Deep Sequencing of 71 Candidate Genes to Characterize Variation Associated with Alcohol Dependence.

BACKGROUND: Previous genomewide association studies (GWASs) have identified a number of putative risk loci for alcohol dependence (AD). However, only a few loci have replicated and these replicated variants only explain a small proportion of AD risk. Using an innovative approach, the goal of this study was to generate hypotheses about potentially causal variants for AD that can be explored further through functional studies. METHODS: We employed targeted capture of 71 candidate loci and flanking regions followed by next-generation deep sequencing (mean coverage 78X) in 806 European Americans. Regions included in our targeted capture library were genes identified through published GWAS of alcohol, all human alcohol and aldehyde dehydrogenases, reward system genes including dopaminergic and opioid receptors, prioritized candidate genes based on previous associations, and genes involved in the absorption, distribution, metabolism, and excretion of drugs. We performed single-locus tests to determine if any single variant was associated with AD symptom count. Sets of variants that overlapped with biologically meaningful annotations were tested for association in aggregate. RESULTS: No single, common variant was significantly associated with AD in our study. We did, however, find evidence for association with several variant sets. Two variant sets were significant at the q-value <0.10 level: a genic enhancer for ADHFE1 (p = 1.47 × 10-5 ; q = 0.019), an alcohol dehydrogenase, and ADORA1 (p = 5.29 × 10-5 ; q = 0.035), an adenosine receptor that belongs to a G-protein-coupled receptor gene family. CONCLUSIONS: To our knowledge, this is the first sequencing study of AD to examine variants in entire genes, including flanking and regulatory regions. We found that in addition to protein coding variant sets, regulatory variant sets may play a role in AD. From these findings, we have generated initial functional hypotheses about how these sets may influence AD.

Deep Sequencing of Three Loci Implicated in Large-Scale Genome-Wide Association Study Smoking Meta-Analyses.

INTRODUCTION: Genome-wide association study meta-analyses have robustly implicated three loci that affect susceptibility for smoking: CHRNA5\CHRNA3\CHRNB4, CHRNB3\CHRNA6 and EGLN2\CYP2A6. Functional follow-up studies of these loci are needed to provide insight into biological mechanisms. However, these efforts have been hampered by a lack of knowledge about the specific causal variant(s) involved. In this study, we prioritized variants in terms of the likelihood they account for the reported associations. METHODS: We employed targeted capture of the CHRNA5\CHRNA3\CHRNB4, CHRNB3\CHRNA6, and EGLN2\CYP2A6 loci and flanking regions followed by next-generation deep sequencing (mean coverage 78×) to capture genomic variation in 363 individuals. We performed single locus tests to determine if any single variant accounts for the association, and examined if sets of (rare) variants that overlapped with biologically meaningful annotations account for the associations. RESULTS: In total, we investigated 963 variants, of which 71.1% were rare (minor allele frequency < 0.01), 6.02% were insertion/deletions, and 51.7% were catalogued in dbSNP141. The single variant results showed that no variant fully accounts for the association in any region. In the variant set results, CHRNB4 accounts for most of the signal with significant sets consisting of directly damaging variants. CHRNA6 explains most of the signal in the CHRNB3\CHRNA6 locus with significant sets indicating a regulatory role for CHRNA6. Significant sets in CYP2A6 involved directly damaging variants while the significant variant sets suggested a regulatory role for EGLN2. CONCLUSIONS: We found that multiple variants implicating multiple processes explain the signal. Some variants can be prioritized for functional follow-up.

The regional differences in the contribution of nitric oxide synthase to skin blood flow at forearm and lower leg sites in response to local skin warming.

