Tariq, Raseen

Background Clostridioides difficile infection (CDI) is associated with frequent recurrences. The role of probiotics in preventing CDI remains unclear despite patients frequently using them. Methods We performed a systematic-review and meta-analysis to evaluate the role of Saccharomyces boulardii, a yeast probiotic, in preventing primary or recurrent CDI in patients on systemic antimicrobial therapy. We searched MEDLINE, Embase, and Web of Science up to December 2021 to identify studies (case-control, cohort, or clinical trial studies) reporting the use of systemic antimicrobials with or without S. boulardii and providing information on primary or recurrent CDI. Pooled odds ratios with 95% confidence intervals were calculated using a random effects model. Results Eight studies (six randomized control trials and two cohort studies) were included. Six studies with 9,712 patients evaluated primary prevention. The rate of CDI in patients who received S. boulardii was 0.73% (44/5977) compared to 1.09% (41/3735) in the control group. Meta-analysis showed no difference in the risk of CDI among the two groups (odds ratio [OR], 0.71; 95%CI, 0.46–1.10; p = 0.124) with no significant heterogeneity (I2 = 0%). In two studies with 292 patients evaluating secondary prevention, the rate of recurrent CDI was 36.73% (54/147) on S. boulardii compared to 46.20% (67/145) in controls, with no significant difference (p = 0.19). Subgroup analysis of studies using S. boulardii (250 mg twice daily) showed no difference in the CDI risk with or without S. boulardii. No serious adverse events from S. boulardii were noted. Conclusion The use of S. boulardii appears to have no benefit for preventing either primary or recurrent CDI in patients taking systemic antimicrobials.

Abstract Background Microscopic colitis (MC) is a common cause of chronic diarrhea. Randomized controlled trials (RCTs) have demonstrated the efficacy of budesonide treatment for MC. However, relapse is frequent after discontinuation of budesonide, and data on maintenance therapy are limited. We performed a systematic review and meta-analysis evaluating these outcomes in clinical trials and real-world settings. Methods A systematic search was performed on October 31, 2022, of Medline, Embase, Cochrane, and Scopus. Case series, case-control, cohort studies, and RCTs of adults with MC were included. Data were pooled using random effects models to calculate weighted pooled estimates and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic. Results We included 35 studies (11 RCTs, 24 observational studies) with 1657 MC patients treated with budesonide induction and 146 for maintenance. The overall pooled clinical remission rate with budesonide treatment was similar between RCTs and observational studies. The pooled remission rate with budesonide maintenance therapy was 84% (95% CI, 0.60-1.00; I2 = 91%). After budesonide discontinuation, the pooled relapse rate was 53% (95% CI, 0.42-0.63; I2 = 76%). On maintenance therapy, no differences were noted in adverse events (eg, metabolic bone disease, hypertension, hyperglycemia, cataracts/glaucoma) in those on budesonide vs placebo or other noncorticosteroid medications for MC (P = .9). Conclusions Budesonide is an effective maintenance treatment for MC. There is a high risk of recurrence after budesonide discontinuation, but long-term use at the lowest effective dose appears to be relatively safe and have limited adverse effects.

Background: Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates >90%) but efficacy in controlled clinical trials appears to be lower. Objectives: To perform an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs). Design: A systematic review and meta-analysis was conducted. Data Sources and Methods: A systematic search of various databases was performed up to July 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose were included. We calculated weighted pooled rates (WPRs) with 95% confidence intervals (CIs). Results: In all, 19 clinical trials with 1176 recurrent CDI patients were included. Of the patients treated with microbiota restoration, 897 experienced a clinical cure with a single microbiota restoration therapy (WPR, 78%; 95% CI, 71–85%). There was significant heterogeneity among studies with an I2 of 88%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 373 of 523 patients (WPR, 72%; 95% CI, 60–82%) with microbiota restoration. Among the nine open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (WPR, 84%; 95% CI, 74–92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR, 73 versus 84%, p < 0.0001). Conclusions: Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open-label studies were similar to observational studies.

