Comparative phenotypic and CARD15 mutational analysis among African American, Hispanic, and White children with Crohn's disease

BACKGROUND: Despite a large body of literature on the subject of Crohn's disease (CD), very little information is available on racial/ethnic differences related to disease presentation, clinical course, and genetics. The first identified CD susceptibility gene, CARD15, seems to be present in up to 40% of white children with CD. However, the frequency of this gene among patients with CD of other racial/ethnic groups in the United States is not known. METHODS: We conducted a multicenter study on African American and Hispanic children with CD to describe the phenotypic and genotypic (CARD15) features in comparison with white children with CD. We also analyzed the frequency of CARD15 mutations in large control samples from white, African American, and Hispanic children. RESULTS: The disease location and behavior were similar among all 3 groups, with inflammatory behavior and the ileocolonic location being the most frequent phenotype. However, significantly lower frequencies of CARD15 mutations were seen in African American (P < 0.0001) and Hispanic (P < 0.0001) children with CD compared with white children with CD. This lower CARD15 frequency among African American patients with CD was also mirrored in the general population. CONCLUSIONS: Phenotypic features of CD are similar among African American and Hispanic children compared with white children. CARD15 mutations are not increased among African American and Hispanic children with CD. CARD15 mutational frequencies among African American and Hispanic children within the general population are lower compared with white children within the general population. Future genetics studies will be required to determine the relationships between genotype and CD phenotype in various ethnic and racial groups.     

The natural history of corticosteroid therapy for ulcerative colitis in children.

BACKGROUND & AIMS: The aim of this study was to determine the clinical outcome after corticosteroid therapy in children who are newly diagnosed with ulcerative colitis (UC). METHODS: Data were gathered prospectively from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry database between January 2002 and March 2005. All children who were newly diagnosed with inflammatory bowel disease younger than the age of 16 years were managed according to the dictates of their respective physicians. Demographic, clinical, and laboratory data were collected at diagnosis, at 30 days, and then quarterly. Patients were classified as corticosteroid responsive, corticosteroid dependent, or refractory, and outcomes were determined at 3 months and at 1 year. RESULTS: Ninety-seven patients had a diagnosis of UC and a minimum of 1 year of follow-up evaluation; 77 (79%) received corticosteroids (62 within 30 days of diagnosis [early] and 15 between 31 days and 6 months [late]). At diagnosis, 81% of corticosteroid-treated patients (age, 11.3 +/- 3.5 y) had moderate/severe disease, and 81% had pancolitis. For those treated early with corticosteroids, disease activity at 3 months was inactive in 60%, mild in 27%, and moderate/severe in 11%. At 1 year, 31 of 62 (50%) of the early corticosteroid-treated patients were considered corticosteroid responsive and 28 (45%) were corticosteroid dependent. A total of 4 patients receiving corticosteroids (5%) required colectomy in the first year. Immunomodulators were used in 61% of all corticosteroid-treated patients. CONCLUSIONS: Although short-term clinical response to corticosteroids in children with newly diagnosed UC is excellent, even with the common use of immunomodulators corticosteroid dependence is seen in 45% of patients.     

Health-care seeking among people with cough of 2 weeks or more in India. Is passive TB case finding sufficient?

Setting:

Thirty districts of India.

Objectives:

To estimate 1) the proportion of people with cough of ≥2 weeks, 2) those who did not seek care from a health care provider for cough, and 3) their characteristics.

Methodology:

A cross-sectional community-based survey in which 4562 people (aged ≥18 years) were interviewed.

Results:

Of the 4562 individuals interviewed, 437 (9.5%, 95%CI 7.2–11.8) had cough ≥2 weeks; this was more frequent in those >55 years of age (14%) and in those from districts in eastern (12%) and northern (11%) states of India. Of those with cough, 300 (69%, 95%CI 60–77) had not sought care from any health care provider. Not seeking care was more frequent in people residing in rural areas (73%) compared with urban areas (53%), and in the districts of eastern (82%) and northern (74%) states compared to districts from the southern (46%) and western (54%) states.

Conclusions:

Nearly a tenth of those interviewed aged ≥18 years had cough of ≥2 weeks. About two thirds, especially those from rural areas, had not visited a health care provider for the cough. This finding has huge implications for India’s current mostly passive case-finding strategy for detecting and controlling tuberculosis.     

Juvenile Onset Pernicious Anemia, Partial Intestinal Villous Atrophy, Ulcerative Colitis, and Squamous Metaplasia of the Stomach

We report a case of a 13-yr-old white boy with juvenile onset pernicious anemia in association with IgG deficiency. He had marked gastric atrophy, intestinal metaplasia of the stomach, and an intractable antral ulcer that required surgery. In addition, his gastric mucosa showed evidence of a progressive squamous metaplasia. Diffuse squamous metaplasia of the stomach, a very rare gastric lesion, has not previously been described either in association with pernicious anemia, atrophic gastritis, or hypogammaglobulinemia. This patient also has ulcerative colitis involving the entire colon and partial villous atrophy noted on small intestinal biopsy.     