We investigated the role of nitric oxide synthase (NOS) on regional cutaneous vascular function at rest (thermoneutral conditions) and during the vasodilator response to increased local skin temperature (Tloc). Dorsal forearm and lateral leg sites were instrumented with microdialysis fibers, local heaters, and laser-Doppler probes. All sites were heated from 33 °C to 42 °C. Each limb had 1 skin site treated with l-NAME to inhibit NOS, and 1 site infused with lactated Ringer's to serve as a control. Basal cutaneous vascular conductance (CVC) was measured at 33 °C, forearm sites averaged 14 ± 1%max and 17 ± 1%max at l-NAME and control sites, respectively (P = 0.26). CVC sites in the leg were different between l-NAME (17 ± 1%max) and control (27 ± 2%max) (P = 0.04). CVC between the forearm and the leg across control sites differed (P < 0.05). In contrast, at l-NAME treated sites, there was no difference between the forearm and leg sites (P = 0.23). When Tloc was increased to 42 °C, CVC at the control sites differed between the forearm 93 ± 1%max and leg 98 ± 1%max (P = 0.02). There were no differences between the arm and leg at l-NAME treated sites at 42 °C (P = 0.45). The findings of the current study were that the contribution of nitric oxide (NO) to the vasodilator response to an elevated Tloc is consistent between the arm and the leg, and, under thermoneutral conditions (33 °C), NO plays a larger role in the basal vascular function in the legs than that of the forearm. Accordingly, these data suggest, in part, that the differences in basal CVC between the forearm and leg are due to NOS activity.

Genome-wide association studies in psychiatry: what have we learned?

Genome-wide association studies (GWAS) have been the focus of considerable effort in psychiatry. These efforts have markedly increased knowledge of the genetic basis of psychiatric disorders, and yielded empirical data on genetic architecture critical to addressing long-standing debates in the field. There is a now a clear path to increased knowledge of the 'parts lists' for these disorders.

A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19.

Background: Patients with severe coronavirus disease 2019 (COVID-19) develop a febrile pro-inflammatory cytokinemia with accelerated progression to acute respiratory distress syndrome (ARDS). Here we report the results of a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of intravenous (IV) plasma-purified alpha-1 antitrypsin (AAT) for moderate to severe ARDS secondary to COVID-19 (EudraCT 2020-001391-15). Methods: Patients (n = 36) were randomized to receive weekly placebo, weekly AAT (Prolastin, Grifols, S.A.; 120 mg/kg), or AAT once followed by weekly placebo. The primary endpoint was the change in plasma interleukin (IL)-6 concentration at 1 week. In addition to assessing safety and tolerability, changes in plasma levels of IL-1ß, IL-8, IL-10, and soluble tumor necrosis factor receptor 1 (sTNFR1) and clinical outcomes were assessed as secondary endpoints. Findings: Treatment with IV AAT resulted in decreased inflammation and was safe and well tolerated. The study met its primary endpoint, with decreased circulating IL-6 concentrations at 1 week in the treatment group. This was in contrast to the placebo group, where IL-6 was increased. Similarly, plasma sTNFR1 was substantially decreased in the treatment group while remaining unchanged in patients receiving placebo. IV AAT did not definitively reduce levels of IL-1ß, IL-8, and IL-10. No difference in mortality or ventilator-free days was observed between groups, although a trend toward decreased time on ventilator was observed in AAT-treated patients. Conclusions: In patients with COVID-19 and moderate to severe ARDS, treatment with IV AAT was safe, feasible, and biochemically efficacious. The data support progression to a phase 3 trial and prompt further investigation of AAT as an anti-inflammatory therapeutic. Funding: ECSA-2020-009; Elaine Galwey Research Bursary.

Genetic modifiers of MeCP2 function in Drosophila.

The levels of methyl-CpG-binding protein 2 (MeCP2) are critical for normal post-natal development and function of the nervous system. Loss of function of MeCP2, a transcriptional regulator involved in chromatin remodeling, causes classic Rett syndrome (RTT) as well as other related conditions characterized by autism, learning disabilities, or mental retardation. Increased dosage of MeCP2 also leads to clinically similar neurological disorders and mental retardation. To identify molecular mechanisms capable of compensating for altered MeCP2 levels, we generated transgenic Drosophila overexpressing human MeCP2. We find that MeCP2 associates with chromatin and is phosphorylated at serine 423 in Drosophila, as is found in mammals. MeCP2 overexpression leads to anatomical (i.e., disorganized eyes, ectopic wing veins) and behavioral (i.e., motor dysfunction) abnormalities. We used a candidate gene approach to identify genes that are able to compensate for abnormal phenotypes caused by MeCP2 increased activity. These genetic modifiers include other chromatin remodeling genes (Additional sex combs, corto, osa, Sex combs on midleg, and trithorax), the kinase tricornered, the UBE3A target pebble, and Drosophila homologues of the MeCP2 physical interactors Sin3a, REST, and N-CoR. These findings demonstrate that anatomical and behavioral phenotypes caused by MeCP2 activity can be ameliorated by altering other factors that might be more amenable to manipulation than MeCP2 itself.

