Barriers to and requirements for a successful transition in inflammatory bowel disease from pediatric to adult care in Greece.

Background: The incidence of pediatric-onset inflammatory bowel disease (IBD) is rising, while the relapsing and often severe nature of IBD, and its impact on emotional and pubertal development and social maturation underline the need for a successful transition from pediatric to adult care. Methods: A web-based survey was distributed via the Hellenic Group for the Study of IBD, the Hellenic Society of Gastroenterology Department of North Greece, and the Hellenic Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Results: The questionnaire was answered by 98 individuals (78 adult and 20 pediatric gastroenterologists, out of 357 and 30, respectively). The response rate was 25.3%. A higher response rate was found among pediatric (66.6%) vs. adult gastroenterologists 21.8% (P<0.001). Pediatric gastroenterologists believed that the appropriate age for transition was either 16-17 or 17-18 years, whereas 59% of the adult gastroenterologists chose the age group of 16-17 years. Both adult and pediatric gastroenterologists stated that the most significant initiators for a successful transition process were cognitive maturity and patients' ability to manage their disease independently. The lack of communication and collaboration between pediatric and adult gastroenterologists was the main barrier to the transition process, as identified by adult gastroenterologists (27.7%). In contrast, 43.5% of pediatric gastroenterologists suggested that differences in the follow up of patients with IBD between pediatric and adult clinics were the main restrictions. Conclusion: These results highlight the need for a transitional education program for pediatric IBD patients, and the importance of improving collaboration among adult and pediatric gastroenterologists.

The Inflammatory Bowel Disease-Disk Tool for Assessing Disability in Inflammatory Bowel Disease Patients: Validation of the Greek Version.

BACKGROUND: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. METHODS: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency. RESULTS: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86-0.91)]. Cronbach's coefficient alpha for all items achieved 0.90 (95%CI 0.88-0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score. CONCLUSIONS: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD patients.

The burden and management of anemia in Greek patients with inflammatory bowel disease: a retrospective, multicenter, observational study.

BACKGROUND: Anemia is a common extraintestinal manifestation of Inflammatory Bowel Disease (IBD) affecting negatively the patients' quality of life. The aim of this study was to determine the frequency and real-life management of anemia in IBD patients in Greece. METHODS: This study was conducted in 17 Greek IBD referral centers. Demographic, clinical, laboratory, IBD and anemia treatment data were collected and analyzed retrospectively. RESULTS: A total of 1394 IBD patients [560 ulcerative colitis (UC), 834 Crohn's disease (CD)] were enrolled. Anemia at any time was reported in 687 (49.3%) patients of whom 413 (29.6%) had episodic and 274 (19.7%) had recurrent/persistent anemia. Anemia was diagnosed before IBD in 45 (6.5%), along with IBD in 269 (39.2%) and after IBD in 373 (54.3%) patients. In the multivariate analysis the presence of extraintestinal manifestations (p = 0.0008), IBD duration (p = 0.026), IBD related surgeries and hospitalizations (p = 0.026 and p = 0.004 accordingly) were risk factors of recurrent/persistent anemia. Serum ferritin was measured in 839 (60.2%) IBD patients. Among anemic patients, 535 (77.9%) received treatment. Iron supplementation was administered in 485 (90.6%) patients, oral in 142 (29.3%) and intravenous in 393 (81%). CONCLUSIONS: The frequency of anemia in IBD patients, followed at Greek referral centers, is approximately 50%. Development of recurrent/persistent anemia may be observed in 20% of cases and is independently associated with the presence of extraintestinal manifestations, IBD duration, IBD related surgeries and hospitalizations. Anemia treatment is administered in up to [Formula: see text] of anemia IBD patients with the majority of them receiving iron intravenously.

Patients' and Clinicians' Preferences on Outcomes and Medication Attributes for Type 2 Diabetes: a Mixed-Methods Study.

