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For non-persistent chemicals such as phthalates, a single spot urine sample only reflects exposure in the past few hours. Collecting repeated urine samples for each participant over windows of sensitivity is expected to improve exposure characterization but has rarely been done. We aimed to rely on within-subject pools of repeated urine samples to assess phthalate exposure during pregnancy and infancy. Women of the French SEPAGES mother-child cohort were asked to collect three urine samples per day over seven consecutive days, twice during their pregnancy (approximatively second (T2) and third (T3) trimesters). For their infants they also collected one sample per day during a week at two (M2) and twelve months (M12). Samples were pooled (within-subject, within-period) prior to phthalate and DINCH metabolite concentrations assessment. Number of pooled samples assayed was 477, 456, 152 and 100 for T2, T3, M2 and M12, respectively. All metabolites were detected in more than 95% of the pooled samples except for the two DINCH metabolites (oh- and oxo-MINCH), MMCHP and oh-MPHP at M2 for which detection frequencies ranged between 64% and 88%. Maternal concentrations of MiBP, MBzP, DEHP metabolites and oxo-MiNP decreased between 2014 and 2017, whereas concentrations of oh-MiNP and the two DINCH metabolites increased (Mann-Kendall p-values, Graphical abstract Image 1, Highlights • Repeated urine samples were collected and pooled within-subject, within period. • Metabolites of phthalates and DINCH were measured in pooled samples. • Frequencies of detection were overall high. • Pregnancy concentrations of MiBP, MBzP, DEHP and oxo-MINP decreased with time. • Pregnancy concentrations of oh-MiNP and DINCH metabolites increased with time., Relying on a recent cohort (2014–2017) with repeated urine samples collected during pregnancy and infancy, we showed that exposure to phthalates and DINCH is still widespread in the general population.

The human exposome affects child development and health later in life, but its personal external levels, variability, and correlations are largely unknown. We characterized the personal external exposome of pregnant women and children in eight European cities. Panel studies included 167 pregnant women and 183 children (aged 6-11 years). A personal exposure monitoring kit composed of smartphone, accelerometer, ultraviolet (UV) dosimeter, and two air pollution monitors were used to monitor physical activity (PA), fine particulate matter (PM2.5), black carbon, traffic-related noise, UV-B radiation, and natural outdoor environments (NOE). 77% of women performed the adult recommendation of >= 150 min/week of moderate to vigorous PA (MVPA), while only 3% of children achieved the childhood recommendation of >= 60 min/day MVPA. 11% of women and 17% of children were exposed to daily PM2.5 levels higher than recommended >= 25 mu g/m(3)). Mean exposure to noise ranged from Lden 51.1 dB in Kaunas to Lden 65.2 dB in Barcelona. 4% of women and 23% of children exceeded the recommended maximum of 2 Standard-Erythemal-Dose of UV-B at least once a week. 33% of women and 43% of children never reached the minimum NOE contact recommendation of >= 30 min/week. The variations in air and noise pollution exposure were dominated by between-city variability, while most of the variation observed for NOE contact and PA was between-participants. The correlations between all personal exposures ranged from very low to low (Rho

International audience; Introduction: Hypertensive disorders during pregnancy are one of the leading causes of maternal and offspring mortality and morbidity. Exposure to environmental chemicals is suspected to increase blood pressure (BP) but few studies have investigated the impact of non-persistent chemicals, in particular among pregnant women.Methods: Women included in the study were 152 volunteer participants in the Human Early-Life Exposome (HELIX) project. They provided 3 urine samples daily over one week in two pregnancy trimesters (at around 18 and 32 weeks of gestation) to assess their exposure to phthalates (10 metabolites), phenols (7 compounds) and organophosphate pesticides (4 metabolites). BP was measured at the end of the two collection weeks. Associations between biomarkers of exposure and BP were investigated using generalized estimating equations (GEE) and linear regression, and adjusted for potential confounders.Results: A significant decrease in systolic and/or diastolic BP was observed with exposure to some phthalate metabolites, BPA, and parabens (e.g. β GEE models for systolic BP = -0.91 mmHg (95%CI: -1.65; -0.17) per doubling of BPA concentrations). These associations were more frequently observed in the second trimester of pregnancy and remained statistically significant after correction for multiple testing for BPA only. No associations were observed with organophosphate pesticides.Conclusion: This study investigates the effect of exposure to non-persistent chemicals assessed using multiple biospecimens per subject on BP during pregnancy and suggests that higher exposure to some phthalates and phenols but not pesticides is associated with lower BP during pregnancy.

