PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (293)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
more »
1.  Influence of colonoscopy quality measures on patients’ colonoscopist selection 
Background
The Affordable Care Act emphasizes use of quality metrics and greater patient understanding of healthcare options and access to physician performance data. The objectives of this study were to determine patients’ familiarity with colonoscopy quality measures (CQM) and their influence on patient selection of a colonoscopist.
Methods
A prospective survey of patients before screening or surveillance colonoscopy at university hospital, community hospital, and ambulatory procedure center endoscopy units was performed from 2011 to 2012.
Results
Among the 417 participants, 20% (85/417) researched their physician’s rating. Rates of familiarity with CQM were 88 % (353/402) for adequate bowel preparation, 30% (118/398) for adenoma detection rate, 26% (102/397) for cecal intubation rate and 21% (82/394) for greater-than-six-minute withdrawal time. Ninety-six percent (366/386) believed colonoscopists’ reporting of adenoma detection rate to other physicians was important or very important. In selecting a colonoscopist, primary care provider referral was ranked as the first or second-most important of four factors in 87% (339/391). Even among patients who responded “it is very important” to report CQM to other doctors and patients, none ranked CQM as the most important factor in selecting a colonoscopist.
Conclusion
Patient awareness of CQM, other than adequate bowel preparation, was low. Quality measure reporting is important to patients, but primary care provider referral was the most important factor in colonoscopist selection. This suggests that primary care providers as well as patients are important to include in educational strategies regarding quality metrics.
doi:10.1038/ajg.2014.201
PMCID: PMC4413895  PMID: 25070055
2.  Computer-Generated Versus Physician-Documented History of Present Illness (HPI): Results of a Blinded Comparison 
Background
Healthcare delivery now mandates shorter visits with higher documentation requirements, undermining the patient-provider interaction. To improve clinic visit efficiency, we developed a patient-provider portal that systematically collects patient symptoms using a computer algorithm called Automated Evaluation of Gastrointestinal Symptoms (AEGIS). AEGIS also automatically “translates” the patient report into a full narrative history of present illness (HPI). We aimed to compare the quality of computer-generated vs. physician-documented HPIs.
Methods
We performed a cross-sectional study with a paired sample design among individuals visiting outpatient adult gastrointestinal (GI) clinics for evaluation of active GI symptoms. Participants first underwent usual care and then subsequently completed AEGIS. Each individual thereby had both a physician-documented and computer-generated HPI. Forty-eight blinded physicians assessed HPI quality across six domains using 5-point scales: (1) overall impression; (2) thoroughness; (3) usefulness; (4) organization; (5) succinctness; and (6) comprehensibility. We compared HPI scores within patient using a repeated measures model.
Results
Seventy-five patients had both computer-generated and physician-documented HPIs. The mean overall impression score for computer-generated HPIs was higher versus physician HPIs (3.68 vs. 2.80; p<.001), even after adjusting for physician and visit type, location, mode of transcription, and demographics. Computer-generated HPIs were also judged more complete (3.70 vs. 2.73; p<.001), more useful (3.82 vs. 3.04; p<.001), better organized (3.66 vs. 2.80; p<.001), more succinct (3.55 vs. 3.17; p<.001), and more comprehensible (3.66 vs. 2.97; p<.001).
Conclusion
Computer-generated HPIs were of higher overall quality, better organized, and more succinct, comprehensible, complete and useful compared to HPIs written by physicians during usual care in GI clinics.
doi:10.1038/ajg.2014.356
PMCID: PMC4289091  PMID: 25461620
3.  The Presence of Genetic Mutations at Key Loci Predicts Progression to Esophageal Adenocarcinoma in Barrett's Esophagus 
OBJECTIVES:
Risk stratification in Barrett's esophagus (BE) is challenging. We evaluated the ability of a panel of genetic markers to predict progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC).
METHODS:
In this case–control study, we assessed a measure of genetic instability, the mutational load (ML), in predicting progression to HGD or EAC. Cases had nondysplastic BE or low-grade dysplasia (LGD) at baseline and developed HGD/EAC ≥1 year later. Controls were matched 2:1, had nondysplastic BE or LGD, and no progression at follow-up. Formalin-fixed, paraffin-embedded tissue was microdissected for the epithelium. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were assessed. ML was calculated from derangements in 10 genomic loci. High-clonality LOH mutations were assigned a value of 1, low-clonality mutations were assigned a value of 0.5, and MSI 0.75 at the first loci, and 0.5 for additional loci. These values were summed to the ML. Receiver operator characteristic (ROC) curves were created.
RESULTS:
There were 69 patients (46 controls and 23 cases). Groups were similar in age, follow-up time, baseline histology, and the number of microdissected targets. Mean ML in pre-progression biopsies was higher in cases (2.21) than in controls (0.42; P<0.0001). Sensitivity was 100% at ML ≥0.5 and specificity was 96% at ML ≥1.5. Accuracy was highest at 89.9% for ML ≥1. ROC curves for ML ≥1 demonstrated an area under the curve (AUC) of 0.95.