BACKGROUND: Patients' views on the relative importance of treatment outcomes and medication attributes for type 2 diabetes may differ from clinicians' perceptions. OBJECTIVE: To assess which treatment outcomes and medication attributes are considered important by patients and clinicians for therapeutic decisions in type 2 diabetes. DESIGN: Exploratory, sequential, mixed-methods design comprising a qualitative (focus groups) and a quantitative (survey) phase. PARTICIPANTS: Patients in the focus groups (n = 33) and the survey study (n = 656) were recruited from 4 and 9 diabetes clinics across Greece, respectively. Clinicians in the survey study (n = 363) were identified from Greek registries for healthcare professionals. MEASUREMENTS: We conducted 6 focus groups to obtain patients' views regarding the impact of type 2 diabetes on their lives. Identified themes informed the development of a survey, which aimed to assess which outcomes and medication attributes are considered most important by patients and clinicians. We calculated odds ratios to compare patients' and clinicians' responses. RESULTS: The focus groups identified 6 main themes and 15 subthemes. In the survey study, patients were more likely than clinicians to rate prevention of amputation (odds ratio, 9.32; 95% CI, 6.51 to 13.35), diabetic eye disease (6.16; 4.63 to 8.21), sexual dysfunction, and stroke as important, while clinicians were more likely than patients to choose risk for hypoglycemia, and reduction of all-cause mortality, HbA1c, and body weight. Compared with clinicians, patients were less concerned about drug cost (0.16; 0.11 to 0.23), but more concerned about route of administration and need for less frequent glucose self-monitoring. CONCLUSIONS: Patients and clinicians differ in the perception of the relative importance of treatment outcomes and drug characteristics. Individual patient preferences should be explored and implemented in the therapeutic decision-making for type 2 diabetes.

Carvedilol for prevention of variceal bleeding: a systematic review and meta-analysis.

BACKGROUND: Beta-blockers are used for prophylaxis of variceal bleeding. Our aim was to assess the efficacy and safety of carvedilol for primary or secondary prevention of variceal bleeding in patients with cirrhosis. METHODS: We searched Medline, Embase, CENTRAL and gray literature sources for randomized controlled trials (RCTs) comparing carvedilol with placebo or any active intervention. We synthesized data using random effects models. We summarized the strength of evidence using GRADE criteria. RESULTS: We included 13 trials with 1598 patients. Carvedilol was as efficacious as endoscopic variceal ligation (EVL) (4 RCTs, risk ratio [RR] 0.74, 95% confidence interval [CI] 0.37-1.49) or propranolol (3 RCTs, RR 0.76, 95%CI 0.27-2.14) for primary prevention of variceal bleeding. Likewise, carvedilol was as efficacious as EVL (3 RCTs, RR 1.10, 95%CI 0.75-1.61), non-selective beta-blockers (NSBBs) plus isosorbide-5-mononitrate (2 RCTs, RR 1.02, 95%CI 0.70-1.51) or propranolol (2 RCTs, RR 0.39, 95%CI 0.15-1.03) for secondary prevention of variceal bleeding. Carvedilol was associated with lower all-cause mortality compared to EVL (3 RCTs, RR 0.51, 95%CI 0.33-0.79). There was no difference in any other efficacy outcome. Finally, there were no significant differences in the safety profiles compared with EVL and NSBBs. Our confidence in the effect estimates for all outcomes was very low. CONCLUSION: Carvedilol is as efficacious and safe as standard-of-care interventions for the primary and secondary prevention of variceal bleeding.

