Resequencing Study Confirms That Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis.

Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. Objectives: To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. Methods: We performed deep targeted resequencing (3.69 Mb of DNA) in cases (n = 3,624) and control subjects (n = 4,442) across genes and regions previously associated with disease. We tested for associations between disease and 1) individual common variants via logistic regression and 2) groups of rare variants via sequence kernel association tests. Measurements and Main Results: Statistically significant common variant association signals occurred in all 10 of the regions chosen based on genome-wide association studies. The strongest risk variant is the MUC5B promoter variant rs35705950, with an odds ratio of 5.45 (95% confidence interval, 4.91-6.06) for one copy of the risk allele and 18.68 (95% confidence interval, 13.34-26.17) for two copies of the risk allele (P = 9.60 × 10-295). In addition to identifying for the first time that rare variation in FAM13A is associated with disease, we confirmed the role of rare variation in the TERT and RTEL1 gene regions in the risk of IPF, and found that the FAM13A and TERT regions have independent common and rare variant signals. Conclusions: A limited number of common and rare variants contribute to the risk of idiopathic pulmonary fibrosis in each of the resequencing regions, and these genetic variants focus on biological mechanisms of host defense and cell senescence.

Developmental Behavioral Pediatrician Support of the Medical Home for Children with Autism Spectrum Disorders.

OBJECTIVE: To identify challenges primary care providers (PCPs) experience providing a Medical Home for children with autism spectrum disorders (ASDs) and to describe the role developmental behavioral pediatricians (DBPs) play in the Medical Home Neighborhood. METHODS: The authors used purposeful sampling to recruit 25 PCPs from around Colorado to participate in 4 focus groups. Member checking was performed at the end of each group. Sampling continued until themes repeated and saturation was achieved. Focus groups were transcribed verbatim, and transcripts were analyzed using content analysis; an outside reviewer audited the data. RESULTS: Qualitative analysis yielded 30 codes that fell into 7 themes: provider education, shared model of care, initial diagnostic evaluation by the DBP, communication, office factors, cost and coverage, and access. PCPs identified knowledge gaps that led to decreased comfort and desired ongoing education and a centralized resource for providers. They envisioned a shared care model with ongoing specialist collaboration and improved communication within the care team. A specific role desired of the DBP was to provide the initial diagnostic evaluation and treatment plan with specific resources. Office factors, high cost and variable coverage, and poor access to services were barriers to providing a Medical Home for children with ASD. CONCLUSION: Working to remove barriers to shared care as well as providing continued educational opportunities will help improve access to a Medical Home Neighborhood for children with ASD. Advocacy is needed to help remove barriers related to cost, coverage, and access to services.

Seeking and sharing: why the pulmonary fibrosis community engages the web 2.0 environment.

BACKGROUND: Pulmonary fibrosis (PF) is a rare, progressive disease that affects patients and their loved ones on many levels. We sought to better understand the needs and interests of PF patients and their loved ones (collectively "reader-participants") by systematically analyzing their engagement with the World Wide Web (the current version referred to as Web 2.0). METHODS: Data were collected from three PF-focused, interactive websites hosted by physician-investigators with expertise in PF. All data generated by reader-participants for approximately 10 months were downloaded and then analyzed using qualitative content analysis methods. RESULTS: PF experts posted 38 blog entries and reader-participants posted 40 forum entries. Blogs received 363 responses, and forum entries received 108 responses from reader-participants. Reader-participants primarily used the three websites to seek information from or offer a contribution to the PF community. Information was sought about PF symptoms, diagnosis, prognosis, treatments, research, pathophysiology, and disease origin; reader-participants also made requests for new posts and pleas for research and sought clarification on existing content. Contributions included personal narratives about experiences with PF, descriptions of activities or behaviors found to be helpful with PF symptoms, resources or information about PF, and supportive comments to other PF sufferers. CONCLUSIONS: PF patients and their loved ones engage the Web 2.0 environment at these PF-focused sites to satisfy their needs to better understand PF and its impacts and to support others facing similar challenges. Clinicians may find it beneficial to encourage PF patients' involvement in internet forums that foster dynamic, bi-directional information sharing.