Background Although atopic dermatitis (AD) often starts in early childhood, detailed tissue profiling of early-onset AD in children is lacking, hindering therapeutic development for this patient population with a particularly high unmet need for better treatments. Objective We sought to globally profile the skin of infants with AD compared with that of adults with AD and healthy control subjects. Methods We performed microarray, RT-PCR, and fluorescence microscopy studies in infants and young children ( Results Transcriptomic analyses revealed profound differences between pediatric patients with early-onset versus adult patients with longstanding AD in not only lesional but also nonlesional tissues. Although both patient populations harbored TH2-centered inflammation, pediatric AD also showed significant TH17/TH22 skewing but lacked the TH1 upregulation that characterizes adult AD. Pediatric AD exhibited relatively normal expression of epidermal differentiation and cornification products, which is downregulated in adults with AD. Defects in the lipid barrier (eg, ELOVL fatty acid elongase 3 [ELOVL3] and diacylglycerol o-acyltransferase 2 [DGAT2]) and tight junction regulation (eg, claudins 8 and 23) were evident in both groups. However, some lipid-associated mediators (eg, fatty acyl-CoA reductase 2 and fatty acid 2-hydroxylase) showed preferential downregulation in pediatric AD, and lipid barrier genes (FA2H and DGAT2) showed inverse correlations with transepidermal water loss, a functional measure of the epidermal barrier. Conclusions Skin samples from children and adult patients with AD share lipid metabolism and tight junction alterations, but epidermal differentiation complex defects are only present in adult AD, potentially resulting from chronic immune aberration that is not yet present in early-onset disease.

Background Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only T H 2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. Objective We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. Methods Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. Results In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3 + , CD11c + , and FceRI + ) than adults with AD. Similar to adults, strong activation of the T H 2 (IL-13, IL-31, and CCL17) and T H 22 (IL-22 and S100As) axes and some T H 1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of T H 17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), T H 9/IL-9, IL-33, and innate markers (IL-8) than adults ( P P Conclusion The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess T H 2 activation characterizes both, T H 9 and T H 17 are highly activated at disease initiation. Increases in IL-19 levels might link T H 2 and T H 17 activation.

Background— Interhospital transfer of acute stroke patients is becoming increasingly important as regional stroke systems of care continue to evolve. We describe the characteristics and outcomes of stroke cases transferred to hospitals participating in the Michigan Coverdell Stroke Registry. Methods and Results— Thirty-six hospitals participated in the Michigan registry during 2009 to 2011. Transfer patients were transferred from another hospital either acutely or after admission. Multivariable logistic regression was used to determine predictors of transfer and the independent association between transfer and in-hospital mortality and complications. Of 16 202 acute stroke admissions, 19.1% were transferred. Independent predictors of being transferred included younger age, hemorrhagic stroke, and higher stroke severity, but having a past history of stroke decreased the likelihood of being transferred. Transferred cases had higher in-hospital mortality (12.0% versus 6.4%; P P Conclusions— Transferred patients represent a complex admixture of patient characteristics that result in higher risks of poor outcomes. Our results suggest that it is prudent to account for patient transfer status when comparing hospital outcomes and that stroke registries need to expand their data collection capacity to provide a better understanding of the relative benefits and risks of transferring patients.

Craniosynostosis, a condition in which the cranial sutures prematurely fuse, can lead to elevated intracranial pressure and craniofacial abnormalities in young children. Currently surgical intervention is the only therapeutic option for patients with this condition. Craniosynostosis has been associated with a variety of different gene mutations and chromosome anomalies. Here we describe three cases of partial deletion of chromosome 19p. Two of the cases present with syndromic craniosynostosis while one has metopic ridging. A review of the genes involved in the rearrangements between the three cases suggests several gene candidates for craniosynostosis. CALR and DAND5, BMP regulators involved in osteoblast differentiation, and MORG1, a mediator of osteoclast dysregulation may play a role in abnormal cranial vault development. Additionally, CACNA1A, a gene that when mutated is associated with epilepsy and CC2D1A, a gene associated with non-syndromic mental retardation may contribute to additional phenotypic features seen in the patients we describe. In addition, these findings further support the need for genetic testing in cases of syndromic craniosynostosis.

