Predictive factors of irritable bowel syndrome improvement: 1-year prospective evaluation in 400 patients

BACKGROUND: The natural history of the irritable bowel syndrome is poorly understood. AIM: To assess the clinical course of the irritable bowel syndrome and the factors that might predict it. METHODS: An observational prospective study, involving 400 irritable bowel syndrome patients meeting Rome II criteria. Symptoms were recorded in a diary over four non-consecutive months (1, 4, 7 and 10). Demographic data, associated disorders, psychological status and health-related quality of life were obtained. RESULTS: At 1-year follow-up, half of the patients and half of their physicians considered irritable bowel syndrome to have improved, but improvement was minor. Diary data showed that, according to the type of symptom, improvement was small and quite different: diarrhoea in 19% of patients, abdominal pain frequency in 26%, constipation in 33% and abdominal pain intensity in 60%. Factors related to improvement at one year were: severe symptoms and poor health-related quality of life at first visit, irritable bowel syndrome-constipation, good improvement at 3 months, anxiety/depression, stress, symptoms related to meals and absence of comorbidity. By multivariate logistic regression, predictors were: severe basal symptoms and good improvement at 3 months (OR:CI 95%, 1.32:1.09-1.59 and 4.44:2.81-7.05). CONCLUSIONS: At 1-year follow-up, half the patients and their physicians considered the irritable bowel syndrome to have had some improvement but, symptom diaries demonstrated that improvement was small and heterogeneous. Severe basal symptoms and improvement at 3 months were related to better prognosis.     

Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study

Aim:

To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria.

Methods:

Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored.

Results:

The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0% vs. 30.2%; P < 0.05). Bowel disturbance improved in both groups, but without any statistically significant difference. The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide. The investigators’ global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P < 0.01).

Conclusions:

Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/discomfort) more than placebo does.

     

Extra-intestinal manifestations associated with irritable bowel syndrome: a twin study

BACKGROUND: Little is known about the role of genetic and environmental factors in irritable bowel syndrome. Various extra-intestinal manifestations are more prevalent in cases than in controls. Genetic effects may be important in the liability to develop functional bowel disorders. AIMS: To evaluate the associations of irritable bowel syndrome with several disorders co-morbid with the condition, using both a case-control design and a co-twin control design. METHODS: A sample of 850 Swedish twin pairs, aged 18-85 years, was contacted for a telephone interview. Through a diagnostic algorithm, 72 unrelated cases of irritable bowel syndrome and 216 age- and gender-matched controls were identified. Fifty-eight twin pairs discordant for irritable bowel syndrome were evaluated in co-twin analyses. RESULTS: Renal problems (odds ratio (OR)=3.3; confidence interval (CI), 1.3-8.2), obesity (OR=2.6; CI, 1.0-6.4), underweight in the past (OR=2.4; CI, 1.1-6.4), gluten intolerance (OR=9.0; CI, 1.4-60.1), rheumatoid arthritis (OR=3.2; CI, 1.1-9.4) and poor self-rated health (OR=1.8; CI, 1.0-3.2) were significantly associated with irritable bowel syndrome. In the co-twin analyses, the only factors maintaining significance were renal and recurrent urinary tract problems. CONCLUSIONS: The association between irritable bowel syndrome and renal and urinary tract problems does not reflect a genetic or familial mediation. Eating disorders in childhood represent a familial-environmental influence on irritable bowel syndrome, whereas the association with rheumatoid arthritis and perhaps gluten intolerance probably reflects genetic mediation.     

Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: a double-blind placebo-controlled study

BACKGROUND: Melatonin is involved in the regulation of gastrointestinal motility and sensation. AIM : To determine the potential therapeutic effects of melatonin in irritable bowel syndrome (IBS). METHOD: Seventeen female patients satisfying the Rome II criteria for IBS were randomized to receive either melatonin 3 mg nocte or identically appearing placebo 1 nocte for 8 weeks, followed by a 4-week washout period and placebo or melatonin in the reverse order for another 8 weeks. Three validated questionnaires - the GI symptom, the sleep questionnaires and the Hospital Anxiety and Depression Scale - were used to assess symptom severity and to compute the IBS, sleep and anxiety/depression scores, respectively. RESULTS: Improvements in mean IBS scores were significantly greater after treatment with melatonin (3.9 +/- 2.6) than with placebo (1.3 +/- 4.0, P = 0.037). Percent response rate, defined as percentage of subjects achieving mild-to-excellent improvement in IBS symptoms, was also greater in the melatonin-treated arm (88% vs. 47%, P = 0.04). The changes in mean sleep, anxiety, and depression scores were similar with either melatonin or placebo treatment. CONCLUSIONS: Melatonin is a promising therapeutic agent for IBS. Its therapeutic effect is independent of its effects on sleep, anxiety or depression.     