CONCLUSIONS:
ML in pre-progression BE tissue predicts progression to HGD or EAC. Although further validation is necessary, ML may have utility as a biomarker in endoscopic surveillance of BE.
doi:10.1038/ajg.2015.152
PMCID: PMC4471888  PMID: 26010308
4.  Risk Factors for Chronic Liver Disease in Blacks, Mexican Americans, and Whites in the United States: Results From NHANES IV, 1999–2004 
OBJECTIVES
Morbidity and mortality due to liver disease and cirrhosis vary significantly by race/ethnicity in the United States. We examined the prevalence of liver disease risk factors among blacks, Mexican Americans, and whites, including elevated aspartate aminotransferase and alanine aminotransferase activity, infection with viral hepatitis B or hepatitis C, alcohol intake, obesity, diabetes, and metabolic syndrome.
METHODS
Data were obtained from the Fourth National Health and Nutrition Examination Survey (NHANES IV). A logistic regression was used to examine the association of race/ethnicity to liver disease risk factors, controlling for the demographic and socioeconomic variables.
RESULTS
Mexican-American men and women are the most likely to have elevated aminotransferase activity. Among men, Mexican Americans are more likely than whites to be heavy/binge drinkers, and blacks are more likely to have hepatitis B or hepatitis C. Among women, Mexican Americans are more likely than whites to be obese and diabetic, and less likely to be heavy/binge drinkers; blacks are more likely than whites to have hepatitis B or hepatitis C, be obese or diabetic, and less likely to be heavy/binge drinkers.
CONCLUSIONS
In this national sample, the prevalence of risk factors for liver disease varies by race/ethnicity. Mexican Americans and blacks have a greater risk of developing liver disease than their white counterparts. These findings are consistent with the observed racial/ethnic disparities in morbidity and mortality due to chronic liver disease and contribute to the efforts to identify the causes of these disparities. This information can be used by health professionals to tailor screening and intervention programs.
doi:10.1111/j.1572-0241.2008.02022.x
PMCID: PMC4462194  PMID: 18671818
5.  Acid-Based Parameters on pH-Impedance Testing Predict Symptom Improvement With Medical Management Better Than Impedance Parameters 
OBJECTIVES
pH-impedance testing detects reflux events irrespective of pH, but its value in predicting treatment outcome is unclear. We prospectively evaluated subjects treated medically after pH-impedance testing to determine predictors of symptom improvement.
METHODS
Subjects referred for pH-impedance testing completed questionnaires in which dominant symptoms and global symptom severity (GSS) were recorded. Acid-reflux parameters (acid-exposure time, AET; symptom association by Ghillebert probability estimate, GPE; symptom index, SI) and impedance reflux parameters (reflux-exposure time, RET; number of reflux events; GPE and SI with impedance data) were extracted. Symptoms and GSS were prospectively reevaluated after medical therapy. Univariate and multivariate analyses determined predictors of GSS improvement following medical management.
RESULTS
Over 5 years, 128 subjects (mean 53.3 ± 1.3 years, 66.4% female; typical symptoms 57.0%, 53.9% tested on therapy) underwent pH-impedance testing and subsequent medical therapy for reflux symptoms, and completed required questionnaires. On follow-up 3.35 ± 0.14 years later, mean GSS declined by 45.0%, with 42.2% patients reporting ≥50% GSS improvement. On univariate analysis, total AET, AET ≥4.0%, and GPE for all reflux events predicted both linear and ≥50% GSS improvement, but RET and number of reflux events did not. On multivariate analysis, controlling for testing on or off therapy, only AET (P = 0.003) and GPE for all reflux events (P = 0.029) predicted GSS improvement.
CONCLUSIONS
Acid-based reflux parameters offer greater value over impedance-based nonacid-reflux parameters in predicting symptomatic responses to proton pump inhibitor (PPI) therapy. Our findings support conducting pH-impedance studies off PPI therapy to maximize clinical utility in predicting outcome.
doi:10.1038/ajg.2014.63
PMCID: PMC4104528  PMID: 24732868
6.  Assessing Bolus Retention in Achalasia using High Resolution Manometry with Impedance: A Comparator Study with Timed Barium Esophagram 
Background
The aim of this study was to assess whether high-resolution impedance-manometry (HRIM) could be utilized to assess bolus retention similar to the timed barium esophagram (TBE).
Method
20 achalasia patients [10 males, ages 21–79] were prospectively evaluated with HRIM and TBE to determine the correlation between barium column height and the impedance bolus height (IBH). The TBE protocol utilized a 200 ml barium challenge and the HRIM protocol utilized a 200 ml saline challenge protocol. Both protocols were performed in an upright position and the heights of the barium and impedance columns were measured at 1 and 5 minutes. Analysis of IBH was performed with a topographic technique and a spatial impedance variation plot.
Results
There was no significant difference between the median IBH and barium column at 1 minute [IBH 12.0 cm (IQR, 8.0–18.0), TBE 12.0 cm (IQR, 7.0–19.0), P=0.90] or 5 minutes [IBH 11.0 cm (IQR, 1.0–17.0), TBE 9.0 cm (IQR, 4.0–12.0), P=0.47]. Additionally, the correlation between the two measurements at 1 and 5 minutes was 0.60 and 0.86, respectively. Using a barium column or impedance height of >5.0 as a definition of bolus retention was associated with 75% concordance at 1 minute and 95% concordance at 5 minutes.