A randomised, double-blind, placebo-controlled, pilot trial of intravenous plasma purified alpha-1 antitrypsin for SARS-CoV-2-induced Acute Respiratory Distress Syndrome: a structured summary of a study protocol for a randomised, controlled trial.

OBJECTIVES: The primary objective is to demonstrate that, in patients with PCR-confirmed SARS-CoV-2 resulting in Acute Respiratory Distress Syndrome (ARDS), administration of 120mg/kg of body weight of intravenous Prolastin®(plasma-purified alpha-1 antitrypsin) reduces circulating plasma levels of interleukin-6 (IL-6). Secondary objectives are to determine the effects of intravenous Prolastin® on important clinical outcomes including the incidence of adverse events (AEs) and serious adverse events (SAEs). TRIAL DESIGN: Phase 2, randomised, double-blind, placebo-controlled, pilot trial. PARTICIPANTS: The study will be conducted in Intensive Care Units in hospitals across Ireland. Patients with a laboratory-confirmed diagnosis of SARS-CoV-2-infection, moderate to severe ARDS (meeting Berlin criteria for a diagnosis of ARDS with a PaO2/FiO2 ratio <200 mmHg), >18 years of age and requiring invasive or non-invasive mechanical ventilation. All individuals meeting any of the following exclusion criteria at baseline or during screening will be excluded from study participation: more than 96 hours has elapsed from onset of ARDS; age < 18 years; known to be pregnant or breastfeeding; participation in a clinical trial of an investigational medicinal product (other than antibiotics or antivirals) within 30 days; major trauma in the prior 5 days; presence of any active malignancy (other than nonmelanoma skin cancer) which required treatment within the last year; WHO Class III or IV pulmonary hypertension; pulmonary embolism prior to hospital admission within past 3 months; currently receiving extracorporeal life support (ECLS); chronic kidney disease receiving dialysis; severe chronic liver disease with Child-Pugh score > 12; DNAR (Do Not Attempt Resuscitation) order in place; treatment withdrawal imminent within 24 hours; Prisoners; non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available; IgA deficiency. INTERVENTION AND COMPARATOR: Intervention: Either a once weekly intravenous infusion of Prolastin® at 120mg/kg of body weight for 4 weeks or a single dose of Prolastin® at 120mg/kg of body weight intravenously followed by once weekly intravenous infusion of an equal volume of 0.9% sodium chloride for a further 3 weeks. Comparator (placebo): An equal volume of 0.9% sodium chloride intravenously once per week for four weeks. MAIN OUTCOMES: The primary effectiveness outcome measure is the change in plasma concentration of IL-6 at 7 days as measured by ELISA. Secondary outcomes include: safety and tolerability of Prolastin® in the respective groups (as defined by the number of SAEs and AEs); PaO2/FiO2 ratio; respiratory compliance; sequential organ failure assessment (SOFA) score; mortality; time on ventilator in days; plasma concentration of alpha-1 antitrypsin (AAT) as measured by nephelometry; plasma concentrations of interleukin-1ß (IL-1ß), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TNF receptor 1 (sTNFR1, a surrogate marker for TNF-α) as measured by ELISA; development of shock; acute kidney injury; need for renal replacement therapy; clinical relapse, as defined by the need for readmission to the ICU or a marked decline in PaO2/FiO2 or development of shock or mortality following a period of sustained clinical improvement; secondary bacterial pneumonia as defined by the combination of radiographic findings and sputum/airway secretion