Abstract Background Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates &gt;90%) but efficacy in controlled clinical trials appears lower. Purpose We performed an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs). Method A systematic search of Embase, Web of Science and Scopus was performed up to June 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose as the primary outcome were included. We calculated both unweighted and weighted pooled resolution rates (UPR and WPR) with 95% confidence intervals (CI). Result(s) Eighteen studies (9 RCTs and 9 open-label trials) with 1149 CDI patients were included. Of the patients treated with microbiota restoration, 881 experienced symptom resolution (UPR 77%%; WPR 79%, 95% CI, 72%-85%). There was significant heterogeneity among studies with an I2of 86%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 357 of 496 patients (UPR 72%; WPR 73%, 95% CI 63%-82%) with microbiota restoration. Among the 9 open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (UPR 80%; WPR 84%, 95% CI 74%-92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR 73% vs 84%, p&lt;0.0001). Analysis of the 10 trials with non-microbiota restoration revealed CDI resolution in 201 of 397 patients with antibiotics (WPR 52%, 95% CI 43%-60%). There was significant heterogeneity among the included studies with an I2of 61%. Comparison of cure rates with microbiota restoration vs antibiotics showed higher cure rate with microbiota restoration (WPR 73%, [95% CI 63%-82%] vs 52% [95% CI, 43%-60%]; p&lt;0.0001). There were no serious adverse events reported. Conclusion(s) Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open label studies were similar to observational studies. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Abstract Background Clostridioides difficile infection (CDI) is the most common nosocomial infection and is associated with significant morbidity and mortality. Purpose We aimed to identify the burden of CDI in patients undergoing common gastrointestinal (GI) surgical procedures in a national inpatient cohort, as GI surgeries have been thought to be a risk factor for CDI. Method We used the National Inpatient Sample (NIS) database from Unites States for the years 2016-2019 for this study. We included adult patients (age ≥ 18), who underwent common GI surgeries (identified using ICD-10 procedure codes), and among them identified patients with diagnosis of CDI. Outcomes assessed included risk of CDI among different surgeries, inpatient mortality, length of stay (LOS) and cost of hospitalization using regression analyses Result(s) From 2016 to 2019, an estimated total of 4,438,778 patients were hospitalized and underwent any of the studied GI surgeries. CDI was reported in 32,180 admissions (0.72%). Median age for CDI was higher than non-CDI patients (66 vs 56, p&lt;0.001). Incidence of CDI was 2.5 times higher in patients admitted emergently compared to elective admissions (1.00% vs 0.40%, p&lt;0.0001). Among all surgeries, the incidence of CDI was the highest for small bowel resection at 2.1% followed by partial esophagectomy at 1.6% and partial colectomy at 1.4%. Logistic regression analysis showed the patients undergoing esophagectomy had the highest risk with adjusted Odds Ratio (aOR) of 2.48, (95% CI 2.01 – 3.07, p&lt;0.0001), followed by pancreatectomy with aOR 2.03 (95% CI 1.91 – 2.16, p&lt;0.0001). Overall, surgical patients with CDI had a significantly higher in-patient mortality compared to non-CDI patients (8.2% vs 1.4%, p&lt;0.0001). Logistic regression analysis showed an increased risk of inpatient mortality with CDI, with aOR 1.36, 95% CI 1.30 – 1.42, p&lt;0.0001. Median LOS for surgical patients with CDI was higher than non-CDI patients (14 days vs 3 days, p&lt;0.0001). The linear regression analysis for length of stay showed that among patients undergoing surgical procedures, CDI was associated with an increased LOS with beta of 8.39 days ± SE 0.04 (95% CI 8.31 – 8.46, p&lt;0.0001). The mean cost of hospitalization for surgical patients with CDI was higher than non-CDI patients ($90,590 vs $31,702, p&lt;0.0001) after adjusting for inflation over the four-year period. The linear regression analysis showed that CDI was associated with an increased cost of hospitalization with a beta of $25,343 ± SE 166 (95% CI 25,017 – 25,670, p&lt;0.0001). Conclusion(s) CDI among GI surgeries leads to increase in inpatient mortality, length of stay and cost of hospitalization. Although the rate of CDI is showing a downwards trend, its impact on these outcome measures makes it an important complication to prevent and promptly treat in these surgical patients. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Background: Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic. Objectives: To ascertain the frequency of gastrointestinal (GI) manifestations as part of long GI COVID. Design: A systematic review and meta-analysis of studies reporting GI manifestations in long COVID was performed. Data Sources and Methods: Electronic databases (Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were searched till 21 December 2021 to identify studies reporting frequency of GI symptoms in long COVID. We included studies reporting overall GI manifestations or individual GI symptoms as part of long COVID. We excluded pediatric studies and those not providing relevant information. We calculated the pooled frequency of various symptoms in all patients with COVID-19 and also in those with long COVID using the inverse variance approach. All analysis was done using R version 4.1.1 using packages ‘meta’ and ‘metafor’. Results: A total of 50 studies were included. The frequencies of GI symptoms were 0.12 [95% confidence interval (CI), 0.06–0.22, I 2 = 99%] and 0.22 (95% CI, 0.10–0.41, I 2 = 97%) in patients with COVID-19 and those with long COVID, respectively. The frequencies of abdominal pain, nausea/vomiting, loss of appetite, and loss of taste were 0.14 (95% CI, 0.04–0.38, I 2 = 96%), 0.06 (95% CI, 0.03–0.11, I 2 = 98%), 0.20 (95% CI, 0.08–0.43, I 2 = 98%), and 0.17 (95% CI, 0.10–0.27, I 2 = 95%), respectively, after COVID-19. The frequencies of diarrhea, dyspepsia, and irritable bowel syndrome were 0.10 (95% CI, 0.04–0.23, I 2 = 98%), 0.20 (95% CI, 0.06–0.50, I 2 = 97%), and 0.17 (95% CI, 0.06–0.37, I 2 = 96%), respectively. Conclusion: GI symptoms in patients were seen in 12% after COVID-19 and 22% as part of long COVID. Loss of appetite, dyspepsia, irritable bowel syndrome, loss of taste, and abdominal pain were the five most common GI symptoms of long COVID. Significant heterogeneity and small number of studies for some of the analyses are limitations of the systematic review.