The effect of non-pooled multi-donor faecal microbiota transplantation for inducing clinical remission in patients with chronic pouchitis: Results from a multicentre randomised double-blinded placebo-controlled trial (MicroPouch).

BACKGROUND AND AIMS: To investigate if treatment with non-pooled multi-donor faecal microbiota transplantation (FMT) for four weeks was superior to placebo to induce clinical remission in patients with chronic pouchitis. METHODS: The study was a randomised double-blinded placebo-controlled study with a 4-week intervention period and 12-month follow-up. Eligible patients with chronic pouchitis were recruited from five Danish hospitals. Participants were randomised to non-pooled multi-donor FMT derived from four faecal donors, or placebo. Treatment was delivered daily by enema for two weeks followed by every second day for two weeks. Disease severity was accessed at inclusion and 30-day follow-up, using the Pouchitis Disease Activity Index (PDAI); PDAI <7 was considered equivalent to clinical remission. Faecal samples from participants and donors were analysed by shotgun metagenomic sequencing. RESULTS: Inclusion was stopped after inclusion of 30 participants who were randomised 1:1 for treatment with FMT or placebo. There was no difference in participants achieving clinical remission between the two groups at 30-day follow-up, relative risk 1.0 (95%CI(0.55;1.81)). Treatment with FMT resulted in a clinically relevant increase in adverse events compared to placebo, incidence rate ratio 1.67 (95%CI(1.10;2.52)); no serious adverse events within either group. Faecal microbiota transplantation statistically significantly increased the similarity of participant faecal microbiome to the faecal donor microbiome at 30-days follow-up (p=0.01), which was not seen after placebo. CONCLUSIONS: Non-pooled multi-donor FMT was comparable to placebo in inducing clinical remission in patients with chronic pouchitis but showed a clinically relevant increase in adverse events compared to placebo.

The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.

BACKGROUND: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe. METHODS: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT. FINDINGS: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres. INTERPRETATION: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need. FUNDING: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).

Patient goals after operation in the posterior vaginal compartment.

OBJECTIVE: Success after operation for a pelvic organ prolapse in the posterior vaginal compartment is often related to restoration of anatomy, but success for the patient is linked to achievement of patient-reported goals. We investigated patient-reported goals after an operation in the posterior compartment and to which extent the goals had been achieved. STUDY DESIGN: A prospective case series study including 87 women undergoing operation in the posterior compartment at Aalborg University Hospital. The women were asked to list up to three goals they wished to fulfil with the operation. Three months after surgery a telephone interview was conducted in which the women were asked whether each single goal was fulfilled, partly fulfilled or not fulfilled and to estimate the extent to which the goals had been achieved on a VAS scale from 1 to 10. RESULTS: All patient-reported goals were divided into eight groups: 1: bulging, 2: bowel problems, 3: urinary problems, 4: sexual problems, 5: psychological problems, 6: physical activity, 7: pain and 8: others. A total of 233 goals were stated. Most goals were related to bowel problems (37.3%) and bulging (21.0%). Median total VAS score was 9. Overall 58.8% of all goals were categorized as fulfilled and 22.3% as partly fulfilled. Fulfilled goals were 83.7% in the group with bulging problems, sexuality problems 65%, and bowel problems 57.5%. Urinary problems had fewest fulfilled goals (18.5%). Bowel problems were further divided into evacuation problems, incontinence, constipation and others. Goals concerning evacuation problems were most often fulfilled (76.1%), and goals concerning anal incontinence were rarely fulfilled (25.0%). CONCLUSIONS: Approximately 80% of the patient-reported goals after posterior compartment operation were fulfilled or partly fulfilled. Most goals were related to bowel problems and bulging. Bowel problems in the form of evacuation problems were more often solved than incontinence and constipation, and women should be advised about this. All goals should be discussed with the patient prior to an operation.

Incidental detection of colorectal lesions on 18 F-FDG-PET/CT is associated with high proportion of malignancy: A study in 549 patients.

Background and study aims Further diagnostics of incidental colorectal lesions on 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is questionable. Therefore, we aimed to evaluate the clinical importance of incidentally detected colorectal lesions on FDG-PET/CT. Patients and methods In the North Denmark Region, a retrospective study was performed among 19,987 patients who had an FDG-PET/CT from January 2006 to December 2015. Among these patients, we identified patients with a colonoscopy within 12 months from the PET/CT scan and a description of incidental colorectal PET-avid lesions on the PET/CT. PET findings were compared with colonoscopy-detected lesions and eventually histopathology. Results Incidental PET-avid lesions were observed in 549 patients. Colonoscopy revealed lesions in 457 (83 %), among whom 338 patients had a final histopathological diagnosis. Malignant and premalignant lesions were found in 297 patients (54 % among patients with a PET-avid lesion). The lesions were cancer in 76 patients and adenoma in 221 patients of whom 30 had high-grade and 191 low-grade adenomas. The findings changed patient management in 166 cases (30 % of all patients with a PET-avid lesion). A colonoscopy-based surveillance program was initiated for 80 % of patients with high-grade adenoma. No patients with PET-avid lesions but normal colonoscopy developed colorectal cancer during 3 years of observation (median observation time 7 years). Conclusions Incidental colorectal FDG uptake was infrequently observed, but when present, it was associated with a high rate of malignant or premalignant lesions. Our results indicate that patients with incidental colorectal FDG uptake should be referred to diagnostic work-up including colonoscopy.

The Microbiota Profile in Inflamed and Non-Inflamed Ileal Pouch-Anal Anastomosis.

The objective was to determine the bacterial composition in inflamed and non-inflamed pouches for comparison to the microbiota of healthy individuals. Pouch patients and healthy individuals were included between November 2017 and June 2019 at the Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark. A faecal sample was collected from all participants for microbiota analysis using 16S rRNA amplicon sequencing. Overall, 38 participants were included in the study. Eleven patients with a normally functioning pouch, 9 patients with chronic pouchitis, 6 patients with familial adenomatous polyposis, and 12 healthy individuals. Patients with chronic pouchitis had overall lower microbial diversity and richness compared to patients with a normal pouch function (p < 0.001 and p = 0.009) and healthy individuals (p < 0.001 and p < 0.001). No significant difference was found between patients with familial adenomatous polyposis and chronic pouchitis (microbial diversity p = 0.39 and richness p = 0.78). Several taxa from the family Enterobacteriaceae, especially genus Escherichia, were associated primarily with patients with chronic pouchitis, while taxa from the genus Bacteroides primarily were associated with healthy individuals and patients with a normally functioning pouch. Finally, a microbial composition gradient could be established from healthy individuals through patients with normal pouch function and familial adenomatous polyposis to patients with chronic pouchitis.

Fecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Systematic Review.

The objective was to evaluate available literature on treatment of chronic pouchitis with fecal microbiota transplantation (FMT) focusing on clinical outcomes, safety, and different approaches to FMT preparation and delivery. A systematic review of electronic databases was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials Library from inception through April 2020. Human studies of all study types reporting results of FMT to treat chronic pouchitis were included. Nine studies, reporting FMT treatment of 69 patients with chronic pouchitis were found eligible for the review. Most studies were case series and cohort studies rated as having fair to poor quality due to high risk of bias and small sample size. Only one randomized controlled trial was included, finding no beneficial effect of FMT. In total clinical response after FMT was reported in 14 (31.8%) out of 44 evaluated patients at various timepoints after FMT, and clinical remission in ten (22.7%) patients. Only minor self-limiting adverse events were reported. FMT varied greatly regarding preparation, length of treatment, and route of delivery. The effects of FMT on symptoms of chronic pouchitis are not established, though some studies show promising results. Future controlled well-designed studies are warranted.

Consumption of yoghurt favours remission after faecal microbiota transplantation for chronic pouchitis.

PURPOSE: The gut microbiota is conceivably a key factor in the aetiology of pouchitis. Faecal microbiota transplantation (FMT) has been suggested as a promising new treatment for chronic pouchitis, where treatment options often are few. However, little is known about the influence of the diet on the clinical effects of FMT. We assessed the diet of patients with chronic pouchitis undergoing FMT to investigate the influence of diet on the clinical outcome after FMT. METHODS: Nine patients with chronic pouchitis were allocated to treatment with FMT delivered by enema from five faecal donors for 14 consecutive days in a 6-month prospective, open-label, single-centre cohort pilot study. A dietary questionnaire was completed at baseline for all patients and donors. Patients underwent a pouchoscopy at baseline and at 30-day follow-up, and the Pouchitis Disease Activity Index (PDAI) was assessed. RESULTS: Patients' diets were generally similar, when comparing patients in remission post-FMT (PDAI < 7) with those who relapsed (PDAI ≥ 7). Consumption of grains trended to be different between the two groups (p = 0.06), where patients in relapse consumed more bread products than did patients in remission. However, consumption of yoghurt was significantly different between the two groups (p = 0.04), with patients in remission consuming more yoghurt (mean 1.1 s/d vs 0.2 s/d). CONCLUSION: Gastroenterologist performing clinical studies on FMT for chronic pouchitis should be aware of dietary habits as contributing factors for the clinical effect of FMT.