Conclusion
There was excellent agreement between TBE and HRIM for assessing bolus retention at 5 minutes. Thus, HRM with impedance may be utilized as a single test to assess bolus retention and motor function in the management of achalasia.
doi:10.1038/ajg.2014.61
PMCID: PMC4307753  PMID: 24710506
Achalasia; manometry; esophagram; impedance
7.  Expression of Bile Acid Transporting Proteins in Barrett’s Esophagus and Esophageal Adenocarcinoma 
OBJECTIVES
Barrett’s esophagus (BE) is a metaplastic lesion characterized by replacement of the normal squamous epithelium by columnar intestinal epithelium containing goblet cells. It is speculated that this process is an adaptation to protect cells from components of refluxate, such as gastric acid and bile acids. In contrast to the normal squamous epithelium, enterocytes of the distal ileum are adapted to transport bile acids from the intestinal lumen. Several bile acid transporters are utilized for effective removal of bile acids, including the apical sodium-dependent bile acid transporter (ASBT), the ileal bile acid-binding protein (IBABP), and the multidrug-resistant protein 3 (MRP3). We hypothesized that one of the possible functions of newly arising metaplastic epithelium, in the esophagus, is to transport bile acids. Our major goal was to evaluate the expression of bile acid transporters in normal squamous epithelium, BE with different grades of dysplasia, and esophageal adenocarcinoma (EAC).
METHODS
A total of 101 patients were included in this study. Immunohistochemistry (IHC) and reverse transcriptase (RT)–PCR were used to detect the expression of these transporters at the mRNA and protein levels.
RESULTS
Our immunohistochemical studies showed that all three bile acid transporters are expressed in BE glands, but not in squamous epithelium. ASBT was found in the apical border in BE biopsies. The highest frequency of ASBT expression was in patients with nondysplastic BE (9 of 15, 60%), and a progressive loss of ASBT was observed through the stages of dysplasia. ASBT was not detected in EAC (0 of 15). IBABP staining was observed in the cytoplasm of BE epithelial surface cells. Expression of IBABP was found in 100% of nondysplastic BE (14 of 14), in 93% of low-grade dysplasia (LGD, 15 of 16), in 73% of high-grade dysplasia (HGD, 10 of 14), and in 33% of EAC (5 of 15). MRP3 was expressed in the basolateral membrane in 93% of nondysplastic BE (13 of 14), in 60% of LGD (10 of 16), and in 86% of HGD (11 of 13). Only weak MRP3 staining was detected in EAC biopsies (5 of 15, 33%). In addition, RT–PCR studies showed increased expression of mRNA coding for ASBT (6.1×), IBABP (9.1×), and MRP3 (2.4×) in BE (N = 13) compared with normal squamous epithelium (N = 15). Significantly increased mRNA levels of IBABP (10.1×) and MRP3 (2.5×) were also detected in EAC (N = 21) compared with normal squamous epithelium.
CONCLUSIONS
We found that bile acid transporters expression is increased in BE tissue at the mRNA and protein levels and that expression of bile acid transporter proteins decreased with progression to cancer.
doi:10.1038/ajg.2008.85
PMCID: PMC4450811  PMID: 19174784
8.  PERCEIVED AND ACTUAL QUALITY OF LIFE WITH ULCERATIVE COLITIS: A COMPARISON OF MEDICALLY AND SURGICALLY TREATED PATIENTS 
Purpose
Patients with chronic Ulcerative Colitis (UC) often refuse colectomy despite data indicating that it might improve quality of life. We hypothesized that perceived utility values are different for patients living with UC compared to UC patients after total proctocolectomy. Our aims were to compare the perceived utility assigned by UC patients with and without a colectomy to standardized chronic UC and post-colectomy scenarios, and to compare the utility of actual health states among groups.
Methods
We surveyed patients in a tertiary referral center from 3 groups including non-UC, UC patients without colectomy, and UC patients who were post-colectomy. We measured the Time-Trade-Off utilities of subjects for standardized scenarios describing moderate UC and a post-colectomy state. Among all UC patients (with and without colectomy), we measured Time-Trade-Off utility for their own health state.
Results
Responses were obtained from 150 patients per group (n=450). The non-UC patients regarded UC and colectomy scenarios equally (0.92), which was similar to UC patients without colectomy (0.90 and 0.91). Post-colectomy patients strongly preferred the colectomy scenario to the UC scenario (0.86 vs. 0.92, p<0.001). The median utility of UC patients without colectomy for their actual health state was higher than that of post-colectomy patients (0.96 and 0.92, p<0.05). Patients with more social support were more likely to have undergone colectomy compared with patients with little social support (OR=1.20 per dependent/supporter).
Conclusions
Patients living with UC prefer their actual health state to a perceived UC scenario or a post-colectomy scenario. Patients who have undergone colectomy equate the quality of life in their actual state with that in a post-colectomy scenario and prefer each to a perceived chronic UC state. Given the variety of preferences and the importance of social support, opportunities to interact with UC patients who have previously undergone colectomy could help patients living with UC and their physicians to navigate these complex choices.
doi:10.1038/ajg.2011.39
PMCID: PMC4429766  PMID: 21364547
10.  Underuse of Surveillance Colonoscopy in Patients at Increased Risk of Colorectal Cancer 
OBJECTIVES:
Colorectal cancer incidence and mortality have declined over the past two decades, and much of this improvement is attributed to increased use of screening. Approximately 25% of patients who undergo screening colonoscopy have premalignant adenomas that require removal and follow-up colonoscopy. However, there are few studies of the use of surveillance colonoscopy in increased risk patients with previous adenomas.
METHODS:
We conducted a cross-sectional study to examine factors associated with underuse of surveillance colonoscopy among patients who are at increased risk for colorectal cancer. The study population consisted of patients with previously identified adenomatous polyps and who were due for follow-up colonoscopy. Patients were categorized as attenders (n=100) or non-attenders (n=104) on the basis of completion of follow-up colonoscopy. Telephone surveys assessed the use of surveillance colonoscopy across domains of predisposing patient characteristics, enabling factors, and patient need. Mutlivariable logistic regression was used to identify factors associated with screening completion.
RESULTS:
Perceived barriers, perceived benefits, social deprivation, and cancer worry were associated with attendance at colonoscopy. Higher benefits (odds ratio (OR) 2.37, 95% confidence interval (CI) 1.04–5.41) and cancer worry (OR 1.73, 95% CI 1.07–2.79) increased the odds of attendance at follow-up colonoscopy, whereas greater barriers (OR 0.49, 95% CI 0.28–0.88) and high social deprivation (≥2; OR 0.09, 95% CI 0.01–0.76) were associated with lower odds.
CONCLUSIONS:
Our results suggest that multilevel factors contribute to the use of surveillance colonoscopy in higher risk populations, many of which are amenable to intervention. Interventions, such as patient navigation, may help facilitate appropriate use of surveillance colonoscopy.
doi:10.1038/ajg.2014.344
PMCID: PMC4422764  PMID: 25384901
11.  A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Evaluate the Efficacy, Safety, and Tolerability of Prucalopride in Men With Chronic Constipation 
OBJECTIVES:
Prucalopride is effective at alleviating symptoms of chronic constipation in women. The aim of this study was to assess the efficacy of 12 weeks of prucalopride treatment compared with placebo in men with chronic constipation.
METHODS:
This was a multicenter, stratified, randomized, parallel-group, double-blind, placebo-controlled, phase 3 study (ClinicalTrials.gov identifier: NCT01147926). The primary end point was the proportion of patients with a mean of three or more spontaneous complete bowel movements (SCBMs) per week across the treatment period. Efficacy end points were assessed using daily electronic diaries, global assessment of the severity of constipation and efficacy of treatment, and Patient Assessment of Constipation—Symptoms (PAC-SYM) and Patient Assessment of Constipation—Quality of Life (PAC-QOL) questionnaires.
RESULTS:
In total, 374 patients were enrolled in the study. Significantly more patients achieved a mean of three or more SCBMs per week in the prucalopride group (37.9%) than in the placebo group (17.7%, P<0.0001). The proportion of patients rating their constipation treatment as “quite a bit” to “extremely” effective at the final on-treatment visit was 46.7 and 30.4% in the prucalopride and placebo groups, respectively. The difference between treatment groups was statistically significant (P<0.0001). The proportion of patients with an improvement of at least 1 point in PAC-QOL satisfaction subscale score was 52.7 and 38.8% in the prucalopride and placebo groups, respectively (P=0.0035). Prucalopride had a good safety profile and was well tolerated.
CONCLUSIONS:
Prucalopride is effective, has a good safety profile, and is well tolerated for the treatment of men with chronic constipation.
doi:10.1038/ajg.2015.115
PMCID: PMC4424376  PMID: 25869393
12.  A Randomized, Placebo-Controlled Trial of Lubiprostone for Opioid-Induced Constipation in Chronic Noncancer Pain 
OBJECTIVES:
This multicenter, phase 3 trial evaluated oral lubiprostone for constipation associated with non-methadone opioids in patients with chronic noncancer-related pain.
METHODS:
Adults with opioid-induced constipation (OIC; <3 spontaneous bowel movements [SBMs] per week) were randomized 1:1 to double-blind lubiprostone 24 μg or placebo twice daily for 12 weeks. The primary end point was the overall SBM response rate. Responders had at least moderate response (≥1 SBM improvement over baseline frequency) in all treatment weeks with available observed data, as well as full response (≥3 SBMs per week) for at least 9 of the 12 treatment weeks.
RESULTS:
In total, 431 patients were randomized; 212 each received lubiprostone and placebo, and 7 were not treated. Overall, the SBM response rate was significantly higher for patients treated with lubiprostone vs. placebo (27.1 vs. 18.9%, respectively; P=0.030). Overall mean change from baseline in SBM frequency was significantly greater with lubiprostone vs. placebo (3.2 vs. 2.4, respectively; P=0.001). The median time to first SBM was significantly shorter with lubiprostone vs. placebo (23.5 vs. 37.7 h, respectively; P=0.004). Compared with placebo, the patients treated with lubiprostone exhibited significant improvements in straining (P=0.004), stool consistency (P<0.001), and constipation severity (P=0.010). No significant differences were observed in quality-of-life measures or the use of rescue medication; however, the percentage of patients who used rescue medication was consistently lower in the lubiprostone group than in the placebo group at months 1 (34.9 vs. 37.7%), 2 (23.4 vs. 26.6%), and 3 (20.5 vs. 22.0%). Adverse events (AEs) >5% were diarrhea, nausea, vomiting, and abdominal pain (lubiprostone: 11.3, 9.9, 4.2, and 7.1%, respectively; placebo, 3.8, 4.7, 5.2, and 0%, respectively). None of the serious AEs (lubiprostone, 3.3% placebo, 2.8%) were related to lubiprostone.
