Synthesis and Receptor Binding Studies of α5 GABAAR Selective Novel Imidazodiazepines Targeted for Psychiatric and Cognitive Disorders.

GABA mediates inhibitory actions through various GABAA receptor subtypes, including 19 subunits in human GABAAR. Dysregulation of GABAergic neurotransmission is associated with several psychiatric disorders, including depression, anxiety, and schizophrenia. Selective targeting of α2/3 GABAARs can treat mood and anxiety, while α5 GABAA-Rs can treat anxiety, depression, and cognitive performance. GL-II-73 and MP-III-022, α5-positive allosteric modulators have shown promising results in animal models of chronic stress, aging, and cognitive disorders, including MDD, schizophrenia, autism, and Alzheimer's disease. Described in this article is how small changes in the structure of imidazodiazepine substituents can greatly impact the subtype selectivity of benzodiazepine GABAAR. To investigate alternate and potentially more effective therapeutic compounds, modifications were made to the structure of imidazodiazepine 1 to synthesize different amide analogs. The novel ligands were screened at the NIMH PDSP against a panel of 47 receptors, ion channels, including hERG, and transporters to identify on- and off-target interactions. Any ligands with significant inhibition in primary binding were subjected to secondary binding assays to determine their Ki values. The newly synthesized imidazodiazepines were found to have variable affinities for the benzodiazepine site and negligible or no binding to any off-target profile receptors that could cause other physiological problems.

A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects.

Rho family GTPases act as molecular switches regulating actin cytoskeleton dynamics. Attenuation of their signaling capacity is provided by GTPase-activating proteins (GAPs), including p190A, that promote the intrinsic GTPase activity of Rho proteins. In the current study we have performed a small-scale ENU mutagenesis screen and identified a novel loss of function allele of the p190A gene Arhgap35, which introduces a Leu1396 to Gln substitution in the GAP domain. This results in decreased GAP activity for the prototypical Rho-family members, RhoA and Rac1, likely due to disrupted ordering of the Rho binding surface. Consequently, Arhgap35-deficient animals exhibit hypoplastic and glomerulocystic kidneys. Investigation into the cystic phenotype shows that p190A is required for appropriate primary cilium formation in renal nephrons. P190A specifically localizes to the base of the cilia to permit axoneme elongation, which requires a functional GAP domain. Pharmacological manipulations further reveal that inhibition of either Rho kinase (ROCK) or F-actin polymerization is able to rescue the ciliogenesis defects observed upon loss of p190A activity. We propose a model in which p190A acts as a modulator of Rho GTPases in a localized area around the cilia to permit the dynamic actin rearrangement required for cilia elongation. Together, our results establish an unexpected link between Rho GTPase regulation, ciliogenesis and glomerulocystic kidney disease.

Using a State Birth Registry as a Quality Improvement Tool.

Background Birth registry data are universally collected, generating large administrative datasets. However, these data are typically not used for quality improvement (QI) initiatives in perinatal medicine because the quality and timeliness of the information is uncertain. Objective We sought to identify and address causes of inaccuracy in recording birth registry information so that birth registry data could support statewide obstetrical quality initiatives in Ohio. Study Design The Ohio Perinatal Quality Collaborative and the Ohio Department of Health Vital Statistics used QI techniques in 15 medium-sized maternity hospitals to identify and remove systemic sources of inaccuracy in birth registry data. The primary outcome was the rate of scheduled deliveries without medical indication between 370/7 and 386/7 weeks at participating hospitals from birth registry data. Results Inaccurate birth registry data most commonly resulted from limited communication between clinical and medical record staff. The rate of scheduled births between 370/7 and 386/7 weeks' gestation without a documented medical indication as recorded in the birth registry declined by 35%. Conclusion A QI initiative aimed at increasing the accuracy of birth registry information demonstrated the utility of these data for surveillance of perinatal outcomes and has led to ongoing efforts to support birth registrars in submitting accurate data.