microscopy and culture. RANDOMISATION: Following informed consent/assent patients will be randomised. The randomisation lists will be prepared by the study statistician and given to the unblinded trial personnel. However, the statistician will not be exposed to how the planned treatment will be allocated to the treatment codes. Randomisation will be conducted in a 1:1:1 ratio, stratified by site and age. BLINDING (MASKING): The investigator, treating physician, other members of the site research team and patients will be blinded to treatment allocation. The clinical trial pharmacy personnel and research nurses will be unblinded to facilitate intervention and placebo preparation. The unblinded individuals will keep the treatment information confidential. The infusion bag will be masked at the time of preparation and will be administered via a masked infusion set to maintain blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 36 patients will be recruited and randomised in a 1:1:1 ratio to each of the trial arms. TRIAL STATUS: In March 2020, version 1.0 of the trial protocol was submitted to the local research ethics committee (REC), Health Research Consent Declaration Committee (HRCDC) and the Health Products regulatory Authority (HPRA). REC approval was granted on April 1st 2020, HPRA approval was granted on April 24th 2020 and the HRCDC provided a conditional declaration on April 17th 2020. In July 2020 a substantial amendment (version 2.0) was submitted to the REC, HRCDC and HPRA. Protocol changes in this amendment included: the addition of trial sites; extending the duration of the trial to 12 months from 3 months; removal of inclusion criteria requiring the need for vasopressors; amendment of randomisation schedule to stratify by age only and not BMI and sex; correction of grammatical error in relation to infusion duration; to allow for inclusion of subjects who may have been enrolled in a clinical trial involving either antibiotics or anti-virals in the past 30 days; to allow for inclusion of subjects who may be currently enrolled in a clinical trial involving either antibiotics or anti-virals; to remove the need for exclusion based on alpha-1 antitrypsin phenotype; removal of mandatory isoelectric focusing of plasma to confirm Pi*MM status at screening; removal of need for mandatory echocardiogram at screening; amendment on procedures around plasma analysis to reflect that this will be conducted at the central site laboratory (as trial is multi-site and no longer single site); wording amended to reflect that interim analysis of cytokine levels taken at 7 days may be conducted. HRCDC approved version 2.0 on September 14th 2020, and HPRA approved on October 22nd 2020. REC approved the substantial amendment on November 23rd. In November 2020, version 3.0 of the trial protocol was submitted to the REC and HPRA. The rationale for this amendment was to allow for patients with moderate to severe ARDS from SARS-CoV-2 with non-invasive ventilation. HPRA approved this amendment on December 1st 2020 and the REC approved the amendment on December 8th 2020. Patient recruitment commenced in April 2020 and the last patient will be recruited to the trial in April 2021. The last visit of the last patient is anticipated to occur in April 2021. At time of writing, patient recruitment is now complete, however follow-up patient visits and data collection are ongoing. TRIAL REGISTRATION: EudraCT 2020-001391-15 (Registered 31 Mar 2020). FULL PROTOCOL: The full protocol (version 3.0 23.11.2020) is attached as an additional file accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease.

