Abstract: Conventionally, irritable bowel syndrome (IBS) is subgrouped using predominant stool form, yet it is a complex disorder, with multiple biopsychosocial contributors. We previously derived and validated a latent class model subgrouping people with IBS into seven clusters based on gastrointestinal and extraintestinal symptoms and psychological profile. Aims To conduct longitudinal follow‐up examining the natural history and prognostic value of these clusters. Methods Participants completed a 12‐month follow‐up questionnaire. We applied our model to these data, comparing cluster membership between the two time points in those still meeting Rome IV criteria at follow‐up, including stratifying the analysis by predominant stool pattern, and level of psychological burden, at baseline. We examined whether baseline cluster predicted the course of IBS, and whether starting new treatment was associated with changing cluster. Results Eight hundred and eleven participants met Rome IV criteria for IBS at baseline, of whom 452 (55.7%) responded, and 319 (70.6%) still met Rome IV criteria for IBS at follow‐up. Of these, 172 (53.9%) remained in the same IBS cluster as at baseline and 147 changed cluster. Cluster membership stratified according to psychological comorbidity was more stable; 84% of those in a cluster with high psychological burden at baseline remained in such a cluster at follow‐up. People in clusters with high psychological burden at baseline had more severe symptoms ( P   〈  0.001), received a higher mean number of subsequent treatments ( P   〈  0.001), and were more likely to consult a doctor than people in clusters with low psychological burden ( P   〈  0.001). There was no significant association between starting a new treatment and changing cluster at follow‐up. Conclusions Longitudinal follow‐up demonstrated little transition between clusters with respect to psychological burden, and these appeared to predict disease course. Directing treatment according to cluster, including earlier use of psychological therapies, and exploring how this approach influences outcomes in IBS, should be examined.

Abstract: The m.3243A 〉 G MTTL1 mutation is the most common cause of mitochondrial disease; yet there is limited awareness of intestinal pseudo‐obstruction (IPO) in this disorder. We aimed to determine the prevalence, severity, and clinical outcome of patients with m.3243A 〉 G‐related mitochondrial disease manifesting with IPO. Methods In this large, observational cohort study, we assessed the clinical, molecular, and radiological characteristics of patients with genetically determined m.3243A 〉 G‐related mitochondrial disease, who presented with severe symptoms suggestive of bowel obstruction in the absence of an occluding lesion. Results Between January 2009 and June 2015, 226 patients harbouring the m.3243A 〉 G mutation were recruited to the Medical Research Council Centre Mitochondrial Disease Patient Cohort, Newcastle. Thirty patients (13%) presented acutely with IPO. Thirteen of these patients had a preceding history of stroke‐like episodes, whereas 1 presented 27 years previously with their first stroke‐like episode. Eight patients developed IPO concomitantly during an acute stroke‐like episode. Regression analysis suggested stroke was the strongest predictor for development of IPO, in addition to cardiomyopathy, low body mass index and high urinary mutation load. Poor clinical outcome was observed in 6 patients who underwent surgical procedures. Interpretation Our findings suggest, in this common mitochondrial disease, that IPO is an under‐recognized, often misdiagnosed clinical entity. Poor clinical outcome associated with stroke and acute surgical intervention highlights the importance of the neurologist having a high index of suspicion, particularly in the acute setting, to instigate timely coordination of appropriate care and management with other specialists. Ann Neurol 2016;80:686–692

Abstract: Conventionally, patients with irritable bowel syndrome (IBS) are subgrouped based on their predominant bowel habit. Given the relevance of psychological comorbidity to IBS symptoms, our aim was to explore an alternative approach to subgrouping by incorporating factors beyond stool form and frequency. METHODS: We collected demographic, symptom, and psychological health data from 1,375 adult subjects in the community who self-identified as having IBS, identifying 2 cohorts meeting either Rome III or Rome IV criteria. In each cohort, we performed latent class analysis, a method of model-based clustering, to identify specific subgroups (clusters). For each cluster, we drew a radar plot and compared these by visual inspection, describing cluster characteristics. RESULTS: In total, 1,080 individuals met the Rome III criteria for IBS, and 811 met the Rome IV criteria. In both cohorts, a 7-cluster model was the optimum solution, and the characteristics of the clusters were almost identical between Rome III and IV. Four clusters were defined by the pattern of gastrointestinal symptoms (loose stools and urgency or hard stools and bloating), further differentiated by the presence of abdominal pain not relieved by defecation, and by the extent of psychological comorbidity. Two clusters had below-average gastrointestinal symptoms, differentiated by the extent of psychological comorbidity. The final cluster had well-above-average gastrointestinal symptoms and high levels of psychological comorbidity. The proportion of subjects with severe IBS symptom scores, high levels of perceived stress, and high levels of gastrointestinal symptom–specific anxiety was significantly higher in clusters with high psychological comorbidity ( P 〈 0.001). DISCUSSION: Latent class analysis identified 7 distinct IBS subgroups characterized by varying degrees of gastrointestinal symptoms, extraintestinal symptoms, and psychological comorbidity. Further research is needed to assess whether they might be used to direct treatment.

Abstract: Transanal irrigation (TAI) is a treatment for bowel dysfunction, with UK approval in patients with constipation and faecal incontinence. This article is intended for health-care professionals involved in the management of patients with bowel dysfunction and describes what TAI is and the proposed method of action. It also considers the latest evidence related to the safety and efficacy of TAI. There is now a potentially overwhelming range of equipment available on prescription to deliver this treatment. The factors to consider in the appropriate selection of equipment for individual patients will be considered, alongside an algorithm for the selection of equipment to aid health professionals with this choice.

Abstract: Chronic constipation affects 1–2% of adults and significantly affects quality of life. Beyond the use of laxatives and other basic measures, there is uncertainty about management, including the value of specialist investigations, equipment-intensive therapies using biofeedback, transanal irrigation and surgery. Objectives (1) To determine whether or not standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback is more clinically effective than standardised specialist-led habit training alone, and whether or not outcomes of such specialist-led interventions are improved by stratification to habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback or habit training alone based on prior knowledge of anorectal and colonic pathophysiology using standardised radiophysiological investigations; (2) to compare the impact of transanal irrigation initiated with low-volume and high-volume systems on patient disease-specific quality of life; and (3) to determine the clinical efficacy of laparoscopic ventral mesh rectopexy compared with controls at short-term follow-up. Design The Chronic Constipation Treatment Pathway (CapaCiTY) research programme was a programme of national recruitment with a standardised methodological framework (i.e. eligibility, baseline phenotyping and standardised outcomes) for three randomised trials: a parallel three-group trial, permitting two randomised comparisons (CapaCiTY trial 1), a parallel two-group trial (CapaCiTY trial 2) and a stepped-wedge (individual-level) three-group trial (CapaCiTY trial 3). Setting Specialist hospital centres across England, with a mix of urban and rural referral bases. Participants The main inclusion criteria were as follows: age 18–70 years, participant self-reported problematic constipation, symptom onset 〉  6 months before recruitment, symptoms meeting the American College of Gastroenterology’s constipation definition and constipation that failed treatment to a minimum basic standard. The main exclusion criteria were secondary constipation and previous experience of study interventions. Interventions CapaCiTY trial 1: group 1 – standardised specialist-led habit training alone ( n  = 68); group 2 – standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback ( n  = 68); and group 3 – standardised radiophysiological investigations-guided treatment ( n  = 46) (allocation ratio 3 : 3 : 2, respectively). CapaCiTY trial 2: transanal irrigation initiated with low-volume (group 1, n  = 30) or high-volume (group 2, n  = 35) systems (allocation ratio 1 : 1). CapaCiTY trial 3: laparoscopic ventral mesh rectopexy performed immediately ( n  = 9) and after 12 weeks’ ( n  = 10) and after 24 weeks’ ( n  = 9) waiting time (allocation ratio 1 : 1 : 1, respectively). Main outcome measures The main outcome measures were standardised outcomes for all three trials. The primary clinical outcome was mean change in Patient Assessment of Constipation Quality of Life score at the 6-month, 3-month or 24-week follow-up. The secondary clinical outcomes were a range of validated disease-specific and psychological scoring instrument scores. For cost-effectiveness, quality-adjusted life-year estimates were determined from individual participant-level cost data and EuroQol-5 Dimensions, five-level version, data. Participant experience was investigated through interviews and qualitative analysis. Results A total of 275 participants were recruited. Baseline phenotyping demonstrated high levels