Comprehensive Assessment of Nutrition and Dietary Influences in Hypermobile Ehlers-Danlos Syndrome-A Cross-Sectional Study.

INTRODUCTION: Disorders of gut-brain interaction (DGBI) are common in patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder (hEDS/HSD). Food is a known trigger for DGBI symptoms, which often leads to dietary alterations and, increasingly, nutrition support. We aimed to explore dietary behaviors and influencing factors in patients with hEDS/HSD. METHODS: In a cross-sectional study, patients with hEDS/HSD were recruited from Ehlers-Danlos Support UK (nontertiary) and tertiary neurogastroenterology clinics to complete questionnaires characterizing the following: dietary behaviors, nutrition support, DGBI (Rome IV), gastrointestinal symptoms, anxiety, depression, avoidant restrictive food intake disorder (ARFID), mast cell activation syndrome, postural tachycardia syndrome (PoTS), and quality of life. We used stepwise logistic regression to ascertain which factors were associated with dietary behaviors and nutrition support. RESULTS: Of 680 participants (95% female, median age 39 years), 62.1% altered their diet in the last year and 62.3% regularly skipped meals. Altered diet was associated with the following: reflux symptoms ( P < 0.001), functional dyspepsia ( P = 0.008), reported mast cell activation syndrome ( P < 0.001), and a positive screen for ARFID, specifically fear of eating and low interest ( P < 0.001). Approximately 31.7% of those who altered their diet required nutrition support. The strongest predictor of requiring nutrition support was a positive screen for ARFID, specifically fear of eating (OR: 4.97, 95% CI: 2.09-11.8, P < 0.001). DISCUSSION: Altered diet is very common in the patients with hEDS/HSD we studied and influenced by functional dyspepsia, reflux symptoms, and ARFID. Those with ARFID have a 4-fold increased risk of requiring nutrition support, and therefore, it is paramount that psychological support is offered in parallel with dietary support in the management of DGBI in hEDS/HSD.

Young persons and healthcare professionals experience of virtual gastroenterology consultations: a multicentre survey conducted during the COVID-19 pandemic.

Objective: To explore Young Persons (YP) and healthcare professionals (HCP) experiences of virtual consultations (VC) and establish whether developmentally appropriate healthcare can be delivered virtually. Method: YP and HCP questionnaire surveys were designed and piloted. Electronic questionnaire links were sent by post, email or text message January-April 2021 to YP aged 13-25 years old, with predefined chronic gastrointestinal conditions, attending a gastroenterology/hepatology VC. HCP undertaking VC were invited to complete staff questionnaire. Results were anonymous and collated using Excel version 2302. Results: Five UK hospital trusts participated, with 35 HCP responses. Of the 100 YP completing the survey 66% were female and 34% male aged between 13 years and 25 years (median: 18 years). 13% were new appointments and 87% follow ups, 29% were by video, 69% by phone and 2% gave no response. 80% of HCP spoke to YP directly but not privately (69%). 87% of YP and 88% HCP found VC useful. 83% of YP want VC again, although 20% preferred face to face. 43% of HCP required improved phone/internet connection. 77% of YP required hospital appointments for tests following VC. Conclusions: Overall respondents were satisfied with VC, finding them useful, convenient and time saving. Successful VC rely on appropriate patient selection and availability of reliable technology. Patient preference is key which may alter with time.

Low prevalence of positive hydrogen breath tests in patients with functional gastrointestinal conditions and hypermobile Ehlers-Danlos syndrome.