Up to 30% of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication associated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed association analysis with 297 single nucleotide polymorphisms (SNPs) in 49 candidate genes in patients with sickle cell anemia (Hb SS) who had been screened for pHTN by echocardiography (n = 111). Evidence of association was primarily identified for genes in the TGFbeta superfamily, including activin A receptor, type II-like 1 (ACVRL1), bone morphogenetic protein receptor 2 (BMPR2), and bone morphogenetic protein 6 (BMP6). The association of pHTN with ACVRL1 and BMPR2 corroborates the previous association of these genes with primary pHTN. Moreover, genes in the TGFbeta pathway have been independently implicated in risk for several sickle cell complications, suggesting that this gene pathway is important in overall sickle cell pathophysiology. Genetic variation in the beta-1 adrenergic receptor (ADRB1) was also associated with pHTN in our dataset. A multiple regression model, which included age and baseline hemoglobin as covariates, retained SNPs in ACVRL1, BMP6, and ADRB1 as independently contributing to pHTN risk. These findings may offer new promise for identifying patients at risk for pHTN, developing new therapeutic targets, and reducing the occurrence of this life-threatening SCD complication.

Central nervous system serotonin and clustering of hostility, psychosocial, metabolic, and cardiovascular endophenotypes in men.

OBJECTIVE: To use measures of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA) and genotype of a functional polymorphism of the monoamine oxidase A gene promoter (MAOA-uVNTR) to study the role of central nervous system (CNS) serotonin in clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes. METHODS: In 86 healthy male volunteers, we evaluated CSF levels of the primary serotonin metabolite 5HIAA and MAOA-uVNTR genotype for association with a panel of 29 variables assessing hostility, other psychosocial, metabolic, and cardiovascular endophenotypes. RESULTS: The correlations of 5HIAA with these endophenotypes in men with more active MAOA-uVNTR alleles were significantly different from those of men with less active alleles for 15 of the 29 endophenotypes. MAOA-uVNTR genotype and CSF 5HIAA interacted to explain 20% and 22% of the variance, respectively, in scores on one factor wherein high scores reflected a less healthy psychosocial profile and a second factor wherein high score reflected increased insulin resistance, body mass index, blood pressure and hostility. In men with less active alleles, higher 5HIAA was associated with more favorable profiles of hostility, other psychosocial, metabolic and cardiovascular endophenotypes; in men with more active alleles, higher 5HIAA was associated with less favorable profiles. CONCLUSIONS: These findings indicate that, in men, indices of CNS serotonin function influence the expression and clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes that have been shown to increase risk of developing cardiovascular disease. The findings are consistent with the hypothesis that increased CNS serotonin is associated with a more favorable psychosocial/metabolic/cardiovascular profile, whereas decreased CNS serotonin function is associated with a less favorable profile.

Effects of postnatal parental smoking on parent and teacher ratings of ADHD and oppositional symptoms.

To assess the effects of postnatal parental smoking on subsequent parent and teacher ratings of DSM-IV attention deficit hyperactivity disorder (ADHD) symptoms and oppositional behaviors in children diagnosed with ADHD and their siblings. Children between 5 and 12 years of age with ADHD and their siblings were included. DSM-IV ADHD symptom subscales (Inattentive and hyperactive-impulsive), and oppositionality subscale scores from Conners' Rating Scales were predicted on the basis of parental smoking status in the first 7 years after birth using Generalized Estimating Equations controlling for a range of relevant covariates. Postnatal parental smoking was associated with both parent and teacher ratings of ADHD symptoms and oppositional behavior. After controlling for a number of covariates, several of these relationships were still significant. The risk of maternal smoking for the development of ADHD symptoms does not end during pregnancy. Research on the mechanisms underlying the observed associations is needed.

5-HTTLPR and gender moderate changes in negative affect responses to tryptophan infusion.

Expression of the serotonin transporter is affected by the genotype of the 5-HTTLPR (short and long forms) as well as the genotype of the SNP rs25531 within this region. Based on the combined genotypes for these polymorphisms, we designated each allele as a high or low expressing allele according to established expression levels-resulting in HiHi, HiLo, & LoLo genotype groups for analysis. We evaluated effects of gender and the promoter genotype on induction of negative affect by intravenous infusion of L: -tryptophan (TRP). The protocol consisted of a day-1 sham saline infusion and a day-2 active TRP infusion. Models assessed 5-HTTLPR composite genotype and gender as predictors of change in ratings of negative emotion during TRP infusion. During sham infusion there were no significant changes from baseline in mood ratings. During TRP infusion all negative affect ratings increased significantly from baseline (P's < .02). The genotype x gender interaction was a significant predictor of depression-dejection (P = .013), and trended towards predicting anger-hostility (P = .084). Males in the HiHi group had greater increases in negative affect during infusion, compared to all groups except LoLo females, who also showed increased negative affect.

The transition from child and adolescent to adult mental health services with a focus on diagnosis progression.

Aims and methodThis article examines mental health disorders as individuals transition from adolescence to adulthood. Data were collected from clinical records of patients who had transitioned from child and adolescent mental health services to adult mental health services in a region in South Wales. Demographics and clinical diagnoses under both services were recorded. Patterns between adolescent and adult disorders as well as comorbidities were investigated using Pearson's χ2-test and Fisher's exact test. RESULTS: Of the 98 patients that transitioned from one service to the other, 74 had changes to their diagnoses. There were 164 total changes to diagnoses, with patients no longer meeting diagnostic criteria for 64 disorders and 100 new disorders being diagnosed. Comorbidity increased in adulthood.Clinical implicationsDiagnoses can evolve, particularly during adolescence and early adulthood. Therefore regular reassessment is paramount for successful treatment.Declaration of interestNone.