of symptom burden and psychological morbidity. CapaCiTY trial 1: all interventions (standardised specialist-led habit training alone, standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback and standardised radiophysiological investigations-guided habit training alone or habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback) led to similar reductions in the Patient Assessment of Constipation Quality of Life score (approximately –0.8 points), with no statistically significant difference between habit training alone and habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback (–0.03 points, 95% confidence interval –0.33 to 0.27 points; p  = 0.8445) or between standardised radiophysiological investigations and no standardised radiophysiological investigations (0.22 points, 95% confidence interval –0.11 to 0.55 points; p  = 0.1871). Secondary outcomes reflected similar levels of benefit for all interventions. There was no evidence of greater cost-effectiveness of habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback or stratification by standardised radiophysiological investigations compared with habit training alone (with the probability that habit training alone is cost-effective at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year gain; p  = 0.83). Participants reported mixed experiences and similar satisfaction in all groups in the qualitative interviews. CapaCiTY trial 2: at 3 months, there was a modest reduction in the Patient Assessment of Constipation Quality of Life score, from a mean of 2.4 to 2.2 points (i.e. a reduction of 0.2 points), in the low-volume transanal irrigation group compared with a larger mean reduction of 0.6 points in the high-volume transanal irrigation group (difference –0.37 points, 95% confidence interval –0.89 to 0.15 points). The majority of participants preferred high-volume transanal irrigation, with substantial crossover to high-volume transanal irrigation during follow-up. Compared with low-volume transanal irrigation, high-volume transanal irrigation had similar costs (median difference –£8, 95% confidence interval –£240 to £221) and resulted in significantly higher quality of life (0.093 quality-adjusted life-years, 95% confidence interval 0.016 to 0.175 quality-adjusted life-years). CapaCiTY trial 3: laparoscopic ventral mesh rectopexy resulted in a substantial short-term mean reduction in the Patient Assessment of Constipation Quality of Life score (–1.09 points, 95% confidence interval –1.76 to –0.41 points) and beneficial changes in all other outcomes; however, significant increases in cost (£5012, 95% confidence interval £4446 to £5322) resulted in only modest increases in quality of life (0.043 quality-adjusted life-years, 95% confidence interval –0.005 to 0.093 quality-adjusted life-years), with an incremental cost-effectiveness ratio of £115,512 per quality-adjusted life-year. Conclusions Excluding poor recruitment and underpowering of clinical effectiveness analyses, several themes emerge: (1) all interventions studied have beneficial effects on symptoms and disease-specific quality of life in the short term; (2) a simpler, cheaper approach to nurse-led behavioural interventions appears to be at least as clinically effective as and more cost-effective than more complex and invasive approaches (including prior investigation); (3) high-volume transanal irrigation is preferred by participants and has better clinical effectiveness than low-volume transanal irrigation systems; and (4) laparoscopic ventral mesh rectopexy in highly selected participants confers a very significant short-term reduction in symptoms, with low levels of harm but little effect on general quality of life. Limitations All three trials significantly under-recruited [CapaCiTY trial 1, n  = 182 (target 394); CapaCiTY trial 2, n  = 65 (target 300); and CapaCiTY trial 3, n  = 28 (target 114)]. The numbers analysed were further limited by loss before primary outcome. Trial registration Current Controlled Trials ISRCTN11791740, ISRCTN11093872 and ISRCTN11747152. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research ; Vol. 9, No. 14. See the NIHR Journals Library website for further project information.