The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Significant Differences in IBD Care and Education across Europe: Results of the Pan-European VIPER Survey.

BACKGROUND: Inflammatory bowel disease (IBD) care and education might differ around Europe. Therefore, we conducted this European Variation In IBD PracticE suRvey (VIPER) to investigate potential differences between countries. METHODS: This trainee-initiated survey, run through SurveyMonkey®, consisted of 47 questions inquiring basic demographics, IBD training, and clinical care. Results were compared according to gross domestic product (GDP) per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). RESULTS: The online survey was completed by 1,285 participants from 40 European countries, with a majority of specialists (65.3%) working in academic institutions (50.4%). Significant differences in IBD-specific training (55.9% vs. 38.4%), as well as availability of IBD units (58.4% vs. 39.7%) and multidisciplinary meetings (73.2% vs. 40.1%), were observed between respondees from high and low GDP countries (p < 0.0001). In high GDP countries, IBD nurses are more common (85.9% vs. 36.0%), also mirrored by more nurse-led IBD clinics (40.6% vs. 13.7%; p < 0.0001). IBD dieticians (33.4% vs. 16.5%) and psychologists (16.8% vs. 7.5%) are mainly present in high GDP countries (p < 0.0001). In the current COVID era, telemedicine is available in 73.2% versus 54.1% of the high/low GDP countries, respectively (p < 0.0001). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. CONCLUSION: Much variability in IBD practice exists across Europe, with marked differences between high and low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardize IBD care and training across Europe.

Prevalence of 'pouch failure' of the ileoanal pouch in ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The ileoanal pouch (IPAA) provides patients with ulcerative colitis (UC) that have not responded to medical therapy an option to retain bowel continuity and defecate without the need for a long-term stoma. Despite good functional outcomes, some pouches fail, requiring permanent diversion, pouchectomy, or a redo pouch. The incidence of pouch failure ranges between 2 and 15% in the literature. We conducted a systematic review and meta-analysis aiming to define the prevalence of pouch failure in patients with UC who have undergone IPAA using population-based studies. METHODS: We searched Embase, Embase classic and PubMed from 1978 to 31st of May 2021 to identify cross-sectional studies that reported the prevalence of pouch failure in adults (≥ 18 years of age) who underwent IPAA for UC. RESULTS: Twenty-six studies comprising 23,389 patients were analysed. With < 5 years of follow-up, the prevalence of pouch failure was 5% (95%CI 3-10%). With ≥ 5 but < 10 years of follow-up, the prevalence was 5% (95%CI 4-7%). This increased to 9% (95%CI 7-16%) with ≥ 10 years of follow-up. The overall prevalence of pouch failure was 6% (95%CI 5-8%). CONCLUSIONS: The overall prevalence of pouch failure in patients over the age of 18 who have undergone restorative proctocolectomy in UC is 6%. These data are important for counselling patients considering this operation. Importantly, for those patients with UC being considered for a pouch, their disease course has often resulted in both physical and psychological morbidity and hence providing accurate expectations for these patients is vital.

The impact of the ileoanal pouch on female fertility in ulcerative colitis: A systematic review and meta-analysis.

AIM: Ileal pouch-anal anastomosis is a restorative option for patients with ulcerative colitis (UC) requiring surgery. The primary outcome of this study was the relative risk of infertility in women with UC undergoing restorative proctocolectomy (RPC) compared to the same patients before undergoing RPC. Infertility was defined as the inability to conceive after 1 year of regular sexual intercourse without contraception. METHODS: A systematic review and meta-analysis were performed to include all relevant articles from 1946 from MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Studies included reported on the fertility rate of a cohort with UC and also reported the rate after RPC in those within the cohort who underwent surgery. This study was registered on PROSPERO (CRD42021259745). RESULTS: Thirteen studies met the inclusion criteria and accounted for 793 patients pre-pouch and 802 post-pouch. The mean and median age of the patients at analysis was 36.8 and 32.7 years respectively; and the median duration of follow-up following ileal pouch-anal anastomosis was 110.4 (68-139) months. Our results highlight that following RPC the relative risk of infertility is 4.17 (95% CI 1.99, 8.74) compared with patients before RPC who had UC. CONCLUSIONS: The findings of this meta-analysis provide an update on a previous meta-analysis published over a decade ago and results remain congruent. This suggests that despite advancements in surgical techniques the risk to fertility remains similar to a decade ago. However, further high quality studies are needed to try and decipher independent risk factors associated with a decrease in infertility.

