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Background The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. Methods This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. Results In total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups. Conclusions Administration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection. Clinical Trials Registration NCT04323800.

Purpose: Obstructive sleep apnea (OSA) leads to endothelial dysfunction and platelet hyperactivity, which arelinked to increased risk of cardiovascular disease and implicated in the development of aspirin resistance. We hypothesized that aspirin resistance is prevalent among OSA patients and aimed to explore effects of continuous positive airway pressure (CPAP) therapy on aspirin responsiveness. Methods: In Phase 1, prevalence of aspirin resistance was determined cross-sectionally in a group of OSA patients (n=59) on daily low-dose aspirin (81 mg) taken before entering the study, for primary or secondary prevention. In Phase 2, aspirin responsiveness before and after initiation of CPAP therapy was compared and stratified by endothelial function in a cohort of aspirin-naïve patients with newly diagnosed OSA (n=18). Results: In Phase 1, prevalence of aspirin resistance was 17%; most patients (56%) were on CPAP therapy. In Phase 2, initiation of CPAP therapy was associated with significant improvement in endothelial function (p=0.03). The mean pre-CPAP aspirin resistance units (ARU) was 569 (SD=75). In subjects with endothelial dysfunction (44%), the mean decrease after initiation of CPAP therapy was 43 ARU (SD=81, p=0.18). In contrast, subjects with normal endothelial function experienced the mean decrease of 8 ARU (SD=116, p=0.83). Conclusion: Aspirin resistance may be prevalent among OSA patients. After initiation of CPAP therapy, we observed a trend towards improvement in aspirin responsiveness among patients with endothelial dysfunction. The role of endothelial dysfunction and aspirin resistance should be explored in further studies that focus on the effect of CPAP on cardiovascular outcomes.

INTRODUCTION: The outbreak of COVID-19 disrupted lives across the United States. Evidence shows that such a climate is deleterious to mental health and may increase demand for mental health services in emergency departments. The purpose of this study was to determine the difference in emergency department utilization for mental health diagnoses before and after the COVID-19 surge. METHODS: We conducted a cross-sectional study between January-August 2019 and January-August 2020 with emergency department encounter as the sampling unit. The primary outcome was the proportion of all emergency department encounters attributed to mental health. We performed chi-square analyses to evaluate the differences between 2019 and 2020. RESULTS: We found that overall emergency department volume declined between 2019 and 2020, while the proportion attributable to mental health conditions increased (p < 0.01). Substance abuse, anxiety, and mood disorders accounted for nearly 90% of mental health diagnoses during both periods. When stratified by sex, substance abuse was the leading mental health diagnosis for males and anxiety and substance abuse disorders combined accounted for the largest proportion for females. DISCUSSION: The emergency department is an important community resource for the identification and triage of mental health emergencies. This role is even more important during disasters and extended crises, making it imperative that emergency departments employ experienced mental health staff. This study provides a comparison of emergency department utilization for mental health diagnoses before the pandemic and during the spring 2020 surge and may serve as a useful guide for hospitals, health systems and communities in future planning.

Objectives Data regarding the pathogenesis and clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, however, there’s limited data in regard to maternal and neonatal outcomes. Therefore, we conducted a retrospective analysis of all pregnant women who tested positive for SARS-CoV-2 within Nuvance Health system. Methods Data were abstracted from the medical records of each patient and descriptive analysis was performed. Variables included demographics, COVID testing results, symptoms, management, labor course, neonatal information, and complications. Results Total of 40 patients were identified. Average age was 29.6 years old, 35% were Hispanic, and approximately one in three patients had comorbidities. Of the patients who had repeated testing, the average number of days between first positive test and negative test was 36.8 days (± 19.9 days). Three out of four women reported symptoms. Of the 40 pregnant women who were positive for SARS-CoV-2, 25 of them delivered. About 84% of the women delivered after 37 weeks. Twelve percent of the women delivered under 33 and 6/7 weeks. Most patients had vaginal deliveries (68%) and the remaining had cesarean deliveries. Neonatal outcomes included: mean 1 and 5 min Apgar scores of 8 and 8.8, respectively and the mean birth weight was 3212 g. Twenty neonates were tested for SARS-CoV-2 and were all found to be negative. Conclusions Overall, with routine prenatal care and preventive measures, pregnant patients and neonates in our study had good outcomes. At this time, there appears to be no evidence of vertical transmission.

The human oral and gut microbiomes influence health via competition for a distinct niche in the body with pathogens, via metabolic capabilities that increase host digestive capacity and generate compounds engaged in signaling pathways and modulation of immune system functions. Old age alters our metabolic and regenerative capacity. Following recruitment of 65 human subjects in the age range of 70 to 82, we discerned healthy aging (HA) and non-healthy aging (NHA) cohorts discordant in the occurrence of one or more major diseases: (1) cancer, (2) acute or chronic cardiovascular diseases, (3) acute or chronic pulmonary diseases, (4) diabetes, and (5) stroke or neurodegenerative disorders. We analyzed these cohorts’ oral microbiomes (saliva) and gut microbiomes (stool) to assess diversity and identify microbial biomarkers for HA. In contrast to the gut microbiome where no change was observed, we found that the saliva microbiome had higher α-diversity in the HA compared with the NHA group. We observed the genus Akkermansia to be significantly more abundant in the gut microbiota of the HA group. Akkermansia muciniphila is a colonic mucin-degrading bacterium believed to have beneficial effects on gastrointestinal health, particularly in the context of diabetes and obesity. Erysipelotrichaceae UCG-003 was a taxon increased in abundance in the HA cohort. Streptococcus was the only genus observed to be significantly decreased in abundance in both the gut and oral microbiomes of the HA cohort compared with the NHA cohort. Our data support the notion that these microbes are potential probiotics to decrease the risks of non-healthy aging. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11357-019-00098-8) contains supplementary material, which is available to authorized users.

