Leukocyte Transcriptional Response in Sepsis.

BACKGROUND: The complex host response to sepsis is incompletely understood. The aim of this investigation is to use leukocyte RNA sequencing to characterize biological functions, cellular pathways, and key regulatory molecules driving sepsis pathophysiology. METHODS: This was a prospective, observational study of emergency department patients with sepsis, at an urban, academic, tertiary care center. In the derivation cohort, we collected blood at enrollment and 90 days after hospital discharge allowing each patient to serve as an internal control. We performed RNA sequencing to quantify transcriptional expression changes during sepsis and non-sepsis states. We then performed unsupervised and supervised analyses, as well as functional and pathway analyses. We selected the top down and upregulated genes and key regulatory molecules for validation. Validation occurred in a cohort of septic and non-septic using real-time PCR. RESULTS: The derivation cohort included 5 patients, and RNA sequencing revealed 916 unique mRNA transcripts differentially expressed during sepsis. Among these, 673 (73%) genes were upregulated, and 243 (27%) were downregulated. Functional enrichment analysis revealed a highly dynamic downstream effect of the transcriptional activity during sepsis. Of the 43 functional cellular pathways activated during sepsis, the top pathways were closely associated with inflammation and response to infection. Validation occurred in 18 septic and 25 non-septic control patients, with 34/45 (76%) of identified genes validated. The regulatory analysis identified several key regulators of sepsis. CONCLUSIONS: Highly dynamic transcriptional activity occurs in leukocytes during sepsis, activating key cellular pathways and master regulatory molecules that drive the sepsis process.

Targeted Physician Education and Standardizing Documentation Improves Documented Reporting with Inflammatory Bowel Disease Quality Measures in a Large Academic and Private Practice.

BACKGROUND: Prior studies have shown poor compliance with quality measures for IBD at academic and private practices. We sought to provide focused interventions to improve compliance and documentation with the IBD measures. METHODS: Two centers, academic practice (AP) and private practice (PP), initially reviewed their compliance with eight established IBD quality measures in consecutive charts. A multi-faceted intervention was developed to improve awareness and documentation of these measures. The initial data and the quality measures were reviewed at a group meeting. Following this, a handout summarizing the measures was placed in each exam room. The AP added a new screen to the EHR that summarized the relevant IBD history, while the PP added a new template that was filled out and imported into the charts. Three months after this intervention, charts were reviewed for compliance with the measures. RESULTS: The intervention cohort consisted of 768 patients (AP = 569/PP = 199) compared to the initial cohort of 566 patients (AP = 367/PP = 199). Improvement was seen throughout all measures compared to the initial cohort. The AP reported compliance with all relevant measures in 21% and the PP in 60% compared to 7 and 10% in the initial cohort. PP had ≥ 75% compliance with every measure, of which only assessment for bone loss and pneumococcal vaccination was under 80%. In contrast, the AP compliance ranged from 35 to 100% with assessment for bone loss, influenza, and pneumococcal vaccination scoring lowest. CONCLUSION: Our study demonstrates that focused low-cost interventions can significantly improve compliance with IBD quality measures in different practice settings.

Systematic Analysis and Critical Appraisal of the Quality of the Scientific Evidence and Conflicts of Interest in Practice Guidelines (2005-2013) for Barrett's Esophagus.

