Vitamin D3 Supplementation in Diarrhea-Predominant Irritable Bowel Syndrome Patients: The Effects on Symptoms Improvement, Serum Corticotropin-Releasing Hormone, and Interleukin-6 - A Randomized Clinical Trial.

OBJECTIVES: This study aimed to evaluate whether vitamin D deficiency is associated with the severity of symptoms of irritable bowel syndrome (IBS) patients. Stress and gut inflammation can increase the serum level of corticotropin-releasing hormone (CRH) and interleukin-6 (IL-6), leading to a change in bowel movements. The aim of this study was to evaluate the anti-inflammatory and psychological effects of vitamin D3 supplementation on the symptom improvement of patients with a diarrhea-predominant form of IBS (IBS-D). METHODS: Eighty-eight IBS-D patients (age: 18-65 years) based on Rome IV criteria who suffered from vitamin D deficiency and/or insufficiency were enrolled in this randomized, placebo-controlled trial from February 2017 to May 2018 at Rasoul-e-Akram Hospital, Tehran, Iran. Participants were randomly divided into two groups. The intervention group received 50,000 IU vitamin D3 weekly and the control group received a placebo for 9 weeks. All patients received Mebeverine 135 mg twice a day besides supplementation. The IBS Severity Score System (IBS-SSS), serum 25(OH) vitamin D3, CRH, and IL-6 were measured before and after interventions. RESULTS: Seventy-four patients completed the study. The severity of IBS symptoms (p < 0.01) and IL-6 (p = 0.02) decreased significantly in the intervention group as compared to the control group, but there was no significant difference in the serum level of CRH. Also, in the treatment group, IBS-SSS and IL-6 were significantly reduced at the end of the study from baseline (p < 0.01 and p < 0.03, respectively). CONCLUSION: Our findings indicate that vitamin D3 supplementation can modulate the serum level of CRH and IL-6 and can improve symptoms in IBS-D patients. Vitamin D3 supplementation should be considered in IBS-D patients who suffer from vitamin D deficiency and/or insufficiency.

Cost-effectiveness analysis of sacral nerve stimulation as treatment for severe irritable bowel syndrome.

AIM: Early results from sacral nerve stimulation (SNS) for severe irritable bowel syndrome (IBS) are promising but estimates of cost-effectiveness are lacking. Our object was to perform a cost-effectiveness analysis for SNS as an alternative to no treatment of IBS. METHOD: This retrospective analysis was based on the results from a randomized controlled crossover study with a cost-utility analysis performed on patient-level data and modelling of censored data over a projected period of time of up to 20 years. The analysis was conducted on an intention-to-treat approach. For estimation of the uncertainty of the incremental cost-effectiveness ratio a bias corrected bootstrap analysis was performed. RESULTS: Cost-effectiveness was not reached for 4 years after permanent implantation (£31 270 per quality-adjusted life years), which was the upper limit for patient follow-up, but our data imply a cost-effectiveness from a 7-year perspective onwards. CONCLUSION: The study indicates the SNS treatment for IBS is cost effective from a 7-year perspective onwards.

Cost-effectiveness of acupuncture for irritable bowel syndrome: findings from an economic evaluation conducted alongside a pragmatic randomised controlled trial in primary care.

BACKGROUND: There is insufficient evidence to determine whether acupuncture is a cost-effective treatment for irritable bowel syndrome. The objective of this study is to assess the cost-effectiveness of acupuncture as an adjunct to usual care versus usual care alone for the treatment of Irritable Bowel Syndrome (IBS). METHODS: Cost-utility analysis conducted alongside a pragmatic, multicentre, randomised controlled trial. 233 patients with irritable bowel syndrome were randomly allocated to either acupuncture plus usual care, or usual care alone. Cost-effectiveness outcomes are expressed in terms of incremental cost per quality adjusted life year (QALY) at one year after randomisation. Costs were estimated from the UK National Health Service perspective for a time horizon of one year. Cost-utility ratios were estimated based on complete case analysis for the base case analysis, where only patients with available EQ-5D and cost data were included. Sensitivity analyses comprised a multiple imputation approach for missing data and a subgroup analysis for the more severe cases of IBS. RESULTS: The base case analysis showed acupuncture to be marginally more effective than usual care (gain of 0.0035 QALYs, 95% CI: -0.00395 to 0.0465) and more expensive (incremental cost of £218 per patient (95% CI: 55.87 to 492.87) resulting in an incremental cost-effectiveness ratio of approximately £62,500. Sensitivity analysis using multiple imputation for missing data resulted in acupuncture appearing less effective and more costly than usual care, so usual care is dominant. Subgroup analysis selecting the most severe cases of IBS (Symptom Severity Score of over 300) suggested that acupuncture may be a cost-effective treatment option for this group, with a cost-per-QALY of £6,500. CONCLUSIONS: Acupuncture as an adjunct to usual care is not a cost-effective option for the whole IBS population; however it may be cost-effective for those with more severe irritable bowel syndrome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN08827905.