Introduction COVID‐19, caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is a public health crisis. Prior studies demonstrated successful use of convalescent plasma therapy for treatment of other viral illnesses. Our primary objective was to evaluate treatment efficacy of convalescent plasma in patients with COVID‐19. Materials and Methods In this retrospective matched cohort study, we enrolled recipients of convalescent plasma collected from donors recovered from laboratory‐confirmed SARS‐CoV‐2 infection under the single patient eIND process. We individually matched 35 cases with 61 controls based on age, gender, supplemental oxygen requirements, and C‐reactive protein level at the time of hospital admission. We compared the outcomes of in‐hospital mortality and hospital length of stay between the groups. Results In‐hospital mortality was 20% among the cases and 24.6% among the controls (P = .61). A multivariable logistic regression model that included age, gender, duration of symptoms, need for mechanical ventilation, and pharmacologic interventions revealed no significant difference in mortality by study group (P = .71). The median length of stay was significantly greater among convalescent plasma recipients compared with controls, 10 (IQR, 6‐17) vs 7 (IQR, 4‐11) days, P .1). Conclusions We did not find convalescent plasma reduced in‐hospital mortality in our sample, nor did it reduce length of stay. Further investigation is warranted to determine the efficacy of this treatment in patients with COVID‐19, particularly early in the disease process.

ObjectiveThe need for critical care, hemodynamic support, renal replacement therapy, and mechanical ventilation have emerged as key features of the SARS-nCoV-2 (COVID-19) pandemic. The primary aim of this study was to determine the in-hospital mortality rate of mechanically ventilated patients. We also sought to determine the risk of in-hospital mortality by age, gender, race, ethnicity, and body mass index.MethodsWe performed a retrospective cohort study to determine the mortality rate among inpatient adults with COVID-19 on mechanical ventilation in the Nuvance Health system between March 1, 2020 and July 17, 2020. Patients were included if they were 18 years or older, had a laboratory confirmed COVID-19 diagnosis, were admitted to hospitals within the Nuvance Health network (7 hospitals), and were on mechanical ventilation at any time during their inpatient stay.ResultsOverall mortality in our cohort of 304 patients was 53.3%. Multivariable logistic regression including age, gender, race, ethnicity, and BMI demonstrated patients over 71 years old had greater risk of mortality compared to patients ages 61-70, and females had half the risk compared to males. There was no significant difference in risk of mortality given race, ethnicity, or BMI.ConclusionsIn adult patients with confirmed COVID-19 infection requiring mechanical ventilation and intensive care, advanced age (>71 years old) and male gender are associated with increased risk of mortality. This information contributes to a collective body of evidence to support ongoing planning and decision-making among clinicians and for directed infection prevention programming.

BackgroundThis study is the first of its kind to assess the impact of preemptive therapeutic dose anticoagulation on mortality compared to prophylactic anticoagulation among COVID-19 patients. Its findings provide insight to clinicians regarding the management of COVID-19, particularly with the known prothrombotic state.Research QuestionTo determine the impact of anticoagulation on in-hospital mortality among COVID-19 positive patients with the a priori hypothesis that there would be a lower risk of in-hospital mortality with use of preemptive therapeutic over prophylactic dose enoxaparin or heparin.Study Design and MethodsStudy DesignRetrospective cohort study from April 1 - April 25, 2020. The date of final follow-up was June 12, 2020.SettingTwo large, acute care hospitals in Western Connecticut.ParticipantFive hundred and one inpatients were identified after discharge as 18 years or older and positive for SARS-CoV-2. The final sample size included 374 patients after applying exclusion criteria. Demographic variables were collected via hospital billing inquiries, while the clinical variables were abstracted from patients’ medical records.ExposurePreemptive enoxaparin or heparin at a therapeutic or prophylactic dose.Main OutcomIn-hospital mortality.ResultsWhen comparing preemptive therapeutic to prophylactic anticoagulation through multi-variable analysis, risk of in-hospital mortality was 2.3 times greater in patients receiving preemptive therapeutic anticoagulation (95% CI = 1.0, 4.9; p = 0.04).InterpretationAn increase in in-hospital mortality was observed with preemptive therapeutic anticoagulation. Thus, in the management of COVID-19 and its complications, we recommend further research and cautious use of preemptive therapeutic over prophylactic anticoagulation.

Key processes characterizing human aging are immunosenescence and inflammaging. The capacity of the immune system to adequately respond to external perturbations (e.g., pathogens, injuries, and biochemical irritants) and to repair somatic mutations that may cause cancers or cellular senescence declines. An important goal remains to identify genetic or biochemical, predictive biomarkers for healthy aging. We recruited two cohorts in the age range 70 to 82, one afflicted by chronic illnesses (non-healthy aging, NHA) and the other in good health (healthy aging, HA). NHA criteria included major cardiovascular, neurodegenerative, and chronic pulmonary diseases, diabetes, and cancers. Quantitative analysis of forty proinflammatory cytokines in blood plasma and more than 500 proteins in urine was performed to identify candidate biomarkers for and biological pathway implications of healthy aging. Nine cytokines revealed lower quantities in blood plasma for the NHA compared with the HA groups (fold change > 1.5; p value 1.5; p value

