Profile of Tofacitinib in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Recent Data.

Recent advances in the understanding of the pathophysiology of ulcerative colitis (UC) have led to the expansion of our therapeutic arsenal. Conventional treatment options, including aminosalicylates, corticosteroids, thiopurines, and calcineurin inhibitors, fail to control the disease in a significant proportion of patients. Approximately 25-50% of the patients treated with tumor necrosis factor antibodies (anti-TNFα) are primary and secondary non-responders to therapy. Tofacitinib is a novel orally administered small synthetic molecule that inhibits a homologous family of enzymes, termed Janus kinases that modulate multiple key cytokines involved in the pathogenesis of UC. Phase II and III trials showed promising results in UC, leading the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to approve its administration for the induction and maintenance of remission in moderate-to-severe UC. Herein, we review tofacitinib for the management of UC, its mechanism of action pharmacokinetic properties, efficacy, and safety.

Pre-intensive care unit intubation and subsequent delayed intensive care unit admission is independently associated with increased occurrence of ventilator-associated pneumonia.

INTRODUCTION: Critically ill intubated patients are at risk for ventilator-associated pneumonia. However, intubation may not occur in intensive care unit (ICU) and subsequent ICU admission may be delayed. OBJECTIVES: To evaluate whether intubation >24 h prior ICU admission and delay in ICU admission is associated with ventilator-associated pneumonia (VAP) in non-trauma critically ill patients. MATERIALS AND METHODS: Prospective observational study conducted in a medical-surgical ICU of a tertiary hospital. Consecutive patients with >48 h of invasive mechanical ventilation and >72 h hospitalization, were recruited in the study. Pre-ICU intubation and delay in ICU admission, demographical, clinical, microbiological data and ICU interventions were assessed as risk factors for VAP and ICU mortality. RESULTS: 100 patients were included in the study. Pre-ICU intubation and delayed (>24 h) ICU admission (PDA patients) (P = 0.014, OR = 3.294, confidence interval 1.268-8.557) and SOFA score on ICU admission (P = 0.045, OR = 1.154, confidence interval 1.003-1.328) were independent risk factors for VAP in ICU care setting. Yet, PDA patients, presented significantly increased incidence of VAP due to MDR bacteria, mainly from Acinetobacter baumannii. Acinetobacter baumannii infection was the only independent risk factor for ICU mortality (P = 0.049, OR = 3.253, confidence interval 1.006-10.521). SOFA score on ICU admission, presented a fair prognostic accuracy of overall ICU mortality (SOFA ≥ 8.5, AUC = 0.850, P < 0.001). CONCLUSIONS: Pre-ICU intubation and delayed ICU admission was independent risk factor for VAP Acinetobacter baumannii infection and a high SOFA score on ICU admission were predictors of increased ICU mortality.

Disability in Patients with Inflammatory Bowel Disease: Correlations with Quality of Life and Patient's Characteristics.

BACKGROUND: Inflammatory bowel diseases may cause significant disability. However, little is known regarding the life domains where patients encounter most limitations. OBJECTIVES: To assess patients' overall disability and determine the life domains where most restrictions were applied. Secondarily, we sought for possible relationships among disability, quality of life (HRQoL), and population characteristics. METHOD: The study lasted for two years (2013-2015) and included 200 patients [52% ulcerative colitis (UC)] from a referral centre. Disability was evaluated using the 36-item version of WHODAS 2.0 questionnaire. The influence of population characteristics on overall disability was assessed with linear regression. RESULTS: Crohn's disease (CD) patients showed greater overall disability compared to UC (19.22 versus 15.01, p = 0.001), with higher scores in the domains of relationships, life activities, and participation. Disability was negatively associated with HRQoL (p < 0.001). Long activity, extensive disease, rural residence, and employment independently influenced the overall disability in both groups. Additionally, significant influence was recorded for lower education in the UC and for operation and celibacy in the CD group. CONCLUSIONS: CD patients were facing more limitations compared to those with UC, especially in the domains of relationships, activities, and participation. Other than clinical factors, sociodemographic characteristics were also associated with increased disability.

The Rating Form of IBD Patient Concerns: Translation, Validation, and First Implementation of the Greek Version.

