Biologic monotherapy versus combination therapy with immunomodulators in the induction and maintenance of remission of Crohn's disease and ulcerative colitis.

Despite current guidelines, the optimal treatment of patients with inflammatory bowel disease (IBD) remains challenging. The available medications are not without risk and there is not a single correct treatment regimen for every patient. Personalizing treatment and selecting the most appropriate therapy is crucial for optimal response, remission, quality of life, and healthcare utilization. Biologics, especially anti-tumor necrosis factor-α medications, are widely used in the induction and maintenance of disease remission in patients with IBD. Similarly, immunomodulators, including thiopurines and methotrexate, are traditionally popular for the maintenance of remission. In this manuscript, we review the use of biologic monotherapy vs. combination therapy with immunomodulators for the treatment of ulcerative colitis and Crohn's disease. We examine overall remission, immunogenicity and adverse effects, mainly serious infections and malignancy, in an effort to help guide treatment decisions and weigh the risks and benefits of biologic monotherapy vs. combination therapy.

Incidence, outcome, and risk factors for recurrence of nosocomial Clostridioides difficile infection in adults: A prospective cohort study.

BACKGROUND: Nosocomial Clostridioides difficile infection (CDI) complicates up to 1% of all hospital admissions and is associated with considerable health burden. AIMS: To determine the incidence and outcomes of nosocomial CDI at a major University Medical Center. METHODS: Consecutive adult nosocomial CDI cases were prospectively identified. Stool samples were collected for ribotyping and antibiotic resistance testing. Patients were followed for eight weeks after discharge for relapse. RESULTS: Over a 2-year period, 215 patients developed nosocomial CDI (incidence 2:1000) and 200 (mean age 62.2±19.6 years) gave informed consent. Mean hospital stay was 23.3±28.9 days (range 0-278). Infection was diagnosed within 7 days of admission (range 0-95) in 129 patients (64.5%). More than two-thirds (69.0%) were previously hospitalized within 12 weeks of the index hospitalization. Twenty five percent received prior antibiotics within eight weeks. Fifty-two patients (26.0%) did not receive antibiotics prior to diagnosis. Considerable comorbidities (Charlson Comorbidity Index ≥8) were noted in 33.5% of patients. Recurrence occurred in 43 patients (21.5%). On multivariate logistic regression, fluoroquinolone exposure was the only predictor of recurrence (OR=2.9, 95%CI 1.1-7.7). Overall mortality was 14.0% and CCI ≥8 was the only predictor on multivariate analysis (p=0.004). Genotyping did not identify any known hypervirulent strains and all isolates were susceptible to metronidazole and vancomycin. CONCLUSION: Antibiotic exposure, comorbidities, and prior hospitalization constitute the major risk factors for nosocomial CDI. Recurrence is common and is associated with fluoroquinolones exposure. High baseline comorbidity score was the only predictor of increased mortality in this prospective cohort.

Prevalence of gastroesophageal reflux and risk factors for erosive esophagitis in obese patients considered for bariatric surgery.

BACKGROUND: Gastroesophageal reflux disease (GERD) is common in obese individuals. Prospective studies investigating validated GERD questionnaires and clinical parameters at identifying erosive esophagitis (EE) in this population are limited. OBJECTIVE: To prospectively evaluate the prevalence of GERD in obese patients considered for bariatric surgery and identify risk and predictive factors for EE. METHODS: Eligible patients completed two validated questionnaires: GERDQ and Nocturnal Symptom Severity Impact (N-GSSIQ) before routine esophagogastroduodenoscopy. RESULTS: 242 consecutive patients were enrolled (130 females; mean age 37.8 ± 11.8 years; mean BMI 40.4 ± 5.3 kg/m2). The overall prevalence of gastroesophageal reflux (GERDQ ≥ 8, EE and/or PPI use) was 62.4%. EE was identified in 82 patients (33.9%) including 13/62 (21.0%) receiving PPIs at baseline. Multivariate logistic regression identified GERDQ ≥ 8 (OR = 6.3, 95%CI 3.0-13.1), hiatal hernia (OR = 4.2, 95%CI 1.6-10.7), abnormal Hill grade (OR = 2.7, 95%CI 1.4-5.4), and tobacco use (OR = 2.5, 95%CI 1.2-4.9) as independent risk factors for EE. A pre-endoscopic composite assessment including GERDQ ≥ 8 and presence of severe nocturnal reflux symptoms had 90% specificity and 20.7% sensitivity in identifying EE (NPV 68.9% and PPV 51.5%). CONCLUSION: GERD is highly prevalent in obese patients. Anthropometric data and GERD questionnaires have limited accuracy at predicting erosive disease. Pre-operative endoscopic assessment in this population appears warranted.

Dexlansoprazole is Effective in Relieving Heartburn during the Fasting Month of Ramadan.

BACKGROUND AND AIMS: Proton pump inhibitors are effective at reducing heartburn. No studies have evaluated their efficacy in Ramadan. Dexlansoprazole has a unique active formulation independent of time-of-day dosing or food. The aim is to investigate the efficacy of dexlansoprazole 60 mg during Ramadan in patients with symptomatic heartburn. METHODS: Subjects recruited using poster, radio, and SMS advertisements completed a diary using a mobile-friendly application and received daily SMS reminders. Dexlansoprazole was started on day 8 for 3 weeks. No placebo arm was used in this trial. Primary endpoint was relief of heartburn expressed as mean 24-h free heartburn percentage (24FH%) per weekly period. RESULTS: A total of 32 patients were enrolled. During week 1, only 1 person (3.1%) was heartburn-free and mean 24FH% was 41.1 ± 24.8%. On dexlansoprazole, mean 24FH% rose to 63.4 ± 23.8 and 81.6 ± 24.5% in weeks 2 and 4, respectively (p < 0.001 for both). Median 24FH% increased from 35.7% in week 1 to 71.4 and 85.7% in weeks 2 and 4, respectively. Mean Gastroesophageal Reflux Disease Questionnaire (GERDQ) scores decreased from 10.0 ± 3.2 in week 1 to 6.53 ± 2.2 in week 2 (p < 0.001) and 5.87 ± 2.1 in week 4 (p < 0.001). Mean heartburn severity score decreased from 2.5 ± 1.0 to 1.7 ± 0.8 (p = 0.001). Early response was higher in patients with GERDQ scores ≥8 (p = 0.012). CONCLUSION: Dexlansoprazole is effective in the treatment of heartburn during Ramadan. Clinicaltrials.gov number: NCT03079050.

Molecular characterization, toxin detection and resistance testing of human clinical Clostridium difficile isolates from Lebanon.

Clostridium (Clostridioides) difficile is the main cause for nosocomial diarrhoea in industrialised nations. Epidemiologic data on the pathogen's occurrence in other world regions are still scarce. In this context we characterized with phenotypic and molecular genetic methods C. difficile isolates stemming from hospitalised patients with diarrhoea in Lebanon. From 129 stool samples of symptomatic patients at a tertiary care University hospital in Lebanon, a total of 107 C. difficile strains were cultivated and underwent ribotyping, toxin gene detection and antibiotic resistance testing. Ribotype 014 (RT014, 16.8%) predominated, followed by RT002 (9.3%), RT106 (8.4%) and RT070 (6.5%). Binary toxin gene-positive isolates (RT023, RT078 and RT126) were rarely detected and RT027 was absent. Interestingly, within one isolate only the toxin A gene (tcdA) was detected. Multiple-locus variable-number tandem repeat analysis (MLVA) revealed strong strain diversity in most RTs. The isolates were sensitive to metronidazole and vancomycin, and only a small proportion of strains displayed resistance against moxifloxacin, rifampicin, and clarithromycin (5.6%, 1.9%, and 2.8%), respectively. The data indicate that the genetic strain composition of Lebanese strains differs markedly from the situation seen in Europe and North America. Especially the epidemic RTs seen in the latter regions were almost absent in Lebanon. Interestingly, most strains showed almost no resistance to commonly used antibiotics that are suspected to play a major role in the development of C. difficile infection, despite frequent use of these antibiotics in Lebanon. Thus, the role of antimicrobial resistance as a major driving force for infection development remains uncertain in this area.