Intrauterine fetal demise after prenatal diagnosis of congenital heart disease: assessment of risk.

OBJECTIVES: Elective deliveries in fetal congenital heart disease (CHD) attempt to balance fetal and neonatal risk with the goal of optimizing overall outcome. However, the magnitude of the risk for intrauterine fetal demise (IUFD) is unclear. This study aimed to (1) determine the rate of IUFD and (2) identify fetal risk factors associated with IUFD. METHODS: Retrospective review of pregnancies complicated by CHD between 1998 and 2010. Data were collected regarding pregnancy outcome, extracardiac anomalies (ECA), genetic and cardiac diagnoses, severity of valve regurgitation, gestational age at birth and birth weight. Fisher's exact test and odds ratios were used to compare outcomes between groups. RESULTS: A total of 501 pregnancies analyzed resulted in 445 live births, 22 IUFD, 16 terminations and 18 unknown outcomes. Amongst IUFD, 27% had a genetic diagnosis, 50% had an ECA and 27% had severe valve regurgitation. IUFD odds increased threefold with ECA and sevenfold with severe valve regurgitation. IUFD occurred in 1.2% without risk factors. CONCLUSIONS: IUFD in fetuses with CHD is associated with ECA, genetic syndromes and severe valve regurgitation. In absence of these fetal characteristics, the occurrence of IUFD is low, although it remains higher than in fetuses without CHD.

Nephric duct insertion is a crucial step in urinary tract maturation that is regulated by a Gata3-Raldh2-Ret molecular network in mice.

Urinary tract development depends on a complex series of events in which the ureter moves from its initial branch point on the nephric duct (ND) to its final insertion site in the cloaca (the primitive bladder and urethra). Defects in this maturation process can result in malpositioned ureters and hydronephrosis, a common cause of renal disease in children. Here, we report that insertion of the ND into the cloaca is an unrecognized but crucial step that is required for proper positioning of the ureter and that depends on Ret signaling. Analysis of Ret mutant mice at birth reveals hydronephrosis and defective ureter maturation, abnormalities that our results suggest are caused, at least in part, by delayed insertion of the ND. We find a similar set of malformations in mutants lacking either Gata3 or Raldh2. We show that these factors act in parallel to regulate ND insertion via Ret. Morphological analysis of ND extension in wild-type embryos reveals elaborate cellular protrusions at ND tips that are not detected in Ret, Gata3 or Raldh2 mutant embryos, suggesting that these protrusions may normally be important for fusion with the cloaca. Together, our studies reveal a novel Ret-dependent event, ND insertion, that, when abnormal, can cause obstruction and hydronephrosis at birth; whether ND defects underlie similar types of urinary tract abnormalities in humans is an interesting possibility.

Gene regulatory network of renal primordium development.

Animal development progresses through the stepwise deployment of gene regulatory networks (GRN) encoded in the genome. Comparative analyses in different species and organ systems have revealed that GRN blueprints are composed of subcircuits with stereotypical architectures that are often reused as modular units. In this review, we report the evidence for the GRN underlying renal primordium development. In vertebrates, renal development is initiated by the induction of a field of intermediate mesoderm cells competent to undergo lineage specification and nephric (Wolffian) duct formation. Definition of the renal field leads to the activation of a core regulatory subcircuit composed of the transcription factors Pax2/8, Gata3 and Lim1. These transcription factors turn on a second layer of transcriptional regulators while also activating effectors of tissue morphogenesis and cellular specialization. Elongation and connection of the nephric duct to the cloaca (bladder/urethra primordium) is followed by metanephric kidney induction through signals emanating from the metanephric mesenchyme. Central to this process is the activation and positioning of the glial cell line-derived neurotrophic factor (Gdnf)-Ret signaling pathway by network subcircuits located in the mesenchyme and epithelial tissues of the caudal trunk. Evidence shows that each step of the renal primordium developmental program is regulated by structured GRN subunits organized in a hierarchical manner. Understanding the structure and dynamics of the renal GRN will help us understand the intrinsic phenotypical variability of congenital anomalies of the kidney and urinary tract and guide our approaches to regenerative medicine.