Objectives. We assessed the burden of systemic lupus erythematosus (SLE) among Arab and Chaldean Americans residing in southeast Michigan. Methods. For those meeting SLE criteria from the Michigan Lupus Epidemiology and Surveillance Registry, we determined Arab or Chaldean ethnicity by links with demographic data from birth certificates and with a database of Arab and Chaldean names. We compared prevalence and incidence of SLE for Arab and Chaldean Americans with estimates for non-Arab and non-Chaldean American Whites and Blacks. Results. We classified 54 individuals with SLE as Arab and Chaldean Americans. The age-adjusted incidence and prevalence estimates for Arab and Chaldean Americans were 7.6 and 62.6 per 100 000, respectively. Arab and Chaldean Americans had a 2.1-fold excess SLE incidence compared with non-Arab and non-Chaldean American Whites. Arab and Chaldean American women had both significantly higher incidence rates (5.0-fold increase) and prevalence estimates (7.4-fold increase) than did Arab and Chaldean American men. Conclusions. Recognizing that Arab and Chaldean Americans experience different disease burdens from Whites is a first step toward earlier diagnosis and designing targeted interventions. Better methods of assigning ethnicity would improve research in this population.

The pathophysiology of nonsyndromic craniosynostosis remains poorly understood. The authors seek to understand the cause of this condition with a specific focus on how osteoclasts may contribute to craniosynostosis. Here, the authors characterize proteins differentially expressed in patent and fused cranial sutures by comparing their respective proteomes.Fused and patent suture samples were obtained from craniosynostotic patients undergoing surgery at a single academic medical center. Extracted protein from samples was interrogated using mass spectrometry. Differential protein expression was determined using maximum likelihood-based G-test with a q-value cutoffs of 0.5 after correction for multiple hypothesis testing. Immunolocalization of lead protein candidates was performed to validate proteomic findings. In addition, quantitative polymerase chain reaction analysis of corresponding gene expression of proteins of interest was performed.Proteins differentially expressed in patent versus fused sutures included collagen 6A1 (Col6A1), fibromodulin, periostin, aggrecan, adipocyte enhancer-binding protein 1, and osteomodulin (OMD). Maximum likelihood-based G-test suggested that Col6A1, fibromodulin, and adipocyte enhancer-binding protein 1 are highly expressed in patent sutures compared with fused sutures, whereas OMD is up-regulated in fused sutures compared with patent sutures. These results were corroborated by immunohistochemistry. Quantitative polymerase chain reaction data point to an inverse relationship in proteins of interest to RNA transcript levels, in prematurely fused and patent sutures that potentially describes a feedback loop mechanism.Proteome analysis validated by immunohistochemistry may provide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required.

Background and Purpose— Stroke education, 1 of 8 endorsed stroke performance measures, consists of 5 specific subcomponents: risk factors, stroke warning signs, emergency medical service activation, physician follow-up, and discharge medications. We identified predictors of stroke education performance measure compliance in the Michigan Paul Coverdell National Acute Stroke Registry. Methods— Data were collected on 9609 acute stroke admissions to 20 registry hospitals during 2008 and 2009. Predictors of measure compliance (delivery of all 5 subcomponents) were determined using multivariable logistic regression. Results— Overall compliance with the stroke education measure was 61.8% (hospital-level compliance ranged between 16% and 93%). Compliance with individual subcomponents were risk factors (65.5%), stroke warning signs (68.9%), emergency medical service activation (66.8%), physician follow-up (92.9%), and discharge medications (91.5%). Age, gender, stroke subtype, prestroke ambulation, discharge destination, and hospital size were all significant independent predictors of compliance. Stroke education was delivered less often to patients who were ≥70 years of age, nonambulatory prestroke, not discharged to home, had transient ischemic attack, or hemorrhagic stroke. Conclusions— Only 60% of patients received stroke education consistent with the endorsed performance measures. Strategies to increase stroke education, including the impact of incorporating stroke-specific education measures into hospital care protocols, should be explored.