Prevalence of pouchitis in both ulcerative colitis and familial adenomatous polyposis: A systematic review and meta-analysis.

AIM: Pouchitis is a clinically significant complication of ileal pouch-anal anastomosis with its prevalence varying in the literature. Pouchitis is thought to occur more commonly in patients with ulcerative colitis (UC) than in patients with familial adenomatous polyposis (FAP). We conducted a systematic review with meta-analysis of all published literature to report the prevalence of pouchitis in all pouch patients as well as specifically in UC and FAP. We also investigated the prevalence of acute and chronic pouchitis in UC and FAP. METHODS: A meta-analysis was conducted by searching the Embase, Embase Classic and PubMed databases between 1978 and 2021 exploring the prevalence of pouchitis in UC and FAP. We then performed a random effects model in order to find the pooled prevalence of pouchitis and used odds ratios to report differences in the prevalence of pouchitis in UC and FAP. RESULTS: Fifty-nine full papers and conference abstracts were included in the meta-analysis comprising 18 117 patients with UC and 860 with FAP. The prevalence of pouchitis in UC was 0.32 (95% CI 0.27-0.37) and in FAP was found to be 0.06 (95% CI 0.03-0.15). The odds ratio of pouchitis in UC patients compared with FAP patients was 4.95 (95% CI 3.17-7.72, P < 0.0001). CONCLUSIONS: Our findings support the consensus that the prevalence of pouchitis is higher in UC than in FAP. More significantly our findings suggest that the true prevalence of pouchitis is higher than commonly reported in the literature. This literature may help counsel patients prior to undergoing restorative proctocolectomy.

Telavancin pharmacokinetics in patients with chronic kidney disease receiving haemodialysis.

BACKGROUND: Telavancin is a lipoglycopeptide antibiotic with limited pharmacokinetic data to guide drug dosing in patients receiving haemodialysis. OBJECTIVES: This study characterized telavancin pharmacokinetics in patients receiving haemodialysis. PATIENTS AND METHODS: This was a Phase IV, prospective, open-label, single-centre, crossover pharmacokinetic study (ClinicalTrials.gov: NCT02392208). Eight subjects with end-stage kidney disease requiring maintenance haemodialysis (mean ±â€ŠSD: 47 ±â€Š20 years, 69.5 ±â€Š17.1 kg) received 5 mg/kg telavancin IV 3 h before starting a 3.5 hour haemodialysis treatment with a high-permeability haemodialyser (haemodialysis period). After a 14 day washout period, a second 5 mg/kg dose was administered post-haemodialysis (control period). Telavancin plasma concentrations were measured over a 2 day period after each dose and non-compartmental pharmacokinetic analyses were performed. RESULTS: The geometric mean (GM) of telavancin overall clearance was 11.2 mL/h/kg (intrinsic clearance and dialytic clearance) in the haemodialysis period and 5.9 mL/h/kg (off-haemodialysis clearance) in the control period [GM ratio (GMR) = 1.89; 90% CI: 1.70-2.10; P < 0.01]. The GM t½ was 13.1 h when haemodialysis occurred 3 h post-dosing in the haemodialysis period but extended to 20.9 h with post-haemodialysis dosing in the control period (GMR = 0.63; 90% CI: 0.54-0.73; P < 0.01). The GM of telavancin plasma concentrations removed by haemodialysis was 27.7%. The GMR of peak plasma concentration and volume of distribution of the haemodialysis period and the control period were 0.88 (90% CI: 0.79-0.98; P = 0.08) and 1.17 (90% CI: 1.05-1.30; P = 0.048), respectively. CONCLUSIONS: Haemodialysis with high-permeability haemodialysers removes telavancin considerably (∼⅓ of body load). Telavancin 5 mg/kg every 48 h post-haemodialysis dosing is recommended, but dose adjustments may be warranted if haemodialysis starts within 3 h of telavancin administration.

