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Background Many critically ill children are initially evaluated in front-line settings by clinicians with variable pediatric training before they are transferred to a pediatric intensive care unit (PICU). Because clinicians learn from past performance, communicating outcomes of patients back to front-line clinicians who provide pediatric emergency care could be valuable; however, referring clinicians do not consistently receive this important feedback. Objectives Our aim was to determine the feasibility, usability, and clinical relevance of a semiautomated electronic health record (EHR)-supported system developed at a single institution to deliver timely and relevant PICU patient outcome feedback to referring emergency department (ED) physicians. Methods Guided by the Health Information Technology Safety Framework, we iteratively designed, implemented, and evaluated a semiautomated electronic feedback system leveraging the EHR in one institution. After conducting interviews and focus groups with stakeholders to understand the PICU-ED health care work system, we designed the EHR-supported feedback system by translating stakeholder, organizational, and usability objectives into feedback process and report requirements. Over 6 months, we completed three cycles of implementation and evaluation, wherein we analyzed EHR access logs, reviewed feedback reports sent, performed usability testing, and conducted physician interviews to determine the system's feasibility, usability, and clinical relevance. Results The EHR-supported feedback process is feasible with timely delivery and receipt of feedback reports. Usability testing revealed excellent Systems Usability Scale scores. According to physicians, the process was well-integrated into their clinical workflows and conferred minimal additional workload. Physicians also indicated that delivering and receiving consistent feedback was relevant to their clinical practice. Conclusion An EHR-supported system to deliver timely and relevant PICU patient outcome feedback to referring ED physicians was feasible, usable, and important to physicians. Future work is needed to evaluate impact on clinical practice and patient outcomes and to investigate applicability to other clinical settings involved in similar care transitions.

Placental abnormalities have been described in clinical convenience samples, with predominately adverse outcomes. Few studies have described placental patterns in unselected samples.We aimed to investigate associations between co-occurring placental features and adverse pregnancy outcomes in a prospective cohort of singletons.Data were from the Safe Passage study (U.S. and South Africa, 2007-2015). Before 24 weeks' gestation, participants were randomly invited to donate placental tissue at delivery for blinded, standardised pathological examination. We used hierarchical clustering to construct statistically derived groups using 60 placental features. We estimated associations between the placental clusters and select adverse pregnancy outcomes, expressed as unadjusted and adjusted risk ratios (RRs) and robust 95% confidence intervals (CI).We selected a 7-cluster model. After collapsing 2 clusters to form the reference group, we labelled the resulting 6 analytic clusters according to the overarching category of their most predominant feature(s): severe maternal vascular malperfusion (n = 117), fetal vascular malperfusion (n = 222), other vascular malperfusion (n = 516), inflammation 1 (n = 269), inflammation 2 (n = 175), and normal (n = 706). Risks for all outcomes were elevated in the severe maternal vascular malperfusion cluster. For instance, in unadjusted analyses, this cluster had 12 times the risk of stillbirth (RR 12.07, 95% CI 4.20, 34.68) and an almost doubling in the risk of preterm delivery (RR 1.93, 95% CI 1.27, 2.93) compared with the normal cluster. Small infant size was more common among the abnormal clusters, with the highest unadjusted RRs observed in the fetal vascular malperfusion cluster (small for gestational age birth RR 2.99, 95% CI 2.24, 3.98, head circumference10th percentile RR 2.86, 95% CI 1.60, 5.12). Upon adjustment for known risk factors, most RRs attenuated but remained1.Our study adds to the growing body of epidemiologic research, finding adverse pregnancy outcomes may occur through etiologic mechanisms involving co-occurring placental abnormalities.

As part of a multicenter evidence-based intervention for surgical site infection prevention, a qualitative study was conducted with infection control teams and surgical staff members at three Department of Veterans Affairs Healthcare Systems in the USA. This study aimed to identify strategies used by nurses and other facility champions for the implementation of a nasal decolonization intervention. Site visit observations and field notes provided contextual information. Interview data were analyzed with inductive and deductive content analysis. Interview data was mapped to the Expert Recommendations for Implementing Change (ERIC) compilation of implementation strategies. These strategies were then considered in the context of power and relationships as factors that influence implementation. We found that implementation of this evidence-based surgical site infection prevention intervention was successful when nurse champions drove the day-to-day implementation. Nurse champions sustained implementation strategies through all phases of implementation. Findings also suggest that nurse champions leveraged the influence of their role as champion along with their understanding of social networks and relationships to help achieve implementation success. Nurse champions consciously used multiple overlapping and iterative implementation strategies, adapting and tailoring strategies to stakeholders and settings. Commonly used implementation categories included: “train and educate stakeholders,” “use evaluative and iterative strategies,” “adapt and tailor to context,” and “develop stakeholder interrelationships.” Future research should examine the social networks for evidence-based interventions by asking specifically about relationships and power dynamics within healthcare organizations. Implementation of evidence-based interventions should consider if the tasks expected of a nurse champion fit the level of influence or power held by the champion.Trial registrationClinicalTrials.gov, identifier: NCT02216227.

Background: One of the mechanisms suggested to link physical activity (PA) to favorable brain health is through stimulation of neural growth factors such as brain-derived neurotrophic factor (BDNF). Acute bouts of PA stimulate circulating BDNF levels. Objective: In this investigation, we assessed whether habitual, accelerometer-measured PA levels were related to circulating BDNF levels in a middle-aged cohort. Methods: In the Framingham Heart Study Third Generation cohort, 1,769 participants provided reliable accelerometry data and were not missing BDNF measurement or platelet counts. In a cross-sectional analysis, using multivariable regression, we related PA measures to serum BDNF levels, adjusting for age, sex, smoking status, platelet count, depression status, and accelerometer wear time. Results: Our study participants (mean age 47±9 years, 50.8% women) spent an average of 22.3 mins/day in moderate-to-vigorous (MV)PA. Most PA variables (steps, MVPA, light activity, and sedentary time) were not related to BDNF levels (p > 0.05). We observed a non-linear trend, where 15–50 mins/week vigorous activity was associated with lower BDNF compared to those with 0 min vigorous activity (β= –0.049±0.024, p = 0.05), but with no significant associations at lower or higher vigorous activity levels. In smokers, MVPA was also associated with lower BDNF levels (β= –0.216±0.079, p = 0.01). Conclusion: Our study reveals that circulating BDNF is not chronically elevated in individuals with higher levels of habitual PA in middle-aged adults from the community and may even be chronically suppressed with higher PA in subgroups, including current smokers. These results do not contradict previous studies demonstrating that circulating BDNF rises acutely after PA.

