A Novel Provider Education Module to Enhance Detection of Alpha-1 Antitrypsin Deficiency.

Background: Alpha-1 antitrypsin deficiency (AATD) is the most common genetic risk factor for early-onset emphysema. However, AATD continues to be underrecognized and underdiagnosed. Provider awareness about AATD, concerns with testing costs, and limited understanding about therapeutic options contribute to its underdiagnosis. We hypothesized that provider education would improve awareness of AATD and improve screening. Objective: To evaluate the impact of a targeted provider education module on AATD screening. Methods: We developed a web-based education module to address barriers to screening for AATD, deployed the education module using the Medscape Education platform, assessed perceived healthcare provider confidence in AATD screening, and conducted a prospective pre and postintervention study of AATD testing practices at a high-volume academic outpatient subspecialty pulmonary clinic. Results: A total of 11,385 healthcare providers, including eight pulmonologists at our institution, completed the web-based education module. Confidence in identifying patients at high risk for AATD improved after completing the module ("not confident" in AATD screening was 7.7% postintervention compared with 19.4% preintervention). The rate of screening patients at high risk for AATD improved more than twofold (AATD screening rate 9.7% preintervention vs. 20.4% postintervention; P = 0.004). Among patients screened for AATD in our cohort, 27.2% had a genotype/phenotype or low alpha-1 antitrypsin concentration consistent with AATD. Conclusion: Targeted healthcare provider education can improve the confidence in testing for AATD. Improvements in provider confidence corresponded to improvements in AATD screening in a subspecialty pulmonary clinic. More than one-fourth of screening tests suggested AATD, underpinning the value of testing in high-risk individuals.

Knowledge of chronic intestinal failure among US gastroenterologists: Cause for concern and learning opportunity.

BACKGROUND: Chronic intestinal failure (CIF) is an ultrarare disease, with an estimated national prevalence of ∼25,000 cases. There is a suspicion of widespread lack of expertise in CIF care, but no formal assessment tool or data exist. We developed and validated a knowledge test in CIF and now report our preliminary results from testing CIF knowledge in a cohort of US gastroenterologists. METHOD: We developed a 20-question knowledge test in CIF, covering four key components of IF. After internal testing, refinement, and revision, we administered the test to a convenience sample of experts and nonexperts in IF. We then deployed the validated test to a cohort of 100 US gastroenterologists. RESULTS: The test had a Cronbach alpha of 0.74, suggesting a reliable test, with a threshold score to discriminate experts and nonexperts of 13.4 (maximum 20) and with a sensitivity of 81.3% and specificity of 86.4%. The overall mean score of 8.2 for the 100 US gastroenterologists was at the level of nonexperts in our convenience sample. CONCLUSION: The preliminary results of our validated knowledge test in IF among a broad group of US gastroenterologists demonstrate lack of knowledge in IF.

Human blood analysis reveals differences in gene expression of catecholamine-regulated protein 40 (CRP40) in schizophrenia.

Heat shock proteins (HSPs) are important players in neurodegeneration and psychiatric disorders. We previously reported significant reductions of a 40-kDa Catecholamine Regulated Protein (CRP40) in schizophrenia post-mortem brain specimens. This study investigated whether gene expression of CRP40 is altered in living subjects with schizophrenia. CRP40 mRNA was analyzed in white blood cells of first episode and chronic/treated schizophrenia subjects compared to healthy controls. Significant reductions in CRP40 mRNA were found among first episode schizophrenia subjects and chronic schizophrenia subjects compared to healthy controls (p<0.05 for both). These results suggest a possible functional role of CRP40 in the pathogenesis of schizophrenia.

Dramatic differences in the roles in lipid metabolism of two isoforms of diacylglycerol kinase.

Lipid species changes for SV40-transformed fibroblasts from wild-type or from diacylglycerol kinase-epsilon (DGKepsilon) or diacylglycerol kinase-alpha (DGKalpha) knockout mice were determined for glycerophospholipids, polyphosphatidylinositides (GPInsP n ) and diacylglycerol (DAG) using direct infusion mass spectrometry. Dramatic differences in arachidonate (20:4 fatty acid)-containing lipids were observed for multiple classes of glycerophospholipids and polyphosphatidylinositides between wild-type and DGKepsilon knockout cells. However, no difference was observed in either the amount or the acyl chain composition of DAG between DGKepsilon knockout and wild-type cells, suggesting that DGKepsilon catalyzed the phosphorylation of a minor fraction of the DAG in these cells. The differences in arachidonate content between the two cell lines were greatest for the GPInsP n lipids and lowest for DAG. These findings indicate that DGKepsilon plays a significant role in determining the enrichment of GPInsP n with 20:4 and that there is a pathway for the selective translocation of arachidonoyl phosphatidic acid from the plasma membrane to the endoplasmic reticulum. In contrast, no substantial difference was observed in the acyl chain composition of any class of glycerophospholipid or diacylglycerol between lipid extracts from fibroblasts from wild-type mice or from DGKalpha knockout mice. However, the cells from the DGKalpha knockout mice had a higher concentration of DAG, consistent with the lack of downregulation of the major fraction of DAG by DGKalpha, in contrast with DGKepsilon that is primarily responsible for enrichment of GPInsP n with arachidonoyl acyl chains.