Update on sex specific risk factors in cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide and accounts for roughly 1 in 5 deaths in the United States. Women in particular face significant disparities in their cardiovascular care when compared to men, both in the diagnosis and treatment of CVD. Sex differences exist in the prevalence and effect of cardiovascular risk factors. For example, women with history of traditional cardiovascular risk factors including hypertension, tobacco use, and diabetes carry a higher risk of major cardiovascular events and mortality when compared to men. These discrepancies in terms of the relative risk of CVD when traditional risk factors are present appear to explain some, but not all, of the observed differences among men and women. Sex-specific cardiovascular disease research-from identification, risk stratification, and treatment-has received increasing recognition in recent years, highlighting the current underestimated association between CVD and a woman's obstetric and reproductive history. In this comprehensive review, sex-specific risk factors unique to women including adverse pregnancy outcomes (APO), such as hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus, preterm delivery, and newborn size for gestational age, as well as premature menarche, menopause and vasomotor symptoms, polycystic ovarian syndrome (PCOS), and infertility will be discussed in full detail and their association with CVD risk. Additional entities including spontaneous coronary artery dissection (SCAD), coronary microvascular disease (CMD), systemic autoimmune disorders, and mental and behavioral health will also be discussed in terms of their prevalence among women and their association with CVD. In this comprehensive review, we will also provide clinicians with a guide to address current knowledge gaps including implementation of a sex-specific patient questionnaire to allow for appropriate risk assessment, stratification, and prevention of CVD in women.

Ischemic heart disease in pregnancy: a practical approach to management.

Ischemic heart disease is a crucial issue during pregnancy. The term is composed of both preexisting conditions and acute coronary syndrome in pregnancy, including pregnancy-associated myocardial infarction, which can have a significant effect on maternal and fetal outcomes. This review provides a complete guide to managing ischemic heart disease in pregnant women, emphasizing the importance of multidisciplinary care and individualized treatment strategies. Cardiovascular disease, particularly ischemic heart disease, is now the leading cause of maternal mortality worldwide. Pregnancy introduces unique physiological changes that increase the risk of acute myocardial infarction, with pregnancy-associated myocardial infarction cases often associated with factors, such as advanced maternal age, chronic hypertension, and preexisting cardiovascular conditions. This review distinguishes between preexisting ischemic heart disease and pregnancy-associated myocardial infarction. It will emphasize the various etiologies of pregnancy-associated myocardial infarction, including coronary atherosclerosis and plaque rupture presenting as ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, and other nonatherosclerotic causes, including spontaneous coronary artery dissection, vasospasm, and embolism. Our study discusses the practical management of ischemic heart disease in pregnancy, with a focus on preconception counseling, risk assessment, and tailored antenatal planning for women with preexisting ischemic heart disease. Moreover, this document focuses on the challenges of diagnosing cardiovascular disease, especially when presented with nonclassical risk factors and presentation. It provides insight into the appropriate diagnostic testing methods, such as electrocardiogram, cardiac biomarkers, and echocardiography. In addition, the review covers various treatment strategies, from medical management to more invasive procedures, including coronary angiography, percutaneous coronary intervention, and coronary artery bypass graft. Special attention is given to medication safety during pregnancy, including anticoagulation, beta-blockers, and antiplatelet agents. The complexities of delivery planning in women with ischemic heart disease are discussed, advocating for a multidisciplinary team-based approach and careful consideration of the timing and mode of delivery. Furthermore, the roles of breastfeeding and postpartum care are explored, emphasizing the long-term benefits and the suitability of various medications during lactation. Lastly, this review provides crucial insights into the management of ischemic heart disease in pregnancy, stressing the need for heightened awareness, prompt diagnosis, and tailored management to optimize maternal and fetal health outcomes.

The utility of completing adjuvant video lessons based on the unified protocol during psychotherapy: A retrospective study using a telehealth platform in routine clinical care.

Digital supplements to tele-psychotherapy are increasingly needed. The purpose of this retrospective study was to investigate the association between outcomes and the use of supplemental video lessons based on the Unified Protocol (UP), an empirically supported transdiagnostic treatment.Participants included 7,326 adults in psychotherapy for depression and/or anxiety. Partial correlations were calculated between number of UP video lessons completed and change in outcomes after 10 weeks, controlling for number of therapy sessions and baseline scores. Then, participants were divided into those who did not complete any UP video lessons (n = 2355) and those who completed at least 7/10 video lessons (n = 549), and propensity-matched on 14 covariates. Repeated measures analysis of variance compared these groups (n = 401 in each group) on outcomes.Among the entire sample, symptom severity decreased as the number of UP video lessons completed increased, with the exception of lessons on avoidance and exposure. Those watching at least 7 lessons showed significantly greater reduction in both depression and anxiety symptoms than those who did not watch any.Viewing supplemental UP video lessons in addition to tele-psychotherapy had a positive and significant association with symptom improvement and may provide an additional tool for clinicians to implement UP components virtually.

