Person:

Camargo, Carlos

Background: Obesity and asthma have reached epidemic proportions in the US. Their concurrent rise over the last 30 years suggests that they may be connected. Numerous observational studies support a temporally-correct, dose-response relationship between body mass index (BMI) and incident asthma. Weight loss, either induced by surgery or caloric restriction, has been reported to improve asthma symptoms and lung function. Due to methodological shortcomings of previous studies, however, well-controlled trials are needed to investigate the efficacy of weight loss strategies to improve asthma control in obese individuals. Methods/Design: BE WELL is a 2-arm parallel randomized clinical trial (RCT) of the efficacy of an evidence-based, comprehensive, behavioral weight loss intervention, focusing on diet, physical activity, and behavioral therapy, as adjunct therapy to usual care in the management of asthma in obese adults. Trial participants (n = 324) are patients aged 18 to 70 years who have suboptimally controlled, persistent asthma, BMI between 30.0 and 44.9 kg/m2, and who do not have serious comorbidities (e.g., diabetes, heart disease, stroke). The 12-month weight loss intervention to be studied is based on the principles of the highly successful Diabetes Prevention Program lifestyle intervention. Intervention participants will attend 13 weekly group sessions over a four-month period, followed by two monthly individual sessions, and will then receive individualized counseling primarily by phone, at least bi-monthly, for the remainder of the intervention. Follow-up assessment will occur at six and 12 months. The primary outcome variable is the overall score on the Juniper Asthma Control Questionnaire measured at 12 months. Secondary outcomes include lung function, asthma-specific and general quality of life, asthma medication use, asthma-related and total health care utilization. Potential mediators (e.g., weight loss and change in physical activity level and nutrient intake) and moderators (e.g., socio-demographic characteristics and comorbidities) of the intervention effects also will be examined. Discussion: This RCT holds considerable potential for illuminating the nature of the obesity-asthma relationship and advancing current guidelines for treating obese adults with asthma, which may lead to reduced morbidity and mortality related to the comorbidity of the two disorders. Trial registration NCT00901095

Background: Although several chronic obstructive pulmonary disease (COPD) practice guidelines have been published, there is sparse data on the actual emergency department (ED) management of acute exacerbation of COPD (AECOPD). Aims: Our objectives were to examine concordance of ED care of AECOPD in older patients with guideline recommendations and to evaluate whether concordance has improved over time in two academic EDs. Methods: Data were obtained from two cohort studies on AECOPD performed in two academic EDs during two different time periods, 2000 and 2005–2006. Both studies included ED patients, aged 55 and older, who presented with AECOPD, and cases were confirmed by emergency physicians. Data on ED management and disposition were obtained from chart review for both cohorts. Results: The analysis included 272 patients: 72 in the 2000 database and 200 in the 2005–2006 database. The mean age of the patients was 72 years; 50% were women and 80% white. In 2005–2006, overall concordance with guideline recommendations was high (for chest radiography, pulse oximetry, bronchodilators, all ≥ 90%), except for arterial blood gas testing (7% among the admitted) and discharge medication with systemic corticosteroids (42%). Compared to the 2000 data, the use of systemic corticosteroids in the ED improved from 53 to 77% [absolute improvement: 24%, 95% confidence interval (CI): 11–37%], and the use of antibiotics among the patients with respiratory infection symptoms improved from 56 to 78% (absolute improvement: 22%, 95% CI: 6–38%). Conclusions: Overall concordance with guideline-recommended care for AECOPD was high in two academic EDs, and some emergency treatments have improved over time.