Performance of Baveno VI and Expanded Baveno VI Criteria for Excluding High-Risk Varices in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: We aimed to assess the accuracy of Baveno VI criteria for identification of high-risk varices (HRVs) and varices of any size in patients with compensated advanced chronic liver disease (cACLD). METHODS: We performed a systematic search of publications through December 2018 for studies that assessed the accuracy of Baveno VI criteria for screening for varices in patients with cACLD. We used hierarchical models to synthesize evidence. We also conducted a post hoc analysis to assess the accuracy of Εxpanded Baveno VI criteria. We appraised the confidence in estimates using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We identified 30 studies (8469 participants). Pooled values of Baveno VI criteria for HRVs (26 studies) were a sensitivity of 0.97 (95% CI, 0.95-0.98) and a specificity of 0.32 (95% CI, 0.26-0.39). Pooled sensitivity of Εxpanded Baveno VI criteria for HRVs (12 studies) was 0.90 (95% CI, 0.85-0.93) and specificity was 0.51 (95% CI, 0.45-0.57). In 1000 patients with cACLD, with a prevalence of HRVs of 20%, Baveno VI criteria would prevent endoscopy in 262 patients, but 6 patients with HRVs would be missed. Instead, use of the Εxpanded Baveno VI criteria would result in 428 patients avoiding endoscopy, but 20 patients with HRVs would be missed. The credibility of our findings is moderate or low, mainly owing to the retrospective design of most studies. CONCLUSIONS: Baveno VI criteria have high diagnostic accuracy as a triage test for screening for HRVs in patients with cACLD. Expanded Baveno VI criteria could reduce the proportion of unnecessary endoscopies further, nevertheless with a higher rate of missed HRVs.

Systematic review with network meta-analysis: the impact of medical interventions for moderate-to-severe ulcerative colitis on health-related quality of life.

BACKGROUND: Patient-reported outcomes are important in the assessment of efficacy of intervention for ulcerative colitis (UC). AIM: To compare the impact of interventions for moderate-to-severe UC on health-related quality of life (HRQL). METHODS: We searched Medline, Embase, CENTRAL and grey literature sources through October 2017. We included randomised controlled trials (RCTs) that compared infliximab, adalimumab, golimumab, vedolizumab or tofacitinib to each other or placebo. Outcomes included the change in quality of life scores and the proportion of patients with improvement in quality of life. We performed random-effect pairwise and network meta-analysis. We assessed confidence in estimates using the CINeMA (Confidence in Network Meta-Analysis) framework. RESULTS: Fourteen RCTs assessed HRQL using the Inflammatory Bowel Disease Questionnaire (IBDQ) (14 trials), the Short Form questionnaire-36 (SF-36) (seven trials) or the European Quality of Life-5 Dimensions questionnaire (EQ-5D) (three trials). At induction (13 trials), low to very low confidence evidence suggested that all agents significantly improved both generic and disease-specific HRQL scores compared to placebo. However, only infliximab (MD 18.58; 95% CI 13.19-23.97) and vedolizumab (MD 18.00; 95% CI 11.08-24.92) showed clinically meaningful improvement in IBDQ score. Differences among individual interventions were imprecise. For maintenance (four trials), very low confidence evidence suggested that vedolizumab, tofacitinib and adalimumab maintained improvement in HRQL. CONCLUSIONS: Induction treatment with infliximab, adalimumab, golimumab, vedolizumab or tofacitinib improves quality of life compared to placebo. Evidence on maintenance therapy is sparse and uncertain. Head-to-head comparisons could enhance confidence in conclusions about differences between drugs in terms of HRQL.

Tofacitinib for induction of remission in ulcerative colitis: systematic review and meta-analysis.

BACKGROUND: The aim of the study was to assess the efficacy and safety of tofacitinib and its impact on quality of life in patients with moderate-to-severe ulcerative colitis. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing tofacitinib with placebo or any active comparator. We searched Medline, Embase, the Cochrane Library and gray literature for articles published up to May 2017. We synthesized data using a fixed-effect model. We conducted subgroup analysis based on prior exposure to anti-tumor necrosis factor (TNF). We summarized the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included three trials with 1220 participants. Compared with placebo, tofacitinib was effective in inducing clinical remission (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.29-6.44, I2: 41%, GRADE: moderate), clinical response (OR 2.95, 95%CI 2.21-3.95, I2: 0%, GRADE: high), mucosal healing (OR 2.70, 95%CI 1.81-4.03, I2: 0%, GRADE: high). Tofacitinib was effective in both anti-TNF-naïve and -experienced patients. Tofacitinib had a favorable effect on quality of life. There were no significant differences in the safety profile in terms of the incidence of any or serious adverse events compared to placebo. The risk for infections was increased (OR 1.51, 95%CI 1.05-2.19, I2: 0%, GRADE: moderate), but the incidence of serious infections did not differ between tofacitinib and placebo. CONCLUSION: In patients with moderate-to-severe ulcerative colitis, short-term treatment with tofacitinib is effective for induction of remission and improvement of quality of life.

Comparative Benefits and Harms of Basal Insulin Analogues for Type 2 Diabetes: A Systematic Review and Network Meta-analysis.

Background: Basal insulin analogues aim for protracted glycemic control with minimal adverse effects. Purpose: To assess the comparative efficacy and safety of basal insulin analogues for adults with type 2 diabetes mellitus (T2DM). Data Sources: Several databases from inception to April 2018 without language restrictions, ClinicalTrials.gov to April 2018, references of reviews, and meeting abstract books. Study Selection: Randomized trials lasting at least 12 weeks that compared efficacy (change in hemoglobin A1c [HbA1c] level from baseline [primary outcome]; percentage of patients with HbA1c level <7% at end of study and change in body weight [secondary outcomes]) and safety (hypoglycemia) of basal insulin analogues. Data Extraction: Two authors independently extracted data and assessed risk of bias for each outcome. All authors evaluated overall confidence in the evidence. Data Synthesis: Thirty-nine trials (26 195 patients) assessed 10 basal insulin analogues. Low- to very-low-quality evidence indicated that thrice-weekly degludec (Deg-3TW) was inferior to most other regimens for reducing HbA1c level, with mean differences ranging from 0.21% (vs. degludec, 100 U/mL [Deg-100]) to 0.32% (vs. glargine, 300 U/mL [Glar-300]). High- to moderate-quality evidence suggested that detemir had a favorable weight profile versus all comparators, and Glar-300 was associated with less weight gain than glargine, 100 U/mL (Glar-100); Deg-100; degludec, 200 U/mL (Deg-200); Deg-3TW; and LY2963016. Low- and very-low-quality evidence suggested that Deg-100, Deg-200, and Glar-300 were associated with lower incidence of nocturnal hypoglycemia than detemir, Glar-100, LY2963016, and neutral protamine lispro (NPL). Incidence of severe hypoglycemia did not differ among regimens, except NPL, which was associated with increased risk versus Deg-100, detemir, Glar-100, and Glar-300. Limitations: Results are based mostly on indirect comparisons. Confidence in summary estimates is low or very low due to individual-study limitations, imprecision, or inconsistency. Conclusion: Low-quality evidence suggests that basal insulin analogues for T2DM do not substantially differ in their glucose-lowering effect. Low- and very-low-quality evidence suggests some regimens may be associated with lower risk for nocturnal hypoglycemia (Deg-100, Deg-200, and Glar-300) or less weight gain (detemir and Glar-300). Primary Funding Source: None. (PROSPERO: CRD42016037055).

Can Serum Uric Acid Lowering Therapy Contribute to the Prevention or Treatment of Nonalcoholic Fatty Liver Disease?

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in Western countries with potential progression to nonalcoholic steatohepatitis (NASH) and cirrhosis, is associated with cardiovascular disease (CVD) mortality. Several studies have reported a relationship between uric acid and NAFLD/NASH and it seems that serum uric acid (SUA) is a significant independent factor for the development of NAFLD. Potential mediating mechanisms include insulin resistance, endothelial dysfunction, and activation of inflammasome, especially NLRP3. Moreover, emerging evidence indicates a strong association between elevated SUA, metabolic syndrome (MetS), NAFLD, and CVD. The emphasis of the present review is whether common therapy of elevated SUA levels and NAFLD can improve compliance. There are several drugs with "off target" properties that show some separate benefit on SUA reduction (e.g. losartan) or NAFLD/NASH (pioglitazone); however, there is no randomized controlled trial (RCT) of a single drug with beneficial outcome for both diseases. Allopurinol reduces SUA levels and ameliorates NAFLD/NASH; however, no RCTs have been performed up to now to explore potential survival benefits. Atorvastatin, which has proven safe in NAFLD/NASH, reduces SUA levels, ameliorates NAFLD/NASH, prevents liver fibrosis, and above all substantially reduces CVD morbidity and mortality in comparison with those on statins but without NAFLD/NASH. This drug could be a solution to improve compliance in both diseases, which are prevalent and becoming even more common with the obesity, MetS, and type 2 diabetes mellitus epidemic.