A Summer Nutrition Benefit Pilot Program and Low-income Children's Food Security.

BACKGROUND: Federal summer meals programs serve less than one-sixth of children that receive free or reduced-price meals during the school year. To address this gap in food assistance for school-aged children, the Summer Electronic Benefits Transfer for Children (SEBTC) Demonstrations provided summer food assistance in the form of electronic benefits transfer cards to households with school-aged children certified for free or reduced-price meals during the school year. METHODS: Over 2011-2013, the SEBTC demonstrations were evaluated by using a random assignment design. Households were randomly assigned a monthly $60-per-child benefit, a monthly $30-per-child benefit, or no benefit, depending on the study year. Key outcomes included children's food security and consumption of foods and food groups related to a healthful diet (diet quality). At baseline (in the spring) and again in the summer, the evaluation surveyed ∼52 000 households over the course of the 3 years of the impact study. RESULTS: SEBTC reduced the prevalence of very low food security among children by one-third. It also had positive impacts on 6 of the 8 child nutrition outcomes measured (amounts of fruits and vegetables; whole grains; dairy foods; and added sugars). CONCLUSIONS: SEBTC is a promising model to improve food security and the dietary quality of low-income school-aged children in the summer months.

Improving Nutrition by Increasing Supplemental Nutrition Assistance Program Benefits.

The diets of Americans fall far short of recommended dietary guidelines, and those who live in low-income households have even poorer diets than higher-income households. Many low-income Americans rely on the Supplemental Nutrition Assistance Program (SNAP). The program's dual goals are to improve food security and nutrition. Among the possible strategies to address dietary shortfalls among low-income Americans is to increase the SNAP benefit. This article uses data from the random assignment evaluation of the Summer Electronic Benefit Transfer for Children demonstration to add new insights on the impact of SNAP on diet quality for households receiving SNAP who also received SNAP-like benefits through Summer Electronic Benefit Transfer for Children. Households received $60 each month per eligible school-aged child. The objective of the evaluation was to see if Summer Electronic Benefit Transfer for Children improved children's food security and nutrition. The evaluation surveyed these households to collect information about food expenditures, food security, and children's diets. For households receiving SNAP in sites that used the SNAP Electronic Benefit Transfer delivery system, the analysis showed increases in food expenditures and decreases in levels of food insecurity. The analysis also indicates improvements in dietary quality among school-aged children, but the impacts were modest.

Improving Nutrition by Limiting Choice in the Supplemental Nutrition Assistance Program.

In contrast to the Special Supplemental Nutrition Program for Women, Infants, and Children, the Supplemental Nutrition Assistance Program (SNAP) currently allows the purchase of almost any food. This paper reconsiders the role of two forms of limiting choice in SNAP. Using economic theory, descriptive analysis of survey data, and discussion of random assignment evaluation evidence from the Summer Electronic Benefit Transfer for Children Demonstration, the paper argues that because households can substitute cash for SNAP, banning the use of SNAP for less nutritionally desirable foods (e.g., soda, candy) is unlikely to have a large impact. By contrast, because many households currently consume so little of more nutritionally desirable foods (e.g., whole grains, fruits, and vegetables), requiring that some portion of SNAP benefits be spent on those foods is likely to improve dietary intake. Summer Electronic Benefit Transfer for Children Demonstration impact estimates are consistent with this conjecture. Furthermore, these data and evidence from the Healthy Incentives Pilot implementation suggest that such a policy can be feasibly integrated into existing operational processes.

Delivering Summer Electronic Benefit Transfers for Children through the Supplemental Nutrition Assistance Program or the Special Supplemental Nutrition Program for Women, Infants, and Children: Benefit Use and Impacts on Food Security and Foods Consumed.