Using improvement science to increase accuracy and reliability of gestational age documentation.

Our aim was to improve the reliability of recording gestational age (GA) in the mother's obstetric record, as this record is used for clinical management, research databases, and eventual transmission to the Ohio Department of Health birth certificates. We performed a prospective cohort study, including all hospital births. We began quality improvement interventions in October 2009. Improvement test cycles were targeted to four working groups, including nursing staff, community obstetric providers, and the process itself. Test cycle results were evaluated to determine which successful interventions could spread further. Rates of process outcome measurements were compared by statistical process control and univariate analysis pre- and postintervention. During the preintervention period, the median daily GA reliability was 25%. To date, over 30 small sample size tests of change have been completed. Of 8795 births studied, significant improvement in GA accuracy/completeness was detected (median postintervention = 78%, p < 0.01). Increased communication of and completion of the prenatal record, in addition to GA recording in high-risk groups, such as premature infants, were also achieved (all p < 0.01). GA reliability can be increased using standardized improvement science methods. Better communication of GA will enable better clinical decisions and foster population-based perinatal research.

Substance Use and Utilization of Prenatal and Postpartum Care.

OBJECTIVES: Prenatal and postpartum care for women with substance use is important due to increased risk of poor health outcomes. The influence of substance use on perinatal care utilization is not well characterized, especially postpartum care. The objective of this study was to examine the effect of substance use during pregnancy on prenatal and postpartum care utilization in a nationally representative sample and to identify maternal characteristics associated with inadequate prenatal and postpartum care among women with substance use. METHODS: Pregnancy Risk Assessment Monitoring System data (2016-2018) from 8 states were used for this study. Logistic regression models adjusted for complex survey weights and confounder variables were used to estimate the odds of not receiving adequate prenatal care and postpartum care. Weighted Rao-Scott chi-square tests were used to examine maternal characteristics associated with care utilization among women who reported substance use during pregnancy. RESULTS: The study included 15,131 women, with 5.3% who reported illicit substance use during pregnancy. In multivariable models, substance use was associated with an increase in the odds of not receiving adequate prenatal care (OR 1.69, CI 1.32, 2.17) and not receiving postpartum care (OR: 1.47, CI 1.10, 1.95). Among women who reported substance use, depression and smoking status were associated with not receiving adequate prenatal or postpartum care. CONCLUSIONS: Substance use during pregnancy is independently associated with disparities in prenatal and postpartum care access. Future studies are needed to identify how barriers lead to care inequalities and importantly, to identify strategies to improve care utilization.

Symptomatic and neurotrophic effects of GABAA receptor positive allosteric modulation in a mouse model of chronic stress.

Chronic stress is a risk factor for Major Depressive Disorder (MDD), and in rodents, it recapitulates human behavioral, cellular and molecular changes. In MDD and after chronic stress, neuronal dysfunctions and deficits in GABAergic signaling are observed and responsible for symptom severity. GABA signals predominantly through GABAA receptors (GABAA-R) composed of various subunit types that relate to downstream outcomes. Activity at α2-GABAA-Rs contributes to anxiolytic properties, α5-GABAA-Rs to cognitive functions, and α1-GABAA-Rs to sedation. Therefore, a therapy aiming at increasing α2- and α5-GABAA-Rs activity, but devoid of α1-GABAA-R activity, has potential to address several symptomologies of depression while avoiding side-effects. This study investigated the activity profiles and behavioral efficacy of two enantiomers of each other (GL-II-73 and GL-I-54), separately and as a racemic mixture (GL-RM), and potential disease-modifying effects on neuronal morphology. Results confirm GL-I-54 and GL-II-73 exert positive allosteric modulation at the α2-, α3-, α5-GABAA-Rs and α5-containing GABAA-Rs, respectively, and separately reduces immobility in the forced swim test and improves stress-induced spatial working memory deficits. Using unpredictable chronic mild stress (UCMS), we show that acute and chronic administration of GL-RM provide pro-cognitive effects, with mild efficacy on mood symptoms, although at lower doses avoiding sedation. Morphology studies showed reversal of spine density loss caused by UCMS after chronic GL-RM treatment at apical and basal dendrites of the PFC and CA1. Together, these results support using a racemic mixture with combined α2-, α3-, α5-GABAA-R profile to reverse chronic stress-induced mood symptoms, cognitive deficits, and with anti-stress neurotrophic effects.

