Alimentary Pharmacology & Therapeutics

Dorn, S. D.

doi: 10.1111/j.1365-2036.2010.04374.xpmid: 20497137

Aliment Pharmacol Ther 2010; 32: 513–521 Summary Background Irritable bowel syndrome is an extremely common and costly condition. Because there is no cure, patients must be supported to manage their own condition. Aim To assess systematically the interventions used to support irritable bowel syndrome patient self‐management. Methods A search of PubMed, EMBASE, CINAHL and PsycINFO was performed to identify all studies that involved self‐management support interventions for irritable bowel syndrome. Studies that compared the self‐management‐related intervention to a control group were included. Results Eleven studies that involved a total of 1657 patients were included. For nearly all studies, the intervention was associated with statistically significant benefits. However, across studies there was significant heterogeneity in terms of sample size, diagnostic criteria, study setting, study design, primary outcome, statistical analyses and study quality. Therefore, individual study results could not be statistically combined. Conclusions Many self‐management support interventions appear benefit patients with irritable bowel syndrome. However, studies were limited by methodological flaws. Furthermore, feasibility in ‘real world’ clinical practice is uncertain. Thus, practical self‐management interventions that can be applied across various clinical settings should be developed, and then tested in well‐designed clinical trials.

Gies, N.; Kroeker, K. I.; Wong, K.; Fedorak, R. N.

doi: 10.1111/j.1365-2036.2010.04380.xpmid: 20500733

Aliment Pharmacol Ther 2010; 32: 522–528 Summary Background Randomized, controlled trials have demonstrated that anti‐TNF agents are efficacious in inducing remission in cases of Crohn’s disease and ulcerative colitis. However, response rates for anti‐TNF agents in ‘real life’ clinical practice are less well‐defined. Aims To examine the response rates and long‐term outcomes of infliximab and adalimumab treatment for out‐patients with ulcerative colitis and to study the variables associated with response rates. Methods In a prospective study, a single‐centre out‐patient cohort was treated and followed up according to a structured protocol of clinical care. Response to treatment was assessed using a physician’s global assessment that focused on normalization of bowel frequency, absence of blood with defecation and tapering of corticosteroids to zero. Results Fifty‐three ulcerative colitis patients were included in the study. Responses to induction therapy were 96.4% (27/28) for infliximab and 80% (20/25) for adalimumab (P = 0.0889). Responses to maintenance therapy were similar: infliximab 77.8% (14/18) and adalimumab 70.0% (14/20) (P = 0.7190). Multivariate analyses of the induction and maintenance responses did not reveal confounding elements. No new safety signals were identified. Conclusions This long‐term follow‐up of a single‐centre cohort of ulcerative colitis patients demonstrates that ‘real‐life’ out‐patient treatment with infliximab and adalimumab is effective in induction and maintenance of response.

Spaander, M. C. W.; Van Buuren, H. R.; Hansen, B. E.; Janssen, H. L. A.

doi: 10.1111/j.1365-2036.2010.04375.xpmid: 20497136

Aliment Pharmacol Ther 2010; 32: 529–534 Summary Background The clinical significance of ascites in patients with extrahepatic portal vein thrombosis (EPVT) has been poorly defined. Aims To assess the frequency, natural history and prognostic implication of ascites in patients with EPVT and to identify risk factors for this complication. Methods A single‐centre retrospective study of consecutive patients diagnosed with noncirrhotic nonmalignant EPVT between 1985 and 2009. Results One hundred and three patients (35% males; median age 43 (range 16–83) years) were included and followed up for a median time of 5.2 (range 0.9–32.5) years. Twenty‐nine (28%) had ascites at the time of diagnosis. Overall survival was 91% at 5 years vs. 80% at 10 years. Survival in patients presenting with and without ascites was 83% vs. 95% at 5 years and 42% vs. 87% at 10 years (P = <0.01). There was no correlation between the presence of ascites and extension of the thrombus into the large splanchnic veins, duration of thrombosis or presence of gastrointestinal bleeding. Conclusions Ascites is present in a quarter of patients presenting with noncirrhotic nonmalignant extrahepatic portal vein thrombosis. Ascites is a significant and independent prognostic factor and it is associated with a decreased long‐term survival.