Background: Heart failure remains one of the highest disease burdens in the USA and worldwide. Heart failure guidelines recommend starting with a higher or equal to home dose of loop diuretics in acute decompensated heart failure admissions. To date, no study has been published assessing the effect of first 24 h loop diuretic dose on length of hospital stay. Objective: We hypothesize that the higher the first 24 h loop diuretic dose to home dose ratio, the shorter the length of hospital stay will be. Design/Methods: Retrospective chart review was conducted in a community teaching hospital and included patients discharged between February, 2015 and April, 2016, with a primary diagnosis of acute decompensated heart failure. The primary outcome was the length of hospital stay. The study population was divided into three groups based on the hospital to home dose ratio. Results: Among the 609 patients included in the data analysis, there was no statistically significant difference in length of hospital stay among the study groups. Inpatient mortality and incidence of acute kidney injury were highest in the group that received a first-24-hours hospital dose that was less than their home dose. Percentage of weight loss and 30-day readmission were not statistically significantly different among the groups. Conclusion: There was no association between the dose ratio and length of hospital stay in each group. Additional randomized controlled trials need to be conducted to provide more evidence and guidance for dosing loop diuretics in acute decompensated heart failure admissions.

To compare fetal and first day outcomes of American Indian and Alaskan Natives (AIAN) with non-AIAN populations. Singleton deliveries to AIAN and non-AIAN populations were selected from live birth–infant death cohort and fetal deaths files from 1995–1998 and 2005–2008. We examined changes over time in maternal characteristics of deliveries and disparities and changes in risks of fetal, first day (

Purpose Although studies have examined overall temporal changes in gestational age–specific fetal mortality rates, there is little information on the current status of racial/ethnic differences. We hypothesize that differences exist between racial/ethnic groups across gestational age and that these differences are not equally distributed. Methods Using the 2009–2013 data from US fetal death and live birth files for non-Hispanic white (NHW); non-Hispanic black (NHB); Hispanic; and American Indian/Alaska Native (AIAN) women, we conducted analyses to examine fetal mortality rates and estimate adjusted prevalence rate ratios and 95% confidence intervals (CIs). Results There were lower risks of fetal mortality among NHB women (aPRR = 0.76; 95% CI = 0.71–0.81) and Hispanic women (aPRR = 0.89; 95% CI = 0.83–0.96) compared with NHWs at 22–23 weeks’ gestation. For NHB women, the risk was higher starting at 32–33 weeks (aPRR = 1.11; 95% CI = 1.04–1.18) and continued to increase as gestational age increased. Hispanic and AIAN women had lower risks of fetal mortality compared with NHW women until 38–39 weeks. Conclusions Further examination is needed to identify causes of fetal death within the later pregnancy period and how those causes and their antecedents might differ by race and ethnicity.

Background The sharp increase in health care costs over the past decade has prompted health care providers to reevaluate how diagnostic imaging is utilized. In response to the need for more rational use of imaging services, the American College of Cardiology Foundation and the American Society of Echocardiography have developed appropriate use criteria (AUC) for transthoracic echocardiography to guide its utilization. Although community and regional hospitals, such as Danbury Hospital, account for 85% of registered hospitals in the United States, very little is known about adherence to the AUC at these institutions. Methods The electronic medical records of 1,205 patients who underwent inpatient transthoracic echocardiography from January 1 to June 30, 2008, were retrospectively examined to determine the reasons for ordering the studies. The 2007 and 2011 AUC were used to classify indications as appropriate, inappropriate, or uncertain. Results Using the 2007 AUC, 86% of echocardiographic examinations were classified as appropriate. One percent had indications that were inappropriate, and there were no uncertain indications. Thirteen percent of studies were ordered for reasons not defined by the 2007 AUC. The most common appropriate indications were symptoms due to suspected cardiac etiology, initial evaluation after acute myocardial infarction, and acute chest pain with suspected myocardial ischemia. When evaluated using the 2011 AUC, appropriate and inappropriate indications increased to 97% and 2%, respectively. Ninety-three percent of undefined studies, using the 2007 AUC, could be classified using the 2011 guidelines. Conclusions Consistent with studies conducted at university hospitals, Danbury Hospital, a regional hospital, showed good adherence to the AUC. This suggests that the AUC are valuable across a large continuum of inpatient settings and can serve as an excellent guide for utilization and appropriateness.

Background: Takotsubo cardiomyopathy is a syndrome of transient left ventricular dysfunction following acute emotional or physical stress without obstructive coronary artery disease. The leading hypothesis for the etiology is stress-induced catecholamine surge. Hypothesis: People taking outpatient β-adrenergic receptor antagonist therapy have less-severe presentation and clinical course of Takotsubo cardiomyopathy. Methods: We identified patients diagnosed with Takotsubo cardiomyopathy from October 2005 to January 2011 by analyzing our cardiac-catheterization database. Clinical records and angiograms were reviewed by 2 experienced observers independently to confirm the diagnosis. We collected clinical, demographic, laboratory, and angiographic data for the identified patients. We then compared the severity of myocardial dysfunction or damage (cardiac enzymes, left ventricular end diastolic pressure, and left ventricular ejection fraction) between patients taking outpatient β-adrenergic antagonist therapy upon admission vs those who were not. Arrival and peak values for cardiac enzymes were analyzed when available. Analysis of parameters related to the severity of myocardial dysfunction or damage was conducted using the Mann-Whitney U test. Means for age were compared using the Student t test. Statistical significance was set at P < 0.05 (2-tailed). Results: Out of 64 patients identified, 16 (25%) were on one of 3 β-adrenergic antagonists on presentation: metoprolol succinate, metoprolol tartrate, or atenolol, with mean doses of 75 mg daily, 52.5 mg twice daily, and 37.5 mg daily, respectively. Patients on β-blockers were older (mean age 73.1 years vs 66 years; P < 0.05). There was no statistically significant difference in levels of cardiac enzymes, left ventricular end diastolic pressure, or left ventricular ejection fraction between the 2 groups. Conclusion: Prior therapy with low-dose β-adrenergic antagonists does not affect the severity of presentation and clinical course of Takotsubo cardiomyopathy as measured by common markers of myocardial dysfunction. Clin. Cardiol. 2012 DOI: 10.1002/clc.21983 The authors have no funding, financial relationships, or conflicts of interest to disclose.