BACKGROUND: Using hydrogen breath testing (HBT) to diagnose small intestinal bacterial overgrowth (SIBO) remains controversial in patients with functional gastrointestinal (GI) disorders, and unknown in those with hypermobility Ehlers-Danlos syndrome (hEDS). We assessed prevalence of positive HBTs in these groups, evaluated the predictive value of GI symptoms and the potential role of proton pump inhibitors (PPIs) on test results. METHODS: Sequential patients referred for HBT to a tertiary unit were classified into the following groups: GI maldigestion/malabsorption, GI sensorimotor disorders, hEDS, and functional GI disorders. All underwent standardized HBT, and the yield was assessed against symptoms and PPI use. KEY RESULTS: A total of 1062 HBTs were performed over 3 years (70% female, mean age 48 ± 16 years). Overall, 7.5% (80/1062) patients had a positive HBT. Prevalence of positive HBT was highest in patients with GI maldigestion/malabsorption (17.9%; DOR 16.16, p < 0.001), GI sensorimotor disorders (15.9%; DOR 8.84, p < 0.001), compared to functional GI disorders (1.6%; DOR 1.0) (p < 0.0001). None of the hEDS patients tested positive for HBT. A positive HBT was independently associated with increased age (DOR 1.03; p < 0.001) and symptoms of diarrhea (DOR 3.95; p < 0.0001). Patients on PPIs tended towards a positive HBT than patients off PPIs (16.1% vs 6.9%; DOR 2.47; p < 0.0001). CONCLUSIONS & INFERENCES: Less than 2% of patients with functional GI disorders, and none of the patients with hEDS had a positive HBT. Pre-test probability was higher in patients with: GI structural or neurological disorders; use of long-term PPIs and symptoms of diarrhea. These criteria may be helpful in making appropriate therapeutic decisions and avoiding unnecessary hydrogen breath testing.

Gastrointestinal symptoms and nutritional issues in patients with hypermobility disorders: assessment, diagnosis and management.

Patients diagnosed with hypermobile Ehlers-Danlos syndrome and hypermobile spectrum disorders are increasingly presenting to secondary and tertiary care centres with gastrointestinal (GI) symptoms and nutritional issues. Due to the absence of specific guidance, these patients are investigated, diagnosed and managed heterogeneously, resulting in a growing concern that they are at increased risk of iatrogenic harm. This review aims to collate the evidence for the causes of GI symptoms, nutritional issues and associated conditions as well as the burden of polypharmacy in this group of patients. We also describe evidence-based strategies for management, with an emphasis on reducing the risk of iatrogenic harm and improving multidisciplinary team care.

Magnetic resonance imaging assessed enteric motility and luminal content analysis in patients with severe bloating and visible distension.

BACKGROUND: Gastrointestinal symptoms in functional gut disorders occur without any discernible structural gut abnormality. Preliminary observations on enteric MRI suggest possible abnormal content and motility of the terminal ileum (TI) in constipation-predominant IBS (IBS-C) with severe bloating, and in functional bloating and distension (FABD) patients. We investigated whether MRI can quantify differences in small bowel (SB) content and motility between patients and healthy controls (HCs). METHODS: 11 IBS-C (mean age 40 [21-52] years; 10 women) and 7 FABD (36 [21-56]; all women) patients with bloating and 20 HCs (28 [22-48]; 6 women) underwent enteric MRI, including dynamic motility and anatomical sequences. Three texture analysis (TA) parameters assessed the homogeneity of the luminal content, with ratios calculated between the TI and (1) the SB and (2) the ascending colon. Four TI motility metrics were derived. Ascending colon diameter (ACD) was measured. A comparison between HCs and patients was performed independently for: (1) three TA parameters, (2) four TI motility metrics, and (3) ACD. KEY RESULTS: Compared with HCs, patients had TI:colon ratios higher for TA contrast (p < 0.001), decreased TI motility (lower mean motility [p = 0.04], spatial motility variation [p = 0.03], and area of motile TI [p = 0.03]), and increased ACD (p = 0.001). CONCLUSIONS AND INFERENCES: IBS-C and FABD patients show reduced TI motility and differences in luminal content compared with HCs. This potentially indicates reflux of colonic contents or delayed clearance of the TI, which alongside increased ACD may contribute to symptoms of constipation and bloating.

Group education on the low FODMAP diet improves gastrointestinal symptoms but neither anxiety or depression in irritable bowel syndrome.