Background B cells undergo maturation and class-switching in response to antigen exposure and T-cell help. Early B-cell differentiation has not been defined in patients with early-onset atopic dermatitis (AD). Objective We sought to define the frequency of B-cell subsets associated with progressive B-cell maturation and IgE class-switching. Methods We studied 27 children and 34 adults with moderate-to-severe AD (mean SCORAD score, 55 and 65, respectively) and age-matched control subjects (15 children and 27 adults). IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometric panel were used to determine the frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgE) levels were measured by using ImmunoCAP. Results Compared with adults, children showed T-cell predominance in the skin. Circulating CD19 + CD20 + B-cell counts were lower in patients with pediatric AD than in control subjects (24% vs 33%, P = .04), whereas CD3 + T-cell counts were higher (62% vs 52%, P = .05). A decreased B-cell/T-cell lymphocyte ratio with age was observed only in pediatric control subjects ( r = −0.48, P = .07). In pediatric patients with AD, a positive correlation was observed between B-cell/T-cell ratio and nonswitched memory B-cell counts ( r = 0.42, P = .03). Higher frequencies of positive sIgE levels were seen in pediatric patients with AD ( P P P H 1, T H 2, total IgE levels, and B-cell memory subsets. Conclusions Peripheral B and T cells are altered in pediatric patients with early AD, but T cells predominate in skin lesions.

Background and Purpose— Excessive prehospital delay between acute stroke onset and hospital arrival is an ongoing problem. Translating knowledge of stroke warning signs into appropriate action is critical to decrease prehospital delay. Our objectives were to estimate the proportion of Michigan adults who would react appropriately by calling 911 when presented with hypothetical stroke-related scenarios and to examine the association between knowledge of warning signs and calling 911. Methods— In 2004, questions regarding initial response to health-related scenarios were added to the Michigan Behavioral Risk Factor Survey, a population-based telephone survey of adults. We calculated the proportion of respondents who would call 911 in response to 3 stroke-related scenarios and examined the association between stroke warning sign knowledge and 911 activation. Results— Among 4841 adults, 27.6% (95% CI, 26.2 to 29.0) had adequate knowledge of stroke warning signs (defined as reporting 3 correct warning signs), and 14.0% (95% CI, 12.9 to 15.1) reported they would call 911 for all 3 stroke-related scenarios. Knowledge of specific stroke warning signs was only modestly associated with calling 911 in response to medical scenarios that involved the same stroke symptom (OR, 1.17 to 1.39). Even among those with adequate knowledge of stroke warning signs, only 17.6% (95% CI, 15.5 to 20.0) would call 911 for all 3 stroke scenarios. Conclusions— In this population-based survey, stroke symptom knowledge was not associated with the intent to call 911 for stroke. This study emphasizes the critical role of motivation in addition to symptom knowledge to reducing delay time to hospital arrival for stroke.

Connecticut, Michigan, and New York have successfully used Medicaid administrative data to conduct surveillance of asthma prevalence, related health service utilization and costs, and quality of asthma care. Since these assessments utilize beneficiary-level data, a wide range of population-based summaries is feasible. Opportunities exist to build upon the collective experiences of these three states to establish a national framework for asthma surveillance using Medicaid administrative data. This framework could be designed to respond to each state's unique data considerations and asthma management priorities, while establishing standardized criteria to enhance the comparability of asthma surveillance data among states. Importantly, a common asthma case definition using comparable methods is necessary to enable comparisons of prevalence estimates between states. Case definitions that could serve as the foundation for such a framework are presented. Mechanisms to foster sharing of methodologies and experiences will be instrumental for broad implementation across states. This collaboration will be of increasing importance as states experience mounting financial pressures due to increasing Medicaid enrollment and dwindling resources.