Key Points Question Is prenatal exposure to maternal drinking and smoking associated with the risk of stillbirth? Findings In this cohort study of 8506 pregnant women (with 11 892 pregnancies) in Cape Town, South Africa, and the Northern Plains in the US, dual exposure to drinking and smoking after the first trimester of pregnancy had 2.78 times the risk of late stillbirth compared with those with no exposure or who had quit before the end of the first trimester of pregnancy. Meaning These findings suggest that dual exposure to drinking and smoking after the first trimester of pregnancy is associated with nearly 3 times the risk of late stillbirth., Importance Prenatal smoking is a known modifiable risk factor for stillbirth; however, the contribution of prenatal drinking or the combination of smoking and drinking is uncertain. Objective To examine whether prenatal exposure to alcohol and tobacco cigarettes is associated with the risk of stillbirth. Design, Setting, and Participants The Safe Passage Study was a longitudinal, prospective cohort study with data collection conducted between August 1, 2007, and January 31, 2015. Pregnant women from Cape Town, South Africa, and the Northern Plains region of the US were recruited and followed up throughout pregnancy. Data analysis was performed from November 1, 2018, to November 20, 2020. Exposure Maternal consumption of alcohol and tobacco cigarettes in the prenatal period. Main Outcomes and Measures The main outcomes were stillbirth, defined as fetal death at 20 or more weeks’ gestation, and late stillbirth, defined as fetal death at 28 or more weeks' gestation. Self-reported alcohol and tobacco cigarette consumption was captured at the recruitment interview and up to 3 scheduled visits during pregnancy. Participants were followed up during pregnancy to obtain delivery outcome. Results Of 11663 pregnancies (mean [SD] gestational age at enrollment, 18.6 [6.6] weeks) in 8506 women for whom the pregnancy outcome was known by 20 weeks’ gestation or later and who did not terminate their pregnancies, there were 145 stillbirths (12.4 per 1000 pregnancies) and 82 late stillbirths (7.1 per 1000 pregnancies). A total of 59% of pregnancies were in women from South Africa, 59% were in multiracial women, 23% were in White women, 17% were in American Indian women, and 0.9% were in women of other races. A total of 8% were older than 35 years. In 51% of pregnancies, women reported no alcohol or tobacco cigarette exposure (risk of stillbirth, 4 per 1000 pregnancies). After the first trimester, 18% drank and smoked (risk of stillbirth, 15 per 1000 births), 9% drank only (risk of stillbirth, 10 per 1000 pregnancies), and 22% smoked only (risk of stillbirth, 8 per 1000 pregnancies). Compared with the reference group (pregnancies not prenatally exposed or without any exposure after the first trimester), the adjusted relative risk of late stillbirth was 2.78 (98.3% CI, 1.12-6.67) for pregnancies prenatally exposed to drinking and smoking, 2.22 (98.3% CI, 0.78-6.18) for pregnancies prenatally exposed to drinking only after the first trimester, and 1.60 (98.3% CI, 0.64-3.98) for pregnancies prenatally exposed to smoking only after the first trimester. The adjusted relative risk for all stillbirths was 1.75 (98.3% CI, 0.96-3.18) for dual exposure, 1.26 (98.3% CI, 0.58-2.74) for drinking only, and 1.27 (98.3% CI, 0.69-2.35) for smoking only compared with the reference group. Conclusions and Relevance These results suggest that combined drinking and smoking after the first trimester of pregnancy, compared with no exposure or quitting before the end of the first trimester, may be associated with a significantly increased risk of late stillbirth., This cohort study assesses whether prenatal exposure to alcohol, tobacco cigarettes, or both is associated with the risk of stillbirth in pregnant women from Cape Town, South Africa, and the Northern Plains region of the US.

Few cancer patients receive guideline-concordant care for treatment of tobacco dependence. The purpose of this pilot trial was to obtain preliminary estimates of effectiveness of an evidence-based practice intervention on the delivery of tobacco treatment and cessation outcomes in cancer patients. We conducted a pragmatic implementation trial with a before-after design in 119 current or recently quit adult smokers with cancer who met with a clinician at a single National Cancer Institute designated comprehensive cancer center (CCC) (n = 61 pre-implementation, n = 58 post-implementation). We used a multi-component strategy based on the Chronic Care Model to implement National Comprehensive Cancer Network (NCCN) guidelines for smoking cessation. Smoking cessation counseling during the index visit was assessed by exit interview and patients were interviewed by phone to assess cessation outcomes at 3-month follow-up. Performance of cessation counseling and 7-day point prevalence abstinence (PPA) were compared across the pre- and post-implementation periods using log-logistic regression, accounting for clustering by nursing staff. More patients had received assistance in quitting at the index visit during the post-implementation period compared to the pre-implementation period (30 vs. 10%, p.01). At 3-month follow-up, 38 and 14% of participants had discussed smoking cessation medication with a CCC healthcare professional and 57 and 27% of participants had used pharmacotherapy, respectively (p.01 for both comparisons). Seven-day PPA at 3-month follow-up was similar in both periods, however (14 vs. 12%, respectively). A multi-component tobacco treatment intervention increased the proportion of smokers who received assistance in quitting smoking during usual cancer care but did not improve cessation outcomes.Few patients with cancer receive help in quitting smoking. We conducted a pilot before-after trial to determine the effectiveness of an evidence-based practice intervention, including brief cessation counseling during the clinic visit and referral to an onsite tobacco treatment specialist, on the delivery of stop smoking services and cessation outcomes at a NCI-designated Comprehensive Cancer Center. During the post-implementation period, cancer patients who smoke were more likely to have received assistance in quitting in clinic and during 3-month follow-up. This change in process of care did not translate into improved short-term abstinence from tobacco, however. Greater and more sustained participation in tobacco treatment will be needed to improve cessation outcomes in this population.

Lack of access to resources such as medical facilities and grocery stores is related to poor health outcomes and inequities, particularly in an environmental justice framework. There can be substantial differences in quantifying "access" to such resources, depending on the geospatial method used to generate distance estimates.We compared three methods for calculating distance to the nearest grocery store to illustrate differential access at the census block-group level in the Atlanta metropolitan area, including: Euclidean distance estimation, service areas incorporating roadways and other factors, and cost distance for every point on the map.We found notable differences in access across the three estimation techniques, implying a high potential for exposure misclassification by estimation method. There was a lack of nuanced exposure in the highest- and lowest-access areas using the Euclidean distance method. We found an Intraclass Correlation Coefficient (ICC) of 0.69 (0.65, 0.73), indicating moderate agreement between estimation methods.As compared with Euclidean distance, service areas and cost distance may represent a more meaningful characterization of "access" to resources. Each method has tradeoffs in computational resources required versus potential improvement in exposure classification. Careful consideration of the method used for determining "access" will reduce subsequent misclassifications.

