Corticosteroids and Mesalamine Versus Corticosteroids for Acute Severe Ulcerative Colitis: A Randomized Controlled Trial.

BACKGROUND & AIMS: Corticosteroids are the mainstay of treatment for hospitalized patients with acute severe ulcerative colitis (ASUC). However, whether the addition/continuation of mesalamine with corticosteroids during hospitalization is superior to corticosteroids alone is unknown. METHODS: This was a randomized controlled, investigator-blinded, clinical trial conducted in 10 centers in 7 countries. Patients hospitalized with ASUC (Lichtiger score ≥10) were eligible. Patients received corticosteroids alone or corticosteroid + mesalamine (4 g/day mesalamine) by a stratified randomization according to mesalamine use before admission. The primary outcome was the percentage of patients who responded to treatment by day 7, defined by a drop >3 points in the Lichtiger score and an absolute score <10 without the need for rescue medications or colectomy. RESULTS: Three hundred forty-six patients were screened, and 149 were included (70/149 female; median age, 41 years). Of these, 73 received corticosteroids + mesalamine, and 76 received corticosteroids alone. For the primary outcome, 53 of 73 patients (72.6%) receiving corticosteroids with mesalamine responded versus 58 of 76 patients (76.3%) on corticosteroids alone (odds ratio, 0.82; 95% confidence interval, 0.39-1.72; P = .60). There was no difference between groups in duration of hospitalization, C-reactive protein normalization rate, or colectomy rate up to day 90. The need for biologics among patients receiving combination of corticosteroids with mesalamine was numerically lower by day 30 (P = .11) and day 90 (P = .07). CONCLUSIONS: In this randomized controlled trial, combination of mesalamine with corticosteroids did not benefit hospitalized patients with ASUC more than corticosteroids alone. An exploratory signal for a reduced need for biologics at 90 days in the mesalamine group merits further evaluation. CLINICALTRIALS: gov ID: NCT01941589.

Randomized Controlled Trial of Cognitive-Behavioral and Mindfulness-Based Stress Reduction on the Quality of Life of Patients With Crohn Disease.

BACKGROUND: Patients with Crohn disease have debilitating psychological symptoms, mental fatigue, and poor quality of life. Psychological intervention may improve these symptoms. METHODS: We performed a randomized parallel-group physician-blinded trial of cognitive-behavioral and mindfulness-based stress reduction (COBMINDEX) on quality of life and psychological symptoms in adults with mild-moderate Crohn disease. COBMINDEX was taught by social workers in one-on-one video conferences over 3 months; quotidian home practice was mandated. RESULTS: Fifty-five COBMINDEX and 61 waitlist control patients completed the study; mean age was 33 years and 65% of participants were women. At 3 months, COBMINDEX patients had significantly reduced disease activity (per Harvey-Bradshaw Index score, C-reactive protein level, and calprotectin level), increased quality of life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ] score increased from baseline 41 to 50; P < 0.001), decreased psychological symptoms (Global Severity Index [GSI], 0.98-0.70; P < 0.001), reduced fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue, 26-33; P < 0.001), and increased mindfulness disposition (Freiburg Mindfulness Inventory, 33-38; P < 0.001). Waitlist patients had a significant but small change in Harvey-Bradshaw Index, SIBDQ, and GSI scores, without improvement in fatigue or mindfulness. There were significant correlations (0.02 > P < 0.002) in COBMINDEX patients between baseline SIBDQ, GSI, Freiburg Mindfulness Inventory, and Functional Assessment of Chronic Illness Therapy-Fatigue scores with a relative change (baseline to 3 months) of the SIBDQ score, but none among waitlist patients. Predictors of relative change of the SIBDQ score in COBMINDEX patients included the GSI score (90% quantile; coefficient 0.52; P < 0.001), somatization (90%; 0.20; P = 0.001), depression (75%; 0.16; P = 0.03), and phobic anxiety (75%; 0.31; P = 0.008). CONCLUSIONS: COBMINDEX was effective in increasing patients' quality of life and reducing psychological symptoms and fatigue. Patients with severe baseline psychological symptoms benefited the most from COBMINDEX.

Adherence to Anti-Viral Treatment for Chronic Hepatitis B.