Novel Telehealth Adaptations for Evidence-Based Outpatient Suicide Treatment: Feasibility and Effectiveness of the Crisis Care Program.

Background: Suicide rates in the United States have escalated dramatically over the past 20 years and remain a leading cause of death. Access to evidenced-based care is limited, and telehealth is well-positioned to offer novel care solutions. The Crisis Care program is a suicide-specific treatment program delivered within a national outpatient telehealth setting using a digitally adapted version of the Collaborative Assessment and Management of Suicidality (CAMS) as the framework of care. This study investigates the feasibility and preliminary effectiveness of Crisis Care as scalable suicide-specific treatment model. Methods: Patient engagement, symptom reduction, and care outcomes were examined among a cohort of patients (n = 130) over 16 weeks. The feasibility of implementation was assessed through patient engagement. Clinical outcomes were measured with PHQ-9, GAD-7, and the CAMS SSF-4 rating scales. Results: Over 85% of enrolled patients were approved for Crisis Care at intake, and 83% went on to complete at least four sessions (the minimum required to graduate). All patient subgroups experienced declines in depressive symptoms, anxiety symptoms, suicidal ideation frequency, and suicide-specific risk factors. Conclusions: Results support the feasibility and preliminary effectiveness of Crisis Care as a suicide-specific care solution that can be delivered within a stepped-care model in an outpatient telehealth setting.

Sex-specific and sex-independent steroid-related biomarkers in early second trimester maternal serum associated with autism.

BACKGROUND: Prenatal exposure to maternal metabolic conditions associated with inflammation and steroid dysregulation has previously been linked to increased autism risk. Steroid-related maternal serum biomarkers have also provided insight into the in utero steroid environment for offspring who develop autism. OBJECTIVE: This study examines the link between autism among offspring and early second trimester maternal steroid-related serum biomarkers from pregnancies enriched for prenatal metabolic syndrome (PNMS) exposure. STUDY DESIGN: Early second trimester maternal steroid-related serum biomarkers (i.e., estradiol, free testosterone, total testosterone, and sex hormone binding globulin) were compared between pregnancies corresponding to offspring with (N = 68) and without (N = 68) autism. Multiple logistic regression analyses were stratified by sex and gestational duration. One-way ANCOVA with post hoc tests was performed for groups defined by autism status and PNMS exposure. RESULTS: Increased estradiol was significantly associated with autism only in males (AOR = 1.13 per 100 pg/ml, 95% CI 1.01-1.27, p = 0.036) and only term pregnancies (AOR = 1.17 per 100 pg/ml, 95% CI 1.04-1.32, p = 0.010). Autism status was significantly associated with decreased sex hormone binding globulin (AOR = 0.65 per 50 nmol/L, 95% CI 0.55-0.78, p < 0.001) overall and when stratified by sex and term pregnancy status. The inverse association between sex hormone binding globulin and autism was independent of PNMS exposure. LIMITATIONS: The relative racial and ethnic homogeneity of Utah's population limits the generalizability of study results. Although significant differences by autism status were identified in concentrations of sex hormone binding globulin overall and of estradiol in participant subgroups, differences by PNMS exposure failed to reach statistical significance, which may reflect insufficient statistical power. CONCLUSION: Both elevated maternal serum estradiol in males only and low maternal serum sex hormone binding globulin in both sexes are associated with increased autism risk. Further investigation is merited to identify how steroid, metabolic, and inflammatory processes can interact to influence neurodevelopment in early second trimester.

Mass Poisoning From Ethylene Glycol at a U.S. Military Base.

Ethylene glycol (EG) toxicity is an important cause of toxic alcohol poisoning in the USA with over 5,000 exposures reported annually. While classically characterized by solitary accidental or intentional ingestions, mass toxic alcohol poisoning outbreaks and more rarely collective consumptions (typically of methanol) have been described. We describe an ethylene glycol poisoning from collective ingestion that involved soldiers presenting at William Beaumont Army Medical Center in El Paso, Texas. Eleven soldiers presented to the emergency department over a 12-h period after ingestion of an unknown substance. The first two patients exhibited severe neurologic symptoms, while the remainder were asymptomatic. As serum EG levels were not immediately available, treatment decisions were based on surrogate laboratory values. Two patients received immediate hemodialysis, and fomepizole (FOM) because of severe acidosis with elevated anion and osmolal gaps. These patients developed acute kidney injury with renal recovery within a 3-week period. Two patients with elevated lactate received bicarbonate-based intravenous (IV) fluids and FOM. Two patients received IV fluids only and required prolonged observation for worsening acidosis and/or acute kidney injury. Five patients with normal laboratory values were treated with IV fluids and observation. All patients received cofactors including thiamine and pyridoxine. All patients survived. The outbreak occurred in the setting of limited dialysis resources, limited FOM availability, and in a resource-limited community. Additional guidelines are needed to determine allocation of limited resources, optimal dialysis and FOM treatment course, and comorbid conditions, which may prolong recovery.