Alam, I.; Stainbrook, T.; Cecil, B.; Kistler, K. D.

doi: 10.1111/j.1365-2036.2010.04381.xpmid: 20500732

Aliment Pharmacol Ther 2010; 32: 535–542 Summary Background Poor adherence to Hepatitis C virus (HCV) treatment is an important cause of treatment failure. Traditional ribavirin 200 mg (RBV) treatment is associated with a significant daily pill burden. RibaPak (RBP), available as 400 mg and 600 mg ribavirin tablets, offers simplified dosing at two pills daily. Aim To examine whether improved adherence was associated with RBP vs. RBV. Methods Accurate Dosing in Hepatitis C: Examining the RibaPak Experience (ADHERE) was a U.S., multi‐centre, prospective registry capturing data on adherence with RBP vs. RBV in adults with HCV. Adherence was measured by the proportion of subjects remaining on treatment at weeks 4, 12 and 24; by pill counts; and by the proportion of subjects who took ≥80% of their prescribed dose. Results A total of 503 patients (RBP = 346, RBV = 157) from 33 sites were included. A greater proportion of RBV vs. RBP subjects prematurely discontinued treatment. At 12 and 24 weeks, a greater proportion of RBP vs. RBV subjects took ≥80% of their prescribed doses (P < 0.05). For patients who remained on treatment, the mean milligrams missed per day was significantly greater for RBV vs. RBP at 24 weeks. Conclusions First line treatment with RBP may offer the best prospect for less discontinuation and improved treatment adherence.

Nagamatsu, H.; Hiraki, M.; Mizukami, N.; Yoshida, H.; Iwamoto, H.; Sumie, S.; Torimura, T.; Sata, M.

doi: 10.1111/j.1365-2036.2010.04379.xpmid: 20500734

Aliment Pharmacol Ther 2010; 32: 543–550 Summary Background Portal vein tumour thrombosis is a negative prognostic factor for hepatocellular carcinoma (HCC). Aim To assess the efficacy of cisplatin in lipiodol emulsion combined with 5‐fluorouracil (5‐FU) for patients with HCC and portal vein tumour thrombosis. Methods The study subjects were 51 patients with the above‐specified criteria who received injection of cisplatin suspension in lipiodol emulsion followed by intra‐arterial infusion of 5‐FU. The primary objective was to determine tumour response to the treatment, while the secondary objectives were safety and tolerability. Independent factors for survival were also assessed. Results Ten patients had complete response and 34 patients had partial response (response rate, 86.3%). The median survival for all 51 patients was 33 months, while that for 10 complete response patients and 21 patients who showed disappearance of HCC following additional therapies was 39 months. The single factor that significantly influenced survival was therapeutic effect. Treatment was well tolerated and severe toxicity was infrequent, with only grade 3 toxicity (thrombocytopenia) in one patient. Conclusions The present study demonstrated the efficacy of hepatic arterial infusion chemotherapy using cisplatin‐lipiodol emulsion and 5‐FU without serious adverse effects in patients with unresectable HCC and portal vein tumour thrombosis.

White, D. L.; Savas, L. S.; Daci, K.; Elserag, R.; Graham, D. P.; Fitzgerald, S. J.; Smith, S. L.; Tan, G.; El‐Serag, H. B.

doi: 10.1111/j.1365-2036.2010.04387.xpmid: 20528828

Aliment Pharmacol Ther 2010; 32: 551–561 Summary Background Over 1.8 million women in the U.S. are veterans of the armed services. They are at increased risk of occupational traumas, including military sexual trauma. Aim To evaluate the association between major traumas and irritable bowel syndrome among women veterans accessing Veteran Affairs (VA) healthcare. Methods We administered questionnaires to assess trauma history as well as IBS, post‐traumatic stress disorder (PTSD) and depression symptoms to 337 women veterans seen for primary care at VA Women’s Clinic between 2006 and 2007. Logistic regression was used to evaluate the association between individual traumas and IBS risk after adjustment for age, ethnicity, PTSD and depression. Results Irritable bowel syndrome prevalence was 33.5%. The most frequently reported trauma was sexual assault (38.9%). Seventeen of eighteen traumas were associated with increased IBS risk after adjusting for age, ethnicity, PTSD and depression, with six statistically significant (range of adjusted odds ratios (OR) between 1.85 (95% CI, 1.08–3.16) and 2.6 (95% CI, 1.28–3.67)). Depression and PTSD were significantly more common in IBS cases than controls, but neither substantially explained the association between trauma and increased IBS risk. Conclusions Women veterans report high frequency of physical and sexual traumas. A lifetime history of a broad range of traumas is independently associated with an elevated risk of the irritable bowel syndrome.