Rates of substance and polysubstance use through universal maternal testing at the time of delivery.

OBJECTIVE: To report substance and polysubstance use at the time of delivery. STUDY DESIGN: A cross-sectional study was performed on mothers consented for universal drug testing (99%) during hospital admission at six delivery hospitals in Cincinnati, Ohio. Mass spectrometry urinalysis detected positivity rates of 46 substances. Rates of positive drug tests for individual and common co-occurring substances measured were reported. RESULTS: 2531 maternal samples were tested (88%) and 33% contained cotinine, 11.3% THC, 7.2% opioids, 3.8% cocaine, and 1.9% methamphetamines. Polysubstance use prevalence was as high as 15%. Among mothers testing positive for methadone or buprenorphine, 93% also tested positive for cotinine and 39% tested positive for a third substance in addition to cotinine. CONCLUSIONS: Substance use at delivery is more prevalent than previously reported. Many mothers testing positive for opioids also test positive for other substances, which may increase overdose risk and exacerbate neonatal opioid withdrawal syndrome (NOWS).

Neonatal morbidity after documented fetal lung maturity in late preterm and early term infants.

OBJECTIVE: Fetal lung maturity often is used as the sole criterion that late preterm infants are ready for postnatal life. We therefore tested the hypothesis that fetal lung maturity testing does not predict the absence of morbidity in late preterm infants. STUDY DESIGN: We performed a retrospective cohort study to examine 152 infants who were born in the late preterm (34 0/7 to 36 6/7 weeks) and early term (37 0/7 to 38 6/7 weeks) periods after mature fetal lung indices and compared them with 262 infants who were born at ≥39 weeks' gestation and who were matched by mode of delivery. RESULTS: Despite documented fetal lung maturity, infants who were born at <39 weeks had significantly higher rates of neonatal morbidities compared with infants who were born at ≥39 weeks' gestation. After adjustment for significant covariates, we found that infants who were born at <39 weeks' gestation had an increased risk of composite adverse outcome (odds ratio, 3.66; 95% confidence interval, 1.48-9.09; P < .01). CONCLUSION: Fetal lung maturity testing is insufficient to determine an infant's readiness for postnatal life.

Long-term maternal depression after expectant management of early preterm birth.

OBJECTIVE: This study was undertaken to determine factors that affect depression after delivery of infants at the limits of viability. We hypothesized that expectantly managed mothers would have lower risk of depression several years after delivery. STUDY DESIGN: Charts were reviewed for deliveries in the calendar years 2003 through 2005 with a diagnosis of preterm labor, premature rupture of membranes or cervical insufficiency admitted at a gestation between 20 and 25(6/7) weeks. Surveys were sent that included the Edinburgh Postnatal Depression Scale and questions regarding care around the time of delivery. RESULTS: A total of 176 patients met inclusion criteria. Of those, 36 consented and returned surveys. Of patients who were expectantly managed, none (0%) screened positive for depression, while 11 (38%) patients who were not expectantly management screened positive (p=0.08). Between 36 and 72 returned surveys would be needed for this to be significant, using p<0.05. Survey results indicated that 75% of respondents agreed hospitalization was traumatic, 78% would still attempt to delay birth, 97% would accept tocolysis, 89% agreed their child functioned similar to other children, and 77% were happy with how physicians handled their care. CONCLUSION: Expectant management may be associated with lower risk of depression. Larger studies evaluating psychosocial effects of interventions are justified.

Handling Techniques to Reduce Stress in Mice.