Infertility treatment with ovulation stimulation, either as part of assisted reproductive technologies (ARTs) or for non-ART infertility treatment, has been primarily responsible for the marked increase in multiple births in the United States in recent decades. The multiple-gestations resulting from both ART and non-ART treatments are associated with adverse sequelae, including markedly higher risks of pregnancy complications, premature delivery, infant death, and neurodevelopmental impairment in survivors. A number of studies have reported that ART-conceived singletons are also at higher risk of these outcomes than naturally conceived singletons. Although there is an ongoing, population-based surveillance system in the United States for ART-induced births, there is no comparable system to monitor non-ART infertility treatments, thus the contribution of each to multiple births in the United States is not known. The investigators present data from a multistep modeling process that was developed to estimate the proportions of multiple and singleton livebirths conceived in 2005 by use of non-ART ovulation stimulation. Published surveillance data provided an estimate of the proportion of US multiple births conceived naturally and by ART; it was assumed that the remainder was conceived with non-ART treatments. A meta-analysis of peer-reviewed literature published from 1997 to 2007 was used to estimate the contribution of non-ART ovulation treatment to the risk of multiple-gestation in the annual US birth cohort. A non-ART fetal survival factor was applied to obtain multiple-birth risk estimates. This estimate and the investigator's previous estimate of the proportion of US multiple births attributable to non-ART ovulation stimulation provided an estimate of the total and singleton (derived through subtraction of multiple births) proportion of infants conceived using non-ART induction. Based on the model data, the investigators estimated that the mean percentage of all US births in 2005 conceived with non-ART ovulation stimulation was 4.62% (95% uncertainty range, 2.8%-7.8%), which is 4 times more that the number contributed by ART treatment and equates to more than 190,000 livebirths. Of all singleton pregnancies, 3.98% were conceived with non-ART ovulation stimulation, and 22.8% of all multifetal pregnancies resulted from non-ART ovulation stimulation. These findings demonstrate that non-ART ovulation induction treatment in the United States is associated with a higher multiple-birth-attributable risk than ART. The estimated percentage contribution to US births is 2 to 6 times higher than the contribution of ART.

Objective The purpose of this trial was to evaluate the effect of krill oil supplementation, a source of ω-3 fatty acids, on cardiovascular disease risk factors and blood glucose control among participants with type 2 diabetes. Research design and methods A randomized, double-blind controlled cross-over trial was employed. Outcomes assessed were: endothelial function, blood lipids, glucose, glycated hemoglobin, serum antioxidant level, C peptide, and calculated Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores. Participants were randomized to either krill oil or olive oil supplementation for 4 weeks, underwent a 2-week washout period, and then crossed to the other supplementation for 4 weeks. All participants were then offered an additional 17 weeks of krill supplementation. Testing occurred at 3 time points: baseline, after first supplementation, and after second supplementation. Testing also occurred after an optional 17 weeks of krill oil supplementation. Difference scores were calculated for each participant in both sequences (ie, differences in outcome measures in the first and second period of the sequence). The mean and SD of the scores in the 2 sequence groups were used to test for differences between treatment effects at a significance level of p Results A total of 47 participants were included in the initial cross-over study. Participants who received krill oil for 4 weeks had an improvement in their endothelial function and a reduction in blood C peptide levels and HOMA scores as compared with the olive oil. A total of 34 participants completed the additional 17-week supplementation period. When compared with their respective baseline measures, these participants had a statistically significant improvement in endothelial function and blood high-density lipoprotein (HDL). Conclusions Krill oil may lead to moderate improvement of cardiovascular risks, specifically endothelial dysfunction and HDL in patients with type 2 diabetes. Trial registration number Registered with ClinicalTrials.gov: NCT02091193.

Objective: To summarize changes in folic acid awareness, knowledge, and behavior among women of childbearing age in the United States since the U.S. Public Health Service (USPHS) 1992 folic acid recommendation and later fortification. Methods: Random-digit dialed telephone surveys were conducted of approximately 2000 women (per survey year) aged 18–45 years from 1995–2005 in the United States. Results: The percentage of women reporting having heard or read about folic acid steadily increased from 52% in 1995 to 84% in 2005. Of all women surveyed in 2005, 19% knew folic acid prevented birth defects, an increase from 4% in 1995. The proportion of women who reported learning about folic acid from health care providers increased from 13% in 1995 to 26% in 2005. The proportion of all women who reported taking a vitamin supplement containing folic acid increased slightly from 28% in 1995 to 33% in 2005. Among women who were not pregnant at the time of the survey in 2005, 31% reported taking a vitamin containing folic acid daily compared with 25% in 1995. Conclusions: The percentage of women taking folic acid daily has increased modestly since 1995. Despite this increase, the data show that the majority of women of childbearing age still do not take a vitamin containing folic acid daily. Health care providers and maternal child health professionals must continue to promote preconceptional health among all women of childbearing age, and encourage them to take a vitamin containing folic acid daily.