Zhao, Y.; Zou, D.; Wang, R.; Ma, X.; Yan, X.; Man, X.; Gao, L.; Fang, J.; Yan, H.; Kang, X.; Yin, P.; Hao, Y.; Li, Q.; Dent, J.; Sung, J.; Halling, K.; Wernersson, B.; Johansson, S.;

Wild, D.; Robins, G. G.; Burley, V. J.; Howdle, P. D.

doi: 10.1111/j.1365-2036.2010.04386.xpmid: 20528829

Aliment Pharmacol Ther 2010; 32: 573–581 Summary Background The only therapy for coeliac disease (CD) is a long‐term gluten‐free diet (GFD). Little is known about the detailed composition of such a diet. Aim To clarify the nutritional composition of a GFD and to compare it with a non‐GFD diet in representative non‐CD populations. Methods A total of 139 consecutive patients with CD were invited to fill in a prospective validated 5‐day food diary, of whom data from 93 were analysed. Results were compared with data from the National Diet and Nutrition Survey of Adults and the UK Women’s Cohort Study (UKWCS). Results Individuals consuming a strict GFD generally had similar intakes of energy and nutrients to those of comparison populations, but a higher proportion of carbohydrate intake was obtained from nonmilk extrinsic sugars and intakes of nonstarch polysaccharides were low. Compared with the UKWCS sample, female patients adhering to a GFD had lower intakes of magnesium, iron, zinc, manganese, selenium and folate. In male patients, intakes of magnesium and selenium were particularly low. Conclusions This study reinforces the need for clinicians to recognize that avoidance of gluten cannot be the sole focus of a gluten‐free diet. Maintenance of adequate intakes of essential nutrients and in particular complex carbohydrates must also be the goal for patients.

Miele, E.; Giannetti, E.; Martinelli, M.; Tramontano, A.; Greco, L.; Staiano, A.

doi: 10.1111/j.1365-2036.2010.04383.xpmid: 20528827

Aliment Pharmacol Ther 2010; 32: 582–590 Summary Background The demand for paediatric gastrointestinal (GI) endoscopy has increased, resulting in a significant rise of overall costs. Aim To assess the clinical impact of the Rome II criteria for functional gastrointestinal disorders when selecting paediatric patients who underwent GI endoscopy. Methods The indications and findings of GI endoscopic procedures performed before and after the publication of the Rome II criteria were evaluated retrospectively. Results Upper GI endoscopy was performed in 1124 children, whereas colonoscopy was performed in 500 subjects. A total of 607 (54%) oesophago‐gastro‐duodenoscopies (OGDs) were positive and 517 (46%) were negative, whereas 306 (61.1%) colonoscopies were positive and 194 (38.9%) were negative. Of the 1624 procedures, 26% were considered inappropriate according to the Rome II criteria. Inappropriate procedures decreased significantly after publication of the Rome II criteria (OR, 3.7; 95% CI, 1.8–7.5). Of 1202 appropriate GI endoscopies, 502 OGD (62.7%) were significantly contributive, compared with only 105 (32.5%) of the 323 inappropriate procedures (OR, 3.5; 95% CI, 2.6–4.6), whereas 265 (65.8%) colonoscopies were significantly contributive, compared with only 41 (42.3%) of the 97 inappropriate procedures (OR, 2.6; 95% CI, 1.6–4.1). Conclusions The use of the criteria for functional gastrointestinal disorders makes a significant positive impact, they should reduce unnecessary paediatric GI endoscopy.

Spiegel, B. M.; Roberts, L.; Mody, R.; Harding, G.; Kothari‐Talwar, S.; Kahrilas, P. J.; Camilleri, M. L.; Dabbous, O.; Revicki, D. A.

doi: 10.1111/j.1365-2036.2010.04385.xpmid: 20528826

Aliment Pharmacol Ther 2010; 32: 591–602 Summary Background Current questionnaires for assessing gastro‐oesophageal reflux disease (GERD) symptoms are limited in their ability to capture nocturnal symptoms. Aim To develop and validate an instrument, the Nocturnal Gastro‐oesophageal Reflux Disease Symptom Severity and Impact Questionnaire (N‐GSSIQ), to assess severity and impact of nocturnal GERD symptoms. Methods Two focus groups and 16 cognitive debriefing interviews were conducted among GERD patients to identify key issues about nocturnal symptoms. A draft instrument was tested in 196 patients at 11 clinics in the US to evaluate psychometric properties. Exploratory factor and item response theory analyses were conducted to finalize items and subscales. Internal consistency reliability, reproducibility and construct validity were examined. Results Mean age was 45 (s.d. = 13.8) years; 76% were female and 68% were Caucasian. Patient‐rated severity was mild–moderate for 69% of participants; 48% reported symptoms on two to three nights the past week. The final questionnaire includes 20 items and three subscales: Nocturnal GERD Symptoms, Morning Impact of Nocturnal GERD and Concern about Nocturnal GERD. The subscales demonstrated internal consistency reliability (Cronbach’s alpha 0.84–0.94) and were significantly correlated with similar measures and disease severity (0.41–0.81; P < 0.0001). Conclusion The results support the reliability and validity of the N‐GSSIQ as a measure of severity, morning impact and concern about nocturnal GERD.