Laboratory animals are subjected to multiple manipulations by scientists or animal care providers. The stress this causes can have profound effects on animal well-being and can also be a confounding factor for experimental variables such as anxiety measures. Over the years, handling techniques that minimize handling-related stress have been developed with a particular focus on rats, and little attention to mice. However, it has been shown that mice can be habituated to manipulations using handling techniques. Habituating mice to handling reduces stress, facilitates routine handling, improves animal wellbeing, decreases data variability, and improves experimental reliability. Despite beneficial effects of handling, the tail-pick up approach, which is particularly stressful, is still widely used. This paper provides a detailed description and demonstration of a newly developed mouse-handling technique intended to minimize the stress experienced by the animal during human interaction. This manual technique is performed over 3 days (3D-handling technique) and focuses on the animal's capacity to habituate to the experimenter. This study also shows the effect of previously established tunnel handling techniques (using a polycarbonate tunnel) and the tail-pick up technique. Specifically studied are their effects on anxiety-like behaviors, using behavioral tests (Elevated-Plus Maze and Novelty Suppressed Feeding), voluntary interaction with experimenters and physiological measurement (corticosterone levels). The 3D-handling technique and the tunnel handling technique reduced anxiety-like phenotypes. In the first experiment, using 6-month-old male mice, the 3D-handling technique significantly improved experimenter interaction. In the second experiment, using 2.5-month-old female, it reduced corticosterone levels. As such, the 3D-handling is a useful approach in scenarios where interaction with the experimenter is required or preferred, or where tunnel handling may not be possible during the experiment.

The Palmaris Longus and Its Association with Carpal Tunnel Syndrome.

Background The palmaris tendon inserts into the palmar fascia and is positioned in close association with the transverse carpal ligament. Loading of this tendon has been demonstrated to increase carpal tunnel pressures. Purpose The purpose of this study was to determine if a relationship exists between the palmaris tendon, carpal tunnel syndrome (CTS), and handedness. The sensitivity, specificity, positive predictive value, and negative predictive value for Schaeffer's test were calculated. Methods A retrospective review of patient charts undergoing endoscopic carpal tunnel release was performed. Rates of palmaris longus agenesis (PLA) were compared to a population matched data set. Statistical analysis was performed using a one-proportion z -test. Schaeffer's test for the palmaris longus tendon was performed on all patients and compared to intraoperative confirmation. Results A total of 520 carpal tunnel releases were performed in 389 consecutive patients. The frequency of PLA in this surgical cohort was significantly lower compared to the population matched dataset. No correlation between handedness and laterality of CTS or PLA was found. Schaeffer's test was evaluated to yield sensitivity (93.6%), specificity (100%), positive predictive value (100%), and negative predictive value (50.8%). Conclusion The palmaris tendon was more prevalent in a population of patients undergoing carpal tunnel release. These findings can be used to provide further insight into the pathophysiology of CTS. While Schaeffer's test was accurate in detecting the palmaris longus tendon, a negative test was frequently incorrect. Further imaging is recommended in patients with a negative Schaeffer's test when the palmaris longus is desired for surgical utilization. Level of Evidence This is a Level III, prognostic study.

A statewide quality improvement (QI) initiative for better health outcomes and family stability among pregnant women with opioid use disorder (OUD) and their infants.