Objective: To assess health care providers (HCP) knowledge and practices regarding folic acid (FA) use for neural tube defect (NTD) prevention. Methods: Two identical surveys were conducted among 611 obstetricians/gynecologists (OB/GYNs) and family/general physicians (FAM/GENs) (2002), and 500 physician assistants (PAs), nurse practitioners (NPs), certified nurse midwives (CNMs), and registered nurses (2003) to ascertain knowledge and practices regarding FA. For analysis, T-tests, univariate and multivariate logistic regression modeling were used. Results: Universally, providers knew that FA prevents birth defects. Over 88% knew when a woman should start taking folic acid for the prevention of NTDs; and over 85% knew FA supplementation beyond what is available in the diet is necessary. However, only half knew that 50% of all pregnancies in the United States are unplanned. Women heard information about multivitamins or FA most often during well woman visits in obstetrical/gynecology (ob/gyn) practice settings (65%), and about 50% of the time during well woman visits in family/general (fam/gen) practice settings and 50% of the time at gynecology visits (both settings). Among all providers, 42% did not know the correct FA dosage (400 μg daily). HCPs taking multivitamins were more than twice as likely to recommend multivitamins to their patients (Odds Ratio [OR] 2.27 95%, Confidence Interval [CI] 1.75–2.94). HCPs with lower income clients (OR 1.49, CI 1.22–1.81) and HCPs with practices having more than 10% minorities (OR 1.46, CI 1.11–1.92) were more likely to recommend supplements. NPs in ob/gyn settings were most likely and FAM/GENs were least likely to recommend supplements (OR 3.06, CL 1.36–6.90 and OR 0.64, CL 0.45–0.90 respectively). Conclusions: Knowledge about birth defects and the necessity of supplemental FA was high. Increasing knowledge about unintended pregnancy rates and correct dosages of FA is needed. The strongest predictor for recommending the use of FA supplements was whether the provider took a multivitamin.

BACKGROUND: In the United States, birth defects affect approximately 3% of all births, are a leading cause of infant mortality, and contribute substantially to childhood morbidity. METHODS: Population-based data from the National Birth Defects Prevention Network were combined to estimate the prevalence of 21 selected defects for 1999–2001, stratified by surveillance system type. National prevalence was estimated for each defect by pooling data from 11 states with active case-finding, and adjusting for the racial/ethnic distribution of US live births. We also assessed racial/ethnic variation of the selected birth defects. RESULTS: National birth defect prevalence estimates ranged from 0.82 per 10,000 live births for truncus arteriosus to 13.65 per 10,000 live births for Down syndrome. Compared with infants of non-Hispanic (NH) white mothers, infants of NH black mothers had a significantly higher birth prevalence of tetralogy of Fallot, lower limb reduction defects, and trisomy 18, and a significantly lower birth prevalence of cleft palate, cleft lip with or without cleft palate, esophageal atresia/tracheoesophageal fistula, gastroschisis, and Down syndrome. Infants of Hispanic mothers, compared with infants of NH white mothers, had a significantly higher birth prevalence of anencephalus, spina bifida, encephalocele, gastroschisis, and Down syndrome, and a significantly lower birth prevalence of tetralogy of Fallot, hypoplastic left heart syndrome, cleft palate without cleft lip, and esophageal atresia/tracheoesophageal fistula. CONCLUSIONS: This study can be used to evaluate individual state surveillance data, and to help plan for public health care and educational needs. It also provides valuable data on racial/ethnic patterns of selected major birth defects. Birth Defects Research (Part A), 2006. © 2006 Wiley-Liss, Inc.

OBJECTIVE: A multicenter, randomized placebo-controlled trial among women with singleton pregnancies and a history of spontaneous preterm birth found that weekly injections of 17 alpha-hydroxyprogesterone caproate (17P), initiated between 16 and 20 weeks of gestation, reduced preterm birth by 33%. The current study estimated both preterm birth recurrence and the potential reduction in the national preterm birth rate. METHODS: Using 2002 national birth certificate data, augmented by vital statistics from 2 states, we estimated the number of singleton births delivered to women eligible for 17P through both a history of spontaneous preterm birth and prenatal care onset within the first 4 months of pregnancy. The number and rate of recurrent spontaneous preterm births were estimated. To predict effect, the reported 33% reduction in spontaneous preterm birth attributed to 17P therapy was applied to these estimates. RESULTS: In 2002, approximately 30,000 recurrent preterm births occurred to women eligible for 17P, having had a recurrent preterm birth rate of 22.5%. If 17P therapy were delivered to these women, nearly 10,000 spontaneous preterm births would have been prevented, thereby reducing the overall United States preterm birth rate by approximately 2%, from 12.1% to 11.8% (P < .001), with higher reductions in targeted groups of eligible pregnant women. CONCLUSION: Use of 17P could reduce preterm birth among eligible women, but would likely have a modest effect on the national preterm birth rate. Additional research is urgently needed to identify other populations who might benefit from 17P, evaluate new methods for early detection of women at risk, and develop additional prevention strategies. (Obstet Gynecol 2005;105:267‐72. © 2005 by The American College of Obstetricians and Gynecologists.) LEVEL OF EVIDENCE: III

