ObjectiveThe benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP.DesignMajor databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined.ResultsA total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I2=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I2=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking.ConclusionsPERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.

Summary Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose‐optimisation for ustekinumab nonresponse is limited. Aim To assess the effectiveness of dose escalation of ustekinumab. Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard‐dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation. Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose‐escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid‐free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow‐up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow‐up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission. Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.

Background/Objectives The epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and pancreatic enzyme replacement therapy (PERT) requirements for EPI during follow-up of AP by systematic review and meta-analysis. Methods Scopus, Medline and Embase were searched for prospective observational studies or randomized clinical trials (RCTs) of PERT reporting EPI during the first admission (between the start of oral refeeding and before discharge) or follow-up (≥ 1 month of discharge) for AP in adults. EPI was diagnosed by direct and/or indirect laboratory exocrine pancreatic function tests. Results Quantitative data were analyzed from 370 patients studied during admission (10 studies) and 1795 patients during follow-up (39 studies). The pooled prevalence of EPI during admission was 62% (95% confidence interval: 39–82%), decreasing significantly during follow-up to 35% (27–43%; risk difference: − 0.34, − 0.53 to − 0.14). There was a two-fold increase in the prevalence of EPI with severe compared with mild AP, and it was higher in patients with pancreatic necrosis and those with an alcohol etiology. The prevalence decreased during recovery, but persisted in a third of patients. There was no statistically significant difference between EPI and new-onset pre-diabetes/diabetes (risk difference: 0.8, 0.7–1.1, P = 0.33) in studies reporting both. Sensitivity analysis showed fecal elastase-1 assay detected significantly fewer patients with EPI than other tests. Conclusions The prevalence of EPI during admission and follow-up is substantial in patients with a first attack of AP. Unanswered questions remain about the way this is managed, and further RCTs are indicated. Electronic supplementary material The online version of this article (10.1007/s10620-019-05568-9) contains supplementary material, which is available to authorized users.

Resistance rate of H. pylori to antibiotics is high in the northwest of Spain. The high resistance to levofloxacin and clarithromycin advises against their wide empirical use of these antibiotics in eradication regimens.

Background Concomitant quadruple (CQT) or bismuth‐containing quadruple therapy (BQT) is recommended as first‐line treatment for Helicobacter pylori infection depending on antibiotic resistance. Aim To compare the efficacy, safety, and compliance of CQT and BQT as first‐line therapy for H. pylori eradication in real clinical practice in an area of high resistance to clarithromycin. Methods A prospective, open, comparative cross‐sectional study including dyspeptic patients >18 years with H. pylori infection and with no previous eradication treatment was performed. CQT (omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + metronidazole 500 mg, all given twice daily, for 14 days) or BQT (omeprazole 20 mg twice daily + 3 capsules of Pylera® 4 times a day, for 10 days) was prescribed at the discretion of the prescribing physician. Eradication was tested by 13C‐urea breath test. Efficacy was assessed by intention‐to‐treat (ITT) and per‐protocol (PP) analyses. Results One hundred and four consecutive patients were included (64.4% female, age 52.9 years). Fifty patients received CQT and 54 BQT. Eradication rate was similar with both therapies at the PP (CQT 97.9%, 95% CI: 93.9‐100 vs BQT 96.2%, 95% CI: 90.9‐100, P = 0.605) and ITT analyses (CQT 98.0%, 95% CI: 94‐100 vs BQT 94.4%, 95% CI: 88.1‐100, P = 0.346). The rate of adverse events was also similar with CQT (56%) and BQT (46.3%). One patient in each group discontinued the treatment due to significant adverse events. Conclusion The use of CQT and BQT as first‐line treatment against H. pylori is similarly effective and safe strategy in an area of high clarithromycin resistance.

Background Post-marketing data are required to confirm the durability and the long-term benefit and safety of UST in CD in clinical practice. Our aims were: (1) to evaluate the retention rate of UST in CD patients and to identify predictive factors of UST discontinuation; (2) to assess UST short-term effectiveness; (3) to analyse the durability of the response to UST in the long-term; and (4) to evaluate the safety of UST in clinical practice. Methods Retrospective, multicentre study (&gt;60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) &gt;4)] that received at least one dose of UST intravenously before July 2018 were included. Clinical activity plus biochemical parameters were assessed at every UST administration. Clinical remission was defined as HBI score ≤4, and clinical response as a decrease in HBI ≥3 points. Loss of efficacy was defined as reappearance of symptoms that led to intensify the treatment dose, add another medication to control CD, switching or surgery in patients with short-term remission. The retention rate of UST treatment and the cumulative incidence of loss of efficacy were evaluated by survival curves, and predictive factors were assessed by Cox-regression. The short-term response was evaluated at week 8 and after the induction (week 16). Factors associated with short-term remission were assessed by multivariate analysis. Adverse events were recorded. Data quality was assured by remote monitoring. Results 331 CD patients have been included up to date (Table 1). The incidence rate of UST discontinuation was 15% per patient-year of follow-up: 8%, 13% and 20% at 6, 12 and 18 months (Figure 1). Previous surgery was the only factor associated with a higher risk of UST discontinuation [Hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.1–3.6]. Short-term efficacy is shown in Figure 2. Previous surgery (OR = 0.3, 95% CI = 0.2–0.6) and higher HBI score at baseline (OR = 0.8, 95% CI=0.8–0.9) were associated with an impaired response to UST at week 16. The cumulative incidence of loss of response was 32% per-patient-year of follow-up (Figure 3); A higher HBI score at baseline was associated with a higher risk of losing response (HR = 1.2, 95% CI = 1.1–1.3). Neither the concomitant treatment with immunosuppressants nor the number of previous biologics were associated with UST short- and long-term benefit. Thirty adverse events were reported in 25 (7%) patients (Table 2). Conclusion Sustain is the largest real clinical practice study of UST to treat CD patients with the longest follow-up reported to date. UST was demonstrated to be effective in real-world use in the short and long run. Safety was consistent with the known profile of UST.

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

Inflammatory bowel diseases (IBDs) are chronic disabling conditions, characterized by an unpredictable course with flare-ups and periods of remission, that frequently affect young people and require lifelong medical follow-up and treatment. For years, the main endpoints of IBD treatment had been clinical remission and response, followed by biomarker normalization and mucosal healing. In the last decades, different therapies have been proved to be effective to treat IBD and the use of patient reported outcome (PRO) have become more relevant. Therefore, health-related quality of life (HRQoL) that has been defined as the value assigned to the duration of life influenced by physical and mental health, has been suggested as an important endpoint for IBD management since multiple studies have shown that IBD impairs it, both physically and psychologically. Thus, HRQoL has been included as an outcome in numerous studies evaluating different IBD therapies, both clinical trials and real-life studies. It has been assessed by using both generic and specific disease tools, and most treatments used in clinical practice have been demonstrated to improve HRQoL. The relevance of HRQoL as an endpoint for new drugs is going to increase and its management and improvement will also improve the prognosis of IBD patients.