A collaborative led by state health and human service agencies, academic leaders, and stakeholders tested interventions to expand use of medication assisted treatment (MAT) through a maternal medical home (MMH) model that coordinated behavioral health and prenatal care with social supports for pregnant women with opioid use disorder (OUD) enrolled in Medicaid. The program was anchored in four clinical organizations with distinct models of care: community behavioral health, residential behavioral health, hospital-based obstetrical practice, and co-located obstetrical and behavioral health. A modified version of the Institute for Healthcare Improvement Breakthrough Series Model for Improvement was implemented using monthly performance data feedback to conduct small tests of change and improve care. Administrative data from the state's Medicaid, vital statistics, and child welfare systems were linked to evaluate the impact of MOMS on 252 mother-infant dyads compared to a sample of 846 Medicaid beneficiaries with OUD in the third trimester of pregnancy. MOMS participation was associated with increased likelihood of MAT in trimesters one, two and three (AOR = 2.30, 4.40, 2.75, respectively), behavioral health counseling during trimesters two and three (AOR = 3.75 and 2.07, respectively), retention in MAT during postpartum months one through three and four through six (AOR = 2.86, 2.40, respectively), and marginally lower out-of-home placement of infants born to mothers with OUD (AOR = 0.66). Within the MOMS program, greater participation in behavioral health treatment and MAT (χ2(3) ≥ 12.09) was observed in the co-located behavioral health/obstetrical care practice site compared to behavioral health-led and obstetrical provider-led sites.

Risk Factors for Brachial Plexus Birth Injury.

Over the course of decades, the incidence of brachial plexus birth injury (BPBI) has increased despite advances in healthcare which would seem to assist in decreasing the rate. The aim of this study is to identify previously unknown risk factors for BPBI and the risk factors with potential to guide preventative measures. A case control study of 52 mothers who had delivered a child with a BPBI injury and 132 mothers who had delivered without BPBI injury was conducted. Univariate, multivariable and logistic regressions identified risk factors and their combinations. The odds of BPBI were 2.5 times higher when oxytocin was used and 3.7 times higher when tachysystole occurred. The odds of BPBI injury are increased when tachysystole and oxytocin occur during the mother's labor. Logistic regression identified a higher risk for BPBI when more than three of the following variables (>30 lbs gained during the pregnancy, stage 2 labor >61.5 min, mother's age >26.4 years, tachysystole, or fetal malpresentation) were present in any combination.

Statewide Quality Improvement Initiative to Reduce Early Elective Deliveries and Improve Birth Registry Accuracy.

OBJECTIVE: To evaluate the success of a quality improvement initiative to reduce early elective deliveries at less than 39 weeks of gestation and improve birth registry data accuracy rapidly and at scale in Ohio. METHODS: Between February 2013 and March 2014, participating hospitals were involved in a quality improvement initiative to reduce early elective deliveries at less than 39 weeks of gestation and improve birth registry data. This initiative was designed as a learning collaborative model (group webinars and a single face-to-face meeting) and included individual quality improvement coaching. It was implemented using a stepped wedge design with hospitals divided into three balanced groups (waves) participating in the initiative sequentially. Birth registry data were used to assess hospital rates of nonmedically indicated inductions at less than 39 weeks of gestation. Comparisons were made between groups participating and those not participating in the initiative at two time points. To measure birth registry accuracy, hospitals conducted monthly audits comparing birth registry data with the medical record. Associations were assessed using generalized linear repeated measures models accounting for time effects. RESULTS: Seventy of 72 (97%) eligible hospitals participated. Based on birth registry data, nonmedically indicated inductions at less than 39 weeks of gestation declined in all groups with implementation (wave 1: 6.2-3.2%, P<.001; wave 2: 4.2-2.5%, P=.04; wave 3: 6.8-3.7%, P=.002). When waves 1 and 2 were participating in the initiative, they saw significant decreases in rates of early elective deliveries as compared with wave 3 (control; P=.018). All waves had significant improvement in birth registry accuracy (wave 1: 80-90%, P=.017; wave 2: 80-100%, P=.002; wave 3: 75-100%, P<.001). CONCLUSIONS: A quality improvement initiative enabled statewide spread of change strategies to decrease early elective deliveries and improve birth registry accuracy over 14 months and could be used for rapid dissemination of other evidence-based obstetric care practices across states or hospital systems.

Findings from a 10-year follow-up of bone mineral density in competitive perimenopausal runners.