Background. The rating form of IBD patients' concerns (RFIPC) provides a unique assessment of the worries and concerns of inflammatory bowel disease (IBD) patients. Our aims were primarily to validate the Greek version of RFIPC and secondarily to describe the pattern of Greek patients'concerns. Methods. After translating RFIPC, the questionnaire was given to IBD patients at baseline and after 12 weeks. The questionnaire's measuring properties were evaluated based on the consensus-based standards for the selection of health status measurement instruments (COSMIN) recommendations. Premediated factorial structures were tested for goodness of fit with confirmatory factor analysis (CFA). Results. At baseline, 200 patients (94 with Crohn's disease) completed RFIPC. After 12 weeks, the first 100 patients recompleted the questionnaire. CFA results were consistent with a slightly modified than the original factorial structure. Cronbach's α and intraclass correlation coefficients were high. RFIPC scores negatively affected the quality of life. RFIPC was sensitive to detect important changes in patients' condition and was able to discriminate between remission and active disease. Disease activity, full time employment, celibacy, and low education were associated with higher scores. Conclusion. The Greek version of RFIPC is a reliable, valid, and responsive tool to assess Greek IBD patients' concerns.

Acinetobacter baumannii infection in prior ICU bed occupants is an independent risk factor for subsequent cases of ventilator-associated pneumonia.

OBJECTIVE: We aimed to evaluate risk factors for ventilator-associated pneumonia (VAP) due to Acinetobacter baumannii (AbVAP) in critically ill patients. METHODS: This was a prospective observational study conducted in an intensive care unit (ICU) of a district hospital (6 beds). Consecutive patients were eligible for enrolment if they required mechanical ventilation for >48 hours and hospitalization for >72 hours. Clinical, microbiological, and laboratory parameters were assessed as risk factors for AbVAP by univariate and multivariate analysis. RESULTS: 193 patients were included in the study. Overall, VAP incidence was 23.8% and AbVAP, 11.4%. Previous hospitalization of another patient with Acinetobacter baumannii infection was the only independent risk factor for AbVAP (OR (95% CI) 12.016 (2.282-19.521) P < 0.001). ICU stay (25 ± 17 versus 12 ± 9 P < 0.001), the incidence of other infections (OR (95% CI) 9.485 (1.640-10.466) P = 0.002) (urinary tract infection, catheter related infection, and bacteremia), or sepsis (OR (95% CI) 10.400 (3.749-10.466) P < 0.001) were significantly increased in patients with AbVAP compared to patients without VAP; no difference was found with respect to ICU mortality. CONCLUSION: ICU admission or the hospitalization of patients infected by Acinetobacter baumannii increases the risk of AbVAP by subsequent patients.

Diabetes and hemoglobin a1c as risk factors for nosocomial infections in critically ill patients.

UNLABELLED: Objective. To evaluate whether diabetes mellitus (DM) and hemoglobin A1c (HbA1c) are risk factors for ventilator-associated pneumonia (VAP) and bloodstream infections (BSI) in critically ill patients. Methods. Prospective observational study; patients were recruited from the intensive care unit (ICU) of a general district hospital between 2010 and 2012. INCLUSION CRITERIA: ICU hospitalization >72 hours and mechanical ventilation >48 hours. HbA1c was calculated for all participants. DM, HbA1c, and other clinical and laboratory parameters were assessed as risk factors for VAP or BSI in ICU. Results. The overall ICU incidence of VAP and BSI was 26% and 30%, respectively. Enteral feeding OR (95%CI) 6.20 (1.91-20.17; P = 0.002) and blood transfusion 3.33 (1.23-9.02; P = 0.018) were independent risk factors for VAP. BSI in ICU (P = 0.044) and ICU mortality (P = 0.038) were significantly increased in diabetics. Independent risk factors for BSI in ICU included BSI on admission 2.45 (1.14-5.29; P = 0.022) and stroke on admission2.77 (1.12-6.88; P = 0.029). Sepsis 3.34 (1.47-7.58; P = 0.004) and parenteral feeding 6.29 (1.59-24.83; P = 0.009) were independently associated with ICU mortality. HbA1c ≥ 8.1% presented a significant diagnostic performance in diagnosing repeated BSI in ICU. Conclusion. DM and HbA1c were not associated with increased VAP or BSI frequency. HbA1c was associated with repeated BSI episodes in the ICU.