COVID-19 has caused over 300,000 US deaths thus far, but its long-term health consequences are not clear. Policies to contain the pandemic have led to widespread economic problems, which likely increase stress and resulting health risk behaviors, particularly among women, who have been hardest hit both by job loss and caregiving responsibilities. Further, women with pre-existing disadvantage (e.g., those without health insurance) may be most at risk for stress and consequent health risk behavior. Our objective was to estimate the associations between financial stressors from COVID-19 and health risk behavior changes since COVID-19, with potential effect modification by insurance status. We used multilevel logistic regression to assess the relationships between COVID-19-related financial stressors (job loss, decreases in pay, trouble paying bills) and changes in health risk behavior (less exercise, sleep, and healthy eating; more smoking/vaping and drinking alcohol), controlling for both individual-level and zip code-level confounders, among 90,971 US women who completed an online survey in March–April 2020. Almost 40% of women reported one or more COVID-19-related financial stressors. Each financial stressor was significantly associated with higher odds of each type of health risk behavior change. Overall, reporting one or more financial stressors was associated with 56% higher odds (OR = 1.56; 95% CI: 1.51, 1.60) of reporting two or more health risk behavior changes. This association was even stronger among women with no health insurance (OR = 2.46; 95% CI: 1.97, 3.07). COVID-19-related economic stress is thus linked to shifts in health risk behaviors among women, which may have physical health consequences for years to come. Further, the relationship between financial hardship and health risk behavior among women may be modified by health insurance status, as a marker for broader socioeconomic context and resources. The most socioeconomically vulnerable women are likely at highest risk for long-term health effects of COVID-19 financial consequences., Highlights • Over 1/3 of women in this study reported COVID-19-related financial stress. • Financial stress was associated with higher odds of health risk behavior changes. • This relationship was modified by health insurance status among women. • These behavior changes may eventually lead to cardiovascular disease. • Women who are already more vulnerable are likely at even higher risk.

Introduction Physical activity (PA) may play a role in maintenance of cognitive function in both middle and older ages and prevention of outcomes such as dementia and Alzheimer's disease. Methods Cross-sectional regression analyses were performed in Framingham Heart Study Third Generation (n = 1861) and Offspring (n = 909) cohort participants assessing the association of accelerometry-measured PA with cognitive function, adjusting for age, sex, accelerometer wear time, education, occupational status/PA, and smoking status. Results In each cohort, achieving just 10–21.4 min/day moderate-to-vigorous PA related to better executive function (P, Highlights • Physical activity related to better cognition in middle-aged and older adults. • Just 10 minutes of moderate-to-vigorous activity related to better cognition. • Walking more total steps/day is related to better executive function in older adults.

Prenatal alcohol exposure (PAE) has been linked to poor pregnancy outcomes, yet there is no recognized standard for PAE assessment, and the specific effects of quantity, frequency, and timing remain largely unknown. The Safe Passage Study was designed to investigate the role of PAE in a continuum of poor peri- and postnatal outcomes. The objective of this manuscript is to describe the rationale for, and feasibility of, modifications to the traditional Timeline Followback (TLFB) for collecting PAE information in a large cohort of pregnant women. Participants from the Northern Plains region (in the United States) and Cape Town, South Africa, were followed prospectively using a modified 30-day TLFB interview, administered up to five times, to obtain detailed PAE information. Required modifications for our population included capturing information regarding sharing, type/brand, container size, and duration, in order to accurately record the amount of alcohol consumed. PAE status was defined for 99.9% of the 11,892 enrolled pregnancies at least once during pregnancy and for 92% across all trimesters. Of 53,823 drinks reported, 98% had all items necessary for standard drink computation. Sharing was reported for 74% of drinks in Cape Town, South Africa and for 10% in the Northern Plains. Compared to referent values from the traditional TLFB, 74% and 67% of drinks had different alcohol-by-volume and container size, respectively. Furthermore, a statistically significant difference was found between the number of containers reported and the number of standard drinks computed, using information from the modified TLFB. This is the first study of this size to wholly encompass all of these changes into a single measure in order to more accurately calculate daily consumption and assess patterns over time. The methods used to collect PAE information and create alcohol exposure measures likely increased the accuracy of standard drinks reported and could be generalized to other populations.

Precise identification of drinking and smoking patterns during pregnancy is crucial to better understand the risk to the fetus. The purpose of this manuscript is to describe the methodological approach used to define prenatal drinking and smoking trajectories from a large prospective pregnancy cohort, and to describe maternal characteristics associated with different exposure patterns. In the Safe Passage Study, detailed information regarding quantity, frequency, and timing of exposure was self-reported up to four times during pregnancy and at 1 month post-delivery. Exposure trajectories were developed using data from 11,692 pregnancies (9,912 women) where pregnancy outcome was known. Women were from three diverse populations: white (23%) and American Indian (17%) in the Northern Plains, US, and mixed ancestry (59%) in South Africa (other/not specified [1%]). Group-based trajectory modeling was used to identify 5 unique drinking trajectories (1 none/minimal, 2 quitting groups, 2 continuous groups) and 7 smoking trajectories (1 none/minimal, 2 quitting groups, 4 continuous groups). Women with pregnancies assigned to the low- or high-continuous drinking groups were less likely to have completed high school and were more likely to have enrolled in the study in the third trimester, be of mixed ancestry, or be depressed than those assigned to the none/minimal or quit-drinking groups. Results were similar when comparing continuous smokers to none/minimal and quit-smoking groups. Further, women classified as high- or low-continuous drinkers were more likely to smoke at moderate-, high-, and very high-continuous levels, as compared to women classified as non-drinkers and quitters. This is the first study of this size to utilize group-based trajectory modeling to identify unique prenatal drinking and smoking trajectories. These trajectories will be used in future analyses to determine which specific exposure patterns subsequently manifest as poor peri- and postnatal outcomes.

Background: Sudden infant death syndrome (SIDS) is the leading cause of postneonatal mortality. Although the rate has plateaued, any unexpected death of an infant is a family tragedy thus finding causes and contributors to risk remains a major public health concern. The primary objective of this investigation was to determine patterns of drinking and smoking during pregnancy that increase risk of SIDS. Methods: The Safe Passage Study was a prospective, multi-center, observational study with 10,088 women, 11,892 pregnancies, and 12,029 fetuses, followed to 1-year post delivery. Subjects were from two sites in Cape Town, South Africa and five United States sites, including two American Indian Reservations. Group-based trajectory modeling was utilized to categorize patterns of drinking and smoking exposure during pregnancy. Findings: One-year outcome was ascertained in 94·2% infants, with 28 SIDS (2·43/1000) and 38 known causes of death (3·30/1000). The increase in relative risk for SIDS, adjusted for key demographic and clinical characteristics, was 11·79 (98·3% CI: 2·59–53·7, p