Clinical and economic evaluation of a proteomic biomarker preterm birth risk predictor: cost-effectiveness modeling of prenatal interventions applied to predicted higher-risk pregnancies within a large and diverse cohort.

OBJECTIVES: Preterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment. METHODS: The ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with masked risk predictor assessment (TREETOP; NCT02787213). All subjects were included in three arms across 500 simulated trials: standard of care (SoC, control); risk predictor/case management comprising increased outreach, education and specialist care (RP-CM, active); and multimodal management (risk predictor/case management with pharmacological treatment) (RP-MM, active). In the active arms, only subjects stratified as higher risk by the predictor were modeled as receiving the intervention, whereas lower-risk subjects received standard care. Higher-risk subjects' gestational ages at birth were shifted based on published efficacies, and dependent outcomes, calibrated using national datasets, were changed accordingly. Subjects otherwise retained their original TREETOP outcomes. Arms were compared using survival analysis for neonatal and maternal hospital length of stay, bootstrap intervals for neonatal cost, and Fisher's exact test for neonatal morbidity/mortality (significance, p < .05). RESULTS: The model predicted improvements for all outcomes. RP-CM decreased neonatal and maternal hospital stay by 19% (p = .029) and 8.5% (p = .001), respectively; neonatal costs' point estimate by 16% (p = .098); and moderate-to-severe neonatal morbidity/mortality by 29% (p = .025). RP-MM strengthened observed reductions and significance. Point estimates of benefit did not differ by race/ethnicity. CONCLUSIONS: Modeled evaluation of a biomarker-based test-and-treat strategy in a diverse population predicts clinically and economically meaningful improvements in neonatal and maternal outcomes.

Preterm birth, defined as delivery before 37 weeks' gestation, is the leading cause of illness and death in newborns. In the United States, more than 10% of infants are born prematurely, and this rate is substantially higher in lower-income, inner-city and Black populations. Prematurity associates with greatly increased risk of short- and long-term medical complications and can generate significant costs throughout the lives of affected children. Annual U.S. health care costs to manage short- and long-term prematurity complications are estimated to exceed $25 billion.Clinical interventions, including case management (increased patient outreach, education and specialist care), pharmacological treatment and their combination can provide benefit to pregnancies at higher risk for preterm birth. Early and sensitive risk detection, however, remains a challenge.We have developed and validated a proteomic biomarker risk predictor for early identification of pregnancies at increased risk of preterm birth. The ACCORDANT study modeled treatments with real-world patient data from a racially and ethnically diverse U.S. population to compare the benefits of risk predictor testing plus clinical intervention for higher-risk pregnancies versus no testing and standard care. Measured outcomes included neonatal and maternal length of hospital stay, associated costs and neonatal morbidity and mortality. The model projected improved outcomes and reduced costs across all subjects, including ethnic and racial minority populations, when predicted higher-risk pregnancies were treated using case management with or without pharmacological treatment. The biomarker risk predictor shows high potential to be a clinically important component of risk stratification for pregnant women, leading to tangible gains in reducing the impact of preterm birth.

Telehealth-Supported Decision-making Psychiatric Care for Suicidal Ideation: Longitudinal Observational Study.

