There are a number of limitations to using conventional diagnostic markers for patients with clinical suspicion of infection. As a consequence, unnecessary and prolonged exposure to antimicrobial agents adversely affect patient outcomes, while inappropriate antibiotic therapy increases antibiotic resistance. A growing body of evidence supports the use of procalcitonin (PCT) to improve diagnosis of bacterial infections and to guide antibiotic therapy. For patients with upper and lower respiratory tract infection, post-operative infections and for severe sepsis patients in the intensive care unit, randomized-controlled trials have shown a benefit of using PCT algorithms to guide decisions about initiation and/or discontinuation of antibiotic therapy. For some other types of infections, observational studies have shown promising first results, but further intervention studies are needed before use of PCT in clinical routine can be recommended. The aim of this review is to summarize the current evidence for PCT in different infections and clinical settings, and discuss the reliability of this marker when used with validated diagnostic algorithms.

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<p class="abstract"><strong>Background:</strong> Malnutrition is highly prevalent and strongly associated with clincial outcomes of medical inpatients. Still, the benefit of nutritional treatment to prevent adverse outcomes in medical inpatients at risk for malnutrition remains unproven. We describe the trial methods of the largest yet nutritional trial in medical inpatients including the rationale for key design decisions regarding the nutritional strategy, eligibility criteria, choice of control arm, and endpoints.</p><p class="abstract"><strong>Methods:</strong> The Effect of early nutritional therapy on Frailty, Functional Outcomes and Recovery of malnourished medical inpatients Trial (EFFORT) is an investigator-initiated, non-commercial, open-label RCT to compare the effects of an intensified nutritional therapy (intervention group) with a control group on medical outcomes. We include adult medical inpatients at risk of malnutrition based on a Nutritional Risk Screening 2002 (NRS) score of ≥3 points with an expected length of stay of ≥5 days. An individualized systematic nutritional assessment by study dieticians is done to define nutritional targets and to establish an implementation plan. Patients in the intervention group receive individualized early nutritional therapy based on a previously published consensus algorithm, while control group patients receive standard hospital nutrition. The study is powered to compare clinical outcomes (composite adverse outcome and mortality) in the 2 study arms as well as to address several mechanistical questions.</p><p class="abstract"><strong>Conclusion:</strong> EFFORT aims to close important gaps in the literature regarding the controversy about benefit and possible harm of nutritional therapy in medical inpatients at risk for malnutrition.</p><p class="abstract"><strong>Trial Registration: </strong>ClinicalTrials.gov NCT02517476; registered July 30, 2015.</p>

BackgroundAcute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases.The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care.Methods/DesignThis is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial.Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation.The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation.DiscussionWe aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice.