Background

Infliximab (IFX) therapy escalation during maintenance treatment occurs frequently in clinical practice in patients with ulcerative colitis (UC). Outcomes for these patients have not been described.

Aim

To describe the prevalence of, and outcomes after, IFX escalation during maintenance therapy in patients with moderate-severe UC.

Methods

Retrospective observational study of clinical outcomes in ambulatory patients with moderate-severe UC treated with maintenance IFX.

Results

Fifty-six ambulatory patients received IFX for moderate-severe UC; fifty (89%) responded and proceeded to maintenance therapy. Mean duration of maintenance therapy was 14 months, with mean follow-up of 38 months. Twenty-seven patients (54%) required IFX therapy escalation after a mean of 6 maintenance infusions. Clinical remission was noted in 36% of the entire cohort (18/50) at 12 months; 19% in the escalation group, and 56% in the non-escalation group. Patients who required IFX escalation were less likely to be in clinical remission at 12 months (OR 0.2, 95% CI 0.1-0.6, p=0.01) when compared to those who did not. During the follow-up period, 27% of patients required a colectomy, and the mean time to colectomy was 17 months. Patients in the escalation group required a colectomy in 33% of cases, compared with 21% of non-escalation patients.

Conclusions

A significant proportion of ambulatory patients with UC treated with maintenance IFX required therapy escalation over time. This was associated with lower remission, and higher colectomy, rates.

SUMMARY

Background

Community-acquired Clostridium difficile infection (CA-CDI) is an increasingly appreciated condition. It is being described in populations lacking traditional predisposing factors that have been previously considered at low-risk for this infection. As most studies of CDI are hospital-based, outcomes in these patients are not well known.

Aim

To examine outcomes and their predictors in patients with CA-CDI.

Methods

A sub-group analysis of a population-based epidemiological study of CDI in Olmsted County, Minnesota from 1991-2005 was performed. Data regarding outcomes, including severity, treatment response, need for hospitalization and recurrence were analyzed.

Results

Of 157 CA-CDI cases, the median age was 50 years and 75.3% were female. Among all CA-CDI cases, 40% required hospitalization, 20% had severe and 4.4% had severe-complicated infection, 20% had treatment failure and 28% had recurrent CDI. Patients who required hospitalization were significantly older (64 vs 44 years, p<0.001), more likely to have severe disease (33.3% vs 11.7%, p=0.001), and had higher mean Charlson comorbidity index scores (2.06 vs 0.84, p=0.001). They had similar treatment failure and recurrence rates as patients who did not require hospitalization.

Conclusions

CA-CDI can be associated with complications and poor outcomes, including hospitalization and severe CDI. As the incidence of CA-CDI increases, clinicians should be aware of risk factors (increasing age, comorbid conditions and disease severity) that predict the need for hospitalization and complications in patients with CA-CDI.

SUMMARY

Background

The AST to platelet ratio index (APRI), a non-invasive marker of liver fibrosis, has not been well studied in HCV/HIV (hepatitis C virus/human immunodeficiency virus) co-infected patients with advanced HIV.

Aim

To compare the accuracy of APRI in HCV/HIV co-infected patients to that in HCV mono-infected patients and to determine the impact of CD4+ T-cell counts on its performance.

Methods

We identified 106 consecutive HCV/HIV co-infected patients and 105 matched HCV mono-infected patients who underwent liver biopsy at Harborview Medical Center over a 5-year period. Performance characteristics were calculated and receiver operating characteristic (ROC) analysis conducted.

Results

The area under the ROC curve (AUROC) of APRI for predicting significant fibrosis was similar when comparing those with and without HIV co-infection (0.77 vs. 0.86, P = 0.18), but was lower in HIV co-infected patients with CD4 counts <250 cells/mm3 (0.64 vs. 0.86, P = 0.05). In HIV co-infected patients with CD4 counts ≥250, APRI had higher negative predictive value (93% vs. 88%, P = 0.57), positive predictive value (63% vs. 40%, P = 0.43) and specificity (95% vs. 88%, P = 0.05) than in those with lower CD4 counts.

Conclusions

The AST to platelet ratio index (APRI) performance characteristics appear to be suboptimal in HCV/HIV co-infected patients with CD4 counts <250 and they require further study in this population at increased risk for advanced liver disease.

Background

Silymarin is the most commonly used herbal product for chronic liver disease, yet whether silymarin protects against liver disease progression remains unclear.

Aim

To assess the effects of silymarin use on subsequent liver disease progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had failed prior peginterferon plus ribavirin treatment.

Methods

Patients recorded their use of similymarin at baseline and were followed for liver disease progression (two point increase in Ishak fibrosis score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for clinical outcomes.

Results

At baseline, 34% of patients had ever taken silymarin, half of whom were current users. Use of silymarin was associated (p <0.05) with male sex; esophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among other features. Baseline users had less hepatic collagen content on study biopsies and had less histologic progression (HR: 0.57, 95%CI: 0.33–1.00; p-trend for longer duration of use=0.026). No effect was seen for clinical outcomes.

Conclusion

Silymarin use among patients with advanced hepatitis C-related liver disease is associated with reduced progression from fibrosis to cirrhosis, but has no impact on clinical outcomes. The HALT-C Trial was registered with Clinicaltrials.gov (#NCT00006164).

SUMMARY

Background

Thiazolidinediones (TZDs) have been used in the treatment of non-alcoholic steatohepatitis (NASH). However, the magnitude of treatment response associated with TZDs in improving liver histology in NASH has not been quantified systematically.

Aim

To conduct a meta-analysis of randomised, placebo-controlled clinical trials (RPCTs) using pioglitazone and rosiglitazone in the treatment of NASH.

Methods

Pubmed/MEDLINE and Cochrane Central Register of Controlled Trials 2010 were searched until September 2010 and four RPCTs were identified. Peto odds ratios (ORs) and their respective 95% confidence intervals (CIs) were used to assess the efficacy of TZDs in improving liver histological parameters.

Results

Four good quality RPCTs derived from three continents were included. The meta-analysis showed that TZDs (n = 169) were significantly better than placebo (n = 165) in improving ballooning degeneration, lobular inflammation and steatosis with combined ORs of 2.11 (95% CI, 1.33–3.36), 2.58 (95% CI, 1.68–3.97) and 3.39 (95% CI, 2.19–5.25) respectively. The improvement in combined necroinflammation with TZD (n = 58) vs. placebo (n = 52) was also statistically significant (combined OR 6.52[95% CI, 3.03–14.06]), but improvement in fibrosis was not. When pioglitazone (n = 137) was analysed alone, the improvement in fibrosis with pioglitazone (n = 137) vs. placebo (n = 134) (combined OR 1.68 [95% CI, 1.02–2.77]) was statistically significant. The total body fat slightly decreased in the control, while it markedly and highly significantly increased with TZD treatment.

Conclusions

Thiazolidinediones significantly improve ballooning degeneration, lobular inflammation, steatosis and combined necroinflammation in patients with NASH. Pioglitazone may improve fibrosis. Larger randomised, placebo-controlled clinical trials are needed to examine the efficacy of thiazolidinediones in improving NASH fibrosis.

The majority of patients with biliary tract carcinoma (cholangiocarcinoma and cancer of the gall bladder) present with advanced, irresectable tumours associated with poor prognosis. Death commonly occurs secondary to recurrent biliary obstruction and intra-biliary sepsis, rather than metastatic disease. The only current potentially curative treatment is surgical resection, but this remains possible in less than a third of patients.

The incidence and mortality rates associated with biliary tract carcinoma continue to rise, mandating the development of novel strategies for early detection, improved resection techniques and treatment of residual lesions. However, there remains limited data on the use of neo-adjuvant and adjuvant techniques and much of the literature to date concerns palliation of inoperable disease. Here, we review the current evidence base for surgical, neo-adjuvant and adjuvant management techniques in biliary tract carcinoma.

Background

Endoscopic screening has been proposed for patients with symptoms of gastro-oesophageal reflux disease (GERD) in the hope of reducing mortality from oesophageal adenocarcinoma. Assessing the net benefits of such a strategy requires a precise understanding of the cancer risk in the screened population.

Aim

To estimate precisely the association between symptoms of GERD and oesophageal adenocarcinoma.

Methods

Systematic review and meta-analysis of population-based studies with strict ascertainment of exposure and outcomes.

Results

Five eligible studies were identified. At least weekly symptoms of GERD increased the odds of oesophageal adenocarcinoma fivefold (odds ratio = 4.92; 95% confidence interval = 3.90, 6.22), and daily symptoms increased the odds sevenfold (random effects summary odds ratio = 7.40, 95% confidence interval = 4.94, 11.1), each compared with individuals without symptoms or less frequent symptoms. Duration of symptoms was also associated with oesophageal adenocarcinoma, but with very heterogeneous results, and unclear thresholds.

Conclusions

Frequent GERD symptoms are strongly associated with oesophageal adenocarcinoma. These results should be useful in developing epidemiological models of the development of oesophageal adenocarcinoma, and in models of interventions aimed at reducing mortality from this cancer.

BACKGROUND

Pancreatic enzyme supplementation is standard treatment for malabsorption due to chronic pancreatitis. The FDA recently required all manufacturers to submit New Drug Applications (NDAs) to continue to market these agents because published data demonstrated variation in formulation, bioavailability, and shelf-life while providing limited data about efficacy and safety.

AIM

To systematically review the design and results of randomized, parallel-design trials of pancreatic enzyme supplements in chronic pancreatitis patients with steatorrhea.

METHODS

A computer-assisted search of MEDLINE and EMBASE was performed to identify relevant studies. Two authors performed duplicate data extraction on study design, improvement in coefficient of fat absorption (CFA), diarrhea, and adverse events using pre-specified forms. Agreement between investigators for data extraction was greater than 95%.

RESULTS

Of 619 articles found through literature searching, 20 potentially relevant articles were identified and 4 manuscripts met inclusion criteria. No studies performed head-to-head comparisons of different supplements. Enzyme supplementation is more likely to improve CFA compared to placebo, but fat malaborption remained abnormal. Important differences in patient population, study endpoint, study design, pancreatic enzyme dosage, and measurement of CFA were present across trials which precluded comparison of different agents.

CONCLUSIONS

Enzyme supplementation improves CFA compared to placebo but may not abolish steatorrhea.

SUMMARY

Background

Adefovir and tenofovir are nucleotide analogues used as long-term therapy of chronic hepatitis B. Side effects are few, but prolonged and high-dose therapy has been associated with proximal renal tubular dysfunction (RTD).

Aim

To assess the incidence of RTD during long-term nucleotide therapy of chronic hepatitis B.

Methods

A total of 51 patients being treated at the Clinical Center, National Institutes of Health were studied. Diagnosis of RTD required de novo appearance of at least three of five features: hypophosphataemia, hypouricaemia, serum creatinine elevation, proteinuria or glucosuria.

Results

Among 51 patients treated for 1–10 (mean 7.4) years with adefovir (n = 42), tenofovir (n = 4) or adefovir followed by tenofovir (n = 5), 7 (14%) developed RTD. Time to onset ranged from 22 to 94 (mean 49) months with an estimated 10-year cumulative rate of 15%. All seven had low urinary percent maximal tubular reabsorption of phosphate (<82%). Patients with RTD were older (58 vs. 44 years; P = 0.01) and had lower baseline glomerular filtration rates (82 vs. 97 cc/min; P = 0.08) compared to those without; but did not differ in other features. Six patients with RTD were switched to entecavir, all subsequently had improvements in serum phosphate (2.0–3.0 mg/dL), creatinine (1.6–1.1 mg/dL), uric acid (2.7 –3.8 mg/dL) and proteinuria.

Conclusions

Renal tubular dysfunction develops in 15% of patients treated with adefovir or tenofovir for 2–9 years and is partially reversible with change to other antivirals. Monitoring for serum phosphate, creatinine and urinalysis is prudent during long-term adefovir and tenofovir therapy.

SUMMARY

Background

Conventional magnetic resonance imaging (MRI) techniques that measure hepatic steatosis are limited by T1 bias, T2* decay and multi-frequency signal-interference effects of protons in fat. Newer MR techniques such as the proton density-fat fraction (PDFF) that correct for these factors have not been specifically compared to liver biopsy in adult patients with non-alcoholic fatty liver disease (NAFLD).

Aim

To examine the association between MRI-determined PDFF and histology-determined steatosis grade, and their association with fibrosis.

Methods

A total of 51 adult patients with biopsy-confirmed NAFLD underwent meta-bolic-biochemical profiling, MRI-determined PDFF measurement of hepatic steatosis and liver biopsy assessment according to NASH-CRN histological scoring system.

Results

The average MRI-determined PDFF increased significantly with increasing histology-determined steatosis grade: 8.9% at grade-1, 16.3% at grade-2, and 25.0% at grade-3 with P ≤ 0.0001 (correlation: r2 = 0.56, P < 0.0001). Patients with stage-4 fibrosis, when compared with patients with stage 0–3 fibrosis, had significantly lower hepatic steatosis by both MRI-determined PDFF (7.6% vs. 17.8%, P < 0.005) and histology-determined steatosis grade (1.4 vs. 2.2, P < 0.05). NAFLD patients with grade 1 steatosis were more likely to have characteristics of advanced liver disease including higher average AST:ALT (0.87 vs. 0.60, P < 0.02), GGT (140 vs. 67, P < 0.01), and INR (1.06 vs. 0.99, P < 0.01), higher stage of fibrosis and hepatocellular ballooning.

Conclusions

MRI-determined proton density-fat fraction correlates with histology-determined steatosis grade in adults with NAFLD. Steatosis is non-linearly related to fibrosis progression. In patients with NAFLD, a low amount of hepatic steatosis on imaging does not necessarily indicate mild disease.

SUMMARY

Background

Racial and ethnic differences in the risk of premalignant colorectal neoplasia have not been extensively studied.

Aim

To measure adenoma prevalence among asymptomatic white, black and Hispanic patients undergoing screening colonoscopy.

Methods

In this cross sectional cohort study, data from individuals ≥50 years undergoing first-time colonoscopy since 2006 at a single tertiary-care medical centre were obtained from the electronic medical record. Adenoma prevalence among whites, blacks and Hispanics was calculated; multivariate Poisson and logistic regression were used to identify factors independently associated with adenoma rates and the presence of advanced adenomas.

Results

We identified 5075 eligible subjects: 3542 (70%) whites, 942 (18%) Hispanics and 591 (12%) blacks. The mean age was 62.2 years with 58% women. At least one adenoma was detected in 19%, 22% and 26% of whites, Hispanics and blacks respectively (Hispanics vs. whites P = 0.09; blacks vs. whites P = 0.0001). Isolated proximal adenomas were present in 9% of whites, 11% of Hispanics (P = 0.03) and 11% of blacks (P = 0.03). In multivariate analyses, a higher rate of adenomas was present in Hispanics (RR: 1.37, 95% CI: 1.20–1.57) and blacks (RR: 1.76, 95% CI: 1.52–2.04) than whites. Hispanics and blacks also had an increased risk of advanced adenomas compared to whites (ORHispanics: 2.25, 95% CI: 1.62–3.11; ORblacks: 1.91, 95% CI: 1.27–2.86).

Conclusions

Adenoma prevalence was higher in blacks and Hispanics than in whites. Both groups were at greater risk of having proximal adenomas in the absence of any distal pathology than whites, where these lesions would have only been detected by colonoscopy. Efforts to promote screening are necessary among diverse, under-represented populations.

SUMMARY

Background

The association of anaemia with outcomes in the HCV/HIV coinfected persons undergoing HCV treatment remains unclear.

Aims

To study the incidence, predictors and management of anaemia, and its association with outcomes among persons treated with pegylated interferon and weight-based ribavirin.

Methods

Retrospective analysis of a prospective controlled treatment trial of HCV/HIV coinfection.

Results

Among 329 subjects enrolled, 40% developed anaemia during the first 12–18 weeks of treatment (median haemoglobin decrease at week 4: 2.2 g/dL). Among 169 subjects who achieved early virological response and received therapy for 72 weeks, 55% eventually developed anaemia. However, median haemoglobin levels stayed stable after 12–18 weeks of initial therapy. Among these 169 subjects, 45% were prescribed an erythropoiesis stimulating agent (ESA), with 17% receiving it prior to a drop in haemoglobin meeting protocol definition of anaemia. Only 27% completed the study without any ribavirin dose modification. Age >40 years, lower BMI, zidovudine use and lower entry haemoglobin were significant predictors of anaemia in the multi-covariate model. Among all 329, sustained virological response (SVR) rate was similar in those with or without anaemia (23% vs. 30%; P = 0.17) with no evidence of association between anaemia or ESA use and treatment response.

Conclusions

Anaemia is common in HCV/HIV coinfected persons undergoing HCV treatment, and only a minority of them are able to maintain ribavirin dose. Persons with age >40 years, lower baseline haemoglobin and lower baseline BMI should be monitored carefully. Prescription of erythropoiesis stimulating agent is common, but anaemia or erythropoiesis stimulating agent use is not associated with SVR.

SUMMARY

Background

Chronic use of NSAIDs is associated with GI toxicity that increases with age.

Aims

The GI safety and therapeutic efficacy of Ibuprofen chemically associated with phosphatidylcholine (PC) was evaluated in osteoarthritic (OA) patients.

Methods

A randomized, double-blind trial of 125 patients was performed. A dose of 2400 mg/day of ibuprofen or an equivalent dose of Ibuprofen-PC was administered for 6 weeks. GI safety was assessed by endoscopy. Efficacy was assessed by scores of analgesia and anti-inflammatory activity. Bioavailability of ibuprofen was pharmacokinetically assessed.

Results

Ibuprofen-PC and ibuprofen provided similar bioavailability/therapeutic efficacy. In the evaluable subjects a trend for improved GI safety in the Ibuprofen-PC group compared with ibuprofen was observed, that did not reach statistical significance. However, in patients >55 years of age, a statistically significant advantage for Ibuprofen-PC treatment vs ibuprofen in the prevention of NSAID-induced gut injury was observed with increases in both mean Lanza scores and the risk of developing > 2 erosions or an ulcer. Ibuprofen-PC was well tolerated with no major adverse events observed.

Conclusions

Ibuprofen-PC is an effective osteoarthritic agent with an improved GI safety profile compared to ibuprofen in older OA patients, who are most susceptible to NSAID-induced gastroduodenal injury.

Background

Prospective data are lacking to determine if IBS a risk factor for cholecystectomy, or if biliary disease and cholecystectomy predisposes to the development of IBS.

Methods

Validated symptom surveys sent to cohorts of Olmsted County, MN, (1988–1994) with follow-up in 2003. Medical histories were reviewed to determine any “biliary events” (defined by gallstones or cholecystectomy). Analyses examined: 1) time to a biliary event post initial survey and separately, 2) risk of IBS (Rome II) in those with vs. without a prior biliary event.

Results

1908 eligible subjects mailed a follow-up survey. For aim 1) of the 726 without IBS at initial survey, 44 (6.1%) had biliary events during follow up, in contrast to 5 of 93 (5.4%) with IBS at initial survey (HR 0.8, 95% CI 0.3-2.1). For aim 2) of the 59 subjects with a biliary event at initial survey, 10 (17%) reported new IBS on the follow-up survey, while in 682 without a biliary event up to 1.5 years prior to the second survey, 58 (8.5%) reported IBS on follow-up (OR=2.2, 95% CI 1.1-4.6, p=0.03).

Conclusion

There is an increased risk of new IBS in community subjects who have been diagnosed as having a biliary event.

Background

Liver stiffness assessed by transient elastography is described as a potential risk factor for hepatocellular carcinoma (HCC) in cirrhosis. However, the strict assessment of hepatic parenchymal areas uninvolved with HCC has not been investigated.

Aims

To determine if liver stiffness of non-malignant hepatic parenchyma by MR elastography (MRE) is higher in patients with HCC compared to controls.

Methods

Cases were defined by compensated cirrhosis with a Child-Turcotte-Pugh (CTP) score < 7 and HCC by radiological criteria or histology. Control subjects with compensated cirrhosis were frequency matched to cases by sex and disease etiology. Overt manifestations of portal hypertension and previous therapy for liver disease or HCC were exclusion criteria. Region of interest analyses were performed on hepatic parenchyma regions distant to HCC location among cases.

Results

30 patients with HCC and 60 matched controls comprised the study cohort. The mean age for cases was 64 ± 10 years (range, 45–85) with 70% men. Major disease etiologies were chronic viral hepatitis (57%), nonalcoholic fatty liver disease (33%), and alcohol (10%). Twenty-eight (93%) patients had solitary HCC lesions with a mean size of 5.2 cm (range, 2–14 cm). However, patients with HCC had similar liver stiffness among uninvolved areas distant to HCC lesions as compared to controls without HCC (mean, 6.1±2.0 kPa vs. mean, 6.3 ± 2.5 kPa, p=0.7).

Conclusion

In contrast to previous studies with transient elastography, we did not observe a systematic association between liver stiffness assessed by MRE and the presence of HCC in patients with compensated cirrhosis.

Summary

Background

Cough may be a manifestation of gastro-esophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain.

Aim

To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn.

Methods

Subjects were non-smokers without history of asthma, with chronic cough for > 8 weeks. All subjects underwent a baseline 24 hr pH/impedance study, methacholine challenge test (MCT), and laryngoscopy. Subjects were randomized to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores, and change in laryngeal findings.

Results

40 subjects were randomized (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8, vs. 5.9 in placebo, p = 0.3), or Fisman Cough Severity/Frequency scores. The proportion of patients who improved by >1 standard deviation on the CQLQ was 27.8% (5/18) and 31.8% (7/22) in the placebo and PPI groups respectively.

Conclusions

In subjects with chronic cough and rare or no heartburn, high-dose PPI did not improve cough-related quality of life or symptoms in this randomized controlled trial.

Background

Effectiveness of medical therapies in chronic pancreatitis (CP) has been described in small studies of selected patients.

Aim

To describe frequency and perceived effectiveness of non-analgesic medical therapies in CP patients evaluated at U.S. referral centers.

Methods

Using data on 516 CP patients prospectively enrolled in the NAPS2 Study, we evaluated how often medical therapies (pancreatic enzyme replacement therapy [PERT], vitamins/antioxidants [AO], octreotide, celiac plexus block [CPB]) were utilized and considered useful by physicians.

Results

Oral PERT was commonly used (70.3%), more frequently in the presence of exocrine insufficiency (EI) (87.8 vs. 61%, p<0.001), and pain (73.7 vs. 59.2%, p<0.002). On multivariable analyses, predictors of PERT usage were EI (OR 5.14, 95% CI 2.87-9.18), constant (OR 3.42, 95% CI 1.93-6.04) or intermittent pain (OR 1.98, 95% CI 1.14-3.45). Efficacy of PERT was predicted only by EI (OR 2.16, 95% CI 1.36-3.42). AO were tried less often (13.8%) and were more effective in idiopathic and obstructive vs. alcoholic CP (25% vs. 3.6%, p=0.03). Other therapies were infrequently used (CPB-5.4%, octreotide-6.6%) with efficacy generally <50%.

Conclusions

PERT is commonly utilized, but is considered useful in only subsets of CP patients. Other medical therapies are used infrequently and have limited efficacy.

Background

Although direct medical costs for constipation related medical visits are thought to be high, to date there have been no studies examining longitudinal resource utilization in adults with constipation.

Aim

To estimate the incremental direct medical costs associated with constipation in women.

Methods

This is a nested case-control study. The study population consisted of all mothers of 5,718 children in the population-based birth cohort born during 1976-1982 in a community. The cases presented to the medical facilities with constipation. The controls were randomly selected and matched to cases in a 2:1 ratio. Direct medical costs for constipated women and controls were collected for the years 1987-2002.

Results

We identified 168 women with a diagnosis of constipation. The total direct medical costs over a 15-year period for constipated subjects were more than double those of controls ($63,591 [95%CI: 49,786- 81,396]) vs. $24,529 [95%CI: 20,667-29,260]). The overall outpatient costs for constipated women were $38,897 (95% CI: 31,381-48,253) compared to $15,110 (95% CI: 12,904-17,781) for controls. The median annual outpatient visits for constipated women was 0.16 compared to 0.11 for controls.

Conclusion

Women with constipation have significantly higher medical care utilization and expenditures compared to women without constipation.

Background

Although consensus guidelines for eosinophilic esophagitis (EoE) have been published, it is unclear whether gastroenterologists follow these recommendations.

Aim

To assess academic and community practice patterns for the evaluation and treatment of EoE and to compare these practices with current guidelines.

Methods

This was a prospective study of academic and community gastroenterologists using a self-administered online survey.

Results

A total of 60% (34 of 57) of academic and 29% (38 of 133) of community gastroenterologists completed the survey. Only 24% of academic and 3% of community gastroenterologists follow consensus guidelines to diagnose EoE (p=0.007). A proton pump inhibitor trial or negative pH study prior to diagnosis was required by just 25% of all gastroenterologists. The majority (60%) do not use the recommended threshold of 15 eosinophils per high powered field to diagnosis EoE. Half (51%) mistakenly require a positive endoscopic finding. For first line treatment, about half of the gastroenterologists surveyed treat with a swallowed topical steroid (53% academic, 56% community; p=NS), consistent with the guidelines.

Conclusions

There is variability in practice patterns for both diagnosis and treatment of EoE. Ongoing education and research concerning diagnosis and treatment is needed.

Background

Body-mass-index (BMI) and alcohol consumption predict elevated serum alanine (ALT) and aspartate (AST) aminotransferase levels in young adults. It is unclear if alcohol intake and BMI and their joint association have a differential effect on ALT and AST levels in older adults.

Objective

To determine the association between alcohol, BMI, and their combined effect with serum ALT and AST in older community-dwelling adults in the United States.

Design and Setting

A cross-sectional, population-based study in older adults

Participants

(n=2364) from the Rancho Bernardo Study (54% women; mean age: 70 years, BMI: 25 kg/m2, alcohol users: 63%) who attended a research visit in 1984-87. BMI was recorded by a trained nurse and alcohol use ascertained by a validated questionnaire.

Outcome

Multiply adjusted odds-ratio (OR) and 95% confidence intervals (CI) of elevated serum ALT and AST (defined as ≥ 30 U/L in men and ≥ 19 U/L in women) were calculated for alcohol and BMI separately and their joint exposure using multivariate logistic regression models adjusted for age, body mass index, total cholesterol, serum triglycerides, fasting plasma glucose, systolic blood pressure, and diabetes mellitus.

Results

In multivariate-adjusted logistic regression models, obesity independently increased the odds of elevated ALT in this cohort of older men and women by 3.0 (95% CI, 1.7-5.3) and 1.8 (95%CI, 1.1-2.7), respectively. Joint effects of consuming > 3 alcoholic drinks/day and obesity raised the odds of elevated ALT by 8.9 (95%CI, 2.4-33.1) and AST by 21-fold (95%CI, 2.6-170.1), demonstrating synergism. Obese had higher odds of elevated ALT even at 0 ≤ 1 drink/day.

Conclusions

In older men and women, combination of obesity with alcohol is synergistic in increasing the risk of liver injury. Older obese should restrict their alcohol intake as the risk of liver injury is higher.

Background

While knowledge has accumulated regarding health care seeking in several functional gastrointestinal disorders (FGIDs), little is know about health care seeking in those with bloating and distention. We aimed to identify predictors of health care seeking for bloating and distention.

Methods

The validated Talley Bowel Disease Questionnaire was mailed to a cohort selected at random from the population of Olmsted County, Minnesota; 2,259 subjects (53% females; mean age 62 yr) answered questions about bloating and distention. The complete medical record of each respondent was reviewed. Logistic regression was used to compare consulting for bloating and distention to consulting for other GI symptoms, and non-consulters.

Results

A total of 131 (6%) subjects in the community consulted a physician for bloating or distention. Older age (odds ratio(OR), 1.8; 95% confidence interval (CI): 1.5, 2.1), higher somatic symptom scores (OR, 2.0; CI: 1.4, 2.8), lower education level (OR, 2.7; CI: 1.2, 5.6), early satiety (OR, 2.0; CI: 1.1, 3.8), and abdominal pain (OR, 2.4; CI: 1.6, 3.7) were associated with people seeking health care for bloating or distention vs. non-consulters. Similarly, older age (OR, 1.4; CI: 1.2, 1.7), chronic constipation (OR, 2.0; CI: 1.2, 3.2) and visible distention (OR, 3.0; CI: 1.8, 4.9) had greater odds of presenting for bloating or distention compared to presenting for other GI symptoms; somatic symptoms were not a predictor (OR, 1.1; CI: 0.8, 1.5).

Conclusions

Factors that lead people to present for bloating and distention are similar to those for other GI symptoms visits; however, specific biologic rather than somatic features may predict visits for bloating and distention.

Background

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with clinically significant decreases in haemoglobin dependent and independent of acute bleeding events.

Aim

To evaluate the incidence and time to a clinically meaningful decrease in haemoglobin in two double-blind, prospective randomised clinical trials comparing NSAIDs in patients with osteoarthritis (OA) or rheumatoid arthritis (RA).

Methods

In CLASS, patients with OA/RA who were aged ≥18 years and required continuous NSAID treatment were included; patients who were Helicobacter pylori positive and/or using aspirin were not excluded. In contrast, in the CONDOR trial, comparing celecoxib alone to diclofenac sustained release (plus omeprazole), patients were aged ≥60 years or ≥18 years with a history of gastroduodenal ulcer and were H. pylori negative; aspirin or other anti-platelet users were excluded. To make a parallel post hoc analysis we limited our study to 6 months and the populations to only the non-aspirin users in CLASS and those patients receiving either celecoxib or diclofenac. A decrease in haemoglobin of ≥2 g/dL defined the primary end point.

Results

At 6 months, in the CLASS and CONDOR trials, 1.9% and 2.0% of patients treated with celecoxib and 3.3% and 5.7% of patients treated with diclofenac developed a ≥2 g/dL decrease in haemoglobin, respectively, [CLASS: odds ratio (OR) 1.80 (95% confidence interval (CI), 1.22–2.65) and CONDOR: OR 2.93 (95% CI, 2.06–4.15), respectively].

Conclusion

In these two large, independent trials, clinically-meaningful decreases in haemoglobin ≥2 g/dL occurred in a relatively similar fashion over time despite differences in trial designs.

Background

Colorectal cancer (CRC) screening and treatment are rapidly evolving.

Aims

To reappraise stool-based CRC screening in light of changing test performance characteristics, lower test cost, and increasing CRC care costs.

Methods

Using a Markov model, we compared fecal DNA testing every 3 years (F-DNA), annual fecal occult blood testing (FOBT) or immunochemical testing (FIT), and colonoscopy every 10 years (COLO).

Results

In the base case, FOBT and FIT gained life-years/person and cost less than no screening. F-DNA version 1.1 at $300 (the current PreGen Plus test) gained 5,323 life-years/100,000 persons at $16,900/life-year gained, and F-DNA version 2 (enhanced test) gained 5,795 life-years/100,000 persons at $15,700/life-year gained vs. no screening. In the base case and most sensitivity analyses, FOBT and FIT were preferred over F-DNA. F-DNA version 2 cost $100,000/life-year gained vs. FIT when per-cycle adherence with FIT was 22%. FIT with excellent adherence was superior to COLO.

Conclusions

As novel biological therapies increase CRC treatment costs, FOBT and FIT could become cost-saving. The cost-effectiveness of F-DNA compared with no screening has improved, but FOBT and FIT are preferred over F-DNA when patient adherence is high. FIT may be comparable to COLO in persons adhering to yearly testing.

Background

Women with fecal incontinence (FI) and rectal urgency have increased rectal stiffness and sensation.

Aims

To evaluate the effects of clonidine, an (α2-adrenergic agonist, in FI.

Methods

In this open-label uncontrolled study, bowel symptoms and anorectal functions (anal pressures, rectal compliance, and sensation) were assessed before and during treatment with transdermal clonidine (0.2 mg daily, 4 weeks) in 12 women with urge-predominant FI.

Results

Clonidine reduced the frequency (17.8 ± 3.1 before vs 8.8 ± 3.9 after, p = 0.03), and number of days with FI (11.8 ± 1.6 before vs 6.1 ± 1.8 after, p = 0.02), FI symptom severity score (max = 13, 8.3 ± 0.7 vs 5.6 ± 0.9, p<0.01), and allowed patients to defer defecation for a longer duration (p = 0.03). While overall effects on anorectal functions were not significant, the treatment-associated reduction in FI episodes was associated with increased rectal compliance (r = −0.58, p < 0.05) and reduced rectal sensation. (r = −0.73, p = 0.007 versus desire to defecate pressure threshold).

Conclusions

Clonidine improves symptoms in women with FI; this improvement is associated with increased rectal compliance and reduced rectal sensitivity. A controlled study is necessary to confirm these observations.

Background

The aim of the study was to evaluate gender differences and the effect of menstrual cycle and menopausal status on irritable bowel syndrome (IBS) symptoms.

Methods

We performed a systematic review of MEDLINE to search for studies comparing IBS symptoms between gender, menstrual cycle phases, and menopausal states in IBS and/or healthy individuals. We performed meta-analyses to compare the relative risk (RR) of individual IBS symptoms between men and women.

Results

Twenty-two studies measured gender differences in IBS symptoms. Women were more likely to report abdominal pain (RR=1.12, CI [1.02, 1.22]) and constipation-related symptoms (RR=1.12, CI [1.02, 1.23]) than men (all p<0.05). However, men with IBS were more likely to report the diarrhea-related symptoms than women with IBS (RR=0.84, CI [0.75, 0.94], p<0.05). A systematic review of 13 studies demonstrated that both IBS and healthy women reported increased IBS symptoms during menses vs. other phases. There were insufficient data to determine the effect of menopause and hormone supplementation on IBS symptoms.

Conclusion

In the general and IBS populations, gender differences in IBS symptoms exist although these differences are modest. Studies suggest that female sex hormones influence the severity of IBS symptoms, but more studies are needed.