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Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial: The EFFORT I and II Projects

Research Project | 1 Project Members

Effect of early nutritional therapy on Frailty, Functional Outcomes and Recovery of malnourished medical inpatients Trial (EFFORT) is the largest yet nutritional randomized trial proved that individualized nutritional therapy is a cost-effective strategy to prevent complications and to improve survival in patients at nutritional risk. This project was supported by the Swiss National Science Foundation (SNSF) over a time period of 6 years with a clinical professorship and a total of > 2.5 Million of funding was raised for the project (http://p3.snf.ch/project-150531 and *http://p3.snf.ch/project-150531). In 2019 the trial was published in the LANCET and in 2023, Prof. Schuetz received the Theodor-Näggeli Price for this project (100`000 CHF).***
Within EFFORT, we first performed an aggregate data meta-analysis on efficacy and safety of different nutritional therapy strategies in medical inpatients in collaboration with COCHRANE (JAMA Intern Med. 2016 Jan 1;176(1):43-53). Through a consensus conference, we then developed a “state-of-the-art” nutritional strategy for individualized management of medical inpatients. This algorithm was also published as an international guideline for the nutritional workup and treatment of malnourished medical inpatients (ESPEN guideline, Clin Nutr. 2018 Feb;37(1):336-353.). To ultimately proof that nutritional support improves clinical outcomes and reduces malnutrition-associated risks beyond weight gain, we then conducted a trial in 8 Swiss hospitals and 2028 patients comparing nutritional therapy based on an up-to-date nutritional strategy (intervention group) with a control group (“EFFORT trial”, https://clinicaltrials.gov/ct2/show/NCT02517476). The trial showed significant improvements in different clinical outcomes including risk for adverse outcome, mortality, quality of life and functionality and was published in the Lancet including an editorial comment (The Lancet. 2019 Jun 8;393(10188):2312-2321). The large sample of patients with an existing biobank also allowed us to study the physio-pathological mechanisms underlying the effects of nutritional therapy in specific patient populations and resulted in multiple secondary publications with focus on effect of inflammation on nutritional support, cost-effectiveness of nutritional support, risks of refeeding, long term prognostic effect of nutritional risk screening tools among others. In collaboration with researchers from the functional genomic center at the ETH Zürich, we also looked at new metabolomic markers that may severe as malnutrition markers in the future. Several research cooperations and analyses are currently still ongoing.
Importantly, based on the promising results, we currently conduct the multicenter EFFORT II randomized trial in 10 Swiss hospitals looking at the effect of nutritional support on mortality and other outcomes in the post-discharge outpatient setting. This trial is again funded by the Swiss National Science Foundation (SNSF) (https://data.snf.ch/grants/grant/207474).

Biomarker research regarding antibiotic stewardship

Research Project | 1 Project Members

Main investigator of a large antibiotic stewardship trial using the biomarker procalcitonin (PCT) and several subsequent individual patient data meta-analyses to understand safety of early stopping antibiotics based on biomarker kinetics. This research on antibiotic stewardship has led to several high impact publications and inclusion of recommendations in different international guidelines.
For the last 10 years we conducted research to better understand the clinical value of biomarkers for the purpose of antibiotic stewardship starting with several trials done in Switzerland lead by our group (i.e., “ProHOSP trial”, JAMA, 2009, Sep 9;302(10):1059-66) and “PARTI trial” Arch Intern Med. 2008 Oct 13;168(18):2000-7). These trials found strong reductions in antibiotic use particularly for patients with respiratory infections including pneumonia, COPD exacerbation and bronchitis. We also looked at other types of infection such as Legionella, heart failure with superinfection, patients with post-operative fever, patient with positive cultures for coagulase-negative staphylococci among others. To better understand safety of using PCT for antibiotic stewardship, it is important to study large numbers of patients. We thus pooled available trial data in ineividual patient data meta-analysis in collaboration with Cochrane and our international network of researchers participating in previous stewardship trials. In the most recent update published in 2018 (Lancet Infect Dis. 2018 Jan;18(1):95-107 and Cochrane Database Syst Rev. 2017 Oct 12;10(10):CD007498), our analysis included 6708 patients from 26 eligible trials in 12 countries showed a reduction in mortality when PCT was used for antibiotic stewardship efforts. These effects were paralleled with lower antibiotic consumptions and lower risk of antibiotic side effects. Based on this database, we have also published several studies focusing on best use of PCT in different patient populations including patients with positive blood cultures (Clin Infect Dis. 2019 Jul 18;69(3):388-396), ICU patients with sepsis (Crit Care. 2018 Aug 15;22(1):191.), outpatients (Ann Emerg Med. 2018 Aug;72(2):226-228) among others. Together with international expert we currently further advance the field of biomarker research in infectious disease also focusing on safe and efficient implementation of PCT in clinical routine.

Comprehensive Effectiveness Research („Versorgerforschung“)

Research Project | 1 Project Members

Principal investigator and Co-investigator of several studies with the aim to improve everyday patient care with the derivation and validation of evidence-based diagnostic and risk stratification tools („Triage“) for a more targeted use of resources. This project is supported by the Swiss National Science Foundation (SNF 74) and we received > 0.9 Million of funding for the project (http://p3.snf.ch/Project-167376).
In the TRIAGE project, we included over 7000 patients from different centers and countries (US, France, Switzerland) to study the importance of initial triage based on clinical parameters, nursing scales, blood biomarkers and TRIAGE scores for site of care decisions and reduction of time to effective treatment. In collaboration with nursing staff, we are investigating how the PACD discharge score can be used for better planning of patient discharge (OPTIMA-PACD). Funded bei the SNSF, we currently conduct the InHospiTOOL study to understand the effect of the use of an interdisciplinary electronic medical chart to better manage patients in regard to care transition. We aim to include >45`000 data of patients in 5 Swiss hospitals.

Endocrine and diabetes research

Research Project | 1 Project Members

Lead author for several observational research projects investigating whether endocrine dysfunction and impairments in glucose metabolism interact with the recovery of medical inpatients, and whether or not such dysfunction and impairments can be prevented.
Using our large clinical databases, we studied the effects of novel insulin treatment algorithms on glucose control and outcomes of medical inpatients. We also studied the association of hormonal disturbances (thyroid hormones, IGF1 and growth hormone, sex hormones) and patient outcomes and found different hormones to be associated with adverse clinical outcome. We then asked the question whether hormone levels can provide prognostic and/or diagnostic information to better understand the course of medical disease. Further, we ask the question whether hormonal treatment may improve outcomes, which has been found for some but not all hormones. In collaboration with physicians from neurosurgery, we studied the diagnostic value of pro-vasopressin (copeptin, the stable peptide of the vasopressin precursor) for early diagnosis of diabetes insipidus.