Background: The Safe Passage Study is a large, prospective, multidisciplinary study designed to (1) investigate the association between prenatal alcohol exposure, sudden infant death syndrome (SIDS), and stillbirth, and (2) determine the biological basis of the spectrum of phenotypic outcomes from exposure, as modified by environmental and genetic factors that increase the risk of stillbirth, SIDS, and in surviving children, fetal alcohol spectrum disorders. Methods: The results provided are based on an interim assessment of 6004 women enrolled, out of the 12 000 projected, from the Northern Plains, US, and Cape Town, South Africa, areas known to be of high risk for maternal drinking during pregnancy. Research objectives, study design, and descriptive statistics, including consent, recruitment, and retention information, are provided. Results: Overall visit compliance is 87%, and includes prenatal, delivery/newborn, and postnatal contacts through 1 year post-delivery. Pregnancy outcome ascertainment is 98% prior to medical chart review; less than 2% of women withdraw. Consent for the use of DNA and placental tissue exceed 94%, and consent to participate in the autopsy portion of the study is 71%. Conclusions: The Safe Passage Study is the first multi-site study of SIDS and stillbirth to integrate prospectively collected exposure information with multidisciplinary biological information in the same maternal and fetal/ infant dyad using a common protocol. Essential components of the study design and its success are close ties to the community and rigorous systems and processes to ensure compliance with the study protocol and procedures.

Objective To evaluate nuchal translucency measurement quality assurance techniques in a large-scale study. Methods From 1999 to 2001, unselected patients with singleton gestations between 10 + 3 weeks and 13 + 6 weeks were recruited from 15 centers. Sonographic nuchal translucency measurement was performed by trained technicians. Four levels of quality assurance were employed: (1) a standardized protocol utilized by each sonographer; (2) local-image review by a second sonographer; (3) central-image scoring by a single physician; and (4) epidemiological monitoring of all accepted nuchal translucency measurements cross-sectionally and over time. Results Detailed quality assessment was available for 37 018 patients. Nuchal translucency measurement was successful in 96.3% of women. Local reviewers rejected 0.8% of images, and the single central physician reviewer rejected a further 2.9%. Multivariate analysis indicated that higher body mass index, earlier gestational age and transvaginal probe use were predictors of failure of nuchal translucency measurement and central image rejection (P = 0.001). Epidemiological monitoring identified a drift in measurements over time. Conclusion Despite initial training and continuous image review, changes in nuchal translucency measurements occur over time. To maintain screening accuracy, ongoing quality assessment is needed. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Background: Analysis of fetal DNA from maternal plasma by PCR offers great potential for noninvasive prenatal genetic diagnosis. To further evaluate this potential, we developed and validated a standard protocol to determine whether fetal DNA sequences could be reproducibly amplified and measured across multiple laboratories in a common set of specimens. Methods: Each of five participating centers in a National Institute of Child Health and Human Development consortium collected 20 mL of peripheral blood from 20 pregnant women between 10 and 20 weeks of gestation. The plasma fraction was separated according to a common protocol, divided, and frozen in five aliquots. One aliquot was shipped to each participating laboratory, where DNA was extracted according to a standard protocol. All plasma samples (n = 100) were then analyzed blindly for the presence and quantity of total DNA (GAPDH) and male fetal DNA (SRY) by real-time PCR. Genomic DNA was isolated from female and male cells at one center, quantified, and shipped to the others to serve as calibrators for GAPDH and SRY, respectively. Results: The amplification of known quantities of DNA was consistent among all centers. The mean quantity of male DNA amplified from maternal plasma when the fetus was male ranged from 51 to 228 genome equivalents (GE)/mL. Qualitative concordance was found overall among centers. The sensitivity of the assay for detection of male DNA when the fetus was male varied from 31% to 97% among centers. Specificity was more consistent (93–100%) with only four false-positive results obtained across the entire study. Conclusions: All centers were able to consistently amplify frozen and shipped DNA. The PCR procedure used here is reliable and reproducible. Centers that extracted and amplified more DNA per milliliter of maternal plasma had superior sensitivities of Y chromosome sequence detection. The specificity of the assay was more consistent among centers. A robust and thoroughly optimized protocol for the extraction of DNA from maternal plasma is needed to make testing of fetal DNA in maternal plasma a clinically relevant analytical tool.

BACKGROUND We investigated agreement between self-reported prenatal alcohol exposure (PAE) and objective meconium alcohol markers to determine the optimal meconium marker and threshold for identifying PAE. METHODS Meconium fatty acid ethyl esters (FAEE), ethyl glucuronide (EtG), and ethyl sulfate (EtS) were quantified by LC-MS/MS in 0.1 g meconium from infants of Safe Passage Study participants. Detailed PAE information was collected from women with a validated timeline follow-back interview. Because meconium formation begins during weeks 12–20, maternal self-reported drinking at or beyond 19 weeks was our exposure variable. RESULTS Of 107 women, 33 reported no alcohol consumption in pregnancy, 16 stopped drinking by week 19, and 58 drank beyond 19 weeks (including 45 third-trimester drinkers). There was moderate to substantial agreement between self-reported PAE at ≥19 weeks and meconium EtG ≥30 ng/g (κ = 0.57, 95% CI 0.41–0.73). This biomarker and associated cutoff was superior to a 7 FAEE sum ≥2 nmol/g and all other individual and combination marker cutoffs. With meconium EtG ≥30 ng/g as the gold standard condition and maternal self-report at ≥19 weeks' gestation as the test condition, 82% clinical sensitivity (95% CI 71.6–92.0) and 75% specificity (95% CI 63.2–86.8) were observed. A significant dose–concentration relationship between self-reported drinks per drinking day and meconium EtG ≥30 ng/g also was observed (all P < 0.01). CONCLUSIONS Maternal alcohol consumption at ≥19 weeks was better represented by meconium EtG ≥30 ng/g than currently used FAEE cutoffs.

Data from large-scale registers is often underutilized when evaluating addiction treatment programs. Since many programs collect register data regarding clients and interventions, there is a potential to make greater use of such records for program evaluation. The purpose of this article is to discuss the value of using large-scale registers in the evaluation and program planning of addiction treatment systems and programs. Sweden is used as an example of a country where register data is both available and is starting to be used in national evaluation and program planning efforts. The article focuses on possibilities, limitations and practicalities when using large-scale register data to conduct evaluations and program planning of addiction treatment programs. Main conclusions are that using register data for evaluation provides large amounts of data at low cost, limitations associated to the use of register data may be handled statistically, register data can answer important questions in planning of addiction treatment programs, and more accurate measures are needed to account for the diversity of client populations.