BACKGROUND: Suicide is a leading cause of death in the United States, and suicidal ideation (SI) is a significant precursor and risk factor for suicide. OBJECTIVE: This study aimed to examine the impact of a telepsychiatric care platform on changes in SI over time and remission, as well as to investigate the relationship between various demographic and medical factors on SI and SI remission. METHODS: Participants included 8581 US-based adults (8366 in the treatment group and 215 in the control group) seeking treatment for depression, anxiety, or both. The treatment group included patients who had completed at least 12 weeks of treatment and had received a prescription for at least one psychiatric medication during the study period. Providers prescribed psychiatric medications for each patient during their first session and received regular data on participants. They also received decision support at treatment onset via the digital platform, which leveraged an empirically derived proprietary precision-prescribing algorithm to give providers real-time care guidelines. Participants in the control group consisted of individuals who completed the initial enrollment data and completed surveys at baseline and 12 weeks but did not receive care. RESULTS: Greater feelings of hopelessness, anhedonia, and feeling bad about oneself were most significantly correlated (r=0.24-0.37) with SI at baseline. Sleep issues and feeling tired or having low energy, although significant, had lower correlations with SI (r=0.13-0.14). In terms of demographic variables, advancing age and education were associated with less SI at baseline (r=-0.16) and 12 weeks (r=-0.10) but less improvement over time (r=-0.12 and -0.11, respectively). Although not different at baseline, the SI expression was evident in 34.4% (74/215) of the participants in the control group and 12.32% (1031/8366) of the participants in the treatment group at 12 weeks. Although the participants in the treatment group improved over time regardless of various demographic variables, participants in the control group with less education worsened over time, after controlling for age and depression severity. A model incorporating the treatment group, age, sex, and 8-item Patient Health Questionnaire scores was 77% accurate in its classification of complete remission. Those in the treatment group were 4.3 times more likely (odds ratio 4.31, 95% CI 2.88-6.44) to have complete SI remission than those in the control group. Female participants and those with advanced education beyond high school were approximately 1.4 times more likely (odds ratio 1.38, 95% CI 1.18-1.62) to remit than their counterparts. CONCLUSIONS: The results highlight the efficacy of an antidepressant intervention in reducing SI, in this case administered via a telehealth platform and with decision support, as well as the importance of considering covariates, or subpopulations, when considering SI. Further research and refinement, ideally via randomized controlled trials, are needed.

Feasibility and acceptability of a novel telepsychiatry-delivered precision prescribing intervention for anxiety and depression.

BACKGROUND: Major Depressive Disorder and Generalized Anxiety Disorder are pervasive and debilitating conditions, though treatment is often inaccessible and based on trial-and-error prescribing methods. The present observational study seeks to describe the use of a proprietary precision prescribing algorithm piloted during routine clinical practice as part of Brightside's telepsychiatry services. The primary aim is to determine the feasibility and acceptability of implementing this intervention. Secondary aims include exploring remission and symptom improvement rates. METHODS: Participants were adult patients enrolled in Brightside who completed at least 12 weeks of treatment for depression and/or anxiety and received a prescription for at least one psychiatric medication. A prescription recommendation was made by Brightside's algorithm at treatment onset and was utilized for clinical decision support. Participants received baseline screening surveys of the PHQ-9 and GAD-7, and at weeks 2,4,6,8,10 and 12. Intent-to-treat (ITT) sensitivity analyses were conducted. Feasibility of the implementation was measured by the platform's ability to enroll and engage participants in timely psychiatric care, as well as offer high touch-point treatment options. Acceptability was measured by patient responses to a 5-star satisfaction rating. RESULTS: Brightside accessed and treated 6248 patients from October 2018 to April 2021, treating a majority of patients within 4-days of enrollment. The average plan cost was $115/month. 89% of participants utilized Brightside's core medication plan at a cost of $95/month. 13.4% of patients in the study rated Brightside's services as highly satisfactory, averaging a 4.6-star rating. Furthermore, 90% of 6248 patients experienced a MCID in PHQ-9 or GAD-7 score. Remission rates were 75% (final PHQ-9 or GAD-7 score < 10) for the study sample and 59% for the ITT sample. 69.3% of Brightside patients were treated with the medication initially prescribed at intake. CONCLUSIONS: Results suggest that the present intervention may be feasible and acceptable within the assessed population. Exploratory analyses suggest that Brightside's course of treatment, guided by precision recommendations, improved patients' symptoms of anxiety and depression.

Lowering platelet count threshold to 10,000/µL for peripherally inserted central catheter placement safely conserves blood products.

Despite the low risk of peripherally inserted central catheter (PICC) insertion-related bleeding, the practice of administering prophylactic platelets varies greatly. Limiting unnecessary blood product transfusions reduces transfusion-related adverse events, financial cost, and delays in care. We assessed the impact of lowering prophylactic platelet administration threshold on blood product utilization patterns and bleeding events. This quasi-experimental study was conducted in an urban academic tertiary medical center. The study population included patients with platelet counts ≥ 10,000/µL and < 50,000/µL undergoing PICC placement in 2018 and 2019 when the minimum platelet thresholds were 50,000/µL and 10,000/µL, respectively. The primary outcome was blood product utilization and the secondary outcome was PICC insertion-related bleeding complications. Thirty-five patients using the 10,000/µL (10 K) platelet threshold and 46 patients using the 50,000/µL (50 K) platelet threshold were enrolled. The 50 K group received more platelets before PICC insertion (0.870 ± 0.885 and 0.143 ± 0.430 pools of platelets-per-person, p < 0.001). No patients experienced clinically significant bleeding. Immediately following PICC insertion, minor bleeding occurred in five patients (two [4.3%] and three [8.6%] in the 50 K and 10 K groups, respectively). Bleeding rates between the two cohorts did not differ (p = 0.647). Lowering the minimum platelet threshold from 50,000/µL to 10,000/µL resulted in less prophylactic platelet and total blood product administration with no appreciable difference in PICC insertion-related bleeding.

