Point-of-Care test screening versus Case finding for paediatric coeliac disease: A pragmatic study in primary care

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Comparison of Direct Oral Anticoagulant Use for the Treatment of Non-Valvular Atrial Fibrillation in Pivotal Clinical Trials vs. the Real-World Setting: A Population-Based Study from Southern Italy

Patients enrolled into pivotal randomized controlled trials (RCTs) may differ substantially from those treated in a real-world (RW) setting, which may result in a different benefit\u2013risk profile. The aim of the study was to assess the external validity of pivotal RCT findings concerning direct oral anticoagulants (DOACs) for the treatment of nonvalvular atrial fibrillation (NVAF) by comparing patients recruited in RCTs to those treated with DOACs registered in a southern Italian local health unit (LHU) in the years 2013\u20132017. The Palermo LHU claims database was used to describe the baseline characteristics of incident DOAC users (washout > 1 year) with NVAF compared with those of enrolled patients in DOAC pivotal RCTs. In the RW, DOAC treatment discontinuation was calculated during the follow-up and compared with DOAC treatment discontinuation of enrolled patients in DOAC pivotal RCTs. Rates of effectiveness and safety outcomes during the follow-up were calculated in an unmatched and in a simulated RCT population, by matching individual incidental RW and RCT DOAC users (excluding edoxaban users) on age, sex, and CHADS2 score. Overall, 42,336 and 7092 incident DOAC users with NVAF were identified from pivotal RCTs and from the RW setting, respectively. In RCTs, DOAC use was more common among males (62.6%) compared with an almost equal sex distribution in the RW. RCT patients were younger (mean age \ub1 standard deviation: 70.7 \ub1 9.2 years) than RW patients (76.0 \ub1 8.6 years). Compared with RCTs, a higher proportion of RW dabigatran users (30.4% vs. 19.6%) and a lower proportion of RW apixaban (15.9% vs. 25.3%) and rivaroxaban (20.4% vs. 23.7%) users discontinued the treatment during the follow-up (p-value < 0.001). The rate of ischemic stroke was lower in RW high-dose dabigatran users (unmatched/-matched population: 0.40\u20130.11% per year) than in the Randomized Evaluation of Long- Term Anticoagulation Therapy (RE-LY) population (0.93% per year). Major bleeding rates were lower in RW users than in RCT users. In conclusion, except for dabigatran, a lower proportion of DOAC discontinuers was observed in the real-world than in pivotal RCT settings. This study provides reassurance to practicing physicians that DOAC use appears to be effective in stroke prevention and is likely safer in RW patients than in RCT enrolled patients. These results may be related to a lower burden of comorbidities despite more advanced age in the RW population compared to the pivotal RCT population

Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase

Pharmacokinetics of new oral anticoagulants: implications for use in routine care

Introduction: Since 2008, new oral anticoagulants (NOACs) have been approved for the prevention of venous thromboembolism (VTE) in patients receiving hip or knee replacement surgery, prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pre-marketing randomized clinical trials of NOACs demonstrated their non-inferiority in terms of efficacy vs. warfarin (traditional oral anticoagulant \u2013 TOA), with lower risk of serious adverse drug reactions, especially cerebral haemorrhages. In clinical practice, pharmacokinetic aspects of NOACs have to be carefully taken into account to optimize the benefit-risk profile of these drugs. Areas covered: An overview of major issues related to pharmacokinetics of NOACs, such as drug-drug interactions, over- and under-dosage in special populations (e.g. elderly, underweight and patients with chronic kidney disease patients), and impact on adherence and persistence to NOACs therapy and ultimately clinical outcomes in real world setting is provided. Expert Opinion: NOACs have been proven to be a better option than traditional anticoagulants due to better tolerability and ease of use. However, given specific pharmacokinetic characteristics, NOACs therapy has to be carefully tailored and monitored in relation to patients\u2019 characteristics with the final goal to maximize benefits and minimize risks

Diagnostic accuracy of faecal calprotectin in a symptom-based algorithm for early diagnosis of inflammatory bowel disease adjusting for differential verification bias using a Bayesian approach

Background: Diagnostic delay in IBD is a major problem and diagnosis is frequently arrived when irreversible damage has already occurred. This study evaluated accuracy of faecal calprotectin (fCAL) integrated with diagnostic criteria for early diagnosis of IBD in a primary care setting.Methods: General practitioners (GPs) were trained to recognize alarm symptoms for IBD classified as major and minor criteria. Fulfilment of one major or at least two minor criteria was followed by free fCAL testing and a visit by an IBD specialist and follow-up over 12 months. All patients with positive fCAL testing, i.e., 6570 \u3bcg/g underwent colonoscopy. The diagnostic accuracy of fCAL was estimated after adjusting for differential-verification bias following a Bayesian approach.Results: Thirty-four GPs participated in the study and 133 patients were tested for fCAL between July 2016 and August 2017. Positivity of fCAL was seen in 45/133 patients (34%) and a final IBD diagnosis was made in 10/45 (22%). According to the threshold of 70 \u3bcg/g, fCAL achieved a sensitivity of 74.8% (95%CI: 39.10-96.01%), a specificity of 70.4% (95%CI: 61.76-78.16%) and an overall diagnostic accuracy of 70.6% (95%CI: 61.04-78.37%). As for prognostic accuracy, despite positive predictive value being low, 21.9% (95%CI: 11.74-35.18%), the negative predictive value was definitely higher: 96.2% (95%CI: 84.96-99.51%).Conclusions: fCAL with a threshold set at 70 \u3bcg/g seems to represent a potentially reliable negative test to be used in primary care settings for patients with symptoms suggestive of IBD