Objectives The National Institute of Child Health and Human Development Fetal Cell Isolation Study (NIFTY) is a prospective, multicenter clinical project to develop non-invasive methods of prenatal diagnosis. The initial objective was to assess the utility of fetal cells in the peripheral blood of pregnant women to diagnose or screen for fetal chromosome abnormalities. Methods Results of fluorescence in situ hybridization (FISH) analysis on interphase nuclei of fetal cells recovered from maternal blood were compared to metaphase karyotypes of fetal cells obtained by amniocentesis or chorionic villus sampling (CVS). After the first 5 years of the study we performed a planned analysis of the data. We report here the data from 2744 fully processed pre-procedural blood samples; 1292 samples were from women carrying singleton male fetuses. Results Target cell recovery and fetal cell detection were better using magnetic-based separation systems (MACS) than with flow-sorting (FACS). Blinded FISH assessment of samples from women carrying singleton male fetuses found at least one cell with an X and Y signal in 41.4% of cases (95% CI: 37.4%, 45.5%). The false-positive rate of gender detection was 11.1% (95% CI: 6.1,16.1%). This was higher than expected due to the use of indirectly labeled FISH probes in one center. The detection rate of finding at least one aneuploid cell in cases of fetal aneuploidy was 74.4% (95% CI: 76.0%, 99.0%), with a false-positive rate estimated to be between 0.6% and 4.1%. Conclusions The sensitivity of aneuploidy detection using fetal cell analysis from maternal blood is comparable to single marker prenatal serum screening, but technological advances are needed before fetal cell analysis has clinical application as part of a multiple marker method for non-invasive prenatal screening. The limitations of the present study, i.e. multiple processing protocols, are being addressed in the ongoing study. Copyright © 2002 John Wiley & Sons, Ltd.

Purpose: The NICHD Fetal Cell Isolation Study (NIFTY) was a multicentered project to isolate fetal cells from maternal blood to detect fetal chromosomal abnormalities. The project included a psychosocial component, which is the basis of this article. We examined the attitudes of high-risk pregnant women toward the availability of a maternal blood test to identify fetal chromosomal abnormalities, how women would respond to hypothetical normal and abnormal maternal blood testing results, and the factors associated with a woman's preference to have an invasive procedure in response to a normal maternal blood test. Methods: High-risk pregnant women (N = 854) planning to have prenatal diagnostic invasive testing (amniocentesis or chorionic villus sampling) completed a survey. Results: The women highly favored maternal blood testing. Almost all women would seek invasive testing after an abnormal blood test. Only half of the women would seek invasive testing after a normal blood test; these women were older, more willing to terminate their pregnancy, and valued the increased accuracy of invasive testing more highly than women who would not have invasive testing after a normal maternal blood test. Conclusions: Women having invasive diagnostic testing welcome a noninvasive procedure that uses fetal cells in maternal blood, and its availability would decrease invasive testing by approximately 50%. Research needs to examine the attitudes and anticipated responses of other risk groups as well as the effects of information about maternal blood test sensitivity and specificity on attitudes and responses.

Objectives. Numerous studies have demonstrated the importance of comorbid illness when analyzing medical outcomes. The purpose of this study was to adapt a generic comorbidity index, the Total Illness Burden Index (TIBI), for use in men with prostate cancer, and to evaluate the usefulness of the new instrument in adjusting for the impact of comorbidity on functional outcomes in a prostate cancer cohort. Methods. The TIBI uses patients’ self-report of symptoms and diagnoses to determine not only the presence but also the severity of comorbidities in each of 16 body system domains. To create the TIBI-P (prostate cancer modification), some domains were added and others were modified according to clinical criteria. The TIBI-P was completed by 1638 men with prostate cancer followed up longitudinally in 29 urology practices in the United States. TIBI-P scores were calculated for each patient and analyzed with scores on the SF-36 quality-of-life questionnaire and with patient report of days confined to bed. Results. After adjusting for age and income, lower SF-36 scale scores and increases in confinement to bed were associated with a greater burden of comorbid illness as measured by the TIBI-P, independent of the extent of prostate cancer. The TIBI-P explained 24% of the variance in the SF-36 physical functioning domain score. Conclusions. The TIBI-P is a powerful measure of the impact of comorbid illness on the quality of life and functioning among patients with prostate cancer. This index may prove valuable in research on clinical and economic outcomes of prostate cancer.

Importance The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. Objective To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. Design, Setting, and Participants Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression–Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children’s Yale-Brown Obsessive-Compulsive Scale. Interventions Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). Main Outcomes and Measures A positive response was defined as having a score of at least much improved on the Clinical Global Impression–Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale–Revised, and the Children’s Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. Results Several baseline predictors of response were identified, and a principal component analysis yielded 3 composite measures (disruptive behavior, autism/mood, and caregiver strain) that significantly predicted response at week 12. Specifically, participants in the placebo group were significantly less likely than participants in the citalopram group to respond at week 12 if they entered the study more symptomatic on each of the 3 composite measures, and they were at least 2 times less likely to be responders. Conclusions and Relevance This analysis suggests strategies that may be useful in anticipating and potentially mitigating the nonspecific response in randomized clinical trials of children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier:NCT00086645

This study explores the manifestation and measurement of anxiety symptoms in 415 children with ASDs on a 20-item, parent-rated, DSM-IV referenced anxiety scale. In both high and low-functioning children (IQ above vs. below 70), commonly endorsed items assessed restlessness, tension and sleep difficulties. Items requiring verbal expression of worry by the child were rarely endorsed. Higher anxiety was associated with functional language, IQ above 70 and higher scores on several other behavioral measures. Four underlying factors emerged: Generalized Anxiety, Separation Anxiety, Social Anxiety and Over-arousal. Our findings extend our understanding of anxiety across IQ in ASD and provide guidance for improving anxiety outcome measurement.

OBJECTIVES: To determine the extent to which family members participate in the day-to-day management of diabetes mellitus in older persons, and in older diabetics' medical encounters, and to identify patient and family member characteristics associated with this participation. DESIGN: A longitudinal observational study, with baseline data being reported herein. SETTING: Three primary care practice settings in Seattle, Washington, Boston, Massachusetts, and Indianapolis, Indiana. PARTICIPANTS: Family members of patients 70 years of age or older participating in the Patient Outcomes Research Team (PORT) Study of type II diabetics. MAIN OUTCOME MEASUREMENTS: The two dependent variables represent, respectively, the extent of family members' assistance with diabetes-related care and participation in older diabetics' medical encounters. RESULTS: The 357 family members enrolled were older (mean age = 66.3 years), were mostly women (76.2%), and were usually the spouses of diabetic patients (71.3%). Between 22% and 50% of family members reported helping with various aspects of diabetes care; 35.6% of family members participated regularly in their diabetic patients' medical encounters. A multiple linear regression model relating family assistance with diabetes-related care to patient and family member characteristics included four variables: patients' physical function, and the family member's relationship to the patient, assistance with basic activities of daily living (ADLs), and understanding of diabetes management issues (all P < .05). A multiple logistic regression model relating family member participation in the medical encounter to patient and family member characteristics also included four variables: patient age and physical function, and family member assistance with instrumental activities of daily living (IADLs) and with diabetes-related care (all P < .05). CONCLUSION: The family members studied frequently assisted older diabetics with diabetes-specific care; more than one-third were regular participants in older diabetics' medical encounters. Family member involvement in the day-to-day management of diabetes and in the medical encounter was more likely when patients were functionally disabled. Health care systems and physicians need to educate their older patients, and involved family members when patients are frail, about diabetes-related care issues and support them in their roles in the management of diabetes as well as other chronic diseases. J Am Geriatr Soc 44:1314–1321, 1996.