A Comparative Evaluation of Measurement-Based Psychiatric Care Delivered via Specialized Telemental Health Platform Versus Treatment As Usual: A Retrospective Analysis.

Background and objective A significant proportion of the adult population in the United States (US) live with some form of mental illness. The more prevalent conditions of depression and anxiety are typically managed in primary care settings rather than specialty care. The aim of this study was to determine the efficacy of a novel, measurement-driven psychiatric treatment platform delivered via an online telemental health platform as compared to treatment as usual (TAU). Methods The TAU dataset and the telemental health platform (Brightside) dataset were constructed based on the total populations of adult patients receiving care for depression from January 2018 through December 2020 (November 2018 through March 2021 for the Brightside group). Patients in both groups had a primary mental health diagnosis of depression and the presence of a positive screen for depression as measured by the Patient Health Questionnaire-9 (PHQ-9) upon initiation of treatment. HITLAB, an independent digital health verification and testing lab, conducted comparative analyses of the two groups using the Chi-square test of independence. Results Close to 80% of telemental health platform patients experienced a reduction of 5 or more points from their baseline PHQ-9 score as compared to 52% of TAU patients. The mean reduction in PHQ-9 score was slightly higher in the Brightside group (-11.5) versus the TAU group (-10.1). Chi-square tests of independence [x2 (1, n=6281) = 256.75, p≤0.001] for meaningful reduction and for remission [x2 (1, n=6281) = 105.50 p≤0.001] were highly significant. Conclusion The telemental health platform patients performed significantly better than those under psychiatric TAU in terms of reduction in symptoms of depression in adults.

Viability of acellular biologic graft for nipple-areolar complex reconstruction in a non-human primate model.

Many of the > 3.5 million breast cancer survivors in the US have undergone breast reconstruction following mastectomy. Patients report that nipple-areolar complex (NAC) reconstruction is psychologically important, yet current reconstruction techniques commonly result in inadequate shape, symmetry, and nipple projection. Our team has developed an allogeneic acellular graft for NAC reconstruction (dcl-NAC) designed to be easy to engraft, lasting, and aesthetically pleasing. Here, dcl-NAC safety and host-mediated re-cellularization was assessed in a 6-week study in rhesus macaque non-human primates (NHPs). Human-derived dcl-NACs (n = 30) were engrafted on the dorsum of two adult male NHPs with each animal's own nipples as controls (n = 4). Weight, complete blood counts, and metabolites were collected weekly. Grafts were removed at weeks 1, 3, or 6 post-engraftment for histology. The primary analysis evaluated health, re-epithelialization, and re-vascularization. Secondary analysis evaluated re-innervation. Weight, complete blood counts, and metabolites remained mostly within normal ranges. A new epidermal layer was observed to completely cover the dcl-NAC surface at week 6 (13-100% coverage, median 93.3%) with new vasculature comparable to controls at week 3 (p = 0.10). Nerves were identified in 75% of dcl-NACs (n = 9/12) at week 6. These data suggest that dcl-NAC is safe and supports host-mediated re-cellularization.

Performance of a proteomic preterm delivery predictor in a large independent prospective cohort.

BACKGROUND: Preterm birth remains a common and devastating complication of pregnancy. There remains a need for effective and accurate screening methods for preterm birth. Using a proteomic approach, we previously discovered and validated (Proteomic Assessment of Preterm Risk study, NCT01371019) a preterm birth predictor comprising a ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin. OBJECTIVE: To determine the performance of the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin to predict both spontaneous and medically indicated very preterm births, in an independent cohort distinct from the one in which it was developed. STUDY DESIGN: This was a prospective observational study (Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor, NCT02787213) at 18 sites in the United States. Women had blood drawn at 170/7 to 216/7 weeks' gestation. For confirmation, we planned to analyze a randomly selected subgroup of women having blood drawn between 191/7 and 206/7 weeks' gestation, with the results of the remaining study participants blinded for future validation studies. Serum from participants was analyzed by mass spectrometry. Neonatal morbidity and mortality were analyzed using a composite score by a method from the PREGNANT trial (NCT00615550, Hassan et al). Scores of 0-3 reflect increasing numbers of morbidities or length of neonatal intensive care unit stay, and 4 represents perinatal mortality. RESULTS: A total of 5011 women were enrolled, with 847 included in this planned substudy analysis. There were 9 preterm birth cases at <320/7 weeks' gestation and 838 noncases at ≥320/7 weeks' gestation; 21 of 847 infants had neonatal composite morbidity and mortality index scores of ≥3, and 4 of 21 had a score of 4. The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio was substantially higher in both preterm births at <320/7 weeks' gestation and there were more severe neonatal outcomes. The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio was significantly predictive of birth at <320/7 weeks' gestation (area under the receiver operating characteristic curve, 0.71; 95% confidence interval, 0.55-0.87; P=.016). Stratification by body mass index, optimized in the previous validation study (22