OBJECTIVE: To evaluate bone mineral density (BMD) in perimenopausal competitive runners with long-term follow-up. STUDY DESIGN: Fifteen master female runners between 40 and 50 years old who ran at least 20 miles per week were evaluated. BMD was measured by dual-energy x-ray absorptiometry (DEXA) at baseline and at the 10-year follow-up. RESULTS: The median age was 46 and median miles run per week, 25. At baseline, after a median of 11 years of competitive running, hip BMD was above peak bone mass (T-score = 0.8) and that of age-matched controls (Z-score = 1.6), while lumbar spine BMD was below peak bone mass (T-score = -0.8) and equal to that of age-matched controls (Z-score = -0.1). At the 10-year follow-up, hip BMD fell below peak bone mass (T-score = -0.2, p = 0.0004) but was still above that of age-matched controls (Z-score = 0.5, p = 0.002), while there was little change in lumbar spine BMD. CONCLUSION: Competitive running prior to the perimenopausal period seems to be associated with improved hip BMD. However, continued competitive running during the perimenopausal period is not associated with prevention of a perimenopausal hip BMD decline. In contrast, competitive running had little effect on peri-menopausal lumbar spine BMD.

A Statewide Progestogen Promotion Program in Ohio.

OBJECTIVE: To promote use of progestogen therapy to reduce premature births in Ohio by 10%. METHODS: The Ohio Perinatal Quality Collaborative initiated a quality improvement project in 2014 working with clinics at 20 large maternity hospitals, Ohio Medicaid, Medicaid insurers, and service agencies to use quality improvement methods to identify eligible women and remove treatment barriers. The number of women eligible for prophylaxis, the percent prescribed a progestogen before 20 and 24 weeks of gestation, and barriers encountered were reported monthly. Clinics were asked to adopt protocols to identify candidates and initiate treatment promptly. System-level changes were made to expand Medicaid eligibility, maintain Medicaid coverage during pregnancy, improve communication, and adopt uniform data collection and efficient treatment protocols. Rates of singleton births before 32 and 37 weeks of gestation in Ohio hospitals were primary outcomes. We used statistical process control methods to analyze change and generalized linear mixed models to estimate program effects accounting for known risk factors. RESULTS: Participating sites tracked 2,562 women eligible for treatment between January 1, 2014, and November 30, 2015. Late entry to care, variable interpretation of treatment guidelines, maintenance of Medicaid coverage, and inefficient communication among health care providers and insurers were identified as treatment barriers. Births before 32 weeks of gestation decreased in all hospitals by 6.6% and in participating hospitals by 8.0%. Births before 32 weeks of gestation to women with prior preterm birth decreased by 20.5% in all hospitals, by 20.3% in African American women, and by 17.1% in women on Medicaid. Births before 37 weeks of gestation were minimally affected. Adjusting for risk factors and birth clustering by hospital confirmed a program-associated 13% (95% confidence interval 0.3-24%) reduction in births before 32 weeks of gestation to women with prior preterm birth. CONCLUSION: The Ohio progestogen project was associated with a sustained reduction in singleton births before 32 weeks of gestation in Ohio.

A novel amniocentesis model for learning stereotactic skills.

OBJECTIVE: This study developed a lifelike amniocentesis model to allow effective acquisition of the stereotactic skills necessary and comfort level with this procedure. STUDY DESIGN: An amniocentesis model is constructed using a formalin preserved gravid pig uterus. A large Ziploc freezer bag (Dow, Indianapolis, Ind) filled with ultrasound gel is placed on the uterus to simulate the skin and subcutaneous layer. RESULTS: Amniocentesis can be performed in the usual fashion using this lifelike model. No leak was observed in the Ziploc bag (Dow) or gravid uterus despite more than 50 needle insertions. The cost of 4 to 5 learning stations is approximately $50.00. This model enjoys the advantages of being changeable to reproduce a variety of real-life situations, including poly/oligo/anhydramnios, varied fetal positions and different thickness of subcutaneous tissue. CONCLUSION: This low-cost novel model provides realistic tissue resistance and yields a sonographically accurate amniocentesis-training tool. The use of this model permits resident instruction in a nonthreatening environment.