Although the numbers of women in training and in entry-level academic positions in medicine have increased substantially in recent years, the proportion of women in senior faculty positions has not changed. We conducted a study to determine the contributions of background and training, academic productivity, distribution of work time, institutional support, career attitudes, and family responsibilities to sex differences in academic rank and salary among faculty members of academic pediatric departments.We conducted a cross-sectional survey of all salaried physicians in 126 academic departments of pediatrics in the United States in January 1992. Of the 6441 questionnaires distributed, 4285 (67 percent) were returned. The sample was representative of U.S. pediatric faculty members. Multivariate models were used to relate academic rank and salary to 16 independent variables.Significantly fewer women than men achieved the rank of associate professor or higher. For both men and women, higher salaries and ranks were related to greater academic productivity (more publications and grants), more hours worked, more institutional support of research, greater overall career satisfaction, and fewer career problems. Less time spent in teaching and patient care was related to greater academic productivity for both sexes. Women in the low ranks were less academically productive and spent significantly more time in teaching and patient care than men in those ranks. Adjustment for all independent variables eliminated sex differences in academic rank but not in salary.Lower rates of academic productivity, more time spent in teaching and patient care and less time spent in research, less institutional support for research, and lower rates of specialization in highly paid subspecialties contributed to the lower ranks and salaries of female faculty members.

The Studies to Advance Autism Research and Treatment Network conducted a randomized trial with citalopram in children with Pervasive developmental disorders (PDDs). We present the rationale, design and sample characteristics of the citalopram trial. Subjects (128 boys, 21 girls) had a mean age of 9.3 (±3.12) years; 132 (88.6%) were diagnosed with autistic disorder (4.7% with Asperger’s Disorder; 6.7% with PDD-not otherwise specified). Less than half of the subjects were intellectually disabled; 117 (78.5%) were rated Moderate or Marked on the Clinical Global Impression for Severity. Study measures were similar to previous Research Units on Pediatric Psychopharmacology trials. Subjects in this trial were slightly older and more likely to have complaints of repetitive behavior than participants in RUPP trials.

Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders.To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders.National Institutes of Health-sponsored randomized controlled trial.Six academic centers, including Mount Sinai School of Medicine, North Shore-Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School.One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders.Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d).Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form.There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P.99). There was no difference in score reduction on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], -2.0 [3.4] points for the citalopram-treated group and -1.9 [2.5] points for the placebo group; P = .81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus.Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier: NCT00086645.

This study examined whether psychosocial variables predict pregnant women's attitudes toward maternal serum screening and invasive diagnostic testing, beyond the influence of traditional obstetric risk status (based on advanced maternal age, history of genetic disorders, etc.). In a sample of 612 pregnant women (66.5% high risk, 33.5% low risk) we assessed responses to hypothetical scenarios of invasive testing following normal or abnormal maternal serum screening. We also assessed psychosocial variables stemming from the theory of planned behavior (e.g., knowledge, concern for fetus, attitudes toward termination, health locus of control). Overall, two thirds of the women would want serum screening. Follow-up invasive diagnostic testing would be sought by 37.2% of the women after a negative screening, and by 75.0% after a positive screening. As expected, traditional risk status predicted desire for screening and also invasive testing following either a negative or positive screen. Yet, controlling for risk status, many psychosocial variables predicted a women's interest in screening and in invasive testing: more knowledge about prenatal testing, concern about fetal health, willingness to terminate a pregnancy, and an internal or medical profession health locus of control. We conclude that psychosocial variables influence women's desire for screening or invasive testing beyond traditional risk status.

background It is uncertain how best to screen pregnant women for the presence of fetal Down’s syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters. methods Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency). results First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down’s syndrome. At a 5 percent false positive rate, the rates of detection of Down’s syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening. conclusions First-trimester combined screening at 11 weeks of gestation is better than secondtrimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down’s syndrome, with low false positive rates.

To estimate prevalence, natural history, and outcome of septated cystic hygroma in the first trimester in the general obstetric population, and to differentiate this finding from simple increased nuchal translucency.Patients at 10.3-13.6 weeks of gestation underwent nuchal translucency sonography as part of a multicenter clinical trial. Septated cystic hygroma cases were offered chorionic villi sampling for karyotype, and targeted fetal anatomical and cardiac evaluations. Survivors were followed up for fetal and long-term pediatric outcome (median 25 months, range 12-50 months). Cases of septated cystic hygroma were also compared with cases of simple increased nuchal translucency.There were 134 cases of cystic hygroma (2 lost to follow-up) among 38,167 screened patients (1 in 285). Chromosomal abnormalities were diagnosed in 67 (51%), including 25 trisomy-21, 19 Turner syndrome, 13 trisomy-18, and 10 others. Major structural fetal malformations (primarily cardiac and skeletal) were diagnosed in 22 of the remaining 65 cases (34%). There were 5 cases (8%) of fetal death and 15 cases of elective pregnancy termination without evidence of abnormality. One of 23 (4%) normal survivors was diagnosed with cerebral palsy and developmental delay. Overall, survival with normal pediatric outcome was confirmed in 17% of cases (22 of 132). Compared with simple increased nuchal translucency, cystic hygroma has 5-fold, 12-fold, and 6-fold increased risk of aneuploidy, cardiac malformation, and perinatal death, respectively.First-trimester cystic hygroma was a frequent finding in a general obstetric screening program. It has the strongest prenatal association with aneuploidy described to date, with significantly worse outcome compared with simple increased nuchal translucency. Most pregnancies with normal evaluation at the completion of the second trimester resulted in a healthy infant with a normal pediatric outcome.

