.008) and cardiac output (r2 = 0.06, p = 0.039) predict creatinine clearance. Measures of adiposity are not independently predictive of either measure. CONCLUSIONS: In healthy young women, measures of adiposity and insulin resistance correlate positively with renal filtration. Preclinical manifestations of renal hyperfiltration may have implications for pregnancy outcomes.

Subclinical cardiac stiffness is associated with arterial stiffness in healthy young nulligravid women: Potential links to preeclampsia.

OBJECTIVES: Preeclampsia is an independent risk factor for subsequent cardiovascular disease and diastolic dysfunction and has been linked to arterial stiffness. We hypothesized that arterial stiffness would be associated with echocardiographic markers of diastolic dysfunction in healthy nulligravid women. STUDY DESIGN: 31 healthy nulligravid women underwent assessment of peripheral arterial stiffness via aorto-femoral pulse wave velocity, popliteal distensibility and ß stiffness measures as well as hemodynamic response to volume challenge. 22 underwent cardiac assessment via conventional and stress echocardiography with a focus on diastolic function utilizing tissue/pulse wave Doppler imaging and 3D speckle tracking. Bivariate associations between variables were evaluated using correlation coefficients (Pearson r) and Student's t-tests. RESULTS: No participants had echocardiographic values meeting criteria for overt diastolic dysfunction. Baseline global circumferential strain was significantly correlated with distensibility and ß stiffness (n = 18, r = -0.61, p = 0.007, n = 18, r = 0.56, p = 0.01). Peak deceleration time was correlated with ßstiffness (n = 9; r = 0.80, p = 0.01). Pulse wave velocity was not significantly correlated with cardiac measures (p > 0.05). Family history of a first or second degree relative with myocardial infarction or hypertension was associated with decreased popliteal artery distensibility (p = 0.02 and p = 0.03, respectively). CONCLUSIONS: In healthy nulligravid women there is evidence that markers of decreased left ventricular relaxation are associated with increased peripheral vascular stiffness as is a family history of myocardial infarction or hypertension. These findings raise the possibility that the diastolic dysfunction and arterial stiffness observed in the setting of preeclampsia are driven by underlying properties present prior to pregnancy and contribute to lifetime cardiovascular risk.

The Stimulant Selective Severity Assessment: A replication and exploratory extension of the Cocaine Selective Severity Assessment.

BACKGROUND: Cocaine and methamphetamine have similar withdrawal symptoms and many individuals concurrently use both substances; however, no measures concurrently assess withdrawal from multiple stimulants. OBJECTIVES: This study's aim was to explore the Stimulant Selective Severity Assessment (SSSA), a modified version of the Cocaine Selective Severity Assessment (CSSA), in a sample of stimulant users to determine if it can assess withdrawal symptoms in users of one or more stimulants. METHODS: Baseline data were analyzed from the STimulant Reduction Intervention using Dosed Exercise trial, a multisite randomized clinical trial that evaluated exercise versus health education on drug use outcomes in individuals with stimulant use disorders. Data were analyzed for internal consistency, construct validity, and scale dimensionality. RESULTS: Internal consistency for the full sample was good (α = 0.81; N = 302), with similar alphas in Cocaine (0.81; n = 177) and Cocaine/Other Stimulant (0.82; n = 92) groups, but with much lower alpha for the group without cocaine use (Other Stimulant, i.e., primarily methamphetamine, α = 0.66; n = 32). Support for construct validity was evidenced by significant positive correlations (r = 0.17 to 0.67) with measures of stimulant craving, depressive symptoms, and pain. Four factors were revealed. Conclusions/Importance: The Stimulant Selective Severity Assessment is a new measure that can be used to assess withdrawal symptoms in users of cocaine or cocaine plus methamphetamine, but it should not be administered to users of methamphetamine only.

Combined financial incentives and behavioral weight management to enhance adherence with gestational weight gain guidelines: a randomized controlled trial.

BACKGROUND: Excessive gestational weight gain, particularly among overweight and obese women, is associated with adverse perinatal outcomes. Current interventions to limit gestational weight gain have achieved only modest success. OBJECTIVE: We sought to improve adherence to gestational weight gain guidelines with a dual intervention of financial incentives and antenatal behavioral weight management. STUDY DESIGN: This was a prospective randomized controlled trial at a single academic medical center in which women were assigned randomly to the intervention group or standard care. The primary outcome was adherence to gestational weight gain guidelines. Secondary outcomes included total gestational weight gain, mode of delivery, birthweight, neonatal intensive care unit admission, and development of gestational diabetes mellitus and hypertensive disorders of pregnancy. RESULTS: A total of 136 women were assigned randomly, with data available for analysis of 124 women. Gestational weight gain within the Institutes of Medicine guidelines was similar (30% vs 29%) in the intervention and standard care groups, respectively. There were no statistically significant differences in total gestational weight gain or perinatal outcomes. There was a nonstatistically significant decrease in macrosomia in the intervention compared with standard care condition. CONCLUSION: A combined financial incentive and behavioral weight management intervention did not improve adherence to gestational weight gain guidelines. Modifications to the intervention may achieve improved results.

Attitudes and Beliefs of Pediatric Surgical Specialists on Costs of Care and High Deductible Health Plans.

Health care consumers are burdened with rising out-of-pocket medical expenses. Surgical specialists' experience and attitude towards patients' out-of-pocket costs and the influence of these factors on healthcare utilization are unknown. Our aim was to define the pediatric surgeons' experience with the financial concerns of their patients. Members from the American Academy of Pediatrics Sections on Plastic Surgery, Surgery and Urology were surveyed. Analysis of variance was used to investigate practice differences. Two hundred and eighteen out of 973 surgeons representing 38 states completed the survey. Nearly half of the surveyed surgeons did not know if cost was a determinant for their patients' choice in surgical facility, or if parents compared costs prior to the visit. Eighty four per cent of the surgeons would consider patient costs if medically appropriate, to entertain less costly alternatives, and adjust surgical scheduling to decrease economic burden. Most pediatric surgical specialists are unaware if out-of-pocket costs influenced patients' preoperative decisions. Nonetheless, they are sympathetic to the issue. As the financial burden of health care shifts to consumers, our survey indicates that surgeons are open to candid discussion surrounding finances and may alter recommendations accordingly if appropriate.