Background and Purpose— Although tissue plasminogen activator (tPA) is an effective therapy for acute ischemic stroke, treatment rates remain low. Efforts to address the underuse of tPA include public education to increase the recognition of stroke symptoms and the awareness of tPA treatment. Our objective was to determine the level of knowledge about tPA treatment for acute stroke among a representative sample of Michigan adults. Methods— The Michigan Behavioral Risk Factor Survey (BRFS) is a random-digit-dial telephone survey of adults conducted annually as part of the national BRFS. Questions regarding tPA treatment for acute stroke were included in the 2004 Michigan BRFS. We examined the prevalence of awareness using χ 2 tests and generated multivariable logistic regression models. Results— Among 4724 respondents, only 32.2% (95% CI=30.8 to 33.8%) were aware of the existence of tPA treatment for acute stroke, of whom 52.7% (50.0 to 55.4%) knew that it needed to be administered within 3 hours of symptom onset. Awareness of tPA was higher among middle aged adults, females, whites, and those with higher education and income. Awareness of the time window for tPA was higher among middle aged adults and whites. Conclusions— In this population-based survey only a third of the public were aware of tPA as a treatment for stroke, and only 1 in 6 were aware that the treatment exists and needs to be given within 3 hours of symptom onset. Continuing efforts are necessary to increase public knowledge about tPA treatment for acute stroke.

SummaryRationalePatients with fatal asthma have been hypothesized as representing two distinct subgroups according to the onset of symptoms prior to death.ObjectivesTo determine if these two groups may be reliably identified and determine if they differ clinically and pathologically.MethodsPatients with autopsies, 2–34 years of age, dying from asthma were classified slow-onset (Type 1) or rapid-onset (Type 2). The consistency of classification by two independent observers was determined. Clinical and pathologic data was compared between groups.Main resultsAmong 37 subjects there were 21 Type 1 and 16 Type 2 mortalities. Inter-observer agreement was good; κ 0.63 (95% CI 0.38, 0.87). Subjects did not differ by age, race, sex, presence of obesity, insurance status, or use of corticosteroids. Type 1 mortalities were hospitalized more (2.5+1.3 versus 0.1+0.1; p=0.048) and made more emergency room visits (10.5+4.9 versus 0.8+0.2; p=0.023) in the year prior to death than Type 2 mortalities. At autopsy, bronchial eosinophils (p

Rosacea is a common inflammatory condition characterized by transient or persistent facial erythema, telangiectasias, papules and pustules, for which an association has been reported to exist with Parkinson's disease (PD). We used a large, urban, single center, electronic medical record repository by searching the Northwestern Medicine Enterprise Data Warehouse (NMEDW) (> 4 million patients) for this association. Patients were included if they had an in-person encounter (Jan 2001 to May 2016) and with 1 year documentation of follow-up. Of these, all patients diagnosed with rosacea (ICD-9 codes: 372.31; 695.3, ICD-10 codes: L71.8; L71.9) and with a subsequent diagnosis of PD (ICD-9 code: 332; ICD-10 code: G20) were selected. Data on age, gender, race and tetracycline class therapy were collected. Adjusted odds ratio (OR) was obtained by using logistic regression analysis. A total of 815,210 patients were detected. 18,066 were diagnosed with rosacea, of whom 51 were subsequently diagnosed with PD (mean age: 74.5 years, range 53-89). A significant association between rosacea and PD was detectable after adjusting for age, gender, race and tetracycline class therapy (OR =1.7; 95%CI 1.27-2.22; p

Objective. We developed a surveillance system to investigate asthma deaths in children and young adults. Methods. A rapid asthma death notification and investigation system for Michigan was developed to identify interventions to prevent future deaths among people aged 2–34 years. Multidisciplinary panels to determine causal factors and recommend preventative actions reviewed information from death certificates, autopsies, next-of-kin interviews, and medical records. An annual report was disseminated to public health workers, health-care providers, insurers, and others. Results. Eighty-six asthma deaths in Michigan residents, aged 2–34, occurred from 2002–2004. Sixty-one next of kin were interviewed and medical records were obtained for 84 of the deceased. Summaries were prepared on each of the deceased and were reviewed by expert panels, which reached consensus on causal factors and potential preventive action for each death. Each year an annual report, which summarized the causal factors and potential preventive activity, was prepared. Conclusion. This review has informed and catalyzed interventions to improve asthma care and management in Michigan. Factors leading to the review's success and future activities are discussed.