BACKGROUND: The low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet is an effective dietitian-led treatment for irritable bowel syndrome (IBS). An increasing demand of IBS patient referrals has warranted group FODMAP education led by specialist dietitians. Psychological co-morbidities are common in IBS, although how the low FODMAP diet influences psychological outcomes is not understood. The present study aimed to evaluate symptom related outcomes of the diet following group education and assess its effect on psychological profiles. METHODS: An observational, prospective study was conducted in 55 IBS patients who attended FODMAP Restriction and FODMAP Reintroduction group sessions. Data were collected at baseline and follow-up after FODMAP Restriction and analysed using descriptive and McNemar's tests. Primary outcome was evaluated by IBS Symptom Severity Score (IBS-SSS). Secondary psychological outcomes included anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and risk of eating disorder questionnaire (SCOFF). RESULTS: After FODMAP Restriction, 27 of 55 (54%) patients reported clinically relevant symptom improvement, as defined by a reduction in the IBS-SSS ≥50 points, whereas no differences were recorded in the proportion of patients identified with clinical anxiety (p = 1.000) or clinical depression (p = 0.375). Positively, no increased risk of an eating disorder was observed. CONCLUSIONS: The present study provides data supporting the efficacy of the low FODMAP diet in IBS patients who attended dietitian led group education settings in tertiary care. Clinically significant improvements in gastrointestinal symptoms were observed, although with no impact on clinical levels of anxiety, depression or the risk of an eating disorder.

Oral and parenteral anti-neuropathic agents for the management of pain and discomfort in irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a highly prevalent and economically burdensome condition; and pain is often the most unpleasant, disruptive, and difficult-to-treat symptom. Visceral hypersensitivity is a common feature driving pain in IBS, suggesting that neuropathic mechanisms may be implicated. We conducted a systematic review of available evidence to examine the role of anti-neuropathic medicines in the management of pain in IBS. METHODS: We systematically searched scientific repositories for trials investigating conventional oral, and/or parenteral, pharmaceutical antineuropathic treatments in patients with IBS. We summarized key participant characteristics, outcomes related to pain (primary outcome), and selected secondary outcomes. KEY RESULTS: We included 13 studies (n = 629 participants): six investigated amitriptyline, three duloxetine, three pregabalin, and one gabapentin. There was considerable methodological and statistical heterogeneity, so we performed a narrative synthesis and limited meta-analysis. Amitriptyline was most extensively studied, though only in diarrhea-predominant patients. In individual trials, amitriptyline, pregabalin and gabapentin generally appeared beneficial for pain outcomes. While duloxetine studies tended to report improvements in pain, all were un-controlled trials with high risk of bias. Meta-analysis of three studies (n = 278) yielded a pooled relative-risk of 0.50 (95%CI 0.38-0.66) for not improving with anti-neuropathic agent vs control. We did not identify any eligible studies investigating the role of parenteral anti-neuropathics. CONCLUSIONS AND INFERENCES: Anti-neuropathic analgesics may improve pain in IBS, and deserve further, high-quality investigation, potentially considering parenteral administration and agents with minimal gastrointestinal motility effects. Investigation of amitriptyline's efficacy in non-diarrhea-predominant subtypes is currently lacking, and we recommend particular caution for its use in IBS-C.

Constipation in ulcerative colitis: pathophysiology and practical management.

Clinical experience suggests that there is a cohort of patients with refractory colitis who do have faecal stasis that contributes to symptoms. The underlying physiology is poorly understood, partly because until recently the technology to examine segmental colonic motility has not existed. Patients are given little information on how proximal faecal stasis can complicate colitis. Treatment guidelines are scanty and many patients are offered little apart from laxatives and advice on increasing fibre intake, which often makes symptoms worse. This article aims to review the history, pathology and management, and create impetus for future research on this underappreciated condition.

Functional gastrointestinal disorders: History taking skills in practice.

This article offers a framework in history taking for functional gastrointestinal disorders (FGIDs). Clinicians rely on history taking and knowledge of the latest 'Rome IV criteria' rather than biomarkers to make a positive diagnosis of FGIDs. Improving one's history-taking skills is imperative, as early diagnosis can improve patient outcomes by avoiding over investigation and/or chronicity.Our suggested structure for history taking adopts the bio-psycho-social model of disease. We describe the assessment of gastrointestinal symptoms with open and closed questions, the importance of ruling out 'alarm' signs or symptoms, the use of a multi-system approach to identify coexisting functional disorders and eliciting patients' nutritional history. We explore the increased psychological comorbidity present in FGIDs and the significance of the social history in identify predisposing, precipitating, perpetuating and protective factors, which will ultimately guide treatment recommendations.We believe history taking should be used to build rapport with patients while, at the same time, validating their problems and reducing stigma. Reattribution of symptoms is then achieved through education of the gut-brain axis and can be used to provide reassurance to patients at the first encounter. Success of treatment depends on engagement and acceptance of such explanations.