CONCLUSIONS:
Lubiprostone significantly improved symptoms of OIC and was well tolerated in patients with chronic noncancer pain.
doi:10.1038/ajg.2015.106
PMCID: PMC4424379  PMID: 25916220
13.  The Spectrum of Constipation-Predominant Irritable Bowel Syndrome and Chronic Idiopathic Constipation: US Survey Assessing Symptoms, Care Seeking, and Disease Burden 
Introduction:
The irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are associated with substantial symptom and disease burden. Although typically classified as distinct diseases, symptoms frequently overlap.
Aim:
The objective of this study was to characterize symptom and disease burden in IBS-C and CIC sufferers and examine a subset of CIC sufferers with abdominal symptoms.
Methods:
In a US population-based survey, respondents meeting the Rome III criteria for IBS-C or CIC rated symptom frequency and bothersomeness, missed work and disrupted productivity, and degree of obtaining and satisfaction with physician care. CIC respondents were analyzed in two subgroups: those with abdominal symptoms ≥once weekly (CIC-A) and those without (CIC-NA).
Results:
Of the 10,030 respondents, 328 met the criteria for IBS-C and 552 for CIC (363 CIC-A; 189 CIC-NA). All symptoms were significantly more frequent in IBS-C vs. CIC respondents (P<0.0001). Constipation was extremely/very bothersome in 72% of IBS-C respondents, 62% of CIC-A, and 40% of CIC-NA (P<0.01 all pairs). All 11 other measured symptoms were significantly more bothersome in IBS-C and CIC-A vs. CIC-NA respondents. In IBS-C vs. CIC-A, abdominal discomfort, bloating, straining, and pellet-like stools were also significantly more bothersome, with other remaining symptoms similar. Gastrointestinal symptoms disrupted productivity a mean of 4.9 days per month in IBS-C respondents, 3.2 in CIC-A, and 1.2 in CIC-NA (P<0.001 all pairs); missed days were similar in IBS-C and CIC-A respondents.
Conclusion:
CIC respondents with abdominal symptoms experience greater disease burden compared with CIC respondents without frequent abdominal symptoms and have a disease burden profile that is similar to IBS-C respondents.
doi:10.1038/ajg.2015.67
PMCID: PMC4424385  PMID: 25781368
14.  What Level of Bowel Prep Quality Requires Early Repeat Colonoscopy: Systematic Review and Meta-Analysis of the Impact of Preparation Quality on Adenoma Detection Rate 
OBJECTIVES
Current guidelines recommend early repeat colonoscopy when bowel preparation quality is inadequate, defined as inability to detect polyps > 5 mm, but no data link specific bowel preparation categories or scores to this definition. Nevertheless, most physicians use a shortened screening/surveillance interval in patients with intermediate-quality preparation. We determined whether different levels of bowel preparation quality are associated with differences in adenoma detection rates (ADRs: proportion of colonoscopies with ≥1 adenoma) to help guide decisions regarding early repeat colonoscopy—with primary focus on intermediate-quality preparation.
METHODS
MEDLINE and Embase were searched for studies with adenoma or polyp detection rate stratified by bowel preparation quality. Preparation quality definitions were standardized on the basis of Aronchick definitions (excellent/good/fair/poor/insufficient), and primary analyses of ADR trichotomized bowel preparation quality: high quality (excellent/good), intermediate quality (fair), and low quality (poor/insufficient). Dichotomized analyses of adequate (excellent/good/fair) vs. inadequate (poor/insufficient) were also performed.
RESULTS
Eleven studies met the inclusion criteria. The primary analysis, ADR with intermediate- vs. high-quality preparation, showed an odds ratio (OR) of 0.94 (0.80–1.10) and absolute risk difference of −1% (−3%, 2%). ADRs were significantly higher with both intermediate-quality and high-quality preparation vs. low-quality preparation: OR = 1.39 (1.08–1.79) and 1.41 (1.21–1.64), with absolute risk increases of 5% for both. ADR and advanced ADR were significantly higher with adequate vs. inadequate preparation: OR = 1.30 (1.19–1.42) and 1.30 (1.02–1.67). Studies did not report other relevant outcomes such as total adenomas per colonoscopy.
CONCLUSIONS
ADR is not significantly different with intermediate-quality vs. high-quality bowel preparation. Our results confirm the need for early repeat colonoscopy with low-quality bowel preparation, but suggest that patients with intermediate/fair preparation quality may be followed up at standard guideline-recommended surveillance intervals without significantly affecting quality as measured by ADR.
doi:10.1038/ajg.2014.232
PMCID: PMC4423726  PMID: 25135006
15.  Mycobacterium chelonae Bacteremia After First Dose of Infliximab for Ulcerative Colitis 
doi:10.1038/ajg.2014.209
PMCID: PMC4423733  PMID: 25196883
Inflammatory bowel disease; nontuberculous mycobacteria; anti-TNF
16.  Involvement of the iNKT Cell Pathway Is Associated With Early-Onset Eosinophilic Esophagitis and Response to Allergen Avoidance Therapy 
OBJECTIVES
Recent experimental evidence suggests that environmental microbial factors early in life determine susceptibility to allergic diseases through inappropriate chemotaxis and local activation of CD1d-restricted, invariant chain natural killer T (iNKT) cells. In this study, we analyzed the involvement of these pathways in pediatric patients with eosinophilic esophagitis (EoE) before and after dietary allergen elimination.