BACKGROUND: The Summer Electronic Benefit Transfers for Children (SEBTC) demonstration piloted summer food assistance through electronic benefit transfers (EBTs), providing benefits either through the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) or the Supplemental Nutrition Assistance Program (SNAP) EBT. OBJECTIVE: To inform food assistance policy and describe how demonstrations using WIC and SNAP models differed in benefit take-up and impacts on food security and children's food consumption. DESIGN: Sites chose to deliver SEBTC using the SNAP or WIC EBT system. Within each site, in 2012, households were randomly assigned to a benefit group or a no-benefit control group. PARTICIPANTS: Grantees (eight states and two Indian Tribal Organizations) selected school districts serving many low-income children. Schoolchildren were eligible in cases where they had been certified for free or reduced-price meals during the school year. Before the demonstration, households in the demonstration sample had lower incomes and lower food security, on average, than households with eligible children nationally. INTERVENTION: Grantees provided selected households with benefits worth $60 per child per summer month using SNAP or WIC EBT systems. SNAP-model benefits covered most foods. WIC-model benefits could only be used for a specific package of foods. OUTCOME MEASURES: Key outcomes were children's food security (assessed using the US Department of Agriculture food security scale) and food consumption (assessed using food frequency questions). STATISTICAL ANALYSES: Differences in mean outcomes between the benefit and control groups measured impact, after adjusting for household characteristics. RESULTS: In WIC sites, benefit-group households redeemed a lower percentage of SEBTC benefits than in SNAP sites. Nonetheless, the benefit groups in both sets of sites had similar large reductions in very low food security among children, relative to no-benefit controls. Children receiving benefits consumed more healthful foods, and these impacts were larger in WIC sites. CONCLUSIONS: Results suggest the WIC SEBTC model deserves strong consideration.

The interval to spontaneous delivery following discontinuation of maintenance tocolysis.

OBJECTIVE: To determine the interval to spontaneous delivery following discontinuation of continuous subcutaneous terbutaline (SQT). METHODS: Singleton and twin gestations receiving outpatient preterm labor management services with SQT were identified from a database. Patients having SQT discontinued at 33.0-35.9 weeks (in a stable condition, not hospitalized and with known cervical status at discontinuation) with subsequent spontaneous labor and delivery were included (n = 1420). Data were compared by gestation type, week of SQT discontinuation and cervical dilatation using Kruskal-Wallis and Fisher's exact test analyses (p < 0.05 statistically significant). RESULTS: Spontaneous preterm delivery occurred in 63.0% of singletons and 87.9% of twins. Although stable at SQT discontinuation, 32.5% of singletons and 59.9% of twins delivered within three days. The interval from discontinuation of SQT to delivery was less for twin than singleton gestations (5.1 +/- 6.5 vs. 11.0 +/- 10.5 days, respectively, p < 0.001). CONCLUSIONS. Preterm discontinuation of SQT should be avoided if additional pregnancy prolongation is desired.

Cost-savings analysis of an outpatient management program for women with pregnancy-related hypertensive conditions.

The aim of this study was to evaluate the cost savings of outpatient management services for women with pregnancy-related hypertensive conditions. The outpatient management program included verbal and written patient education related to the hypertensive disease process during pregnancy as well as self-care procedures. Biometric data (ie, automated blood pressure measurement, qualitative urine protein) were collected at least daily by the patient and transmitted telephonically to a nursing call center. Data were evaluated and subjective symptoms assessed daily. Electronic records were maintained and reports provided to the prescribing physician and case manager. Included for analysis were: patients with pregnancy-related hypertensive conditions receiving outpatient services between January 1999 and November 2003, singleton gestation, no history of chronic hypertension, and gestational age of 20.0-36.9 weeks at start of outpatient program (n = 1,140). Maternal characteristics, antenatal hospitalization and length of stay, progression of disease, and neonatal outcome were analyzed. To evaluate cost-effectiveness, a model was developed to compare the cost of the program plus adjunctive antenatal hospitalization, to control data. The mean gestational age at program start was 32.6 weeks. Antenatal hospital admission was required for 24.8% of patients, with a mean length of stay of 2.3 days per admission. Progression to severe preeclampsia occurred in 14.3% of patients. Mean gestational age at delivery was 37.0 weeks. Antepartum charges averaged 10,327 US dollars per control patient and 4,888 US dollars per program patient, a difference of 5,439 US dollars. For each dollar spent on outpatient management, an average of 2.50 US dollars was saved. Utilizing outpatient management services for women with pregnancy-related hypertension reduces the need for inpatient care and is cost-effective.