The pouch behaving badly: management of morbidity after ileal pouch-anal anastomosis.

AIM: Ileal pouch-anal anastomosis (IPAA), or a 'pouch', allows restoration of intestinal continuity after proctocolectomy for ulcerative colitis or familial adenomatous polyposis. Most patients have a good long-term outcome after IPAA, but in a significant proportion the functional outcome and quality of life are unsatisfactory. We term this outcome 'the pouch behaving badly'. Managing this, especially one is when unfamiliar with the possible underlying pathologies, is a challenge for both patient and clinician. We aim to outline the clinical approach to the pouch behaving badly, highlighting key aspects of investigation and management. METHOD: This is a narrative review of the literature covering the investigation and management of postoperative complications and morbidity after IPAA. RESULTS: Management of the pouch behaving badly requires a careful clinical assessment. The patient may present with multiple symptoms and a clear picture of the symptomatology and past history should be constructed before thorough examination and specialist investigation. We divide the pathology that underlies this clinical scenario into surgical, inflammatory, mechanical, functional and dysplastic causes and outline the investigation and management of each one. CONCLUSION: The pouch behaving badly is a challenging problem for both patient and clinician. A detailed clinical assessment with careful specialist investigation is key to diagnosing the underlying pathology. We stress the importance of patient-centred care - the aim is to improve quality of life.

Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.

The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.

Arteriovenous Fistula Use in the United States and Dialysis Facility-Level Comorbidity Burden.

RATIONALE & OBJECTIVE: Patients with multiple comorbid conditions are less likely to use an arteriovenous fistula (AVF) for hemodialysis vascular access. Some dialysis facilities have high rates of AVF placement despite having patients with many comorbid conditions. This study describes variation in facility-level use of AVFs across the facility-level burden of patient comorbid conditions. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Medicare patients receiving hemodialysis for 1 year or more in US dialysis facilities. PREDICTORS: Facility-level burden of patient comorbid conditions; patient characteristics. OUTCOMES: Odds of AVFs versus other access types; facility-level use of AVFs. ANALYTICAL APPROACH: Facility-level comorbidity burden was calculated by summing individual comorbid conditions, determining the average per patient, then defining 11 groups based on facility percentile ranking. Generalized estimating equations with a logit link were used to estimate the odds of AVF placement at the patient level. For the facility-level analysis, a generalized estimating equation model with the identity link was fit to characterize the percentage of AVF use at each facility. RESULTS: Overall, AVF use was 65.8% in 315,919 prevalent hemodialysis patients among 5,813 facilities. After adjustment for patient characteristics, AVF use was 0.27, 0.30, 1.05, and 1.74 percentage points lower than the median among facilities in the 61st to 70th, 71st to 80th, 81st to 90th, and 91st to 99th percentiles of comorbidity, respectively, and 0.42, 0.63, 1.34, and 1.90 percentage points higher than the median among facilities in the 31st to 40th, 21st to 30th, 11th to 20th, and 1st to 10th percentiles of comorbidity, respectively. Facilities in the greater than 99th percentile of comorbidity burden had AVF use that was 3.47 percentage points lower than the median. Facilities in the less than 1st percentile of comorbidity burden had AVF use that was 2.64 percentage points greater than the median. LIMITATIONS: Limited to Medicare dialysis-dependent patients treated for 1 year or more. CONCLUSIONS: After adjustment for patient characteristics, we found small differences in facility rates of AVF use except in the extremes of high or low levels of comorbidity burden. Our study demonstrates that dialysis facilities with a relatively high patient comorbidity burden can achieve similar fistula rates as facilities with healthier patients. Although high comorbidity burden does not explain low facility AVF use, additional study is needed to understand differences in AVF use rates between facilities with similar comorbidity burdens.

Three-Dimensional Printed Cardiac Models for Focused Cardiac Ultrasound Instruction.