Colonic transit, high-resolution anorectal manometry and MRI defecography study of constipation in Parkinson's disease.

INTRODUCTION: Despite clinical relevance and potential role on the disease pathogenesis, underlying mechanisms of constipation in Parkinson's disease (PD) remain poorly understood. A systematic assessment using complementary physiological investigations was performed to elucidate constipation pathophysiology in order to improve its symptomatic management. METHODS: PD patients with constipation were evaluated with clinical questionnaires, colonic transit, high-resolution anorectal manometry and MRI defecography. Results were compared and correlated with clinical features. RESULTS: A total of 42 patients (69% male; age 68 ±â€¯8 years; disease duration 10.5 ±â€¯6.1 years) were included, of whom 33 (78.6%) had objective constipation defined by < 3 bowel movements per week or straining. Severity of constipation measured by self-administered questionnaires correlated with disease severity, burden of motor and non-motor symptoms but not with age, disease duration or Parkinson's medications. Colonic transit and anorectal function (high-resolution anorectal manometry and/or MRI defecography) was assessed in 15 patients. A combination of both delayed colonic transit and anorectal dysfunction was the pattern most commonly found (60% of patients) and overall anorectal dysfunction was more prevalent than isolated slow transit constipation. Physiological findings were heterogeneous including reduced colonic motility, rectal hyposensitivity, defecatory dyssynergia and poor motor rectal function. CONCLUSION: Subjective constipation in PD is poorly correlated with commonly used definition, assessment questionnaires and physiological results. Multiple complex overlapping pathophysiological mechanisms are responsible including slow transit and anorectal dysfunction. Complementary investigations to assess colonic transit and anorectal function are required in those with refractory symptoms for a systematic assessment and appropriate symptomatic management.

Joint Hypermobility Syndrome Affects Response to a Low Fermentable Oligosaccharide, Disaccharide, Monosaccharide and Polyol Diet in Irritable Bowel Syndrome Patients: A Retrospective Study.

BACKGROUND: The low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet causes significant clinical improvement in patients with irritable bowel syndrome (IBS). Joint hypermobility syndrome (JHS), defined as musculoskeletal symptoms in a hypermobile individual in the absence of systemic rheumatological disease, may be associated with functional gastrointestinal symptoms, including IBS. The aim of this study is to examine whether JHS can affect the response to the low FODMAP diet in patients with IBS. METHODS: In this retrospective study, we included patients with IBS according to Rome III criteria who had followed a low FODMAP diet. Symptoms scores were measured before and after the low FODMAP diet. RESULTS: A total of 165 patients (130 females, age 44 ± 14 years) were included. Diarrhea predominant IBS (IBS-D) was present in 40.6% of our patients while JHS was present in 21.2%. The score for abdominal pain was higher for JHS compared to non-JHS prior to intervention (P = 0.011). Symptoms improved in both groups of patients after a low FODMAP diet (P < 0.0001). The largest effects were shown with significant decreases of the average score and bloating. When broken down by JHS and IBS type, a low FODMAP diet significantly improved pain, bloating, diarrhea, constipation, and the average score with the largest effect in JHS/constipation predominant IBS (IBS-C), JHS/mixed IBS and unclassified IBS (IBS-M), JHS/IBS-D, non-JHS/IBS-C and JHS/IBS-M, respectively. CONCLUSIONS: Our study suggests that a low FODMAP diet has a greater effect on IBS symptoms in JHS than non-JHS patients.

Adherence with a low-FODMAP diet in irritable bowel syndrome: are eating disorders the missing link?

