A genome-wide association scan in Crohn disease by the Wellcome Trust Case Control Consortium1 detected strong association at 6 novel loci. We tested 37 SNPs from these and other loci for association in an independent case control sample. Replication was obtained for the IRGM gene on chromosome 5q33.1 which induces autophagy (replication P = 6.6 × 10 −4 , combined P = 2.1 × 10 −10 ), and for 9 other loci including NKX2-3 and gene deserts on chromosomes 1q and 5p13. Crohn disease (CD) is a common form of chronic inflammatory bowel disease. Established CD susceptibility genes NOD2 (CARD15), IL23R and ATG16L1 2-5 showed strong evidence of association in the Wellcome Trust Case Control Consortium (WTCCC) genome-wide scan of 1748 CD cases and 2938 controls genotyped using the Affymetrix 500K chip. Six other loci also showed highly significant association. Although satisfying stringent statistical thresholds for significance (P < 5 × 10 −7 ), replication in independent panels represents a key validation step.We followed up 37 SNPs from 31 distinct loci associated at P < 10 −5 on initial analysis of the WTCCC dataset. Support for some of these markers diminished in the final WTCCC analysis after extensive data filtering1. Three other associations with genome-wide significance in the WTCCC scan produced strong evidence of replication (P≤0.01), two of which are novel. The strongest was SNP rs9292777 (P rep =2.9×10 −7 ; P comb =3.2×10 −18 ) which maps to a 1.2 Mb gene desert on chromosome 5p13.1 recently associated with CD.9 The most significant novel association was SNP rs10883365 (P rep =0.0037, P comb =3.7 × 10 −10 ), which maps within the NKX2-3 gene (NK2 transcription factor related, locus 3) on chromosome 10q24.2. Nkx2.3-deficient mice develop splenic and gut-associated lymphoid tissue abnormalities with disordered segregation of T-and B-cells.10 The second novel locus at rs9858542 (P rep =0.010, P comb =4.9×10 −8 ) on chromosome 3p21 is a 1 Mb region of high LD that contains over 20 genes, including MST1 (macrophage stimulating 1), encoding a protein which induces phagocytosis by resident peritoneal macrophages.The modest evidence of replication for SNP rs2542151 (P = 0.048) at the PTPN2 locus (protein tyrosine phosphatase, non-receptor type 2) on chromosome 18p11 (P comb = 3.2 × 10 −8 ) is of interest since PTPN2 encodes a T cell protein tyrosine phosphatase, a key negative regulator of inflammation and is also associated with Type 1 Diabetes.11 Allele frequencies for rs10761659 on chromosome 10q21, strongly associated in the WTCCC scan, were similar in replication CD cases and population controls (SOM table 2), but association in this intergenic region was recently detected in a North American whole-genome CD scan. 12Allele frequencies for most of the markers from the 25 other loci studied that did not achieve genome-wide significance in the WTCCC scan but had an initial P<10 −5 converged with control frequencies in the CD replication panel (Supplementary Table 2). Five of these loci, however, provided ev...
We conclude that the intervention substantially increased the Bureau of Child Health staff's ability to identify children with asthma, involve them in continuing care, and provide them with state-of-the-art care for asthma.
BackgroundIn the midst of an opioid epidemic, health care workers are encountering an increasing number of patients who have opioid use disorder in addition to complex social, behavioral and medical issues. Of all the clinicians in the hospital, nurses spend the most time with hospitalized patients who have opioid use disorder, yet there has been little research exploring their experiences in caring for this population. The objective of this study was to assess the attitudes, perceptions, and training needs of nurses in the inpatient setting when caring for patients who have opioid use disorder.MethodsOne-on-one in-depth interviews were conducted with nurses working at a large academic medical center in Boston, MA, using a semi-structured interview guide. Nurses were recruited via email notifications and subsequent snowball sampling. Interviews were recorded, transcribed and analyzed using a grounded theory approach.ResultsData from in-depth interviews with 22 nurses were grouped into six themes: (1) stigma, (2) assessing & treating pain, (3) feelings of burn out, (4) communication between providers, (5) safety & security, and (6) opportunities for change. These themes were organized within four ecological levels of the Socio-Ecological Model: I) societal context, II) hospital environment, III) interpersonal interactions, and IV) individual factors. Nurses were cognizant of the struggles that patients who have opioid use disorder confront during hospitalization such as pain, withdrawal and stigma, and elaborated on how these challenges translate to professional and emotional strain among nurses. Nurses offered recommendations by which the hospital could streamline care for this population, including expanded role support for nurses and more structured policies regarding care for patients who present with a comorbid opioid use disorder.ConclusionOur results highlight the need for the development of programs targeting both organizational culture and the inpatient nurse quality of life to ultimately enhance quality of care for patients who present with opioid use disorder.
The existence of a distinctive form of chronic gastritis characterized by marked infiltration of the surface and pitlining epithelium by mature T lymphocytes has been confirmed. Seventeen cases were identified amongst 382 patients with active chronic gastritis (4.5 per cent). The cases with lymphocytic gastritis had significantly higher counts of intraepithelial lymphocytes than sex and age-matched controls drawn from a series of patients with the usual form of active Type B chronic gastritis. Furthermore, the lymphocytic gastritis group exhibited unusual endoscopic findings, namely erosions and 'raised lesions', in the body of the stomach. Such appearances have been previously described as 'varioliform' gastritis. Only seven of the patients (41 per cent) had C. pylori-positive biopsies, compared with over 90 per cent in the generality of active chronic gastritis, but all but two of the eleven cases tested had serological evidence of C. pylori infection. While the pathogenesis of this condition is unclear, the histological resemblance to coeliac disease suggests that lymphocytic gastritis might also represent an abnormal response to a local antigen to which the patient has become sensitized. It is possible that this antigen is C. pylori.
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