Clinical results and microbiota changes after faecal microbiota transplantation for chronic pouchitis: a pilot study.

Objectives: Research evidence suggests that chronic pouchitis is associated with intestinal dysbiosis. Faecal microbiota transplantation (FMT) has been proposed as a possible treatment. We performed a 6-month prospective, open-label, single-centre cohort pilot-study (NCT03538366) to investigate if FMT could improve clinical outcome and alter gut microbiota in patients with chronic pouchitis.Materials and methods: Nine adult patients with chronic pouchitis were included and allocated to 14 days FMT by enemas from five faecal donors, with a 6-month follow-up. Pouchitis severity was assessed using pouchitis disease activity index (PDAI) before and after FMT. Changes in gut microbiota, and engraftment of donor's microbiota were assessed in faecal samples.Results: All patients were treated with FMT for 14 continuous days. Overall, four of nine patients receiving FMT were in clinical remission at 30-day follow-up, and three patients remained in remission until 6-month follow-up. Clinical symptoms of pouchitis improved significantly between inclusion and 14-day follow-up (p = .02), but there was no improvement in PDAI between inclusion (mean 8.6) and 30-day follow-up (mean 5.2). Treatment with FMT caused a substantial shift in microbiota and increased microbial diversity in six patients, resembling that of the donors, with a high engraftment of specific donor microbiota.Conclusions: Symptomatic benefit in FMT treatment was found for four of nine patients with chronic pouchitis with increased microbial diversity and high engraftment of donor's microbiota. A larger, randomised controlled study is required to fully evaluate the potential role of FMT in treating chronic pouchitis.

The effect of having a child with ADHD or ASD on family separation.

PURPOSE: The primary aim of this study was to estimate the risk of parental separation associated with having a child with ADHD or ASD when controlling for a large range of known risk factors for parental separation using Danish registries. METHODS: The study included all children with ADHD or ASD born between 1990 and 1998 in Denmark and a sex and age matched random sample of children from the background population. We followed these children and their parents from birth until the child's 25th birthday, parental separation or December 31, 2015, whichever came first. Data were analyzed using Cox Proportional Hazard models by estimating hazard ratios (HR) and 95% confidence intervals. Models were adjusted for a range of child, parental, and family variables. RESULTS: The study included the parents of 12,916 children with ADHD, 7496 children with ASD and 18,423 controls. The study found that, even after controlling for a range of potential risk factors, having a child with either ADHD (HR = 1.8, 95% CI 1.6-2.0) or ASD (HR = 1.2, 95% CI 1.1-1.3) significantly increased parents' risk of separating compared with non-affected families. Other factors associated with parental separation were parental imprisonment, parental psychopathology, low parental education level, low household income and living in a larger city. CONCLUSION: Parents of children diagnosed with ADHD or ASD were more likely to separate than control parents. It is important to improve our knowledge about the particular characteristics of families at risk of separating to prevent distress for the families and their child.

Effects of Intramuscular Midazolam and Lorazepam on Acute Agitation in Non-Elderly Subjects - A Systematic Review.

Benzodiazepines are commonly used for the treatment of acute agitation in a psychiatric setting.We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant publications. Randomized trials evaluating intramuscular (IM) midazolam or lorazepam given as monotherapy or as add-on treatment, with more than 10 patients aged 18-65 years, conducted in a psychiatric setting, and published between January 1, 1980, and February 3, 2016, were included. 16 studies from a search result of 5 516 studies were included. In total, 577 patients were treated with lorazepam IM 2-4 mg, and 329 patients were treated with midazolam IM 5-15 mg. It is unclear whether lorazepam IM or midazolam IM is as efficacious as an antipsychotic IM. It is a bit more certain that the combination of benzodiazepines IM and a low dose antipsychotic IM is more efficacious than the benzodiazepine and the antipsychotic alone. However, there is no doubt that benzodiazepines are less likely to be associated with treatment emergent side effects, as compared to antipsychotics.