OBJECTIVES: The low-FODMAP diet has emerged as an option for the treatment of irritable bowel syndrome (IBS). This diet is very restrictive, and compliance is usually low. Preliminary findings suggest an association between eating disorders (EDs) and the risk of developing IBS. The aim of this study was to assess the correlation between compliance with a low-FODMAP diet and the risk of ED behaviours among patients with IBS. PATIENTS AND METHODS: A single-centre prospective study was carried out among 233 IBS patients (79.8% females) at University College London Hospital, who commenced a low FODMAPs group programme for IBS (Rome III or IV). Self-reported diet adherence at the end of the 6-week programme was measured. At baseline, and at the 6-week follow-up visit, participants completed the validated IBS-Symptom Severity Score, the SCOFF ED screening questionnaire and the Hospital Anxiety and Depression Scale. RESULTS: Adherence with a low-FODMAP diet was found in 95 (41%) patients. Overall, 54 (23%) patients were classified to be at risk for ED behaviour. Adherence was 57% in the ED group (31/54) versus 35% in the non-ED group (64/179); P<0.05. Adherence with a low-FODMAP diet was highest (51%) in the IBS with diarrhoea subtype and lowest (10%) in IBS with constipation. There was no significant correlation between IBS-Symptom Severity Score and either adherence (P=0.39) or ED behaviour (P=0.28). CONCLUSION: In this IBS cohort, greater adherence to a low-FODMAP diet is associated with ED behaviour. The implications of our study are important in clinical practice for a clinician to have a high index of suspicion of EDs in IBS patients when a high level of low-FODMAP diet achieved.

IGHMBP2 mutation associated with organ-specific autonomic dysfunction.

Biallelic mutations in the IGHMBP2 have been associated with two distinct phenotypes: spinal muscular atrophy with respiratory distress type 1 (SMARD1) and CMT2S. We describe a patient who developed progressive muscle weakness and wasting in her upper and lower limbs from infancy. She developed respiratory involvement at age 9, eventually requiring 24-h non-invasive ventilation, and severe autonomic dysfunction restricted to the gastrointestinal tract. Neurophysiological studies at age 27 years revealed absent sensory and motor responses and severe chronic denervation changes in proximal muscles of the upper limbs. Targeted multigene panel sequencing detected a novel homozygous missense variant in the IGHMBP2 gene (c.1325A > G; p.Tyr442Cys). This variant was validated by Sanger sequencing and co-segregation analysis confirmed that both parents were asymptomatic heterozygous carriers. This case report confirms that IGHMBP2 related disorders can result in a severe peripheral neuropathy with gastrointestinal autonomic dysfunction requiring parenteral nutrition.

Posterior Tibial Nerve Stimulation for the Treatment of Fecal Incontinence Following Obstetric Anal Sphincter Injury.

OBJECTIVES: Obstetric anal sphincter injuries (OASI) are a major risk factor for fecal incontinence (FI). Neuromodulation is often used as second-line therapy for FI, but evidence for its efficacy is conflicting. We aimed to evaluate the efficacy and predictive factors of posterior tibial nerve stimulation for obstetric anal sphincter injury-induced FI. MATERIALS AND METHODS: Consecutive females with FI related to past OASI who had not responded to first-line therapy and had received 8-12 weeks of posterior tibial nerve stimulation were included. Subjects aged more than 50 and/or having other causes of FI were excluded. Patients underwent anorectal physiology and endoanal ultrasound pretherapy. Symptom burden was evaluated pretherapy and posttherapy using Rockwood and Wexner scales. A Wexner score reduced to below 10 or halved was used to define responders. RESULTS: A total of 37 females (mean age 38 years, median parity 2) were included. About 17 (46%) had ultrasonographically visualized anal sphincter defects and 41% had a history of third or second-degree perineal tears. About 14 subjects (38%) were deemed responders. Compared with nonresponders, responders had lower baseline rectal distension thresholds and tended to have disrupted (59%) than intact sphincters (20%, p < 0.01). Responders demonstrated improvement in Rockwood score for depression and embarrassment, visual analogue score for bowel symptoms and stool consistency (median baseline Bristol score 5, to 3 posttherapy; p < 0.01). CONCLUSIONS: Of a well-defined cohort of females with FI secondary to OASI, 38% responded to posterior tibial nerve stimulation. Much of this improvement may relate to improvement in stool consistency.

Severe eosinophilic colitis caused by neuropathic agents in a patient with chronic fatigue syndrome and functional abdominal pain: case report and review of the literature.