Diagnostic Accuracy of Fecal Immunochemical Test in Patients at Increased Risk for Colorectal Cancer: A Meta-analysis.

Importance: The potential role of the fecal immunochemical test (FIT) for screening patients at increased risk for colorectal cancer (CRC) has not yet been elucidated. Objective: To assess the diagnostic accuracy of FIT for CRC or advanced neoplasia (AN) in asymptomatic patients at above-average risk. Data Sources: MEDLINE, EMBASE, Cochrane Library, and gray literature sources through August 2016. Study Selection: Diagnostic studies evaluating the accuracy of FIT for CRC or AN in patients with a personal or familial history of CRC using colonoscopy as the reference standard. Data Extraction and Synthesis: Two authors (A.K. and P.P.) independently extracted data and evaluated study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, and evaluated the quality of the body of evidence by means of GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Hierarchical models were used to synthesize available evidence. Main Outcomes and Measures: The primary outcome was the diagnostic performance of FIT for detecting CRC or AN. Results: We included 12 studies (6204 participants). Seven studies were deemed at high or unclear risk of bias. The average sensitivity of FIT for CRC was 93% (95% CI, 53%-99%), and the average specificity was 91% (95% CI, 89%-92%), yielding a positive likelihood ratio (LR+) of 10.30 (CI 7.7-13.9) and a negative likelihood ratio (LR-) of 0.08 (95% CI, 0.01-0.75) (GRADE: very low). The average sensitivity of FIT for AN was 48% (95% CI, 39%-57%); and the average specificity was 93% (95% CI, 91%-94%), yielding an LR+ of 6.55 (95% CI, 5.0-8.5) and an LR- of 0.57 (95% CI, 0.48-0.67) (GRADE: very low). Subgroup analyses indicated that FIT cutoff values between 15- and 25-µg/g feces provided the best combination of sensitivity and specificity for the diagnosis of CRC (93% and 94%, respectively). Quantitative and 1-sample FIT showed adequate test performance, but data on other FIT brands and multiple samples were insufficient. Conclusions and Relevance: The FIT has high overall diagnostic accuracy for CRC but moderate accuracy for AN in patients at above-average personal or familial risk. Heterogeneity and wide confidence intervals limit the trustworthiness of our findings.

Once-weekly dipeptidyl peptidase-4 inhibitors for type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of omarigliptin and trelagliptin, novel dipeptidyl peptidase-4 inhibitors administered once-weekly (DPP-4i QW). METHODS: We systematically searched for placebo- and active-controlled randomized trials in adults with type 2 diabetes mellitus. RESULTS: Fifteen primary studies with 5709 participants were included. DPP-4i QW were more effective than placebo in reducing hemoglobin A1c (HbA1c) (Weighted Mean Difference (WMD) -0.63%; 95% CI -0.80, -0.46; I2 = 84%) and had a similar glucose-lowering effect with daily DPP-4i (WMD 0.01%; -0.08, 0.11%; I2 = 34%). Omarigliptin was less effective compared with oral antidiabetic agents, other than daily DPP-4i, (WMD 0.24%; 0.10, 0.38; I2 = 12%). Omarigliptin did not affect body weight (WMD versus placebo 0.60 kg; 0.25, 0.96; I2 = 0%). Risk for any hypoglycemia was similar between DPP-4i QW and placebo (Odds Ratio 1.32; 0.78, 2.22; I2 = 0%). Incidence of other adverse events did not differ between DPP-4i QW and control. CONCLUSIONS: DPP-4i QW were superior to placebo and similar to daily DPP-4i in terms of glycemic control, and were not associated with any specific adverse events. There is limited comparative effectiveness evidence against other agents, while their effect on hard clinical safety outcomes is unknown.