BACKGROUND: Focused cardiac ultrasonography (FCU) is an increasingly integral component of routine medical training and practice. While various instructional methods have been described, few attempts have been made to incorporate a physical 3-dimensional (3D) instructional aid. OBJECTIVE: The aim of this study was to determine if a 3D printed heart model workshop for FCU instruction leads to equivalent structure recognition and scanning ability compared to traditional didactic FCU instruction. INTERVENTION: Twenty first-year medical students with no point-of-care ultrasonography experience were randomly assigned to a traditional lecture (n = 10) or a 3D printed heart model workshop (n = 10). Written examinations at 0 and 3 months as well as image acquisition at 3 months were compared. RESULTS: The median scores from the initial written structure identification in the traditional and 3D heart groups were 74% and 90%, respectively (P = 0.7). The second written exam at 3 months yielded median scores of 56% and 58% in the traditional and 3D heart groups, respectively (P = 0.8). The average scores on the image acquisition practical at 3 months were 3.3 of 5 and 2.7 of 5 (P = 0.1) in the traditional and 3D heart groups, respectively. CONCLUSIONS: Utilizing 3D heart models in an FCU workshop format results in similar skill acquisition and knowledge retention as traditional didactics. The 3D heart models are relatively inexpensive, portable, and reusable, enabling learners to practice repeatedly and at flexible intervals. The reduction in ongoing expenses and the ability to teach large groups may decrease training costs as well as the need for local faculty expertise.

Single dose oral ranolazine pharmacokinetics in patients receiving maintenance hemodialysis.

PURPOSE: Ranolazine is a novel anti-angina treatment approved in the United States for chronic stable angina. Ranolazine pharmacokinetics have not been studied previously in patients who receive maintenance hemodialysis. This study describes the pharmacokinetics of ranolazine and three major metabolites (CVT-2738, CVT-2512, CVT-2514) in patients receiving thrice weekly hemodialysis. METHODS: Eight participants receiving maintenance hemodialysis completed this prospective, open-label study (study identifier NCT01435174 at Clinicaltrials.gov). Three participants received a single tablet of ranolazine 500 mg (followed by an interim analysis), and five received 2 tablets of ranolazine 500 mg. Blood samples were collected over 65 h to determine the pharmacokinetic characteristics during and between hemodialysis sessions. Non-compartmental analysis was used to determine the individual pharmacokinetic parameters. RESULTS: Ranolazine off-hemodialysis elimination phase half-lives were 3.6 and 3.9 h for 500 mg and 1000 mg doses, respectively. The time to maximum concentration ranged from 2 to 18 hours and the average maximum concentration was 0.65 ± 0.27 mcg/mL and 1.18 ± 0.48 mcg/mL for ranolazine 500 mg and 1000 mg dose, respectively. The mean hemodialysis percent reduction ratio for the ranolazine 500 mg dose was 52.3 ± 8.1% and for the ranolazine 1000 mg dose was 69.2 ± 37.6%. CONCLUSIONS: Data on ranolazine dosing in patients receiving maintenance hemodialysis is almost non-existent. Given the extent of pharmacokinetic variability observed with the 500 mg and 1000 mg oral doses of ranolazine, neither can be recommended as a starting dose in patients receiving maintenance hemodialysis. Guided by the information gained form this study about the extent of hemodialytic drug clearance, further multi-dose clinical trials of ranolazine are needed to optimize therapeutic outcomes in this patient population.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.

Incidence and Long-term Implications of Prepouch Ileitis: An Observational Study.