OBJECTIVES. To describe the development and evaluation of a pilot emergency department (ED)-based asthma surveillance system for childhood asthma visits based on billing data and to illustrate how the data can be used to document trends and patterns in ED visits for asthma in children.METHODS. During 2001 and 2002, aggregate reports based on ED billing data from 3 hospitals in western Michigan were obtained from a single physician billing company. Data were tabulated and graphed to show trends in the monthly number of ED visits for asthma in children. Comparisons were made by age, gender, and site. We evaluated the system by using established guidelines.RESULTS. The data illustrated strong seasonal trends, as well as marked differences in ED use according to age and gender. The total numbers of asthma ED visits were remarkably similar between the 2 years evaluated; however, the timing and duration of the seasonal peaks differed. Our evaluation of the system found that it met many of the characteristics that define successful surveillance systems, including simplicity, flexibility, acceptability, sensitivity and positive predictive value, timeliness, and stability. However, the surveillance system's representativeness was limited by the inability to calculate valid population-based ED-visit rates. Despite this limitation, the data provided useful information by documenting the burden and demographic profile of children who use the ED for asthma care and in identifying seasonal and time-related trends.CONCLUSIONS. We were able to successfully implement a pilot ED-based surveillance system for childhood asthma visits by using billing data. This system promotes the understanding of the burden of asthma among children visiting the ED. The development of an ED-based surveillance system for childhood asthma visits using billing data is recommended, particularly when there is a desire to understand the characteristics of children with asthma who use the ED and/or a need to understand the impact of local asthma quality-improvement programs.

To obtain culture-specific information to guide the design of female condom education and distribution in transcultural urban US communities 28 African American women and 24 Puerto Rican women living in Springfield Massachusetts were enrolled in a 30-day trial of this contraceptive method. The health education component of the trial emphasized use of the female condom to protect against HIV/AIDS other sexually transmitted diseases and pregnancy. During the 30-day trial African American women used the female condom an average of 4.6 times compared with 5.7 times among Latinas. Puerto Rican respondents who did not use the device more than once were motivated primarily by their partners objections while African American women tended to focus on their own negative experiences. The majority of Puerto Rican women used indirect statements and progressive exposure to information when introducing the female condom to their partners while African Americans were more open and direct. Most participants experienced initial difficulties with the insertion process mechanics and physical experience. Both groups of women agreed that female condom users should be provided with information addressing the following five areas: general information mechanics of use protective functions and effectiveness ability to increase womens own protection and partner negotiation. All participants indicated they would recommend the female condom to a friend especially because of its ability to protect against HIV/AIDS but African American women were more aggressive in promoting the method through established womens networks in the community.

BACKGROUND Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis, and sepsis-associated ARDS is associated with significant morbidity and mortality. To date, no study has directly examined the epidemiology of ARDS in severe sepsis from the earliest presentation to the health care system, the emergency department (ED). METHODS This was a single-center retrospective, observational cohort study of 778 adults with severe sepsis presenting to the ED. The primary outcome was the development of ARDS requiring mechanical ventilation during the first 5 hospital days. Acute respiratory distress syndrome was defined using the Berlin definition. We used multivariable logistic regression to identify risk factors associated independently with ARDS development. RESULTS The incidence of ARDS was 6.2% (48/778 patients) in the entire cohort. Acute respiratory distress syndrome development varied across the continuum of care: 0.9% of patients fulfilled criteria for ARDS in the ED, 1.4% admitted to the ward developed ARDS, and 8.9% admitted to the intensive care unit developed ARDS. Acute respiratory distress syndrome developed a median of 1 day after admission and was associated with a 4-fold higher risk of in-hospital mortality (14% vs. 60%, P < 0.001). Independent risk factors associated with increased risk of ARDS development included intermediate (2-3.9 mmol/L) (P = 0.04) and high (≥4) serum lactate levels (P = 0.008), Lung Injury Prediction score (P < 0.001), and microbiologically proven infection (P = 0.01). CONCLUSIONS In patients presenting to the ED with severe sepsis, the rate of sepsis-associated ARDS development varied across the continuum of care. Acute respiratory distress syndrome developed rapidly and was associated with significant mortality. Elevated serum lactate levels in the ED and a recently validated clinical prediction score were independently associated with the development of ARDS in severe sepsis.