Effect of Antibiotic Treatment of Amniotic Fluid Sludge.

BACKGROUND: Amniotic fluid sludge refers to the sonographic presence of echogenic, free-floating aggregates of debris located within the amniotic cavity near the internal cervical os of women with intact membranes. Clinically, it is independently associated with increased obstetric, infectious, and neonatal morbidity, including: short cervix, chorioamnionitis, and an increased risk of preterm birth. It is thought to be infectious in nature and has been described as an intrauterine bacterial biofilm. There is little evidence on the impact of treatment with antibiotics on outcome. OBJECTIVE: To determine whether outpatient antibiotics administered to women with amniotic fluid sludge would reduce preterm birth risk compared to no antibiotic treatment. MATERIALS AND METHODS: This was a retrospective cohort study of all patients diagnosed with amniotic fluid sludge by transvaginal sonography between 15 and 25 weeks' gestation in the outpatient ultrasound unit at a single academic center between 2010 and 2017. Patients were segregated according to whether they were treated with oral antibiotics at the time of diagnosis. Women with multiple gestation, fetal anomalies, preterm rupture of membranes prior to initial diagnosis of amniotic fluid sludge, and active preterm labor placenta previa and/or suspected accreta were excluded from analysis. Primary outcome of preterm birth at less than 37 weeks' gestation was compared by univariate and regression analysis to control for potential co-linear and/or confounding variables. Additional outcomes were compared by univariate analysis. RESULTS: A total of 181 patients were initially identified, and 97 patients met inclusion criteria. Of these patients, 51 were treated with oral antibiotics (46 azithromycin and 5 moxifloxacin), and 46 were not treated. The overall incidence of preterm birth at <37 weeks was 49.4 % (48 of 97) and preterm birth <28 weeks was 22.7% (22 of 97). There was no significant difference in preterm birth, either at <37 weeks (P = .47) or <28 weeks (P = .83) between the treated and untreated women. After adjusting for race, body mass index, tobacco use, cervical length, and preterm birth history, antibiotic treatment did not reduce the risk of preterm birth (adjusted odds ratio, 1.3; confidence interval, 0.77-1.9). No differences were seen in the incidence of preterm premature rupture of membranes (P = .94) or median latency from diagnosis to delivery (P = .47). Birthweight (P = .99), sepsis (P = .53), intraventricular hemorrhage (P = .95), and neonatal intensive care unit (NICU) admission (P = .08) were not affected by antibiotic treatment. Antibiotic treatment did not affect the incidence of either clinical or histologic chorioamnionitis (P = .92 and .14, respectively) or histologic stage 2-3 maternal or fetal inflammation (P = .94 and 0.58, respectively). Sonographic resolution of amniotic fluid sludge on first subsequent scan was seen in 34% of antibiotic-treated women and 43% of untreated women (P = .42). There was no difference in latency from diagnosis to delivery or mean gestational age at delivery according to whether sludge resolved or persisted at the first subsequent scan (P = .14 for each). CONCLUSION: Antibiotic treatment of amniotic fluid sludge is not associated with a reduction in premature birth. Likewise, antibiotic treatment of amniotic fluid sludge was not associated with improvement in other obstetric, neonatal, or pathologic variables. These findings suggest that the presumed infectious nature of sludge and subsequent adverse outcomes are not treated or improved by administration of azithromycin following midtrimester sonographic diagnosis.

Utility of Nonspecific Laboratory Testing for Psychiatric Patients Undergoing Medical Screening in a Military Emergency Department.