BACKGROUND: Barrett's esophagus (BE) is a condition that has a small but important risk of progressing to esophageal cancer. To date, no study has assessed the strength of evidence supporting the recommendations for BE. We sought to assess the overall quality of the recommendations and strength of the BE using the AGREE II instrument. METHODS: A PubMed search was performed to identify guidelines published pertaining to BE. Every guideline was reviewed using the AGREE II format to assess the methodological rigor and validity of the guideline. Additionally, guidelines were reviewed for the level of evidence used to support recommendations, conflicts of interest (COI), and differences in recommendations. Statistical analysis was performed using Stata (version 12). RESULTS: In total, 234 manuscripts were identified of which 8 guidelines published between 2005 and 2013 pertained to BE. Seventy-five percentage (6/8) graded the evidence used to formulate recommendations. Of the 126 recommendations with supporting evidence, 6 % were supported by level A evidence, 49 % level B evidence, and 45 % level C evidence. Using the AGREE II format, the highest overall assessment grade was the BSG BE guideline (6.5 ± 0.6) followed by the AGA (5.5 ± 0.6). The highest rated domains were scope and purpose (mean 77 range 24-96) and clarity of presentation (mean 75), while the lowest rated domains were editorial independence (mean 32 range 0-92) and applicability of the guideline (mean 35 range 7-90). There was significant variability in recommendations regarding who to screen for BE and surveillance intervals. Finally, only 50 % of the guidelines disclosed if COI were present and 75 % (3/4) reported potentially relevant COI. CONCLUSIONS: Majority of the BE guideline fail to meet the AGREE II domains, and most of the recommendations are level B or C quality evidence. Further interventions are necessary to improve the overall quality of the guidelines.

Poor Documentation of Inflammatory Bowel Disease Quality Measures in Academic, Community, and Private Practice.

BACKGROUND & AIMS: Quality measures are used to standardize health care and monitor quality of care. In 2011, the American Gastroenterological Association established quality measures for inflammatory bowel disease (IBD), but there has been limited documentation of compliance from different practice settings. METHODS: We reviewed charts from 367 consecutive patients with IBD seen at academic practices, 217 patients seen at community practices, and 199 patients seen at private practices for compliance with 8 outpatient measures. Records were assessed for IBD history, medications, comorbidities, and hospitalizations. We also determined the number of patient visits to gastroenterologists in the past year, whether patients had a primary care physician at the same institution, and whether they were seen by a specialist in IBD or in conjunction with a trainee, and reviewed physician demographics. A univariate and multivariate statistical analysis was performed to determine which factors were associated with compliance of all core measures. RESULTS: Screening for tobacco abuse was the most frequently assessed core measure (89.6% of patients; n = 701 of 783), followed by location of IBD (80.3%; n = 629 of 783), and assessment for corticosteroid-sparing therapy (70.8%; n = 275 of 388). The least-frequently evaluated measures were pneumococcal immunization (16.7% of patients; n = 131 of 783), bone loss (25%; n = 126 of 505), and influenza immunization (28.7%; n = 225 of 783). Only 5.8% of patients (46 of 783) had all applicable core measures documented (24 in academic practice, none in clinical practice, and 22 in private practice). In the multivariate model, year of graduation from fellowship (odds ratio [OR], 2.184; 95% confidence interval [CI], 1.522-3.134; P < .001), year of graduation from medical school (OR, 0.500; 95% CI, 0.352-0.709; P < .001), and total number of comorbidities (OR, 1.089; 95% CI, 1.016-1.168; P = .016) were associated with compliance with all core measures. CONCLUSIONS: We found poor documentation of IBD quality measures in academic, clinical, and private gastroenterology practices. Interventions are necessary to improve reporting of quality measures.

Fellowship Colonoscopy Training and Preparedness for Independent Gastroenterology Practice.

GOALS: To objectively assess when gastroenterology (GI) fellows achieve technical competency to perform colonoscopy independently. BACKGROUND: New guidelines to assess the procedural competency of GI fellows in training have been developed. Although comprehensive, they do not account for the quality metrics to which independently practicing gastroenterologists are held. STUDY: We performed a prospective study examining consecutive colonoscopies performed by GI fellows from November 2013 through March 2014 at an academic medical center. Using a brief postprocedure questionnaire and the online medical record, we measured rates of independent fellow cecal intubation rate (CIR), insertion time to the cecum (cecal IT), and independent polypectomy rate. Our secondary outcomes were adenoma detection rate and polyp detection rate. RESULTS: A total of 898 colonoscopies performed by 10 GI fellows were analyzed. In the multivariate analysis, CIR [odds ratio (OR)=1.29, P=0.012], cecal IT (ß-coefficient=0.19, P=0.006), and rates of unassisted independent snare polypectomy (OR=1.36, P<0.001) all improved significantly with increased number of procedures performed (OR and ß-coefficient per 100 colonoscopies performed). After performing 500 colonoscopies, fellows achieved a mean CIR>90%, cecal IT between 7 and 10 minutes, and independent polypectomy rate of 90% with further improvement in cecal IT to <7 minutes, and independent snare polypectomy of >95% after 700 cases. CONCLUSIONS: Current procedural recommendations for fellowship training may underestimate the technical skill necessary for independent GI practice upon completion of fellowship. Technical proficiency in snare polypectomy may lag behind proficiency in cecal intubation.

