Add-on interventions for the prevention of recurrent Clostridioides Difficile infection: A systematic review and network meta-analysis.

OBJECTIVES: We aimed to assess the comparative efficacy and safety of adjunctive interventions for the prevention of Clostridioides difficile recurrence. METHODS: We searched Medline, Embase, CENTRAL, and clinicaltrials.gov up to May 2021. We included randomized controlled trials comparing interventions added to antibiotic therapy for prevention of CDI recurrence, to placebo or each other. Efficacy outcomes were CDI and diarrhea recurrence. Safety outcomes included the incidence of any adverse event (AE), serious AEs, and discontinuation due to AEs. We performed random-effects network meta-analysis. We ranked interventions based on SUCRA (surface under the cumulative ranking curve) probabilities. We assessed confidence in estimates utilizing the CINeMA (Confidence in Network Meta-Analysis) framework. RESULTS: Fifteen trials (3909 patients) assessed 9 interventions. Oligofructose (OR 0.17; 95% CI, 0.07 to 0.46), NTCD-M3 (OR 0.29; 95% CI, 0.12 to 0.68), rifaximin (OR 0.47; 95% CI, 0.24 to 0.93), RBX2660 (OR 0.47; 95% CI, 0.22 to 0.99), the combination bezlotoxumab/actoxumab (OR 0.47; 95% CI, 0.37 to 0.60), and bezlotoxumab (OR, 0.53; 95% CI, 0.42 to 0.68) were associated with lower incidence of CDI recurrence than placebo (moderate confidence). Oligofructose was ranked highest, however data for oligofructose were derived solely from one small trial. Probiotics, actoxumab and SER-109 were not superior to placebo (low confidence). Probiotics were not well tolerated (low confidence) and actoxumab showed high rates of serious AEs (moderate confidence). CONCLUSION: Add-on treatment with oligofructose, NTCD-M3 spores, rifaximin, RBX2660, and bezlotoxumab likely reduces the risk of CDI. Evidence on probiotics and SER-109 are uncertain, thus adequately powered trials are warranted.

Is everolimus linked to metabolic syndrome in liver transplant recipients?

BACKGROUND: As the mortality rates after liver transplantation (LT) have been reduced, the attention has shifted to additional conditions which still compromise the quality of life and the survival of these patients, such as the post-LT metabolic syndrome (MS). In order to determine the prevalence and the factors associated with the post-LT MS, we carried out the present study. METHODS: One hundred and six LT recipients, after completing at least 1 year follow up after LT, were included in the study. Data on clinical, laboratory parameters and immunosuppressive therapy before and after LT were recorded. MS was defined as per current diagnostic criteria. RESULTS: MS was prevalent in 47.2% (50 of 106 patients) and was not associated with the LT indications and the time period after LT. Univariate analysis showed that history of diabetes mellitus before (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.046-9.918, p = 0.042) and after LT (OR 6.03, 95% CI 2.18-16.67, p = 0.001), the age at the time of baseline visit (OR 1.077, 95% CI 1.033-1.124, p = 0.001) and the everolimus-based immunosuppression (OR 1.23, 95% CI 1.003-1.33, p = 0.019) were significantly associated with MS. Notably, everolimus administration was the only factor independently associated with the presence of post-LT MS (OR 1.026, 95% CI 1.004-1.047, p = 0.019). More specifically, everolimus was linked to the presence of arterial hypertension (OR 1.02, 95% CI 1.0-1.03, p = 0.05) and hyperlipidemia (OR 2.87, 95% CI 1.28-6.56, p = 0.011). CONCLUSIONS: Our study demonstrated for the first time that everolimus was independently associated with post-LT MS. Nevertheless, more robust studies are required to confirm these findings.

Prioritization for interferon-free regimens and potential drug interactions of current direct-acting anti-hepatitis C agents in routine clinical practice.

BACKGROUND: We determined the proportions of patients with chronic hepatitis C (CHC) in association with possible prioritized indications for interferon-free regimens and the use of co-medications with potential drug-drug interactions (DDIs). METHODS: Five hundred consecutive mono-infected CHC patients seen in 2015 at 5 Greek centers were included. Priorities for interferon-free regimens were based on liver disease severity, contraindication(s) for interferon and prior interferon-treatment failure. All co-medications were classified into those with no DDIs/no clear data for DDIs, potential DDIs, and contraindication due to DDI for each agent, according to the HEP Drug Interaction Checker. RESULTS: Of the 500 patients, 1% had undergone liver transplantation, whereas 6.6% had decompensated cirrhosis, 21.8% F4, 17.1% F3, 10.4% F2, and 34.8% F0-1 fibrosis. Contraindications for interferon were present in 38.5% of non-transplant patients with compensated liver disease. The probability of contraindications/potential DDIs was greater for boceprevir/telaprevir and ombitasvir/paritaprevir/ritonavir±dasabuvir, compared to all other agents (P<0.001), and least for sofosbuvir (P<0.05). Contraindications/potential DDIs were more frequently present in patients ≥50 than <50 years old (P≤0.034), and more common in F3-4 than F0-2, and F4 than F0-3 fibrosis (P≤0.019) for all direct-acting antivirals (DAAs). CONCLUSIONS: The expansion of the criteria for prioritization of interferon-free regimens from cirrhosis to F3 and perhaps F2 fibrosis will increase the proportion of patients with DAA access by only 10-15% and 10%, respectively. A potential for DDIs is frequently present with protease inhibitors, but also exists with other DAAs. The probability of DDIs is higher in patients with priority for DAAs, including those who have advanced liver disease and are usually of older age.