Eosinophilic colitis is a rare clinical condition that belongs to the group of eosinophilic gastrointestinal disorders. Its occurrence can be primary or secondary to infection, medications, or autoimmune/hematological conditions. We present a case of a young female adult with severe chronic fatigue syndrome, widespread chronic pain, including functional abdominal pain, who developed severe eosinophilic colitis following successive treatments with gabapentin and pregabalin. On both occasions, symptoms manifested as abdominal pain, diarrhea, and eosinophilia and improved upon discontinuation of the medications. Magnetic resonance imaging of the small bowel demonstrated an ascending colon colitis, and endoscopic investigations confirmed florid colitis mainly in the ascending colon with biopsies demonstrating a dense eosinophilic infiltrate with micro-abscesses. Serum eosinophil counts correlated well with the timing of the agents' administration. There was no other organ involvement. Symptoms improved upon discontinuation of the drugs and steroid administration. Eosinophilic colitis is an exceptionally rare entity and its mechanism of action is still unclear. Suspicion of eosinophilic colitis should be raised if a patient presents with abdominal pain, diarrhea, and peripheral eosinophilia following treatment with pregabalin or gabapentin.

Efficacy of Percutaneous Posterior Tibial Nerve Stimulation for the Management of Fecal Incontinence in Multiple Sclerosis: A Pilot Study.

BACKGROUND: Fecal incontinence is a debilitating and highly prevalent problem among multiple sclerosis patients. Conservative therapies often fail to provide benefit. Posterior tibial nerve stimulation is a minimally invasive neuromodulatory therapy with proven efficacy for fecal incontinence in non-neurological settings. OBJECTIVE: To evaluate the efficacy of posterior tibial nerve stimulation in treating multiple sclerosis-related fecal incontinence. METHODS: Consecutive multiple sclerosis patients with fecal incontinence that had failed conservative therapy received posterior tibial nerve stimulation between 2012 and 2015. All patients had previously undergone anorectal physiology tests and endoanal ultrasound. Patients whose Wexner incontinence score reduced below 10 post-therapy or halved from baseline were deemed responders. RESULTS: Thirty-three patients (25 female, median age 43 years) were included. Twenty-three (70%) had urge, 4 (12%) passive, and 9 (27%) mixed fecal incontinence. Twenty-six (79%) were classified as responders. The majority of subjects had relapsing-remitting multiple sclerosis (67%); those had a significantly higher response rate (95% vs. 67% and 50% in primary and secondary progressive respectively, P < 0.05). Responders tended to be more symptomatic at baseline and had greater improvements in bowel symptom scores and quality of life scores with therapy. CONCLUSION: Posterior tibial nerve stimulation demonstrates potential as an effective therapy for fecal incontinence in multiple sclerosis. These findings provide the basis for future more definitive controlled studies.

What about clonidine for diarrhoea? A systematic review and meta-analysis of its effect in humans.

BACKGROUND: Clonidine is considered an alternative treatment for refractory diarrhoea. The evidence in the literature is scarce and not conclusive. The present paper's purpose is to gather available evidence and provide a systematic answer regarding the effectiveness of clonidine for diarrhoea. METHOD: We performed a systematic review of clonidine and its effect on diarrhoea. Meta-analysis was performed with a random effects model of the standardized mean difference (SMD) or the weighted mean difference and heterogeneity was quantified with I (2) and publication bias was assessed with Egger's and Begg's test. Subgroup analyses and meta-regression were performed to investigate sources of heterogeneity. Any empirical study describing use of clonidine for diarrhoea in humans independent of age was included. For the meta-analysis, papers had to provide sufficient data to produce an effect measure, while case reports were not included in the meta-analysis and are discussed narratively only. RESULTS: A total of 24 trials and seven case reports were identified. Clonidine (median dose 300 µg/day) has been used for treatment of diarrhoea in irritable bowel syndrome, faecal incontinence, diabetes, withdrawal-associated diarrhoea, intestinal failure, neuroendocrine tumours and cholera; studies were also performed on healthy volunteers. Results indicate a strong effect of clonidine on diarrhoea (SMD = -1.02, 95% confidence interval [CI] -1.46 to -0.58) with a decrease of stool volume by 0.97 l/day, stool frequency by 0.4 times/day and increase in transit time by 31 minutes. In a sensitivity analysis of studies with functional diarrhoea and sample size over 10 subjects, the effect was similar -0.99 (95% CI -1.54 to -0.43). There is however significant heterogeneity and publication bias. Heterogeneity decreased in subgroup analyses by condition but not with other factors examined. A limitation of the present study includes small study effects. CONCLUSION: Clonidine is effective for treatment of diarrhoea and should be considered as an alternative when all other medications have failed.