Multicenter Study Assessing Physician Recommendations Regarding the Continuation of Aspirin and/or NSAIDs Prior to Gastrointestinal Endoscopy.

BACKGROUND: In 2009 the American Society for Gastrointestinal Endoscopy (ASGE) guidelines advised that both aspirin and NSAIDs be continued prior to low-risk gastrointestinal endoscopic procedures. We sought to determine physician knowledge regarding these guidelines. METHODS: A survey questionnaire was developed based on the ASGE guidelines. Physicians were queried about whether they would continue/stop aspirin in a patient with cardiac disease and in a patient taking NSAIDs for arthritis whether they would continue/stop NSAIDs prior to endoscopy. The survey was administered at three academic medical centers. Demographic information: level of training, board certification, teaching trainees, percentage of time in clinical practice, year of medical school graduation, and location of medical school were all reviewed. The primary outcome was number of questions answered correctly and predictors of correct responses. RESULTS: The survey was administered to 941 participants with 12 declining to participate, while 80% (740/929) of the subjects completed the survey; 20% (150/740) respondents answered both questions correctly and 42% (310/740) answered one question correctly. There was no significant difference between institutions (p = 0.6) or between attendings and trainees (p = 0.75). Multivariate predictors of correct answers were self-reported familiarity with the guideline (-0.029; 95% CI -0.003 to -0.056, p < 0.031), level of training (0.050; 95% CI 0.012-0.088, p = 0.010), and specialty (0.108; 95% CI 0.058-0.159, p < 0.0001). Finally, there was an inverse, linear relationship between postgraduate year and percent questions correct. CONCLUSION: Physician knowledge of guidelines regarding the use of aspirin and NSAIDs prior to endoscopy is suboptimal. Interventions are necessary to improve knowledge of the current pre-procedure guidelines.

Surgery for Ulcerative Colitis Is Associated with a High Rate of Readmissions at 30 Days.

BACKGROUND: Currently, the predictors of readmission after colectomy specifically for ulcerative colitis (UC) are poorly investigated. We sought to determine the rates and predictors of 30-day readmissions after colectomy for UC. METHODS: Patients undergoing total proctocolectomy and end ileostomy, abdominal colectomy with end ileostomy, proctocolectomy with ileoanal pouch anastomosis (IPAA) formation and diverting ileostomy, one stage IPAA, or abdominal colectomy with ileorectal anastomosis at a tertiary care center between January 2002 and January 2012 for UC were included. Patients were identified using ICD-9 code 556.x. Each record was manually reviewed. The electronic record system was reviewed for demographic information, medical histories, UC history, medications, and data regarding the admission and discharge. Charts were reviewed for readmissions within 30 days of surgery. Univariate and multivariate analyses were performed using Stata v.13. RESULTS: Two hundred nine patients with UC underwent a colectomy. Forty-three percent had a proctocolectomy with IPAA and diverting ileostomy and 32% had abdominal colectomy with end ileostomy. Seventy-six percent of surgeries were due to failure of medical therapy and 68% of patients were electively admitted for surgery. Thirty-two percent (n = 67/209) of the cohort was unexpectedly readmitted within 30 days. In multivariate model, proctocolectomy with IPAA and diverting ileostomy (odds ratio [OR] = 2.11; 95% CI, 1.06-4.19; P = 0.033) was the only significant predictor of readmission. Hospital length of stay >7 days (OR = 1.82; 95% CI, 0.98-3.41; P = 0.060), presence of limited UC (OR = 2.10; 95% CI, 0.93-4.74; P = 0.074), and steroid before admission (OR = 1.69; 95% CI, 0.90-3.2; P = 0.100) trended toward significance. CONCLUSIONS: Surgery for UC is associated with a high rate of readmission. Further prospective studies are necessary to determine the means to reduce these readmissions.