METHODS
mRNA expression levels of components of the C-X-C motif chemokine ligand 16 (CXCL16)–iNKT–CD1d axis were compared in esophageal biopsies from EoE patients vs. normal or inflammatory controls and before and after treatment.
RESULTS
CXCL16, iNKT cell–associated cell marker Vα24, and CD1d were significantly upregulated in esophageal biopsies from EoE patients and correlated with the expression of inflammatory mediators associated with allergy. Upregulation of each of these factors was significantly more pronounced in patients aged < 6 years at diagnosis, and this early-onset EoE subpopulation was characterized by a more prominent food allergic disease phenotype in a cohort-wide analysis. Successful, but not unsuccessful, treatment of early-onset EoE patients with dietary elimination of instigating allergens led to reduction in infiltrating iNKT cells and complete normalization of mRNA expression levels of CXCL16 and CD1d.
CONCLUSIONS
Our observations place iNKT cells at the center of allergic inflammation associated with EoE, which could have profound implications for our understanding, treatment and prevention of this and other human allergic diseases.
doi:10.1038/ajg.2014.12
PMCID: PMC4132949  PMID: 24513807
17.  Novel role of the serine protease inhibitor elafin in gluten-related disorders 
Objectives
Elafin, an endogenous serine protease inhibitor, modulates colonic inflammation. We investigated the role of elafin in celiac disease (CD) using human small intestinal tissues and in vitro assays of gliadin deamidation. We also investigated potential beneficial effects of elafin in a mouse model of gluten sensitivity.
Methods
Epithelial elafin expression in the small intestine of patients with active CD, treated CD and controls without CD was determined by immunofluorescence. Interaction of elafin with human tissue transglutaminase-2 (TG-2) was investigated in vitro. The 33-mer peptide, a highly immunogenic gliadin peptide, was incubated with TG-2 and elafin at different concentrations. The degree of deamidation of the 33-mer peptide was analyzed by liquid chromatography-mass spectrometry. Elafin was delivered to the intestine of gluten-sensitive mice using a recombinant Lactococcus lactis vector. Small intestinal barrier function, inflammation, proteolytic activity, and zonula occludens-1 (ZO-1) expression were assessed.
Results
Elafin expression in the small intestinal epithelium was lower in patients with active CD compared to control patients. In vitro, elafin significantly slowed the kinetics of the deamidation of the 33-mer peptide to its more immunogenic form. Treatment of gluten-sensitive mice with elafin delivered by the L. lactis vector normalized inflammation, improved permeability and maintained ZO-1 expression.
Conclusions
The decreased elafin expression in small intestine of patients with active CD, the reduction of 33-mer peptide deamidation by elafin, coupled to the barrier enhancing and anti-inflammatory effects observed in gluten sensitive mice, suggest this molecule may have pathophysiological and therapeutic importance in gluten-related disorders.
doi:10.1038/ajg.2014.48
PMCID: PMC4219532  PMID: 24710505
Gluten-sensitivity; elafin; celiac disease; proteolytic therapy
18.  Complementary and Alternative Medicine Use by U.S. Adults with Gastrointestinal Conditions: Results from the 2012 National Health Interview Survey 
Objectives
Use of complementary and alternative medicine (CAM) has increased over the past two decades, and a growing body of evidence suggests that some CAM modalities may be useful in addressing gastrointestinal (GI) conditions. However, the overall patterns of CAM use for GI conditions remains unknown. We sought to elucidate the prevalence and patterns of CAM use among U.S. adults with GI conditions.
Methods
We used the 2012 National Health Interview Survey (n=34,525), a nationally representative survey of the civilian, non-institutionalized U.S. population, to estimate the prevalence of CAM use among adults with GI conditions (abdominal pain, acid reflux/heartburn, digestive allergy, liver condition, nausea and/or vomiting, stomach or intestinal illness, ulcer). We also examined the reasons for CAM use, perceived helpfulness, and disclosure of use to health care providers among individuals who specifically used CAM to address a GI condition. Prevalence estimates were weighted to reflect the complex sampling design of the survey.
Results
Of 13,505 respondents with a GI condition in the past year, 42% (n=5629) used CAM in the past year and 3% (n=407) used at least one CAM modality to address a GI condition. The top 3 modalities among those using CAM to address GI conditions were herbs and supplements, mind body therapies, and manipulative therapies. Of those using CAM to address a GI condition, 47% used 3 or more CAM therapies, and over 80% felt that it was helpful in addressing a GI condition and was important in maintaining health and well-being. Respondents told their health care provider about use of these therapies 70% of the time.
Conclusions
CAM was used by 42% of respondents with a GI condition in the past year. A small proportion use CAM specifically to address their GI condition, but the majority who do find it helpful. The most commonly used modalities in this group are herbs and supplements, mind body, and manipulative therapies.
doi:10.1038/ajg.2014.108
PMCID: PMC4304651  PMID: 25001257
19.  Psychosocial Characteristics and Pain Burden of Patients With Suspected Sphincter of Oddi Dysfunction in the EPISOD Multicenter Trial 
OBJECTIVES
Patients with several painful functional gastrointestinal disorders (FGIDs) are reported to have a high prevalence of psychosocial disturbance. These aspects have not been studied extensively in patients with suspected Sphincter of Oddi dysfunction (SOD).