A randomised controlled trial on hypnotherapy for irritable bowel syndrome: design and methodological challenges (the IMAGINE study).

BACKGROUND: Irritable Bowel Syndrome (IBS) is a common gastro-intestinal disorder in primary and secondary care, characterised by abdominal pain, discomfort, altered bowel habits and/or symptoms of bloating and distension. In general the efficacy of drug therapies is poor. Hypnotherapy as well as Cognitive Behaviour Therapy and short Psychodynamic Therapy appear to be useful options for patients with refractory IBS in secondary care and are cost-effective, but the evidence is still limited. The IMAGINE-study is therefore designed to assess the overall benefit of hypnotherapy in IBS as well as comparing the efficacy of individual versus group hypnotherapy in treating this condition. METHODS/DESIGN: The design is a randomised placebo-controlled trial. The study group consists of 354 primary care and secondary care patients (aged 18-65) with IBS (Rome-III criteria). Patients will be randomly allocated to either 6 sessions of individual hypnotherapy, 6 sessions of group hypnotherapy or 6 sessions of educational supportive therapy in a group (placebo), with a follow up of 9 months post treatment for all patients. Ten hospitals and four primary care psychological practices in different parts of The Netherlands will collaborate in this study. The primary efficacy parameter is the responder rate for adequate relief of IBS symptoms. Secondary efficacy parameters are changes in the IBS symptom severity, quality of life, cognitions, psychological complaints, self-efficacy as well as direct and indirect costs of the condition. Hypnotherapy is expected to be more effective than the control therapy, and group hypnotherapy is expected not to be inferior to individual hypnotherapy. DISCUSSION: If hypnotherapy is effective and if there is no difference in efficacy between individual and group hypnotherapy, this group form of treatment could be offered to more IBS patients, at lower costs. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN22888906.

Acceptability, effectiveness, and cost-effectiveness of internet-based exposure treatment for irritable bowel syndrome in a clinical sample: a randomized controlled trial.

BACKGROUND: Internet-based cognitive behavior therapy (ICBT) has shown promising effects in the treatment of irritable bowel syndrome (IBS). However, to date no study has used a design where participants have been sampled solely from a clinical population. We aimed to investigate the acceptability, effectiveness, and cost-effectiveness of ICBT for IBS using a consecutively recruited sample from a gastroenterological clinic. METHODS: Sixty-one patients were randomized to 10 weeks of ICBT (n = 30) or a waiting list control (n = 31). The ICBT was guided by an online therapist and emphasized acceptance of symptoms through exposure and mindfulness training. Severity of IBS symptoms was measured with the Gastrointestinal symptom rating scale--IBS version (GSRS-IBS). Patients in both groups were assessed at pre- and post-treatment while only the ICBT group was assessed 12 months after treatment completion. Health economic data were also gathered at all assessment points and analyzed using bootstrap sampling. RESULTS: Fifty of 61 patients (82%) completed the post-treatment assessment and 20 of 30 patients (67%) in the ICBT group were assessed at 12-month follow-up. The ICBT group demonstrated significantly (p < .001) larger improvements on the IBS-related outcome scales than the waiting list group. The between group effect size on GSRS-IBS was Cohen's d = 0.77 (95% CI: 0.19-1.34). Similar effects were noted on measures of quality of life and IBS-related fear and avoidance behaviors. Improvements in the ICBT group were maintained at 12-month follow-up. The ICBT condition was found to be more cost-effective than the waiting list, with an 87% chance of leading to reduced societal costs combined with clinical effectiveness. The cost-effectiveness was sustained over the 12-month period. CONCLUSIONS: ICBT proved to be a cost-effective treatment when delivered to a sample recruited from a gastroenterological clinic. However, many of the included patients dropped out of the study and the overall treatment effects were smaller than previous studies with referred and self-referred samples. ICBT may therefore be acceptable and effective for only a subset of clinical patients. Study dropout seemed to be associated with severe symptoms and large impairment. Objective and empirically validated criteria to select which patients to offer ICBT should be developed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00844961.

Cost-effectiveness of internet-based cognitive behavior therapy for irritable bowel syndrome: results from a randomized controlled trial.