Influence of genetics on irritable bowel syndrome, gastro-oesophageal reflux and dyspepsia: a twin study

BACKGROUND: A genetic contribution has been proposed for irritable bowel syndrome (IBS) and gastro-oesophageal reflux disease (GERD), but is controversial. No twin data exist for dyspepsia. AIM: To determine the relative contribution of genetic factors in GERD, dyspepsia (upper abdominal pain) and IBS. METHODS: A total of 986 twin pairs (from initial mail-out response 51%). Both members completed validated symptom and psychological questionnaires; 481 monozygotic pairs [mean (s.d.) age 53 +/- 5.8 years] and 505 dizygotic pairs (mean age 54 +/- 5.6 years). RESULTS: Prevalence of IBS, dyspepsia and GERD was 12%, 10% and 20%, respectively. Polychoric correlation for monozygotic twins for IBS (0.47) and GERD (0.44) were both substantially larger than those for dizygotic twins (0.17 and -0.37, respectively). Polychoric correlation was slightly lower in monozygotic than dizygotic twins for dyspepsia. Genetic modelling confirmed the independent additive genetic effects in GERD and IBS but not dyspepsia. Estimates of genetic variance were 22% for IBS, 13% for GERD and 0% for dyspepsia, but adjusting for anxiety and depression removed the statistical significance for IBS and GERD. CONCLUSIONS: There is a genetic contribution to GERD and IBS but not dyspepsia; this may be mediated by the hereditability of anxiety and depression.     

Tegaserod: a new 5-HT(4) agonist in the treatment of irritable bowel syndrome

Tegaserod is a selective partial agonist acting on serotonergic type 4 receptors (5-HT(4)). Pharmacodynamic studies indicate that tegaserod is able to stimulate gut propulsion and secretion with a net prokinetic effect. In contrast to other 5-HT(4) agonists endowed with a complex pharmacological profile, tegaserod has a reliable prokinetic activity in the colon. Clinical trials show that tegaserod is effective and safe in the treatment of patients with irritable bowel syndrome. In particular, tegaserod relieves symptoms of abdominal pain, discomfort, abdominal bloating and constipation.     

Tolerability and safety of the intravenous immunoglobulin Octagam: a 10-year prospective observational study

PURPOSE: Following the approval of Octagam in 1995, an open prospective observational cohort study has been initiated to observe the tolerability of the intravenous immunoglobulin Octagam. This study aimed to evaluate the long-term safety profile of Octagam in daily use in the treatment of various primary (PID) and secondary (SID) immunodeficiencies and autoimmune diseases (AID). METHODS: Within a time period of 10 years, data were collected in 310 study sites. The treating physicians documented patient characteristics, treatment parameters and the occurrence of an adverse drug reaction (ADR) by using detailed case record forms (CRF). RESULTS: A total of 6357 patients of all ages received 92 958 infusions of Octagam. ADR occurred in 4.2% of the patients and in 0.35% of all infusions. Most of them (94.8%) were classified as nonserious, the majority (90.2%) were of mild or moderate intensity. The ADR frequency differed slightly between the indication groups, for example in PID patients ADR occurred in 8.3% of patients and 0.5% of infusions, in SID patients in 5.0% of patients and 0.62% of infusions. Rigors were reported most frequently, followed by fever, headache, nausea and flush. The ADR symptoms differed between the indication groups, rigors were predominantly described in SID patients, headache in PID and AID patients including idiopathic thrombocytopenic purpura (ITP). A relation between the ADR frequency and elevated infusion rates or high dosages was not detected. CONCLUSIONS: This unique 10-year observational study demonstrates that Octagam is well tolerated in routine clinical use with an overall ADR frequency of 0.35%.     

The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress

Background: The clinical assessment and investigation of irritable bowel syndrome would be greatly facilitated by the introduction of a simple, easy to use severity scoring system. Such a system, developed in our department over a number of years, has been submitted to validation in a total of 141 patients and 40 healthy controls.
Methods: The system, incorporating pain, distension, bowel dysfunction and quality of life/global well-being, was assessed for its ability to reliably score patients previously classified as mild, moderate or severe. The reproducibility and sensitivity to change of the system was also assessed.
Results: The maximum achievable score was 500. Mild, moderate and severe cases were indicated by scores of 75 to 175, 175 to 300 and >300 respectively. Controls scored below 75 and patients scoring in this range can be considered to be in remission. There was a highly significant difference between controls and patients as a whole ( P =0.0001) as well as significant differences ( P <0.01) between all severity categories. Scores repeated within 24 h were very reproducible and sensitivity to change was also extremely good ( P <0.001) with a change of 50 reliably indicating improvement.
Conclusion: These results suggest that this scoring system should prove to be a valuable instrument in helping to meet the many challenges offered by irritable bowel syndrome.     