To describe changes in the epidemiology of multiple births in the United States from 1980 to 1999 by race, maternal age, and region; and to examine the impact of these changes on birth weight-specific infant mortality rates for singleton and multiple births.Retrospective univariate and multivariable analyses were conducted using vital statistics data from the National Center for Health Statistics.Between 1980 and 1999, the overall multiple birth ratio increased 59% (from 19.3 to 30.7 multiple births per 1000 live births, P.001), with rates among whites increasing more rapidly than among blacks. Women of advanced maternal age, especially those aged 30-34, 35-39, and 40-44 experienced the greatest increases (62%, 81%, and 110%, respectively). Although all regions of the United States experienced increases in multiple birth ratios between 1991 and 1999, the Northeast had the highest twin (33.9 per 1000 live births) and higher order birth ratios (280.5 per 100,000 live births), even after adjusting for maternal age and race. Between 1989 and 1999, multiple births experienced greater declines in infant mortality than singletons in all birth weight categories. Consequently, very low birth weight and moderately low birth weight infant mortality rates among multiples were lower than among singletons.It is important to understand the changing epidemiology of multiple births, especially for women at highest risk (advanced maternal age, white race, Northeast residents). The attribution of infertility management requires further study. The differential birth weight-specific infant mortality for singletons and multiples demonstrates the importance of stratifying by plurality when assessing perinatal outcomes.

Obstructive sleep apnea (OSA) is an independent risk factor for ischemic stroke that is not included in the usual cardioembolic risk assessments for patients with atrial fibrillation (AF). The aim of this study was to investigate the impact of OSA on stroke rate in patients with AF. Patients with AF and new diagnoses of OSA were identified from retrospective chart review. Those with histories of stroke at the time of the sleep study were excluded. The primary outcome was the incidence of stroke, determined by a physician investigator blinded to the results of polysomnography. Subgroup analysis was performed among different CHADS₂ and CHA₂DS₂-VASc scores. Of 5,138 patients screened for OSA, 402 (7.7%) had AF and 332 (6.4%) met the inclusion criteria. Among the study population, the occurrence of first-time stroke was 22.9%. Ischemic stroke was more common in patients with OSA compared with patients without (25.4% vs 8.2% respectively, p = 0.006). After controlling for age, male gender, and coronary artery disease, the association between OSA and stroke remained statistically significant, with an adjusted odds ratio of 3.65 (95% confidence interval 1.252 to 10.623). A positive dose effect of the apnea-hypopnea index on the rate of stroke was observed (p = 0.0045). Subgroup analysis showed significantly higher rates of stroke in patients with CHADS₂ scores of 0 and CHA₂DS₂-VASc scores of 0 and 1 and co-morbid OSA. In conclusion, OSA in patients with AF is an independent predictor of stroke. This association may have important clinical implications in ischemic stroke risk stratification.

And his daughter-in-law, the wife of Phinehas, was pregnant near to giving birth, and got to hear the report that the ark of the true God was captured and that her father-in-law and her husband had died. At that she bowed herself and began giving birth, because her pangs came unexpectedly upon her.

Cancer incidence and mortality are higher in males than in females, suggesting that some gender-related factors are behind such a difference. To analyze this phenomenon the most recent Surveillance, Epidemiology and End Results (SEER) database served to access cancer survival data for the US population. Patients with gender-specific cancer and with limited information were excluded and this fact limited the sample size to 1,194,490 patients. NHANES III provided the distribution of physiologic variables in US population (n = 29,314). Cox model and Kaplan-Meier method were used to test the impact of gender on survival across age, and to calculate the gender-specific hazard ratio of dying from cancer five years following diagnosis. The distribution of the hazard ratio across age was then compared with the distribution of 65 physiological variables assessed in NHANES III. Spearman and Kolmogorov-Smirnov test assessed the homology. Cancer survival was lower in males than in females in the age range 17 to 61 years. The risk of death from cancer in males was about 30% higher than that of females of the same age. This effect was present only in sarcomas and epithelial solid tumors with distant disease and the effect was more prominent in African-Americans than Caucasians. When compared to the variables assessed in the NHANES III study, the hazard ratio almost exactly matched the distribution of free testosterone in males; none of the other analyzed variables exhibited a similar homology. Our findings suggest that male sex hormones give rise to cancer aggressiveness in patients younger than 61 years.

OBJECTIVE: Birth defects are a leading cause of infant mortality in the United States. Previous reports have highlighted black-white differences in overall infant mortality and infant mortality attributable to birth defects (IMBD). We evaluated the impact of gestational age on US racial/ethnic differences in IMBD. METHODS: We estimated the rate of IMBD as the underlying cause of death using the period-linked birth/infant death data for US residents for January 2003 to December 2006. We excluded infants with missing gestational age, implausible values based on Alexander’s index of birth weight for gestational age norms, or gestational ages 44 weeks; we categorized gestational age into 3 groups: 20 to 33, 34 to 36, and 37 to 44 weeks. Using Poisson regression, we compared neonatal and postneonatal IMBD for infants of non-Hispanic black and Hispanic mothers with that for infants of non-Hispanic white mothers stratified by gestational age. RESULTS: IMBD occurred in 12.2 per 10 000 live births. Among infants delivered at 37 to 44 weeks, blacks (and Hispanics, to a lesser degree) had significantly higher neonatal and postneonatal IMBD than whites; however, among infants delivered at 20 to 33 or 34 to 36 weeks, neonatal (but not postneonatal) IMBD was significantly lower among blacks compared with whites. CONCLUSIONS: Racial/ethnic differences in IMBD were not explained in these data by differences in gestational age. Further investigation should include an assessment of possible racial/ethnic differences in severity and/or access to timely diagnosis and management of birth defects.

