Health-related quality of life in patients with recurrent Clostridioides difficile infections

BACKGROUND: The health-related quality of life (HrQoL) can be substantially affected in patients with recurrent Clostridioides difficile infection (rCDI) but the impact of effective treatment of the infection remains unclear. This study aimed to evaluate the HrQoL in patients with rCDI and estimate the gain in HrQoL associated with effective treatment of rCDI. METHODS: Patients’ HrQoL was estimated based on EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaires obtained from a Danish randomised controlled trial (RCT). In the RCT, 64 patients with rCDI were randomised to receive either vancomycin (n = 16), fidaxomicin (n = 24) or faecal microbiota transplantation (FMT) preceded by vancomycin (n = 24). The primary outcome in the RCT was rCDI resolution. Patients were closely monitored during the RCT, and rescue FMT was offered to those who failed their primary treatment. Patients’ HrQoL was measured at baseline and at 8- and 26-weeks follow-up. Linear regression analyses conditional on the differences between baseline and follow-up measurements were used to assess statistical significance (p < 0.05). RESULTS: Within 26 weeks of follow-up, 13 (81%) patients treated with vancomycin, 12 (50%) patients treated with fidaxomicin, and 3 (13%) patients treated with FMT had a subsequent recurrence and received a rescue FMT. The average HrQoL for untreated patients with rCDI was 0.675. After receiving effective treatment, this value increased by 0.139 to 0.813 (p < 0.001) at week 8 and by 0.098 to 0.773 (p = 0.003) at week 26 of follow-up compared with baseline. CONCLUSION: The HrQoL was adversely affected in patients with an active episode of rCDI but increased substantially after receiving an effective treatment algorithm in which rescue FMT was provided in case of a primary treatment failure. TRIAL REGISTRATION: The RCT was preregistered at EudraCT (j.no. 2015-003004-24, https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003004-24/results) and at ClinicalTrials.gov (study identifier NCT02743234, https://clinicaltrials.gov/ct2/show/NCT02743234)

The Citrullinated and MMP-degraded Vimentin Biomarker (VICM) Predicts Early Response to Anti-TNF alpha Treatment in Crohn's Disease

Background: In Crohn's disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor- (TNF) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage. Aim: The aim of this study was to investigated whether early changes in the VICM (citrullinated and matrix metalloproteinase-degraded vimentin) biomarker were associated with response to anti-TNF treatment in patients with CD. Methods: Serum VICM levels were measured by ELISA in 2 independent cohorts of CD patients (n=42) treated with anti-TNF (infliximab or adalimumab). Response was determined by achieving clinical remission (Harvey Bradshaw Index<5). Results: Compared with baseline, VICM serum levels were reduced by anti-TNF in the infliximab cohort (week 6 and 14) and in the adalimumab cohort (week 8). VICM was lower in the responders compared with the nonresponders [infliximab: Week 6, P<0.05; area under the curve (AUC)=0.90; adalimumab: Week 1, P<0.01 (AUC=0.91), and week 8, P<0.05 (AUC=0.86)], and were able to predict response to treatment after 1 week of treatment with an odds ratio of 42.5. Conclusions: The VICM biomarker was time dependently reduced in CD patients responding to anti-TNF treatment. We suggest that VICM may be used as a marker for monitoring early response to anti-TNF in patients with CD

Long-Term Outcomes in Patients with Intestinal Failure Due to Short Bowel Syndrome and Intestinal Fistula

Short bowel syndrome (SBS) and enterocutaneous or enteroatmospheric fistulas are common indications for home parenteral nutrition (HPN). However, there are few data describing factors influencing surgical decision-making or outcomes particularly following fistula development. We aimed to compare outcomes between patients with SBS and fistulas and explore surgical decision-making. HPN-dependent adults from 2001–2018 at a national reference centre were included in this study. HPN cessation was analysed using death as competing risk. In total, 465 patients (SBS (62%), fistula (38%)) were included, with median HPN dependency of 2.6 years. In total, 203 patients underwent reconstructive surgery; while frailty was the commonest reason for not undergoing surgery (49.2%), 22.7% declined surgery. Overall, 170 ceased HPN, with a probability of 13.8%, 34.1% and 38.3% at 1, 5 and 10 years, respectively. Patients undergoing surgery had higher nutritional autonomy rates (109.8 incidences/1000 patient years) compared to those not undergoing surgery (18.1 incidences/1000 patient years; p < 0.001). A total of 295 patients (63.4%) were predicted to cease HPN based on gastrointestinal anatomy but only 162/295 (54.9%) achieved this; those unable to do so were older with a higher comorbidity index. There were no differences in long-term nutritional and survival outcomes or surgical decisions between patients with SBS and fistulas, or between enterocutaneous and enteroatmospheric fistulas. This study represents one of the largest datasets describing the ability of HPN-dependent patients with SBS or fistulas to achieve nutritional autonomy. While reconstructive surgery facilitates HPN cessation, approximately one-fifth of patients declined surgery despite HPN dependency. These data will better inform patient expectation and help plan alternative therapies

Cost savings following faecal microbiota transplantation for recurrent infection

Background: Recurrent Clostridium difficile infection (rCDI) is becoming increasingly common. Faecal microbiota transplantation (FMT) is effective for rCDI, but the costs of an FMT and hospital cost savings related to FMT are unknown. The aim of this study was to calculate the cost of an FMT and the total hospital costs before and after FMT. Methods: This was an observational single-centre study, carried out in a public teaching hospital. We included all patients referred for rCDI from January 2014 through December 2015 and documented costs related to donor screening, laboratory processing, and clinical FMT application. We calculated patient-related hospital costs 1 year before FMT (pre-FMT) and 1 year after FMT (post-FMT). Sensitivity analyses were applied to assess the robustness of the results. Results: We included 50 consecutive adult patients who had a verified diagnosis of rCDI and were referred for FMT. The average cost of an outpatient FMT procedure if donor faeces were applied by colonoscopy was €3,326 per patient and €2,864 if donor faeces were applied using a nasojejunal tube. The total annual pre-FMT hospital costs per patient were €56,415 (95% confidence interval (CI) 41,133–71,697), and these costs dropped by 42% to €32,816 (22,618–42,014) post-FMT ( p = 0.004). The main cost driver was hospital admissions. Sensitivity analyses demonstrated cost reductions in all scenarios. Conclusions: In a public hospital with an implemented FMT service, the average cost of FMT applied by either colonoscopy or nasojejunal tube was €3,095. Total hospital costs dropped by 42% the first year after FMT. The reduction was mainly caused by reductions in the number of hospital admissions and in length of stay