BACKGROUND: Restorative proctocolectomy is the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Prepouch ileitis is characterized by mucosal inflammation immediately proximal to the pouch. Prepouch ileitis is uncommon, and long-term follow-up data are lacking. OBJECTIVE: The aim of this study is to report the long-term outcomes of prepouch ileitis. DESIGN: We followed up a cohort of patients with prepouch ileitis that was originally described in 2009. Patients were followed up until the last recorded clinic attendance or at the point of pouch failure. Follow-up data collected included stool frequency, endoscopic findings, treatment, and overall pouch function. SETTING: We accessed a prospectively maintained database at our institution between January 2009 and January 2017. PATIENTS: Three of the 34 patients originally described in 2009 were lost to follow-up; we reanalyzed data on the remaining 31. MAIN OUTCOME MEASURE: The rate of pouch failure was defined as the need for ileostomy or pouch revision. RESULTS: All 31 patients had coexisting pouchitis at index diagnosis of prepouch ileitis. The median length of follow-up from the index pouchoscopy was 98 (range, 27-143) months. Seven (23%) patients who had an index pouchoscopy with prepouch ileitis went on to pouch failure, which is significantly higher than expected (p = 0.03). Five (71%) of these patients had chronic pouchitis, and 2 (29%) had small-bowel obstruction due to prepouch stricture. Two patients had evidence that would support possible Crohn's disease at long-term follow-up. LIMITATIONS: This was a retrospective analysis. Because of the nature of the study, there was some missing information that may have influenced the results. Our study is further limited by small patient numbers. CONCLUSIONS: Prepouch ileitis is associated with a significantly increased risk of pouch failure compared with the overall reported literature for restorative proctocolectomy. Prepouch ileitis does not appear to be strongly predictive of Crohn's disease at long-term follow-up. See Video Abstract at http://links.lww.com/DCR/A480.

Biofeedback in patients with ileoanal pouch dysfunction: a specialist centre experience.

OBJECTIVES: To report outcomes following biofeedback for functional problems associated with an ileoanal pouch. Incontinence and evacuatory disorders associated with the ileoanal pouch can be particularly problematic and difficult to treat using conventional therapies. Biofeedback therapy is a behavioural treatment that offers a non-surgical approach as an alternative or adjunct for patients. MATERIALS AND METHODS: This was a retrospective single centre study. We reviewed the notes of all patients attending for biofeedback at our institution between January 2012 and October 2017 and identified all those that did so for ileoanal pouch related problems. We recorded patient reported subjective improvements following biofeedback. The validated International Consultation on Incontinence Questionnaire was used to assess improvement in incontinent symptoms and the evacuatory disorder questionnaire was used to assess improvement in evacuatory disorders. RESULTS: Twenty-six patients with ileoanal pouch related problems underwent biofeedback. Based on patients' feedback at next clinical encounter following biofeedback, nine reported much improvement, 11 reported some improvement and six reported no improvement. In the group treated for incontinence, quality of life improved significantly from a median pre-treatment score of 80 to a post-treatment score of 41 (p = .01). Biofeedback reduced pain, bloating straining and laxative use in patients with evacuatory disorders. CONCLUSIONS: Biofeedback may be associated with significant improvement in quality of life as well as possible improvements in symptoms related to both incontinence and evacuatory disorders. It is probably an underused service. Further larger prospective studies are required to properly assess the efficacy of biofeedback in ileoanal pouch related dysfunction.

Long term outcomes of initial infliximab therapy for inflammatory pouch pathology: a multi-Centre retrospective study.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis is considered the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Subsequent inflammation of the pouch is a common complication and in some cases, pouchitis fails to respond to antibiotics, the mainstay of treatment. In such cases, corticosteroids, immunomodulatory or biologic treatments are options. However, our understanding of the efficacy of anti-tumour necrosis factor medications in both chronic pouchitis and Crohn's-like inflammation is based on studies that include relatively small numbers of patients. METHODS: This was an observational, retrospective, multi-centre study to assess the long-term effectiveness and safety of infliximab (IFX) for inflammatory disorders related to the ileoanal pouch. The primary outcome was the development of IFX failure defined by early failure to IFX or secondary loss of response to IFX. RESULTS: Thirty-four patients met the inclusion criteria; 18/34 (53%) who were initiated on IFX for inflammatory disorders of the pouch had IFX failure, 3/34 (8%) had early failure and 15/34 (44%) had secondary loss of response with a median follow-up of 280 days (range 3-47 months). In total, 24/34 (71%) avoided an ileostomy by switching to other medical therapies at a median follow-up of 366 days (1-130 months). CONCLUSIONS: Initial IFX therapy for pouch inflammatory conditions is associated with IFX failure in just over half of all patients. Despite a high failure rate, an ileostomy can be avoided in almost three-quarters of patients at four years by using other medical therapies.