The Gram–Schmidt process is a technique for constructing an orthogonal basis from a basis spanning the same subspace. The technique is used in a number of multivariate applications including battery reduction analyses and multiple regression applications. In the former, the goal is to reduce the number of variables at the same time explaining as much variance in the original variables as possible. In the latter, the goal is to reduce the n-dimensional space (observations) to a p-dimensional space (independent variables). Keywords: orthogonalization; principal components analysis; battery reduction

Cronbach's alpha is used to assess the internal consistency reliability of a multiple item instrument. A multiple item instrument is internally consistent if its items are highly correlated. Cronbach's alpha is computed as the ratio of the true variation to the total variation. Keywords: latent variable; true score; multiple-item scale; measurement error; psychometrics; principal components analysis; reliability; split-half reliability; rating scales; composite scores

Debate continues over whether to screen pregnant women for fetal Down syndrome in the first or the second trimester of pregnancy or in both trimesters. The First- and Second-Trimester Evaluation of Risk Factors (FASTER) Trial obtained direct comparative data on current screening methods from 38,167 women with singleton pregnancies who were cared for at 15 U.S. centers over approximately 3 years in 1999-2002. Down syndrome was found in 117 instances. Inclusion criteria included a maternal age of 16 or older and a fetal crown-rump length of 36 to 79 mm-consistent with a gestational age of 10 weeks 3 days through 13 weeks 6 days. First-trimester screening combined measurement of the nuchal translucency with maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβhCG) levels. Quadruple screening in the second trimester, from 15 to 18 weeks gestation, included alpha-fetoprotein, total hCG, unconjugated estriol, and inhibin. Stepwise sequential screening, in which the Down syndrome risk estimate was provided after each test, was compared with "fully integrated" screening, which yielded only a single risk result after both the first- and second-trimester screening tests had been done. Although first-trimester serum screening and measurement of nuchal translucency gave similar results, the combination proved to be superior for detecting Down syndrome at 11 to 13 weeks gestation. When the false-positive rate was 5%, first-trimester combined screening at 11,12, and 13 weeks identified 87%, 85%, and 82% of Down syndrome cases, respectively. The detection rate for second-trimester quadruple screening was 81%. Quadruple screening outperformed triple screening, resulting in a higher detection rate at a lower false-positive rate. With fully integrated screening, in which the first-trimester studies were performed at 11 weeks gestation, 96% of cases were detected. For women younger than 35 years of age, first-trimester combined screening detected 75% of cases at a 5% false-positive rate, compared with 77% and 2.3%, respectively, for second-trimester quadruple screening and 77% and 0.4% for fully integrated screening. In women aged 35 and older, first-trimester combined screening detected 95% of cases with a false-positive rate of 22%. The respective figures for second-trimester quadruple screening were 92% and 13%, and for integrated screening with first-trimester markers measured at 11 weeks, 91% and 2%. In stepwise sequential screening, women have combined screening in the first trimester and results are provided immediately. Women with positive results are offered chorionic villus sampling. Women with negative results return at 15 weeks for quadruple testing, and a combined risk estimate is provided at that time. Using this approach and setting the false-positive rate for each component at 2.5%, 95% of cases were detected with a false-positive rate of 4.9%. For fully integrated screening, in which both first- and second-trimester tests are done but the woman gets only one risk estimate after the second-trimester tests are completed, setting the Down syndrome detection rate at 95% resulted in a false-positive rate of 4%. First-trimester combined screening is an effective means of detecting Down syndrome, assuming that there is adequate quality control for measuring nuchal translucency. Both stepwise sequential screening and fully integrated screening have high detection rates at acceptably low false-positive results. The lower false-positive rate must be weighed against the advantages of earlier diagnosis using sequential screening.

To test the hypothesis that a delay in initial fetal cell enrichment processing of maternal blood samples (defined as the time between blood draw and the initial density gradient centrifugation step) compromises the ability to recover fetal cells, we performed a randomized comparison of immediate (within 4 hours of draw) versus delayed (between 18-24 hours of draw) processing. Four centers participated: two centers utilized flow cytometry (FLOW), and two centers utilized magnetic-activated cell sorting (MACS) techniques. Each center collected 34 samples. The outcome was the percentage of gamma positive (γ+) cells for FLOW or the number of nucleated red blood cells (NRBCs)for MACS, found in the final enriched cell population. Both outcomes reflect cell properties that are potentially fetal in origin, thus making them representative of the ability to recover fetal cells. Our results did not support our hypothesis that delay in processing compromises fetal cell recovery. Instead, in MACS processing, we observed an increase in recovered NRBCs when blood sample processing was delayed compared with immediate processing. There was no significant difference in 7 cells with FLOW. Time-related changes in the density of target cells, perhaps associated with their progress towards apoptosis during the delay period, may result in increased intact fetal cells with the study methods utilized. (J Soc Gynecol Investig 2004; 11:154-65)

The MedTeams project is a translational research effort to apply crew resource management (CRM) behavioral principles developed in aviation to emergency medical care. Hospital emergency departments share many of the same characteristics with workplaces where CRM is effective, such as time-stress, dispersed and complex information, multiple players, and high-stakes outcomes. Preliminary observations in emergency departments (ED) established that the same CRM behaviors employed by highly effective aviation teams could be useful in the ED (Weiner, Kanki, and Helmreich 1993; Simon, Morey, and Locke 1997). A retrospective review of ED closed claims revealed that failure to engage in one or more of these teamwork behaviors was associated with an adverse event and indemnity payments. In 43 percent of the cases reviewed, teamwork behaviors would have prevented or mitigated the adverse event had they been applied (Risser, Rice et al. 1999). Similar analyses attribute about 80 percent of anesthesia mishaps to human error and 70 percent of commercial aviation accidents to crew errors (Gardner-Bonneau 1993; Taggart 1994). Crew training has led to reductions in aviation mishaps beyond those produced by improvements in equipment and technology. The aviation community began introducing CRM training two decades ago and it is now required for all military and commercial U.S. aviation crews and air carriers operating internationally (Helmreich and Foushee 1993; Helmreich 1997). The basic principle of CRM is that crew communication and coordination behaviors are identifiable, teachable, and applicable to high-stakes environments. An additional principle is that those behaviors, although seen spontaneously, are not practiced reliably, regularly, or well unless specific training and reinforcement has established them. Specific CRM behaviors have been identified through experimentation and observation of high-reliability teams in demanding, time-stressed environments such as combat aviation and naval command and control centers (Leedom and Simon 1995; McIntyre and Salas 1995). Crew resource management training has been shown to be effective in these environments and is being extended into other domains (Helmreich and Foushee 1993; Salas et al. 1999). Finally, an essential principle of CRM is that a team needs to be formally established for teamwork behaviors to be effective. In contrast to the notion of a team as any loosely coordinated group of caregivers and support staff, the formal teamwork structure of this study stipulates that a team be made up of between 3 to 10 members. A team is composed of physicians, nurses, and technicians who are organized for a shift. The number of designated teams for a shift depends on factors such as staffing levels and patient volume. From these larger teams, ad hoc teams are formed to respond to emergent events such as resuscitations. In this model, teamwork is sustained by a shared set of teamwork skills rather than permanent assignments that carry over from day to day. Teamwork theory development has focused on input variables affecting team functioning such as task, work environment, and team member characteristics (Salas et al. 1992), what and how to train (Salas and Cannon-Bowers 2001), and outcome constructs of teamwork effectiveness (McIntyre, Salas 1995). Explanatory mechanisms of team processes exist in the form of constructs such as situational awareness and shared mental models, but relating team processes to work productivity outcomes has been limited by measurement difficulties with these constructs. Because this study examined the applicability of CRM to health care, a goal of this study was to generate a set of testable teamwork process–outcome propositions for future healthcare research. With respect to the training intervention, we sought to gain insight into the effectiveness of the training materials and methods, and features of the curriculum that needed revision. In addition, we sought to determine if the training intervention changed staff attitudes and behaviors and had an impact on patient care. These complementary perspectives are referred to as formative and summative evaluation in the education research literature (Bloom, Hastings, and Madaus 1971). The first objective of this study was to adapt an aviation-oriented teamwork curriculum to the particular circumstances of EDs by developing and then implementing a training curriculum (Emergency Team Coordination Course [ETCC]) organized around five team dimensions (maintain team structure and climate, apply problem-solving strategies, communicate with the team, execute plans and manage workload, and improve team skills) (Risser, Rice et al. 1999; Risser, Simon et al. 1999). The second objective was to evaluate the effectiveness of the intervention with measures developed to address three outcome constructs: Team Behaviors, Attitudes and Opinions, and ED Performance.