BACKGROUND: Irritable Bowel Syndrome (IBS) is highly prevalent and is associated with a substantial economic burden. Cognitive behavior therapy (CBT) has been shown to be effective in treating IBS. The aim of this study was to evaluate the cost-effectiveness of a new treatment alternative, internet-delivered CBT based on exposure and mindfulness exercises. METHODS: Participants (N = 85) with IBS were recruited through self-referral and were assessed via a telephone interview and self-report measures on the internet. Participants were randomized to internet-delivered CBT or to a discussion forum. Economic data was assessed at pre-, post- and at 3-month and 1 year follow-up. RESULTS: Significant cost reductions were found for the treatment group at $16,806 per successfully treated case. The cost reductions were mainly driven by reduced work loss in the treatment group. Results were sustained at 3-month and 1 year follow-up. CONCLUSIONS: Internet-delivered CBT appears to generate health gains in IBS treatment and is associated with cost-savings from a societal perspective.

Acupuncture for irritable bowel syndrome: a protocol for a pragmatic randomised controlled trial.

BACKGROUND: There is insufficient evidence on the effectiveness of acupuncture for irritable bowel syndrome (IBS) for conclusions to be drawn. Given the current interest in acupuncture by patients, it is in the public interest to establish more rigorous evidence. Building on the positive findings from a pilot study, in this paper we present the protocol for a fully-powered trial designed to establish whether or not acupuncture is effective and cost-effective. METHODS/DESIGN: In this pragmatic randomised controlled trial we will randomise patients recruited directly from GP databases to either 10 sessions of acupuncture plus usual GP care or to usual GP care alone. The primary clinical outcome will be the IBS Symptom Severity Score (SSS) (maximum score 500) at three months, and at 12 month assessing whether there is an overall benefit. We estimate the sample size required to detect a minimum clinical difference at 90% power and 5% significance to be 188 patients. To allow for loss to follow up we will recruit 220 patients drawn from an estimated primary care population of 140 000. Analysis will be by intention-to-treat, and multiple imputation is to be used for missing data.In a nested qualitative study using in-depth interviews, we will explore how patients, acupuncturists, and GPs explain and subsequently understand acupuncture to work. We will use purposive sampling to identify patients and flexible topic guides for the interviews. The data analysis will lead to a thematic description of how patients and practitioners explain how acupuncture works, and whether or not the explanations influence treatment outcome and/or referrals.We will undertake a cost-effectiveness analysis at 12 months by comparing resource use in the two groups with any treatment benefit. We will use the EQ-5D to measure health-related quality of life and convert into quality adjusted life years (QALYs). We will generate cost effectiveness acceptability curves (CEACs) exploring the probability that acupuncture will produce an acceptable cost per QALY at different cost-effectiveness thresholds. DISCUSSION: The trial has received NHS ethics approval and recruited 233 patients between November 2008 and June 2009. Results are expected in 2011. TRIAL REGISTRATION: Current Controlled Trials ISRCTN08827905.

Complementary and alternative medicine use and cost in functional bowel disorders: a six month prospective study in a large HMO.

BACKGROUND: Functional Bowel Disorders (FBD) are chronic disorders that are difficult to treat and manage. Many patients and doctors are dissatisfied with the level of improvement in symptoms that can be achieved with standard medical care which may lead them to seek alternatives for care. There are currently no data on the types of Complementary and Alternative Medicine (CAM) used for FBDs other than Irritable Bowel Syndrome (IBS), or on the economic costs of CAM treatments. The aim of this study is to determine prevalence, types and costs of CAM in IBS, functional diarrhea, functional constipation, and functional abdominal pain. METHODS: 1012 Patients with FBD were recruited through a health care maintenance organization and followed for 6 months. Questionnaires were used to ascertain: Utilization and expenditures on CAM, symptom severity (IBS-SS), quality of life (IBS-QoL), psychological distress (BSI) and perceived treatment effectiveness. Costs for conventional medical care were extracted from administrative claims. RESULTS: CAM was used by 35% of patients, at a median yearly cost of $200. The most common CAM types were ginger, massage therapy and yoga. CAM use was associated with female gender, higher education, and anxiety. Satisfaction with physician care and perceived effectiveness of prescription medication were not associated with CAM use. Physician referral to a CAM provider was uncommon but the majority of patients receiving this recommendation followed their physician's advice. CONCLUSION: CAM is used by one-third of FBD patients. CAM use does not seem to be driven by dissatisfaction with conventional care. Physicians should discuss CAM use and effectiveness with their patients and refer patients if appropriate.