Background and Aims The immune system is likely to play a key role in the etiology of gliomas. Genetic polymorphisms in the mannose-binding lectin gene, a key activator in the lectin complement pathway, have been associated with risk of several cancers. Methods: To examine the role of the lectin complement pathway, we combined data from prospectively collected cohorts with available DNA specimens. Using a nested case-control design, we genotyped 85 single nucleotide polymorphisms (SNPs) in 9 genes in the lectin complement pathway and 3 additional SNPs in MBL2 were tested post hoc). Initial SNPs were selected using tagging SNPs for haplotypes; the second group of SNPs for MBL2 was selected based on functional SNPs related to phenotype. Associations were examined using logistic regression analysis. All statistical tests were two-sided. Nominal p-values are presented and are not corrected for multiple comparisons. Results: A total of 143 glioma cases and 419 controls were available for this analysis. Statistically significant associations were observed for two SNPs in the mannose-binding lectin 2 (ML2) gene and risk of glioma (rs1982266 and rs1800450, test for trend p = 0.003 and p = 0.04, respectively, using the additive model). One of these SNPs, rs1800450, was associated with a 58% increase in glioma risk among those carrying one or two mutated alleles (odds ratio = 1.58, 95% confidence interval = 0.99–2.54), compared to those homozygous for the wild type allele. Conclusions: Overall, our findings suggest that MBL may play a role in the etiology of glioma. Future studies are needed to confirm these findings which may be due to chance, and if reproduced, to determine mechanisms that link glioma pathogenesis with the MBL complement pathway.

Introduction: The American College of Emergency Physicians (ACEP) Task Force on Boarding described high-impact initiatives to decrease crowding. Furthermore, some emergency departments (EDs) have implemented a novel initiative we term “vertical patient flow,” i.e. segmenting patients who can be safely evaluated, managed, admitted or discharged without occupying a traditional ED room. We sought to determine the degree that ACEP-identified high-impact initiatives for ED crowding and vertical patient flow have been implemented in academic EDs in the United States (U.S.). Methods: We surveyed the physician leadership of all U.S. academic EDs from March to May 2010 using a 2-minute online survey. Academic ED was defined by the primary site of an emergency residency program. Results: We had a response rate of 73% (106/145) and a completion rate of 71% (103/145). The most prevalent hospital-based initiative was inpatient discharge coordination (46% [47/103] of respondents) while the least fully initiated was surgical schedule smoothing (11% [11/103]). The most prevalent ED-based initiative was fast track (79% [81/103]) while the least initiated was physician triage (12% [12/103]). Vertical patient flow had been implemented in 29% (30/103) of responding EDs while an additional 41% (42/103) reported partial/in progress implementation. Conclusion: We found great variability in the extent academic EDs have implemented ACEP’s established high-impact ED crowding initiatives, yet most (70%) have adopted to some extent the novel initiative vertical patient flow. Future studies should examine barriers to implementing these crowding initiatives and how they affect outcomes such as patient safety, ED throughput and patient/provider satisfaction.

OBJECTIVES: Celiac disease (CD) is common and often cited as an “iceberg” phenomenon (i.e., an assumed large number of undiagnosed cases). Recently, atypical or asymptomatic manifestations are becoming more commonly described in older children and adolescents. Moreover, CD diagnosis in children can be complicated by several factors, including its diverse clinical presentations, delay in recognizing CD signs and symptoms, and premature dietary gluten avoidance before the formal diagnosis of CD. To date, few studies have directly examined age-related differences in clinical characteristics and gluten-related issues among children with CD. The aim of this study was to determine age-related patterns in clinical characteristics and gluten-related issues among children with confirmed CD. METHODS: We performed a structured medical record review of biopsy-proven CD patients, aged 0–19 years, between 2000 and 2010 at a large Boston teaching hospital. Data collection included demographics, medical history, gluten-related issues, and diagnostic investigations (CD-specific serology, upper gastrointestinal endoscopy, and small intestinal biopsy). The first positive duodenal biopsy with Marsh III classification defined age of diagnosis. Patients were divided into three age groups for comparisons of the aforementioned characteristics: infant-preschool group (0–5 years), school-aged group (6–11 years), and adolescence group (12–19 years). RESULTS: Among 411 children with biopsy-proven CD, the mean age was 9.5 (s.d. 5.1) years. Most were female (63%) and white (96%). All children had positive CD-specific serology. Most children presented with either abdominal complaints or bowel movement changes. Overall, boys were more common among infant-preschool group compared with the other age groups. More distinct clinical manifestations (vomiting, bowel movement changes, and weight issues) were apparent in the youngest group, whereas school-aged children had more subjective abdominal complaints at the initial presentation. Conversely, the adolescents were most likely to present without any gastrointestinal (GI) symptoms, but not when this was combined with absence of weight issues. Age of diagnosis was not associated with atypical extraintestinal CD presentations. Regarding the gluten-related issues, 10% of school-aged children avoided dietary gluten before the formal CD diagnosis, and 27% of the adolescents reported dietary gluten transgression within the first 12 months of diagnosis, significantly higher than the other age groups. Age differences in histopathology were also found. Whereas the infant-preschool group had a higher proportion of total villous atrophy, the older children were more likely to have gross duodenal abnormalities and chronic duodenitis suggestive of CD at the time of diagnosis. CONCLUSIONS: Children and adolescents with CD have age-related patterns in both the clinical presentations and gluten-related issues. More pronounced clinical and histological features were determined in younger children, whereas older children more commonly presented with solely subjective abdominal complaints or even without any GI symptoms. However, silent and atypical extraintestinal CD presentations were comparable between age groups. In addition to the aforementioned presentations, the higher rates of dietary gluten avoidance and transgression in older children make CD diagnosis and management particularly challenging. These age-related patterns may further increase awareness, facilitate early diagnosis, and improve patient care of pediatric CD.