Objectives. We examined how changes in risk factors over time influence fetal, first day, and combined fetal–first day mortality and subsequent racial/ethnic disparities. Methods. We selected deliveries to US resident non-Hispanic White and Black mothers from the linked live birth–infant death cohort and fetal deaths files (1995–1996; 2001–2002) and calculated changes over time of mortality rates, odds, and relative odds ratios (RORs) overall and among mothers with modifiable risk factors (smoking, diabetes, or hypertensive disorders). Results. Adjusted odds ratios (AORs) for fetal mortality overall (AOR = 0.99; 95% confidence interval [CI] = 0.96, 1.01) and among Blacks (AOR = 0.98; 95% CI = 0.93, 1.03) indicated no change over time. Among women with modifiable risk factors, the RORs indicated no change in disparities. The ROR was not significant for fetal mortality (ROR = 0.96; 95% CI = 0.83, 1.01) among smokers, but there was evidence of some decline. There was evidence of increase in RORs in fetal death among mothers with diabetes and hypertensive disorders, but differences were not significant. Conclusions. Disparities in fetal, first day, and combined fetal–first day mortality have persisted and reflect discrepancies in care provision or other factors more challenging to measure.

The increasing trend of delivering at earlier gestational ages has raised concerns of the impact on maternal and infant health. The delicate balance of the risks and benefits associated with continuing a pregnancy versus delivering early remains challenging. Among singleton live births in the United States, the proportion of preterm births increased from 9.7% to 10.7% between 1996 and 2004. The increase in singleton preterm births occurred primarily among those delivered by cesarean section, with the largest percentage increase in late preterm births. For all maternal racial/ethnic groups, singleton cesarean section rates increased for each gestational age group. Singleton cesarean section rates for non-Hispanic black women increased at a faster pace among all preterm gestational age groups compared with non-Hispanic white and Hispanic women. Further research is needed to understand the underlying reasons for the increase in cesarean section deliveries resulting in preterm birth.

Objective To evaluate the association between preterm birth and major birth defects by maternal and infant characteristics and specific types of birth defects. Study Design We pooled data for 1995–2000 from 13 states with population-based birth defects surveillance systems, representing about 30% of all U.S. births. Analyses were limited to singleton, live births from 24–44 weeks gestational age. Results Overall, birth defects were more than twice as common among preterm births (24–36 weeks) compared with term births (37–41 weeks gestation) (prevalence ratio [PR] = 2.65, 95% confidence interval [CI] 2.62–2.68), and approximately 8% of preterm births had a birth defect. Birth defects were over five times more likely among very preterm births (24–31 weeks gestation) compared with term births (PR = 5.25, 95% CI 5.15–5.35), with about 16% of very preterm births having a birth defect. Defects most strongly associated with very preterm birth included central nervous system defects (PR = 16.23, 95% CI 15.49–17.00) and cardiovascular defects (PR = 9.29, 95% CI 9.03–9.56). Conclusions Birth defects contribute to the occurrence of preterm birth. Research to identify shared causal pathways and risk factors could suggest appropriate interventions to reduce both preterm birth and birth defects.

OBJECTIVE. The objective of this study was to estimate national hospital costs for infant admissions that are associated with preterm birth/low birth weight.METHODS. Infant (35 million hospital discharges nationwide. Hospital costs, based on weighted cost-to-charge ratios, and lengths of stay were calculated for preterm/low birth weight infants, uncomplicated newborns, and all other infant hospitalizations and assessed by degree of prematurity, major complications, and expected payer.RESULTS. In 2001, 8% (384200) of all 4.6 million infant stays nationwide included a diagnosis of preterm birth/low birth weight. Costs for these preterm/low birth weight admissions totaled $5.8 billion, representing 47% of the costs for all infant hospitalizations and 27% for all pediatric stays. Preterm/low birth weight infant stays averaged $15100, with a mean length of stay of 12.9 days versus $600 and 1.9 days for uncomplicated newborns. Costs were highest for extremely preterm infants (CONCLUSIONS. Costs per infant hospitalization were highest for extremely preterm infants, although the larger number of moderately preterm/low birth weight infants contributed more to the overall costs. Preterm/low birth weight infants in the United States account for half of infant hospitalization costs and one quarter of pediatric costs, suggesting that major infant and pediatric cost savings could be realized by preventing preterm birth.

There is mounting evidence that infants born late preterm (34-36 weeks) are at greater risk for morbidity than term infants. This article examines the changing epidemiology of gestational length among singleton births in the United States, from 1992 to 2002. Analyzing gestational age by mode of delivery, the distribution of spontaneous births shifted to the left, with 39 weeks becoming the most common length of gestation in 2002, compared with 40 weeks in 1992 (P0.001). Deliveries ator =40 weeks gestation markedly decreased, accompanied by an increase in those at 34 to 39 weeks (P0.001). Singleton births with PROM or medical interventions had similar trends. Changes in the distribution of all singleton births differed by race/ethnicity, with non-Hispanic white infants having the largest increase in late preterm births. These observations, in addition to emerging evidence of increased morbidity, suggest the need for investigation of optimal obstetric and neonatal management of these late preterm infants.