Current knowledge of antibiotic prophylaxis guidelines regarding GI open-access endoscopic procedures is inadequate.

BACKGROUND: The American Heart Association (AHA) guidelines from 2007 and the American Society for Gastrointestinal Endoscopy (ASGE) guidelines from 2008 recommended against antibiotic prophylaxis before GI endoscopic procedures to prevent bacterial endocarditis. OBJECTIVE: To determine physician knowledge regarding these guidelines and to identify physician subgroups for which knowledge was suboptimal. DESIGN: A survey questionnaire was developed based on AHA and ASGE guidelines regarding antibiotics before endoscopy. Physicians were queried about 10 theoretical scenarios as to whether or not they would recommend before-procedure antibiotics. SETTING: The survey was administered at 3 academic medical centers. PARTICIPANTS: Attending physicians and trainees in primary care and subspecialties. INTERVENTIONS: Survey. MAIN OUTCOME MEASUREMENTS: Percentage of the survey questions answered correctly and predictors of correct response. RESULTS: The survey was administered to 941 participants of whom 12 declined to participate. Eighty percent (n=740/929) of participants completed the survey. The median number of correct answers was 70% (interquartile range [IQR] 50%-90%) and was similar at each institution (P=.6). A total of 7.3% (n=54) of respondents answered all questions correctly. There was no significant difference in correct responses between attending physicians and trainees or between study centers (median 7, IQR 5-9; P=.75). Gastroenterologists were more likely to answer questions correctly than other subspecialists or primary care physicians (P<.0001). On multivariate analysis, physician knowledge correlated directly with self-reported familiarity with guidelines (0.21; 95% confidence interval [CI], 0.08-0.34; P=.002) and specialty (0.56; 95% CI, 0.30-0.82; P<.001) and inversely with year of medical school graduation (0.22; 95% CI, 0.07-0.37; P=.005). LIMITATIONS: Survey study that used theoretical scenarios. CONCLUSION: Physician knowledge of guidelines regarding antibiotic use before endoscopy is suboptimal. Further interventions are needed to improve the knowledge of before-procedure guidelines.

Documented compliance with inflammatory bowel disease quality measures is poor.

BACKGROUND AND AIMS: Quality metrics allows health care to be standardized and monitored. The American Gastroenterological Association (AGA) established quality metrics for inflammatory bowel disease (IBD) in 2011, but compliance is unknown. METHODS: Patients with IBD seen in the gastroenterology clinics at a tertiary care medical center during April 2013 were included. Charts were reviewed for the current state of compliance with the publicized AGA measures over the prior 12 months. Records were assessed for type of IBD, year of diagnosis, number of medications, comorbidities, hospitalizations and gastroenterology clinic visits in the last year, presence of primary care physician (PCP) at the institution, and involvement of a specialist in IBD or a trainee. Univariate and multivariate logistic regression analyses were done using SPSS. RESULTS: Only 6.5 % (24/367) of patients had all applicable core measures documented. In univariate analysis, year of IBD diagnosis (p = 0.014), number of comorbidities (p = 0.024), seen by a specialist in IBD (p = 0.002), seen by a gastroenterology fellow or resident (p = 0.034), and having a PCP at the institution (p = 0.006) were significant. In multivariate analysis, seen by a specialist in IBD (5.36, 95 % CI 1.22-23.63, p = 0.027), having a PCP at the institution (3.24, 95 % CI 1.23-8.54, p = 0.018), and year of IBD diagnosis (0.967, 95 % CI 0.937-0.999, p = 0.042) remained significant. Screening for tobacco abuse was the most frequently assessed (96 %, n = 352/367) core measure, while pneumococcal immunization (21 %, n = 76/367) was the least. CONCLUSION: Our study demonstrates poor compliance with IBD quality metrics. Additional studies are needed to determine the causes of failure to comply with the quality metrics.