益生菌治疗肠易激综合征疗效的Meta分析

目的探讨益生菌治疗肠易激综合征(IBS)的临床疗效及安全性。方法计算机检索PubMed、国际Cochrane中心、Embase、中国生物医学文献数据库、中国期刊全文数据库、万方数据库、维普数据库,收集益生菌治疗IBS的随机对照试验(RCT),并手工检索已获文献的参考文献,由两位评价者按照纳入和排除标准筛选、提取资料并行方法学质量评价,采用RevMan 5.0软件对数据行Meta分析。结果共纳入19个RCT,2172例患者。Meta分析结果显示,益生菌较安慰剂在改善患者总体症状积分[SMD=-0.18,95%CI(-0.28,-0.08),P=0.000 6]、腹痛[SMD=-0.13,95%CI(-0.21,-0.04),P=0.0031、腹胀[SMD=-0.15,95%CI(-0.25,-0.05),P=0.004]、排便不适感[SMD=-0.15,95%CI(-0.27,-0.02),P=0.02】方面均有显著意义,在总体生活质量[SMD:0.09,95%CI(-0.08,0.25),P=0.301、不良反应发生率[RR=0.91,95%CI(0.71,1.16),P=0.45]方面无显著意义。结论目前证据显示益生菌制剂能有效改善IBS患者的临床症状,且安全性好,但现有RCT在方法质量学以及研究设计上存在一定不足,今后的研究应在菌株、剂量、疗程、IBS亚组患者方面进行严谨、高质量、大样本长期随访的临床研究予以证实。     

Implications of melatonin therapy in irritable bowel syndrome: a systematic review

Irritable bowel syndrome (IBS) is a highly prevalent chronic functional gastrointestinal (GI) disorder associated with abdominal pain and change in bowel habits that its etiology is not known yet. In the recent years, melatonin has been proposed as a possible candidate. In the present work, all clinical or non-clinical data about effects of melatonin in GI tract and IBS obtained from literature without time limit up to August 2010 have been studied and reviewed. Eight clinical trials were reviewed for efficacy and disturbance of melatonin in IBS and other GI disorders. The results showed disturbances in endogenous melatonin concentration in IBS patients and significant benefits of exogenous melatonin in these patients by decreasing abdominal pain and improvement of overall IBS symptom scores. The results of seventeen non-clinical studies showed anxiolytic, anti-inflammatory, anti oxidative and motility regulatory effects of melatonin on GI tract. In conclusion melatonin can be a target of interest in IBS because of its potentials to regulate GI motility.     

Symptomatic efficacy of beidellitic montmorillonite in irritable bowel syndrome: a randomized, controlled trial

BACKGROUND: Beidellitic montmorillonite is a purified clay containing a double aluminium and magnesium silicate. AIM: To assess the efficacy and the safety of beidellitic montmorillonite (3 g, t.d. for 8 weeks) in patients with irritable bowel syndrome (IBS). METHODS: A multicentre, double-blind, placebo-controlled, randomized study with parallel groups, was performed in IBS patients selected according to ROME I criteria. Patients were included after a 1-week washout period to confirm that abdominal pain and/or discomfort was rated at least 2 on a 0-4 graded Likert scale. Patients were then randomized and stratified according to their predominant bowel habit profile into three groups. The use of rescue medication was allowed: polyethylene glycol 4000 (10-20 g/day) as a laxative agent in case of stool absence for three consecutive days, phloroglucinol (80 to a maximum of 320 mg/day) as a spasmolytic agent for no more than 8 days. The main end-point was the improvement of abdominal pain and/or discomfort by at least 1 point on the Likert scale. RESULTS: A total of 524 patients constituted the overall intent-to-treat population (ITT), 263 were assessed in the beidellitic montmorillonite group, i.e. 93 diarrhoea-predominant IBS (D-IBS), 83 constipation-predominant IBS (C-IBS), 87 alternating constipation/diarrhoea-IBS (A-IBS); 261 in the placebo group, i.e. 81 D-IBS, 92 C-IBS and 88 A-IBS. Initial analysis in the ITT population demonstrated a higher rate of success with beidellitic montmorillonite (51.7%) when compared with the placebo group (45.2%); however, the difference was not statistically significant. Improvement was significant in C-IBS both in ITT (beidellitic montmorillonite group = 49.4%, placebo group = 31.5%, P < 0.016) and per protocol populations (59.4% vs. 37.8%) (P < 0.01). The time to improvement of abdominal pain and/or discomfort (log Rank test) was also significantly in favour of beidellitic montmorillonite, (P < 0.04). The average number of stools per day was not different from baseline, either in all patients or in C-IBS patients. Spasmolytic and laxative agent intakes were not different between the two groups. Subjective evaluation by patients of treatment efficacy and visual analogue scale test of treatment efficacy by investigators were significantly better in the beidellitic montmorillonite group (P < 0.05). Tolerance of beidellitic montmorillonite was considered optimal without any significant adverse event. CONCLUSIONS: Although pain or discomfort was not significantly improved in the entire IBS population treated with beidellitic montmorillonite in comparison with placebo, this study demonstrates that beidellitic montmorillonite is efficient for C-IBS patients (P < 0.016). This effect of beidellitic montmorillonite on pain cannot be explained by changes in bowel habits. The efficacy of this well-tolerated therapy warrants further confirmatory therapeutic trials in C-IBS patients.     