INTRODUCTION: Psychiatric complaints account for a sizable and increasing portion of emergency department (ED) visits. Compared with other medical patients, these patients often require substantial resources because of limited specialized resources and prolonged boarding times, which can be detrimental to the safety and satisfaction of other patients. This can prompt early and indiscriminate laboratory testing to expedite early requests for admission consideration. Numerous emergency medicine literature and clinical policies already recommend against indiscriminate screening labs for these patients, yet many psychiatric services require these tests. This study further evidences the limited clinical utility and high associated costs of mandatory protocol screening labs for psychiatric patients evaluated in military EDs. MATERIALS AND METHODS: A retrospective chart review of 441 active duty military patients and their families presenting to Madigan Army Medical Center's ED who received psychiatric diagnoses underwent analysis. A 3-physician review panel evaluated each identified patient case to confirm eligibility and determine whether or not laboratory studies led to a change in patient disposition that was not identified by history, review of systems, physical exam, and known past medical history. The review was approved by the hospital's institutional review board. Contemporary laboratory tests ordered in the evaluation of these patients included complete blood count with differential, complete metabolic panel, thyroid-stimulating hormone, serum ethanol, serum acetaminophen, serum salicylates, urine drug screening, urinalysis, urine human chorionic gonadotropin, and electrocardiograms. RESULTS: Broad screening labs may have altered dispositions for 0.9% (4) of patients. In total, 93% (202) of admitted patients were dispositioned to a psychiatric service. Of the 15 patients admitted to a medical service, 10 involved overdoses or intoxication. One patient had anemia in addition to opioid use disorder as diagnoses and was dispositioned to a medicine service. One pediatric patient was admitted for observation only. The remaining patients had diagnoses based on physical exam and history requiring medical service admission. In total, 7 patients had unknown dispositions, of which 4 carried solely psychiatric diagnoses. CONCLUSIONS: The cumulative reimbursement costs of broad testing in the studied population were estimated at $36,325.17 and rarely altered patient disposition. Further testing does not increase the incidence of disposition altering diagnoses and is associated with increased costs. When individual state laws and the clinical assessment by the responsible emergency physician are considered, future standardized ED lab screening evaluations of psychiatric patients in military EDs may be concentrated to breathalyzer alcohol level, urine drug screen, serum salicylates, serum acetaminophen, and urine human chorionic gonadotropin.

The use of venous Doppler to predict adverse kidney events in a general ICU cohort.

BACKGROUND: Changes in Doppler flow patterns of hepatic veins (HV), portal vein (PV) and intra-renal veins (RV) reflect right atrial pressure and venous congestion; the feasibility of obtaining these assessments and the clinical relevance of the findings is unknown in a general ICU population. This study compares the morphology of HV, PV and RV waveform abnormalities in prediction of major adverse kidney events at 30 days (MAKE30) in critically ill patients. STUDY DESIGN AND METHODS: We conducted a prospective observational study enrolling adult patients within 24 h of admission to the ICU. Patients underwent an ultrasound evaluation of the HV, PV and RV. We compared the rate of MAKE-30 events in patients with and without venous flow abnormalities in the hepatic, portal and intra-renal veins. The HV was considered abnormal if S to D wave reversal was present. The PV was considered abnormal if the portal pulsatility index (PPI) was greater than 30%. We also examined PPI as a continuous variable to assess whether small changes in portal vein flow was a clinically important marker of venous congestion. RESULTS: From January 2019 to June 2019, we enrolled 114 patients. HV abnormalities demonstrate an odds ratio of 4.0 (95% CI 1.4-11.2). PV as a dichotomous outcome is associated with an increased odds ratio of MAKE-30 but fails to reach statistical significance (OR 2.3 95% CI 0.87-5.96), but when examined as a continuous variable it demonstrates an odds ratio of 1.03 (95% CI 1.00-1.06). RV Doppler flow abnormalities are not associated with an increase in the rate of MAKE-30 INTERPRETATION: Obtaining hepatic, portal and renal venous Doppler assessments in critically ill ICU patients are feasible. Abnormalities in hepatic and portal venous Doppler are associated with an increase in MAKE-30. Further research is needed to determine if venous Doppler assessments can be useful measures in assessing right-sided venous congestion in critically ill patients.

Acellular Biologic Nipple-Areolar Complex Graft: In Vivo Murine and Nonhuman Primate Host Response Evaluation.