METHODS
A total of 214 patients with post-cholecystectomy pain and suspected SOD were enrolled in seven US centers in a multicenter-randomized trial (Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction). Baseline assessments included pain descriptors and burden, structured psychosocial assessments of anxiety/depression, coping, trauma, and health-related quality of life. Patients with high levels of depression, suicidal ideation, or psychosis were excluded.
RESULTS
The study population (92 % female, mean age 38) reported anxiety (9 %), depression (8 %), past sexual trauma (18 %), and physical abuse (10 %). Of the total screened population (n = 1460), 3.9 % of the patients were excluded because of the presence of defined severe psychological problems. The mean medical outcomes study short-form-36 (SF-36) physical and mental composite scores were 38.70 (s.d. = 7.89) and 48.74 (s.d. = 9.60), respectively. Most subjects reported symptoms of other FGIDs. There were no correlations between the extent of the pain burden in the 3 months before enrollment and the baseline anxiety scores or victimization history. However, those with greater pain burden were significantly more depressed. There were no meaningful differences in the psychosocial parameters in subjects with or without irritable bowel, and those who had cholecystectomy for stones or functional gallbladder disease. Those declining randomization were comparable to those randomized.
CONCLUSIONS
Psychosocial comorbidity in SOD is high. However, it does not appear to differ significantly from that reported in surveys of age-and gender-matched general populations, and may be lower than reported with other FGIDs.
doi:10.1038/ajg.2013.467
PMCID: PMC4409683  PMID: 24445573
20.  Lack of correlation between HRM metrics and symptoms during the manometric protocol 
Background & Aims
Although esophageal motor disorders are associated with chest pain and dysphagia, minimal data support a direct relationship between abnormal motor function and symptoms. This study investigated whether high resolution manometry (HRM) metrics correlate with symptoms.
Methods
Consecutive HRM patients without previous surgery were enrolled. HRM studies included 10 supine liquid, 5 upright liquid, 2 upright viscous, and 2 upright solid swallows. All patients evaluated their esophageal symptom for each upright swallow. Symptoms were graded on a 4 point likert score (0-none, 1-mild, 2-moderate, 3-severe). The individual liquid, viscous or solid upright swallow with the maximal symptom score was selected for analysis in each patient. HRM metrics were compared between groups with and without symptoms during the upright liquid protocol and the provocative protocols separately.
Results
269 patients recorded symptoms during the upright liquid swallows and 72 patients had a swallow symptom score of 1 or greater. 116 of the 269 patients recorded symptoms during viscous or solid swallows. HRM metrics were similar between swallows with and without associated symptoms in the upright, viscous, and solid swallows. No correlation was noted between HRM metrics and symptom scores among swallow types.
Conclusions
Esophageal symptoms are not related to abnormal motor function defined by HRM during liquid, viscous or solid bolus swallows in the upright position. Other factors beyond circular muscle contraction patterns should be explored as possible causes of symptom generation.
doi:10.1038/ajg.2014.13
PMCID: PMC4120962  PMID: 24513804
21.  The Problem of Helicobacter pylori Resistance to Antibiotics: A Systematic Review in Latin America 
OBJECTIVES
Latin America has a high prevalence of Helicobacter pylori infection and associated diseases, including gastric cancer. Antibiotic therapy can eradicate the bacterial infection and decrease associated morbidity and mortality. To tailor recommendations for optimal treatments, we summarized published literature and calculated region- and country-specific prevalences of antibiotic resistance.
METHODS
Searches of PubMed and regional databases for observational studies evaluating H. pylori antibiotic resistance yielded a total of 59 independent studies (56 in adults, 2 in children, and 1 in both groups) published up to October 2013 regarding H. pylori isolates collected between 1988 and 2011. Study-specific prevalences of primary resistance to commonly prescribed antibiotics were summarized using random-effects models. Between-study heterogeneity was assessed by meta-regression. As a sensitivity analysis, we extended our research to studies of patients with prior H. pylori-eradication therapy.
RESULTS
Summary prevalences of antimicrobial primary resistance among adults varied by antibiotic, including 12% for clarithromycin (n = 35 studies), 53% for metronidazole (n = 34), 4% for amoxicillin (n = 28), 6% for tetracycline (n = 20), 3% for furazolidone (n = 6), 15% for fluoroquinolones (n = 5), and 8% for dual clarithromycin and metronidazole (n = 10). Resistance prevalence varied significantly by country, but not by year of sample collection. Analyses including studies of patients with prior therapy yielded similar estimates. Pediatric reports were too few to be summarized by meta-analysis.
CONCLUSIONS
Resistance to first-line anti- H. pylori antibiotics is high in Latin American populations. In some countries, the empirical use of clarithromycin without susceptibility testing may not be appropriate. These findings stress the need for appropriate surveillance programs, improved antimicrobial regulations, and increased public awareness.
doi:10.1038/ajg.2014.24
PMCID: PMC4268863  PMID: 24589670
22.  Tryptase staining of mast cells may differentiate eosinophilic esophagitis from gastroesophageal reflux disease 
Objectives
Mast cells may contribute to the pathogenesis of eosinophilic esophagitis (EoE), but their role in diagnosis is unknown. Our aim was to determine whether tryptase staining of esophageal mast cells differentiates EoE from GERD and has utility for diagnosis of EoE.