Objectives. To assess the proportion of adult asthma at the state level that may be related to work. Design. Work-related asthma questions were added to the 2001 Behavioral Risk Factor Surveillance System (BRFSS) questionnaire in California, Massachusetts, and Michigan. Results. Findings indicate 7.4–9.7% of those with current asthma reported that their asthma may be work related. These results estimate that approximately 137,000 adults in California, 39,000 in Massachusetts, and 63,000 in Michigan have asthma that may be work related. Conclusions. These findings are unique in providing population-based estimates at the state level that illustrate that a substantial portion of adult asthma morbidity is due to exposures in the work environment.

Objective.The purpose of this study was to describe the prevalence of asthma among children using alternative case definitions applied to administrative claims data, and to assess year-to-year classification concordance.Methods.This study was a retrospective cohort analysis of 357,729 children 0–18 years using 2001–2002 Michigan Medicaid claims. Asthma cases were classified using six alternative definitions based on outpatient, emergency department, inpatient, and pharmacy claims for asthma, including the Health Plan Employer Data Information Set (HEDIS) persistent asthma criteria commonly used for assessments of asthma health care quality: at least one asthma inpatient admission or emergency department visit, four or more asthma medications events, or four asthma outpatient visits and two asthma medication events.Results.Overall, asthma prevalence varied widely between alternative case definitions, ranging from 14.9% based on claims evidence of any type of asthma utilization to 3.7% when restricted to those with four or more asthma medication dispensing events. Among cases meeting HEDIS persistent asthma criteria in 2001, 55.5% met these criteria in 2002. Those with four or more asthma medication dispensing events had the best overall classification concordance between 2001 and 2002. Utilization of asthma services and prevalence estimates were highest among children younger than 5 years old, but year-to-year classification concordance was poorest among these cases (pConclusions.While overall asthma prevalence may remain relatively stable from year to year, individuals may not be classified consistently as cases over time, regardless of case definition. Studies that identify asthma cases in one year and assess asthma outcomes in a subsequent year may introduce substantial bias as a result of case misclassification. Among the case definitions considered in this study, our findings suggest that this bias is minimized among cases classified using the four or more asthma medication dispensing events criterion.

Abstract 905 Background. Hemopoietic allogeneic stem cell transplantation (HSCT) still remains the only available curative option for β-thalassaemia major. At today more than 3000 transplants have been performed worldwide and registered. We analyze transplant activity and outcome after 20 years of the European Hemoglobinopathy Bone Marrow Transplant (EBMT) Registry. Methods. Data have been analyzed from promise MED-A form. Survival data have been reported with the method of Kaplan-Meier in patients with complete survival data. Results. One hundred and 34 centres from 28 different countries reported their data to the registry. Three thousands and 821 (3821) consecutive first HSCT for patients affected by a hemoglobinopathy have been registered. There were only 364 (10.5%) patients aged 18 years or older. Further analyses were restricted to patients with thalassemia major and to transplants performed after January 1st, 2000. In this latter period 1493 transplants have been performed (median age 7.2 years, range 0.3–45.1) with 133 (9.8%) patients aged 18 years or older. During the last decade 70% of the transplants have been performed in Europe and 30% in Asia and Africa with a trend to an increase activity in these countries compared to previous decades. Of the 1493 transplants performed after January 2000, 1061 (71%) have been performed from an HLA identical sibling donors, 129 (8.6%) from a matched other relative, 57 (3.8%) from a mismatched relative, 210 (14%) from an unrelated donor and in 36 (2.4%) cases donor information were missing. Source of stem cells was bone marrow in 1011 patients (67.7%), peripheral blood in 303 patients (20.3%), cord blood in 60 patients (4%), mixed in 82 patients (5.5%). Source of stem cell was missing in 37 (2.5%). In matched sibling donor transplant recipients overall survival (OS) and thalassemia free survival (TFS) plotted at 91 ± 0.01% and 83 ± 0.01%, respectively. Significant differences have been reported in OS and TFS when related to different age groups as reported in Table 1 (P < 0.001). Conclusion. This analysis confirms allogeneic transplantation is a worldwide diffuse high success curative procedure for β-thalassaemia major. Bone marrow still remains the principal source of stem cells. The large majority of transplants have been performed from a matched sibling donor with a marginal role of other donors. In addition these data demonstrate the trend to not transplant adult patients. In the univariate analyses 14 years old appears as threshold age for best transplant strategy. Disclosures: No relevant conflicts of interest to declare.