As indoor workers, trainee doctors may be at risk for inadequate vitamin D. All trainee doctors (residents) in a Boston pediatric training program (residency) were invited to complete a survey, and undergo testing for serum 25-hydroxyvitamin D [25(OH)D], PTH, and calcium during a 3-week period in March 2010. We examined the association between resident characteristics and serum 25(OH)D using Chi2 and Kruskal-Wallis test and multivariable linear and logistic regression. Of the 119 residents, 102 (86%) participated. Although the mean serum 25(OH)D level was 67 nmol/L (±26), 25 (25%) had a level <50 nmol/L and 3 (3%) residents had levels <25 nmol/L. In the multivariable model, factors associated with 25(OH)D levels were: female sex (β 12.7, 95% CI 3.6, 21.7), white race (β 21.7, 95% CI 11.7, 31.7), travel to more equatorial latitudes during the past 3 months (β 6.3, 95% CI 2.0, 10.5) and higher daily intake of vitamin D (β 1.1, 95% CI 0.04, 2.1). Although one in four residents in our study had a serum 25(OH)D <50 nmol/L, all of them would have been missed using current Centers for Medicare and Medicaid Services (CMS) screening guidelines. The use of traditional risk factors appears insufficient to identify low vitamin D in indoor workers at northern latitudes.

Background: The epidemiology of acute pancreatitis in the United States is largely unknown, particularly episodes that lead to an emergency department (ED) visit. We sought to address this gap and describe ED practice patterns. Methods: Data were collected from the National Hospital Ambulatory Medical Care Survey between 1993 and 2003. We examined demographic factors and ED management including medication administration, diagnostic imaging, and disposition. Results: ED visits for acute pancreatitis increased over the study period from the 1994 low of 128,000 visits to a 2003 peak of 318,000 visits (p = 0.01). The corresponding ED visit rate per 10,000 U.S. population also increased from 4.9 visits (95%CI, 3.1–6.7) to 10.9 (95%CI, 7.6–14.3) (p = 0.01). The average age for patients making ED visits for acute pancreatitis during the study period was 49.7 years, 54% were male, and 27% were black. The ED visit rate was higher among blacks (14.7; 95%CI, 11.9–17.5) than whites (5.8; 95%CI, 5.0–6.6). At 42% of ED visits, patients did not receive analgesics. At 10% of ED visits patients underwent CT or MRI imaging, and at 13% of visits they underwent ultrasound testing. Two-thirds of ED visits resulted in hospitalization. Risk factors for hospitalization were older age (multivariate odds ratio for each increasing decade 1.5; 95%CI, 1.3–1.8) and white race (multivariate odds ratio 2.3; 95%CI, 1.2–4.6). Conclusion: ED visits for acute pancreatitis are rising in the U.S., and ED visit rates are higher among blacks than whites. At many visits analgesics are not administered, and diagnostic imaging is rare. There was greater likelihood of admission among whites than blacks. The observed race disparities in ED visit and admission rates merit further study.

