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Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations.<br />We systematically searched MEDLINE, Embase, Emcare, and Web of Science for studies published in English from January 2000 to October 2019 (PROSPERO registration CRD42020165005). Reference lists of included studies were assessed. Studies had to report on second measures of diagnostic performance (beyond discovery phase) for biomarkers (single or in panels) used to detect pancreatic, oesophageal, gastric, and biliary tract cancers. We included all designs and excluded studies with less than 50 cases/controls. Data were extracted onoption into clinical practice can be recommended.<br />Most novel biomarkers for the early detection of upper GI cancers are still at an early stage of matureness. Further evidence is needed on biomarker performance in low-prevalence populations, in addition to implementation and health economic studies, before extensive adoption into clinical practice can be recommended.One of the most debilitating symptoms of chronic obstructive pulmonary disease (COPD) is breathlessness, which leads to avoidance of physical activities in daily living and hastens clinical deterioration. Treatment of patients with COPD with inhaled long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combination therapy improves airflow limitation, reduces breathlessness compared with LAMA or LABA monotherapies, and improves health status and quality of life. A large clinical trial programme focusing on the effects of tiotropium/olodaterol combination therapy demonstrated that this LAMA/LABA combination improves lung function and reduces hyperinflation (assessed by serial inspiratory capacity measurements) compared with either tiotropium alone or placebo in patients with COPD. Tiotropium/olodaterol also increases exercise endurance capacity and improves patient perception of the intensity of breathlessness compared with placebo. [https://www.selleckchem.com/products/CAL-101.html CAL-101] In this narrative review, we focus on the relationship between improving symptoms during activity, the ability to remain active in daily life and how this may impact quality of life. We consider the benefits of therapy optimisation by means of dual bronchodilation with tiotropium/olodaterol, and present new data from meta-analyses/pooled analyses showing that tiotropium/olodaterol improves inspiratory capacity compared with placebo and tiotropium and improves exercise endurance time compared with placebo after 6 weeks of treatment. We also discuss the importance of taking a holistic approach to improving physical activity, including pulmonary rehabilitation and exercise programmes in parallel with bronchodilator therapy and psychological programmes to support behaviour change.<br />The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatraemia in hospital inpatients. We present data on treatment setting, patient characteristics, and outcomes for patients treated with tolvaptan for SIADH across a range of real-world settings in Germany and Spain.<br />This was a non-interventional, observational, retrospective chart review study. Management was at the discretion of the treating physician, with tolvaptan prescribed according to local clinical practice. Hospital notes and/or medical charts were reviewed from treatment initiation for 6weeks. Follow-up data were collected when patients were discharged early. Patients were eligible for inclusion if they were ≥ 18years of age and had been treated with ≥ 2 doses of tolvaptan for one episode of hyponatraemia secondary to SIADH in 2014.<br />The Full Analysis Set comprised 100 patients from 8 centres. The mean age of patients was 73.9years. The primary endpoint of the mean increase in serum sodium level from baseline to hospital discharge, or to final available measurement, was 10.3mmol/L (SD 6.4; 95% CI 9.0, 11.6), from 123.0mmol/L (SD 6.0) to 133.3mmol/L (SD 4.9). Seventy-seven patients (77.0%) achieved sodium normalisation within 6weeks of tolvaptan initiation. Mean daily dose of tolvaptan was 12.7mg (SD 9.2), and mean treatment duration 28.0days (SD 16.5). Tolvaptan at off-label doses (&lt; 15mg/day) was prescribed to 72 patients at some point. A favourable safety and tolerability profile was reported.<br />Tolvaptan was well tolerated and effectively corrected sodium levels in hospitalised adults with hyponatraemia secondary to SIADH in real-world settings. CLINICALTRIALS.<br />NCT02545101.<br />NCT02545101.<br />Regions within England, Scotland and Wales show variation in rate of adoption of biosimilar infliximab and etanercept.<br />This study aims to examine how local decisions and practices in regions within England, Scotland and Wales might explain initial variation in market dynamics of biosimilar and originator infliximab and etanercept.<br />Market data provided by the National Health Service (NHS) on biosimilar and originator infliximab and etanercept uptake were analysed for the 10 historical regions of England, 14 health boards in Scotland and 7 health boards in Wales (2015-2018). Findings were discussed in ten semi-structured interviews on a national level with an industry representative (1), on a regional level with NHS employees in England (6), Scotland (1) and Wales (1), and on a local level with a representative of a clinical commissioning group in England (1).<br />Tenders for infliximab and etanercept in England, Scotland and Wales have consistently resulted in a biosimilar as the best value biological. Early and late biosimilar adopters are seen, with overall convergence towards high biosimilar market shares over time. Qualitative results suggest that biosimilar adoption was positively influenced by (a) a price difference between biosimilar and originator product making it worthwhile to switch patients; (b) a good relationship between commissioner and provider in England resulting in gain share agreements; (c) leadership on biosimilars in regional NHS offices in England or Scottish and Welsh health boards; (d) key opinion leaders or leading hospitals that start using biosimilars early and gain experience.<br />This study has shown that the savings potential drives biosimilar use. Regions with a proactive attitude, good stakeholder relationships, and clinician engagement were identified as early adopters.<br />This study has shown that the savings potential drives biosimilar use. Regions with a proactive attitude, good stakeholder relationships, and clinician engagement were identified as early adopters.