Methods
We performed a case-control study comparing patients with EoE, defined by consensus guidelines, to GERD patients with eosinophils on esophageal biopsy. Immunohistochemistry was performed with mast cell tryptase. The density (mast cells/mm2) and intensity (0–4 scale) of mast cell staining was compared between groups after masking the diagnosis. Receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) calculated to assess mast cell staining as both a stand-alone diagnostic test and an adjunctive assay with eosinophil counts.
Results
Fifty-four EoE (mean age: 24; 69% male; mean 146 eos/hpf) and 55 GERD (mean age 34; 60% male; mean 20 eos/hpf) patients were analyzed. The maximum epithelial tryptase density was higher in EoE than in GERD (162 ± 87 mast cells/mm2 vs 67 ± 54; p<0.001). Mast cells were diffusely distributed throughout the biopsy in more EoE than GERD patients (41% vs 7%; p<0.001). Tryptase density and eosinophil count were only weakly correlated (R2=0.09; p=0.002). The AUC was 0.84 for tryptase staining alone, and 0.96 for the combination of mast cells and eosinophils.
Conclusions
Patients with EoE have higher levels of tryptase positive mast cells compared to GERD patients, improving the diagnostic value of biopsies beyond eosinophil counts alone. Mast cell tryptase may have utility as a diagnostic assay for EoE.
doi:10.1038/ajg.2010.412
PMCID: PMC4372242  PMID: 20978486
eosinophilic esophagitis; gastroesophageal reflux disease; mast cells; tryptase; diagnosis
23.  Biliary Multifocal Chromosomal Polysomy and Cholangiocarcinoma in Primary Sclerosing Cholangitis 
OBJECTIVES
Polysomy detected by fluorescence in situ hybridization (FISH) is associated with cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC). However, a subset of PSC patients with polysomy do not manifest CCA even after long-term follow-up. It is unknown if patients with chromosomal gains detected by FISH in multiple areas of the biliary tree (i.e., multifocal polysomy, MFP) are more likely to be diagnosed with CCA than patients with unifocal polysomy (UFP). Therefore, our aim is to determine whether patients with MFP are more likely to manifest CCA compared with patients with other chromosomal abnormalities including UFP and other FISH subtypes.
METHODS
We performed a retrospective review of PSC patients without a mass lesion who underwent FISH testing at our institution from 1 January 2005 to 1 July 2013.
RESULTS
Three-hundred and seventy-one PSC patients were included. Compared with patients with UFP, those with MFP were more likely to have weight loss (32 vs. 9%), suspicious cytology (45 vs. 13%) and develop serial polysomy (91 vs. 35%). MFP was associated with CCA (hazard ratio (HR), 82.42; 95% confidence interval (CI), 24.50–277.31) and was the strongest predictor of cancer diagnosis. Suspicious cytology (HR, 26.31; 95% CI, 8.63–80.24) and UFP (HR, 13.27; 95% CI, 3.32–53.08) were also predictive of CCA. MFP, UFP and suspicious cytology remained associated with CCA in the multivariable model.
CONCLUSIONS
Compared with other FISH subtypes, MFP is the strongest predictor of CCA. However, patients with UFP and suspicious cytology (regardless of FISH status) are also at an increased risk for CCA.
doi:10.1038/ajg.2014.433
PMCID: PMC4349337  PMID: 25623660
25.  Patient Perception of Treatment Burden is High in Celiac Disease Compared to Other Common Conditions 
Introduction
The only treatment for celiac disease (CD) is life-long adherence to a gluten-free diet (GFD). Noncompliance is associated with signs and symptoms of celiac disease, yet long-term adherence rates are poor. It is not known how the burden of the GFD compares to other medical treatments, and there are limited data on the socio-economic factors influencing treatment adherence. In this study we compared treatment burden and health state in CD compared with other chronic illnesses and evaluated the relationship between treatment burden and adherence.
Methods
A survey was mailed to participants with: CD, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), hypertension (HTN), diabetes mellitus (DM), congestive heart failure (CHF), and end stage renal disease on dialysis (ESRD). Surveys included demographic information and visual analog scales measuring treatment burden, importance of treatment, disease-specific and overall health status.
Results
We collected surveys from 341 celiac and 368 non-celiac participants. Celiac participants reported high treatment burden, greater than participants with GERD or HTN and comparable to ESRD. Conversely, patients with CD reported the highest health state of all groups. Factors associated with high treatment burden in CD included poor adherence, concern regarding food cost, eating outside the home, higher income, lack of college education and time limitations in preparing food. Poor adherence in CD was associated with increased symptoms, income, and low perceived importance of treatment.
Discussion
Participants with CD have high treatment burden but also excellent overall health status in comparison with other chronic medical conditions. The significant burden of dietary therapy for celiac disease argues for the need for safe adjuvant treatment as well as interventions designed to lower the perceived burden of the GFD.
doi:10.1038/ajg.2014.29
PMCID: PMC4159418  PMID: 24980880
celiac disease; treatment burden; gluten free diet; adherence

Results 1-25 (293)