Objectives: To determine the association between physical inactivity (that is, a sedentary lifestyle) and incident idiopathic pulmonary embolism. Design: Prospective cohort study. Setting: Nurses’ Health Study. Participants: 69 950 female nurses who completed biennial questionnaires from 1990 to 2008. Main outcome measures: The primary outcome was idiopathic pulmonary embolism confirmed in medical records. Multivariable Cox proportional hazards models controlled for age, body mass index (BMI), energy intake, smoking, pack years, race, spouse’s educational attainment, parity, menopause, non-aspirin non-steroidal anti-inflammatory drugs, warfarin, multivitamin supplements, hypertension, coronary heart disease, rheumatological disease, and dietary patterns. The primary exposure was physical inactivity, measured in hours of sitting each day. The secondary exposure was physical activity, measured in metabolic equivalents a day. Results: Over the 18 year study period, there were 268 cases of incident idiopathic pulmonary embolism. There was an association between time of sitting and risk of idiopathic pulmonary embolism (41/104 720 v 16/14 565 cases in most inactive v least inactive in combined data; P<0.001 for trend). The risk of pulmonary embolism was more than twofold in women who spent the most time sitting compared with those who spent the least time sitting (multivariable hazard ratio 2.34, 95% confidence interval 1.30 to 4.20). There was no association between physical activity and pulmonary embolism (P=0.53 for trend). Conclusions: Physical inactivity is associated with incident pulmonary embolism in women. Interventions that decrease time sitting could lower the risk of pulmonary embolism.

Objective: To examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture. Design Prospective cohort study. Setting: Nurses’ Health Study, which originally recruited from the 11 most populous states in the US. Participants: 79 899 postmenopausal women enrolled in the Nurses’ Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008. Main outcome measure: Incident hip fracture Results: During 565 786 person years of follow-up, we documented 893 incident hip fractures. The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years, compared with 1.51 events per 1000 person years among non-users. Compared with non-users, the risk of hip fracture among women who regularly used PPIs for at least two years was 35% higher (age adjusted hazard ratio 1.35 (95% confidence interval 1.13 to 1.62)), with longer use associated with increasing risk (P({trend})<0.01). Adjustment for risk factors, including body mass index, physical activity, and intake of calcium did not materially alter this association (hazard ratio 1.36 (1.13 to 1.63)). These associations were also not changed after accounting for reasons for PPI use. The relation between PPI use and fracture differed by smoking history (P({interaction})=0.03). Among current and former smokers, PPI use was associated with greater than 50% increase in risk of fracture, with a multivariate hazard ratio for fracture of 1.51 (1.20 to 1.91). In contrast, among women who never smoked there was no association (multivariate hazard ratio 1.06 (0.77 to 1.46)). In a meta-analysis of these results with 10 prior studies, the pooled odds ratio of hip fracture associated with PPI use was 1.30 (1.25 to 1.36). Conclusion: Chronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking.

Objective: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] level and history of community-acquired pneumonia (CAP). Patients and Methods We identified 16,975 individuals (≥17 years) from the third National Health and Nutrition Examination Survey (NHANES III) with documented 25(OH)D levels. To investigate the association of 25(OH)D with history of CAP in these participants, we developed a multivariable logistic regression model, adjusting for demographic factors (age, sex, race, poverty-to-income ratio, and geographic location), clinical data (body mass index, smoking status, asthma, chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, stroke, chronic kidney disease, neutropenia, and alcohol consumption), and season. Locally weighted scatterplot smoothing (LOWESS) was used to depict the relationship between increasing 25(OH)D levels and the cumulative frequency of CAP in the study cohort. Results: The median [interquartile range (IQR)] serum 25(OH)D level was 24 (IQR 18–32) ng/mL. 2.1% [95% confidence interval (CI): 1.9–2.3] of participants reported experiencing a CAP within one year of their participation in the national survey. After adjusting for demographic factors, clinical data, and season, 25(OH)D levels <30 ng/mL were associated with 56% higher odds of CAP [odds ratio 1.56; 95% confidence interval: 1.17–2.07] compared to levels ≥30 ng/mL. LOWESS analysis revealed a near linear relationship between vitamin D status and the cumulative frequency of CAP up to 25(OH)D levels around 30 ng/mL. Conclusion: Among 16,975 participants in NHANES III, 25(OH)D levels were inversely associated with history of CAP. Randomized controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of CAP.