Adherence to treatment of chronic Hepatitis B Virus (HBV) is an important issue and can affect the complication rate. Nucleos(t)ide analogue as oral treatments are used for patients with necro-inflammatory activity and high viral load, with the goal of decline the complication rate such cirrhosis and hepatic cancer. We aimed to investigate the adherence to chronic HBV treatment. Chronic HBV patients with dispensing medication rates (DMR) of at least 80% were defined as high adherence group (HAG) and those who dispensed less than 80% as low adherence group (LAG). The study included 273 patients. 90 patients (33%) were in the LAG and 183 (67%) in the HAG. The All-cause mortality in the LAG was 15.6%, and 8.7% among the HAG (p-value = 0.09). 185 patients were of Jewish origin (mean age of 52.96 ±14.6 years, 30% women) and 88 patients of Arab Bedouin (AB) origin (mean age of 40.86 ± 13.96 years (p-value < 0.001), 42% women). The proportion of Jewish patients with high adherence was 71% (131 patients) versus 59% (52 patients) in AB patients (p-value = 0.054). The all-causes mortality was 14.6% among Jewish origin and 3.4% of AB (p-value = 0.01). We conclude that, two third of HBV carriers are with high level adherence to treatment in southern Israel, with lower but marginally significant all-cause mortality. No-significant differences in adherence patterns were noted between Arab Bedouin and Jews.

NOD2/CARD15 Mutations among Bedouin Arabs with Inflammatory Bowel Disease: Frequency and Phenotype Correlation.

BACKGROUND: Inflammatory bowel disease (IBD) prevalence is increasing among Bedouin Arabs in Israel. This population is known to have a high rate of consanguinity. NOD2/CARD15 mutations are well-studied in IBD. OBJECTIVES: To investigate the frequency of NOD2/CARD15 mutations in IBD Bedouin patients and their relevance to disease phenotype. METHODS: The IBD-Arab cohort in southern Israel included 68 patients, of which 25 Crohn's disease (CD) patients and 25 ulcerative colitis (UC) patients consented to participate (72%). Blood samples were obtained from all participants who were genotyped for NOD2/CARD15 variants Arg702Trp, Gly908Arg, and Leu1007fsinsC. RESULTS: The NOD2/CARD15 mutation frequency was higher in Crohn's disease than in ulcerative colitis patients. Carrier frequency for the Gly908Arg mutation in CD and UC patients was 8/25 (32%) and 3/25 (12%), respectively (P = 0.08). Neither the Arg702Trp nor Leu1007fsinsC mutation was found in our cohort. No homozygous/compound heterozygote mutations were found. Genotype-phenotype analysis revealed that CD patients carrying the Gly908Arg mutation were younger at diagnosis, 22.8 ± 4.5 vs. 28.82 ± 9.1 years (P = 0.04). All carriers were males, compared with 41.2% in non-carriers (P = 0.005). NOD2/CARD15 mutation carriers with UC were older, 67.0 ± 24.5 years compared with 41.2 ± 12.3 years (P = 0.006). No other associations regarding disease localization or other clinical parameter were found. CONCLUSIONS: The frequency of NOD2/CARD15 gene mutations is high in CD and UC among Bedouin Arab IBD patients and is associated with younger age at onset in CD and male gender.

Long-Term Survival of Young Patients Surviving ICU Admission With Severe Sepsis.

OBJECTIVES: Sepsis remains a disease with a high mortality rate. The study goal was to assess long-term survival of severe sepsis in young patients. DESIGN: Retrospective cohort study. SETTING: Patients admitted with sepsis to ICUs in seven tertiary hospitals between 2003 and 2011. PATIENTS: A total of 409 patients less than 45 years who survived to hospital discharge were age and sex matched with 818 patients with infectious disease without sepsis selected from internal medicine or surgical department admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median age in sepsis patients and the comparison group was 31 and 32 years, respectively. The proportions of patients surviving after hospital discharge were significantly lower in the sepsis group compared with the control group; among survivors, 6-month, 1-year, and 3-year mortality rates were 0.7% versus 0%, 4.5% versus 0.7%, 7.9% versus 1.2%, and 10.8% versus 1.8%, respectively (p < 0.001 for all). In a multivariate Cox proportional hazards regression model, sepsis was associated with an increased risk of mortality (hazard ratio, 3.79; 95% CI, 2.27-6.32), while controlling for age, Charlson Comorbidity Index, history of stroke, and congestive heart failure. Past the 24-month landmark, sepsis was not found to be an independent risk for mortality (hazard ratio, 1.79; 95% CI, 0.67-4.79). Based on cause of death analysis, chronic underlying comorbidities might explain the excess mortality in patients with sepsis. CONCLUSIONS: Young patients experiencing an episode of severe sepsis continue to be at higher risk of long-term mortality. The highest mortality rates were observed during the first 24 months following discharge.