Severe methemoglobinemia after transesophageal echocardiography

Methemoglobinemia, an increased concentration of methemoglobin in the blood, is an altered state of hemoglobin whereby the ferrous form of iron is oxidized to the ferric state, rendering the heme moiety incapable of carrying oxygen. This can cause hypoxia, cyanosis, or even death. Severe methemoglobinemia resulting from oral benzocaine spray before endoscopic procedures has been reported as a rare complication. We report a case of severe acquired methemoglobinemia resulting from topical benzocaine use before transesophageal echocardiography. This case serves to highlight the severity of methemoglobinemia that can result from an otherwise innocuous agent even in small doses and the fact that prompt recognition and treatment of this disorder can be lifesaving.     

Lipoprotein-associated phospholipase A<Subscript>2</Subscript> and future risk of subclinical disease and cardiovascular events in individuals with type 2 diabetes: the Cardiovascular Health Study

Aims/hypothesis  

Type 2 diabetes is an established risk factor for cardiovascular disease (CVD). This increased risk may be due in part to the increased levels of inflammatory factors associated with diabetes. Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a risk marker for CVD and has pro-inflammatory effects in atherosclerotic plaques. We therefore sought to determine whether Lp-PLA₂ levels partially explain the greater prevalence of subclinical CVD and greater incidence of CVD outcomes associated with type 2 diabetes in the Cardiovascular Health Study.     

PS1-33: Cancer Screening Guideline Development, Implementation and Dissemination: Connection Points for Researchers and Health Care Delivery Systems for Comparative Effectiveness Research

Background/Aims Cancer Screening Effectiveness And Research in Community-based Healthcare (SEARCH) involves 8 Cancer Research Network (CRN) sites and includes two comparative effectiveness research (CER) proof-of-principle studies anchored in colorectal and cervical cancer screening. This portion of the project was designed to: understand how cancer screening guidelines are developed, implemented and disseminated at each site; identify the appropriate clinical leads within each health plan to further engage in bidirectional discussions about future comparative effectiveness cancer screening research and to help disseminate SEARCH findings across the CRN sites; and identify opportunities for researchers and clinical leaders to collaborate on informing each other and/or conducting comparative effectiveness research together. Methods We conducted 18 semi-structured interviews with clinical leaders across 8 health plans (GHC, Geisinger, Marshfield, Fallon, Harvard Pilgrim, Kaiser: Northwest, Hawaii, Northern California) and with one State-wide quality improvement group. Results There is considerable site variability in guideline development, implementation and dissemination processes. Much work goes into reviewing evidence and developing clinical guidelines; parallel work and evidence reviews happen across. Many different vehicles are used for guideline dissemination; opportunities exist to study how to most effectively disseminate guidelines to patients and providers to yield optimal screening. Clinical leaders provided critical information around principles and required elements for conducting CER. Opportunities, barriers and principles around conducting CER will be presented. Discussion There are a number of areas that can be immediately leveraged: to further facilitate learning health care systems, and for researchers and delivery systems to improve the cancer screening guideline development, dissemination and implementation. We see important opportunities for helping the research network and its member sites develop and use guidelines more efficiently to improve care and enhance the research we conduct. Research teams must work with key leaders to identify high priority CER studies and to hard-wire the conduct of CER trials into standard clinical work-flow.     

PS1-11: Development of an Algorithm to Classify Colonoscopy Indication Using CRN Health Plan Coded Data

Background/Aims Colonoscopy is widely used for colorectal cancer (CRC) screening, surveillance, and diagnosis. To assess colonoscopy utilization, effectiveness, and safety, it is important to distinguish between these indications. Administrative data sources have the advantage of representing real world colonoscopy utilization, but because the codes are primarily intended for billing, it is challenging to identify the reason for the procedure in these data, especially with large datasets. Several studies using administrative data have applied procedure and diagnostic code-based algorithms to classify colonoscopy indication. However, none have demonstrated simultaneously high sensitivity and specificity. The current study uses adjudicated medical records at 4 CRN sites to evaluate the test characteristics of existing algorithms, develop a new algorithm, and compare performance of existing algorithms with the new algorithm. Methods The study included 716 subjects, patients of 4 large health care organizations. Subjects' records were reviewed and adjudicated as part of a late-stage CRC case-control study conducted concurrently with this analysis. Cases were 55 years or older at diagnosis in 2006 through 2008; controls were age-matched to cases. Medical records were abstracted and adjudicated to assign indication for 465 colonoscopy procedures. We first tested the performance of 5 published algorithms. We then identified a superset of candidate predictor variables, which we selected from the published algorithms. We entered the variables in a LASSO prediction model, using the subject-level coded data for values of the predictors, and subjects' colonoscopy outcomes. LASSO is a backwards-selection multiple logistic regression, designed to protect against model over-fitting. The covariates retained by the new model were used to construct a Receiver Operator Curve (ROC) displaying the model's sensitivity at each increment of specificity. Results The existing algorithms had sensitivities and specificities of 65/74%, 60/77%, 74/58%, 77/58%, and 51/30% for classifying CRN data. The ROC curve of the new algorithm encompassed these values, indicating higher sensitivity at each level of specificity than the existing algorithms. For example, at a sensitivity of 80%, specificity was approximately 70%; at sensitivity of 70%, specificity was about 82%. Discussion The new algorithm will allow more accurate classification of colonoscopy indication in CRN data than do existing algorithms.