There are more than 3 million breast cancer survivors living in the United States of which a significant number have undergone mastectomy followed by breast and nipple-areolar complex (NAC) reconstruction. Current strategies for NAC reconstruction are dependent on nonliving or nonpermanent techniques, including tattooing, nipple prosthetics, or surgical nipple-like structures. Described herein is a tissue engineering approach demonstrating the feasibility of an allogeneic acellular graft for nipple reconstruction. Nonhuman primate (NHP)-derived NAC tissues were decellularized and their extracellular matrix components analyzed by both proteomic and histological analyses. Decellularized NHP nipple tissue showed the removal of intact cells and greatly diminished profiles for intracellular proteins, as compared with intact NHP nipple tissue. We further evaluated the biocompatibility of decellularized grafts and their potential to support host-mediated neovascularization against commercially available acellular dermal grafts by performing in vivo studies in a murine model. A follow-up NHP pilot study evaluated the host-mediated neovascularization and re-epithelialization of onlay engrafted decellularized NAC grafts. The murine model revealed greater neovascularization in the decellularized NAC than in the commercially available control grafts, with no observed biocompatibility issues. The in vivo NHP model confirmed that the decellularized NAC grafts encourage neovascularization as well as re-epithelialization. These results support the concept that a biologically derived acellular nipple graft is a feasible approach for nipple reconstruction, supporting neovascularization in the absence of adverse systemic responses. Impact statement Currently, women in the United States most often undergo a mastectomy, followed by reconstruction, after being diagnosed with breast cancer. These breast cancer survivors are often left with nipple-areolar complex (NAC) reconstructions that are subsatisfactory, nonliving, and/or nonpermanent. Utilizing an acellular biologically derived whole NAC graft would allow these patients a living and permanent tissue engineering solution to nipple reconstruction.

Impact of dosing schedule on uptake of neuroprotective magnesium sulfate.

Background: Preterm delivery <32-week gestation is associated with significant neurodevelopmental morbidity ranging from mild delay to profound disability. Several randomized trials have shown that magnesium sulfate (MgSO4) is an effective neuroprotectant, demonstrating reduced rates of cerebral palsy, death, and gross motor dysfunction for the neonate or infant. Dosing was not consistent among the major trials and the onus was placed on institutions by ACOG to develop and implement protocols with respect to MgSO4 as a neuroprotectant. A recent study demonstrated that MgSO4 exposure <12 h prior to delivery was associated with a decrease in CP compared to more remote exposure.Objective: To assess impact of dosing schedule on uptake of neuroprotective MgSO4 in patients delivering <32 weeks gestational age.Study design: A retrospective cohort study of all deliveries occurring <32 weeks' gestation at a single academic center between March-December 2014 and March-December 2015 was conducted. Institutional policy shifted in 2015 from MgSO4 bolus with continuous infusion based on the BEAM trial to a single bolus dose based on the PREMAG trial. Patients with preeclampsia, known fetal anomalies, and/or stillbirth were excluded from this analysis. Patients were identified through query of the Medical University of South Carolina Perinatal Information System (PINS) database with respect to whether or not they had received MgSO4 within 12 h of delivery. Chi-squared analysis was performed to compare the overall rate of MgSO4 exposure and MgSO4 exposure <12 h prior to delivery between groups. Fisher's exact test was used to evaluate maternal, obstetric, and neonatal variables among those receiving MgSO4 within 12 h of delivery in each cohort. Binary logistic regression analysis was performed to control for co-linear or potential confounding variables.Results: A total of 224 patients were identified, 115 delivered between March-December 2014 and 109 delivered between March-December 2015. With respect to MgSO4 exposure prior to delivery, 27 (23.5%) received MgSO4 in the 2014 cohort compared to 44 (40.4%) in the 2015 cohort (OR: 2.2, p < .01). Of those being exposed within 12 h of delivery, there were 16 (13.9%) maternal exposures in the 2014 cohort versus 28 (26.7%) in the 2015 cohort (OR: 2.15, p = .02). Of the 18 neonates delivered in 2014 there were four cases of grade III or IV intraventricular hemorrhage versus one case among the 36 neonates (2.7%) born in 2015 (0.04). This finding holds after controlling for race, preterm labor, gestational age, corticosteroid, birthweight, and indomethacin exposure.Conclusions: Dosing of neuroprotective MgSO4 according to PREMAG trial specifications was associated with a significantly greater percentage of patients having received neuroprotective magnesium at any point prior to delivery or within the 12 h prior to delivery when compared to dosing according to BEAM trial specifications.

Hypothyroidism in Pregnancy.

Hypothyroidism in pregnancy is defined as the presence of an elevated thyroid stimulating hormone during gestation, affecting 2% to 3% of the population. Overt hypothyroidism is diagnosed by a decreased FT4, while patients with a normal FT4 are considered to have subclinical disease. Poorly controlled disease is associated with both pregnancy complications and developmental delays in the offspring. Treatment consists of replacement with levothyroxine and regular monitoring. Most pregnant women will require an increase in their dosing from 25% to 30%. While treatment for SCH remains controversial, current recommendations do not support universal screening of low-risk women during pregnancy.