Development of ATAQ-LAM: a tool to assess quality of life in Lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a progressive lung disease that impairs health-related quality of life (HRQL). OBJECTIVE: To develop and conduct initial testing of ATAQ-LAM (A Tool to Assess Quality of Life in LAM). METHODS: A pilot version of the questionnaire was administered to respondents with LAM. We used a deletion algorithm to retain items and then applied multi-trait scaling to place retained items into appropriate domains, thus generating the ATAQ-LAM. Rasch analysis was used to assess item fit to a unidimensional model of HRQL. We determined internal consistency (IC) and floor and ceiling effects of ATAQ-LAM scores and conducted analyses aimed at supporting the validity of ATAQ-LAM. RESULTS: Sixty-nine LAM patients provided response data. Thirty-two items survived the deletion algorithm. Scaling suggested ATAQ-LAM should have a four-domain structure (Exertional dyspnea, IC = 0.94; Cough, IC = 0.91; Fatigue, IC = 0.91; Emotional Well-Being, IC = 0.89). All items fit the Rasch model. Among 17 respondents with spirometry within three months of questionnaire completion, three of five ATAQ-LAM scores correlated with FEV1% (Exertional Dyspnea: r = -0.72, p = 0.001; Fatigue: r = -0.62, p = 0.007 and total: r = -0.53, p = 0.02). Compared with those in the highest tertile of FEV1%, subjects in the lowest tertile had greater ATAQ-LAM total (121.8 ± 14.3 vs. 79.8 ± 13.1, p = 0.04), Exertional Dyspnea (54.4 ± 6.3 vs. 25.5 ± 5.8, p = 0.005) and Fatigue (2.8 ± 2.4 vs. 14.8 ± 2.3, p = 0.03) scores, indicating greater impairment in HRQL. CONCLUSIONS: ATAQ-LAM is a disease-specific instrument designed to assess HRQL in LAM patients. Additional studies are needed to generate data in support of its validity as an instrument capable of assessing HRQL over time in LAM patients.

Endoscopy training in primary care: innovative training program to increase access to endoscopy in primary care.

BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) is a significant source of morbidity and mortality in the United States. Colonoscopy can be an extension of the care provided by a family physician to help substantially reduce CRC morbidity and mortality. Family physicians trained in colonoscopy can provide access to care in rural and medically underserved areas. METHODS: The Department of Family Medicine and the Colorado Area Health Education Center (AHEC) developed the Endoscopy Training for Primary Care (ETPC) program to teach primary care physicians to perform colonoscopy. The program included online didactic education, a formal endoscopy simulator experience, and proctoring by a current endoscopist. Participants completed a baseline and follow-up survey assessing CRC screening knowledge and the effectiveness of the endoscopy training for ongoing screening activities. RESULTS: To date, 94 practitioners and health professional students have participated in the study. Ninety-one (97%) completed the online didactic portion of the training. Sixty-five participants (77%) were physicians or medical students, and the majority (64%) was in the field of family medicine. The year 4 (2011) follow-up cohort was comprised of 62% respondents working in an urban background and 26% in rural communities. Many participants remain in a queue for proctoring by a trained endoscopist. Several participants are successfully performing a significant number of colonoscopies. CONCLUSIONS: ETPC program showed success in recruiting a large number of physicians and students to participate in training. The program enhanced perceptions about the value of colon cancer screening and providing screening endoscopy in primary care practice. Providing sites for simulation training throughout Colorado provided opportunity for providers in rural regions to participate. As a result of this training, thousands of patients underwent testing to prevent colon cancer. Future research relating to colonoscopy training by family physicians should focus on quality assurance and determining best methods for procedural competence.

Detection of bacteremia in emergency department patients at risk for infective endocarditis using universal 16S rRNA primers in a decontaminated polymerase chain reaction assay.

Prompt definitive diagnosis of acute bacterial endocarditis in febrile injection drug users (IDUs) remains problematic because of delays associated with blood culture. Rapid detection of bacteremia by polymerase chain reaction (PCR) by use of "universal" primers has been hampered by background bacterial contamination. Broad-range eubacterial primers selected from the 16S rRNA gene were used in a PCR assay coupled with a simple pre-PCR decontamination step. All PCR reagents were pretreated with the restriction enzyme AluI, which has multiple digestion sites in the amplicon but none in the primer sets. When 4 different bacterial species were spiked into healthy human blood specimens, the assay identified each pathogen with an analytic sensitivity of 5 bacteria/PCR reaction. A clinical trial with 51 febrile IDUs revealed that PCR had a sensitivity and specificity of 86.7% and 86.9%, respectively, versus blood culture. Importantly, all (8/8) patients with blood culture-positive infective endocarditis were determined to be positive by PCR. This assay provides a promising diagnostic for rapid identification of bacteremia, particularly valuable in acute care settings.