Background Significant resources have been devoted to decreasing the rate of neural tube defects (NTDs) in the United States. Both surveillance data and birth records have strengths and limitations for evaluating the outcomes of this resource allocation. Cause-specific infant mortality data can be used as one measure to support evaluation efforts. Methods Using period linked birth/infant death data from the National Center for Health Statistics (NCHS), a retrospective analysis was performed to assess the NTD-specific IMR at the national, state, and regional level. NTD-specific IMRs for the United States were calculated from 1996 to 1998; stratified rates by race/ethnicity, maternal age, age at death, and gestational age and birthweight by type of NTD for the total US population were based on three-year aggregates (1996–98); state and regional rates were based on four-year aggregates (1995–98). Results Annual US NTD-specific IMRs significantly decreased between 1996 and 1998. Black infants were significantly less likely to die from an NTD when compared to white infants, largely attributed to the high rate of NTD-specific deaths among white Hispanic infants. Infants born to women less than 20 years were more likely than infants born to women in other age groups to die from an NTD. Seventy-six percent of all NTD-specific deaths occurred in the first 23 hours of life. Seventy-four percent of NTD-specific infant deaths were low birthweight and 58 percent were preterm. The Midwest had the highest rate of NTD-specific infant deaths among US regions. Conclusion Enhanced prevention efforts are needed to address the disparities in infant deaths due to NTDs between Hispanics and other populations, as well as women under 20 years. Decreases in NTD-specific IMRs may have been impacted by fortification of enriched grain products with folic acid since these efforts were optional beginning in 1996. While there are limitations in cause-specific IMRs, NTD-specific IMRs can be used as one measure to assess the impact of public health interventions aimed at reducing NTDs, respectful of the relatively small numbers. Teratology 66:S17–S22, 2002. © 2002 Wiley-Liss, Inc.

Background While overall infant mortality rates (IMR) have declined over the past several decades, birth defects have remained the leading cause of infant death in the United States. To illustrate how this leading cause of infant mortality impacts subgroups within the US population a descriptive analysis of the contribution of birth defects to infant mortality at the national and state level was conducted. Methods Descriptive analyses of birth defects-specific IMRs and proportionate infant mortality due to birth defects were conducted for the US using 1999 mortality data from the National Center for Health Statistics. In 1999, the change to ICD-10 impacted how cause-specific mortality rates were coded. Aggregated 1995-1998 state- birth defects infant death statistics were used for state comparisons. Results In 1999, birth defects accounted for nearly 1 in 5 infant deaths in the US. Variation in birth defects-specific IMRs were observed by maternal race with black infants having the highest rates when compared with other race groups. However, among black infants prematurity/low birthweight was the leading cause of death, followed by birth defects. There is substantial variation in state-specific birth defects IMRs and the state-specific proportion of infant deaths due to birth defects. Conclusions Birth defects remain the leading cause of infant death in the United States, despite the changes that resulted in 1999 from an update in the coding of cause of death from ICD-9 to ICD-10. While birth defects-specific IMRs provide an overall picture of fatal birth defects and a gauge of the impact of life-threatening anomalies, they represent only a fraction of the impact of birth defects, missing those who survive past infancy and those birth defects related losses in the antepartum period. Expansion and support of effective birth defects monitoring systems in each state that include the full spectrum of perinatal outcomes must be a priority. However, paralleling these efforts, analyses of this leading cause of infant mortality provide critical insight into perinatal health and should continue, with appropriate adjustments for the 1999 classification changes. Teratology 66:S3–S6, 2002. © 2002 Wiley-Liss, Inc.

Infertility treatments that include ovulation stimulation, both assisted reproductive technologies (ARTs) and non-ART ovulation stimulation, are associated with increased risks of multiple birth and concomitant sequelae and adverse outcomes, even among singletons. While a US surveillance system for ART-induced births is ongoing, no population-based tracking system exists for births resulting from non-ART treatments. The authors developed a multistage model to estimate the uncertain proportion of US infants born in 2005 who were conceived by using non-ART ovulation treatments. Using published surveillance data, they estimated proportions of US multiple births conceived naturally and by ART and assumed that the remainder were conceived with non-ART treatments. They used Bayesian meta-analyses to summarize published clinical studies on the multiple-gestation risk associated with non-ART ovulation treatments, applied a fetal survival factor, and used this multiple-birth risk estimate and their own estimate of the proportion of US multiple births attributable to non-ART ovulation stimulation to estimate the total (and, through subtraction, singleton) proportion of infants conceived with such treatments. On the basis of the model, the authors estimate that 4.6% of US infants born in 2005 (95% uncertainty range: 2.8%-7.1%) resulted from non-ART ovulation treatments. Notably, this figure is 4 times greater than the ART contribution.

Purpose Despite significant declines in the birth defects-specific infant mortality rate (BD-IMR), birth defects continue to be the leading cause of infant death in the United States, with the 1999 to 2001 average being 1.4 per 1000 live births. During this same time period, rates of low birth weight (LBW; Methods We conducted a study of U.S. BD-IMRs by birth weight and gestational age, stratified by plurality using data from the National Center for Health Statistics linked birth/infant death file for the years 1999 to 2001 combined. Rates were calculated for subgroups by race or ethnicity, maternal age, and type of anomaly—variables that potentially contribute to the impact of birth weight and gestational age on BD-IMRs. Results About 60% of infant deaths due to birth defects occurred to LBW infants and about half occurred to preterm infants. BD-IMRs were highest for LBW and preterm births. BD-IMRs increased with increasing plurality. Among LBW and preterm infants, however, these rates decreased with increasing plurality. Among singletons, non-Hispanic black infants (rate of 1.6 per 1000 live births) were more likely than non-Hispanic white (1.3) or Hispanic (1.4) infants to die due to a birth defect; however, non-Hispanic black LBW or preterm infants were less likely than corresponding non-Hispanic whites or Hispanics to die due to a birth defect. Conclusion These analyses provide important insight into the relationship among fatal birth defects, LBW, and preterm births. Prevention initiatives should consider the overlap in these conditions and their associated risk factors. In addition, an enhanced system of fetal death data in the United States would provide useful additions to our understanding of birth defects infant mortality.