Osteonecrosis of the femoral head is an important complication of sickle cell disease. We studied 2590 patients who were over 5 years of age at entry and followed them for an average of 5.6 years. Patients were examined twice a year, and radiographs of the hips were taken at least twice: at study entry and approximately three years later.At study entry, 9.8 percent of patients were found to have osteonecrosis of one or both femoral heads. On follow-up, patients with the hemoglobin SS genotype and alpha-thalassemia were at the greatest risk for osteonecrosis (age-adjusted incidence rate, 4.5 cases per 100 patient-years, as compared with 2.4 in patients with the hemoglobin SS genotype without alpha-thalassemia and 1.9 in those with the hemoglobin SC genotype). Although the rate of osteonecrosis in patients with the hemoglobin SC genotype did not differ significantly from that in patients with the hemoglobin SS genotype without alpha-thalassemia, osteonecrosis tended to develop in these patients later in life. Intermediate rates of osteonecrosis were observed among patients with the hemoglobin S-beta zero-thalassemia and the hemoglobin S-beta(+)-thalassemia genotypes (3.6 and 3.3 cases per 100 patient-years, respectively). Osteonecrosis was found in patients as young as five years old (1.8 cases per 100 patient-years for all genotypes). The frequency of painful crises and the hematocrit were positively associated with osteonecrosis. The mean corpuscular volume and serum aspartate aminotransferase level were negatively associated. Twenty-seven patients had hip arthroplasty during the study; 10 were under 25 years of age. Five of the 27 required reoperation 11 to 53 months after the initial operation.Osteonecrosis of the femoral head is common in patients with sickle cell disease, with an incidence ranging from about 2 to 4.5 cases per 100 patient-years. Patients with the hemoglobin SS genotype and alpha-thalassemia and those with frequent painful crises are at highest risk. The overall prevalence is about 10 percent. The results of hip arthroplasty are poor.

TRANSLUCENCY (NT) SONOGRAPHY FERGAL D. MALONE, HOWARD CUCKLE, ROBERT H. BALL, DAVID A. NYBERG, CHRISTINE H. COMSTOCK, RADEK BUKOWSKI, KEITH EDDLEMAN, SUSAN J. GROSS, LORRAINE DUGOFF, SABRINA D. CRAIGO, ILAN E. TIMOR, STEPHEN R. CARR, HONOR M. WOLFE, KIMBERLY A. DUKES, MARY E. D’ALTON, Royal College of Surgeons in Ireland, Dublin, Ireland, University of Leeds, Leeds, United Kingdom, University of Utah, Salt Lake City, Utah, Swedish Medical Center, Seattle, Washington, William Beaumont Hospital, Royal Oak, Michigan, University of Texas Medical Branch at Galveston, Galveston, Texas, Mount Sinai School of Medicine, New York, New York, Albert Einstein College of Medicine, Bronx, New York, University of Colorado Health Sciences Center, Denver, Colorado, Tufts University, Boston, Massachusetts, NYU Medical Center, New York, New York, Brown University, Providence, Rhode Island, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, DMSTAT, Boston, Massachusetts, Columbia University, New York, New York OBJECTIVE: To compare the two most commonly used approaches for interpretation of nuchal translucency (NT) sonography for Trisomy-21 risk assessment: multiples of the median (MoM) and Delta NT (NT). STUDY DESIGN: 35,087 patients had NT at 11-13 wks, including 116 cases of Trisomy-21. NT measurements were converted to both MoM and NT. NT MoMs were used with Gaussian likelihood ratios (LRs), and NTs were used with empirical LRs from a large prospective study (Spencer et al, Ultrasound Obstet Gynecol, 2003;22:142), to generate individualized patient risk estimates for Trisomy-21. A 1:270 mid-trimester risk cut-off was used to define screen positivity. RESULTS: NT distribution in unaffected pregnancies was not constant, with inter-tertile ranges of 0.67, 0.75 and 0.83 mm at 11, 12 and 13 wks respectively. The sensitivity of NT with maternal age using NT and empirical LRs was 66% (3.1% FPR), compared with 78% (8.2% FPR) when using NT MoM and Gaussian LRs. At a fixed 5% FPR, detection rates were 71% and 72% respectively. The observed prevalence of Trisomy-21 was closer to that expected from NT MoM-based risks than with the NT approach (see Table). CONCLUSION: Calculating individualized patient risk for Trisomy-21 using NT MoMs is superior to use of NT, with more cases detected, and more accurate risk estimates. (NIH-RO1-HD-38652)

The prevalence and incidence of osteonecrosis (ON) of the humeral head in sickle cell disease was determined by a study of 2524 patients who were entered into a prospective study and followed for an average of 5.6 years. At entry, 5.6% had roentgenographic evidence of ON in one or both shoulders. There was little difference in age-adjusted prevalence among genotypes, but there were striking differences in age-specific rates. Observed at ages ranging from five to 24 years, 3.25% of sickle cell anemia (S/S) patients, but only 1.1% of sickle cell disease (S/C) patients, had ON. No S/beta+ thalassemia patients younger than 25 years of age had ON on entry. The highest age-adjusted incidence rate was found in S/S patients with concomitant alpha-thalassemia (4.85 per hundred patient-years), followed by S/beta zero-thalassemia (4.84 per hundred patient-years), S/beta+ thalassemia (2.61 per hundred patient-years), S/S without alpha-thalassemia (2.54 per hundred patient-years), and S/C (1.66 per hundred patient-years). Only 20.9% of patients reported pain or had limited range of movement at the time of diagnosis. Sickle cell disease is a frequent cause of ON of the humeral head, especially in children and young adults.