Significant psychological morbidity occurs in irritable bowel syndrome: a case-control study using a pharmacy reimbursement database

Background  Psychological problems are associated with IBS but the strength of this association is unclear.
Aim  To assess co-prescribing of antispasmodic and CNS-acting drugs through a nested case-control study.
Methods  A national dispensing database identified patients who were first dispensed antispasmodic medicines for a continuous 3-month period or more during 2006, using 2005 as a run-in period. Each patient was matched with four control patients and excluded if they received drugs indicated for IBD.
Results  Four hundred and seven patients commenced antispasmodic drugs during 2006. These patients were matched with 1628 controls. In 2005, patients subsequently prescribed antispasmodics were 2–3 times more likely to receive CNS-acting drugs than controls. In the year following commencement of IBS therapy, patients were 2–4 times more likely than controls to be prescribed CNS-acting drugs including antidepressants (35.4% vs. 9.3%), anxiolytics (27.8% vs. 8.8%), antipsychotics (9.8% vs. 3.3%) and hypno-sedatives (32.7% vs. 11.3%; P  < 0.0001). The adjusted OR (95% CI) for antidepressant, anxiolytic, hypnosedative and antipsychotic prescribing in IBS patients were 3.81 (2.79–5.20), 2.84 (2.12–3.81), 2.62 (1.91–3.60) and 2.58 (1.80–3.66), respectively.
Conclusions  Patients prescribed ongoing therapy for presumed IBS are 2–4 times more likely to be prescribed CNS-acting drugs than controls, providing evidence of psychological comorbidity in IBS.     

Fluoxetine versus placebo in depressed alcoholics: a 1-year follow-up study

The authors conducted a first study to evaluate the long-term efficacy of fluoxetine for decreasing the depressive symptoms and the drinking of patients with comorbid major depressive disorder and alcohol dependence. This study consisted of a 1-year naturalistic follow-up of 31 patients who previously had completed a 3-month double-blind, placebo-controlled study of fluoxetine in depressed alcoholics. The fluoxetine group continued to demonstrate less depressive symptoms and less drinking than the placebo group at the 1-year follow-up evaluation. The results of the 1-year follow-up evaluation suggest persistent efficacy for fluoxetine for treating the depressive symptoms and the drinking of depressed alcoholics.     

Therapeutic value of a gastroenterology consultation in irritable bowel syndrome

BACKGROUND: Functional patients comprise the largest group in gastroenterology practice. Pharmacological therapy of irritable bowel syndrome is disappointing. One treatment strategy for irritable bowel syndrome emphasizes the physician's role; the physician is promoted as the therapeutic modality. AIM: To determine the therapeutic value of the contemporary approach to irritable bowel syndrome by examining health care utilization and patient morbidity. METHODS: We performed an observational study over 4 years using an administrative database and morbidity scales. Health care utilization was assessed for 2 years pre- and post-intervention. Patient morbidity was assessed at baseline and 1 and 2 years post-intervention. The participants included 70 irritable bowel syndrome patients referred by primary physicians. A structured consultation was performed, establishing a positive diagnosis of irritable bowel syndrome and providing disease conceptualization. RESULTS: Health care utilization for gastrointestinal diagnoses increased in the year prior to the intervention and declined immediately after to baseline; psychiatric and other visits remained unchanged for 4 years. Pain was reduced but other morbidity persisted. CONCLUSIONS: A consultation itself is a therapeutic intervention in irritable bowel syndrome with regard to its impact on societal economic burden. It is associated with a durable decrease in illness-specific health care utilization. It may not address all aspects of irritable bowel syndrome; multiple domains of morbidity demonstrated persistent distress.