The Natural History of Incidental Colonic Diverticulosis on Screening Colonoscopy.

Background: The natural history of colonic diverticulosis is unclear. Methods: Patients with incidental diverticulosis identified in a previous prospective cross-sectional screening colonoscopy study were evaluated retrospectively for clinic or hospital visit(s) for diverticular disease (DD= acute diverticulitis or diverticular bleeding) using review of electronic health records and patient phone interview. Results: 826 patients were included in the screening colonoscopy study. Three were excluded for prior DD. In all, 224 patients (27.2%; mean age 62.3 ± 8.2) had incidental diverticulosis distributed in the left colon (67.4%), right colon (5.8%), or both (22.8%). Up-to-date information was available on 194 patients. Of those, 144 (74.2%) could be reached for detailed interview and constituted the study population. Over a mean follow-up of 7.0 ± 1.7 years, DD developed in 6 out of 144 patients (4.2%) (4 acute cases of diverticulitis, 1 probable case of diverticular bleeding, and 1 acute case of diverticulitis and diverticular bleeding). Two patients were hospitalized, and none required surgery. The time to event was 5.1 ± 1.6 years and the incidence rate was 5.9 per 1000 patient-years. On multivariate analysis, none of the variables collected at baseline colonoscopy including age, gender, obesity, exercise, fiber intake, alcohol use, constipation, or use of NSAIDs were associated with DD. Conclusion: The natural history of incidental diverticulosis on screening colonoscopy was highly favorable in this well-defined prospectively identified cohort. The common scenario of incidental diverticulosis at screening colonoscopy makes this information clinically relevant and valuable to physicians and patients alike.

Systematic Review and Meta-analysis: Adalimumab Monotherapy Versus Combination Therapy with Immunomodulators for Induction and Maintenance of Remission and Response in Patients with Crohn's Disease.

BACKGROUND: It is unclear whether the combination of adalimumab (ADA) and immunomodulators is superior to ADA monotherapy in patients with Crohn's disease. METHODS: PubMed, Medline, Embase, Web of Science, and other databases were searched. Randomized controlled trials, open-label, prospective cohort, and retrospective studies, and pooled analyses were included. Primary outcomes were induction (≤12 wk) and maintenance (up to 56 wk) of remission and response. Secondary outcomes were severe adverse events, opportunistic infections, and development of antibodies to adalimumab. RESULTS: Twenty-four of 1194 articles were eligible for inclusion. No significant difference was noted between regimens for induction of remission (odds ratio [OR] 0.86; 95% confidence interval [CI]: 0.70-1.06; P = 0.19) and response (OR 1.01; 95% CI: 0.62-1.65; P = 0.96). Similarly, no difference was noted for maintenance of remission (OR 0.97; 95% CI: 0.79-1.14; P = 0.75) or response (OR 0.91; 95% CI: 0.54-1.54; P = 0.74). Severe adverse events and opportunistic infections were not different between arms. Patients on combination therapy had lower odds of developing antibodies to adalimumab (OR 0.24; 95% CI: 0.07-0.82; P = 0.02). Subgroup and sensitivity analyses showed significantly higher odds of successful induction (OR 1.26; 95% CI: 1.06-1.49, P = 0.008) and opportunistic infections (OR 2.44; 95% CI: 1.07-5.54, P = 0.03) in anti-TNF-experienced patients. CONCLUSIONS: The combination of ADA and immunomodulators does not seem superior to ADA monotherapy for induction and maintenance of remission and response in Crohn's disease. Combination therapy is associated with lower immunogenicity. Analyses associating combination therapy with better induction of remission in anti-TNF-experienced patients and a higher rate of opportunistic infections deserve further evaluation.