Prognostic implications of the arginine metabolism in patients at nutritional risk: A secondary analysis of the randomized EFFORT trial.

BACKGROUND: Arginine, a conditionally essential amino acid, is key component in metabolic pathways including immune regulation and protein synthesis. Depletion of arginine contributes to worse outcomes in severely ill and surgical patient populations. We assessed prognostic implications of arginine levels and its metabolites and ratios in polymorbid medical inpatients at nutritional risk regarding clinical outcomes and treatment response. METHODS: Within this secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT), we investigated the association of arginine, its metabolites and ratios (i.e., ADMA and SDMA, ratios of arginine/ADMA, arginine/ornithine, and global arginine bioavailability ratio) measured on hospital admission with short-term and long-term mortality by means of regression analysis. RESULTS: Among the 231 patients with available measurements, low arginine levels ≤90.05 µmol/l (n = 86; 37 %) were associated with higher all-cause mortality at 30 days (primary endpoint, adjusted HR 3.27, 95 % CI 1.86 to 5.75, p < 0.001) and at 5 years (adjusted HR 1.50, 95 % CI 1.07 to 2.12, p = 0.020). Arginine metabolites and ratios were also associated with adverse outcome, but had lower prognostic value. There was, however, no evidence that treatment response was influenced by admission arginine levels. CONCLUSION: This secondary analysis focusing on medical inpatients at nutritional risk confirms a strong association of low plasma arginine levels and worse clinical courses. The potential effects of arginine-enriched nutritional supplements should be investigated in this population of patients. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov as NCT02517476 (registered 7 August 2015).

Red blood cell distribution width (RDW) - A new nutritional biomarker to assess nutritional risk and response to nutritional therapy?

BACKGROUND & AIMS: Red cell distribution width (RDW) has been proposed as a surrogate marker for acute and chronic diseases and may be influenced by nutritional deficits. We assessed the prognostic value of RDW regarding clinical outcomes and nutritional treatment response among medical inpatients at nutritional risk. METHODS: This is a secondary analysis of EFFORT, a randomized, controlled, prospective, multicenter trial investigating the effects of nutritional support in patients at nutritional risk in eight Swiss hospitals. We examined the association between RDW and mortality in regression analysis. RESULTS: Among 1,244 included patients (median age 75 years, 46.6 % female), high RDW (≥15 %) levels were found in 38 % of patients (n = 473) with a significant association of higher malnutrition risk [OR 1.48 (95%CI 1.1 to 1.98); p = 0.009]. Patients with high RDW had a more than doubling in short-term (30 days) mortality risk [adjusted HR 2.12 (95%CI 1.44 to 3.12); p < 0.001] and a signficant increase in long-term (5 years) mortality risk [adjusted HR 1.73 (95%CI 1.49 to 2.01); p < 0.001]. Among patients with high RDW, nutritional support reduced morality within 30 days [adjusted OR 0.56 (95%CI 0.33 to 0.96); p = 0.035], while the effect of the nutritional intervention in patients with low RDW was markedly smaller. CONCLUSIONS: Among medical patients at nutritional risk, RDW correlated with several nutritional parameters and was a strong prognostic marker for adverse clinical outcomes at short- and long-term, respectively. Patients with high baseline RDW levels also showed a strong benefit from the nutritional intervention. Further research is needed to understand whether monitoring of RDW over time severs as a nutritional biomarker to assess effectiveness of nutritional treatment in the long run. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Adaptation of nutritional risk screening tools may better predict response to nutritional treatment: a secondary analysis of the randomized controlled trial Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT).

BACKGROUND: Nutritional screening tools have proven valuable for predicting clinical outcomes but have failed to determine which patients would be most likely to benefit from nourishment interventions. The Nutritional Risk Screening 2002 (NRS) and the Mini Nutritional Assessment (MNA) are 2 of these tools, which are based on both nutritional parameters and parameters reflecting disease severity. OBJECTIVES: We hypothesized that the adaptation of nutritional risk scores, by removing parameters reflecting disease severity, would improve their predictive value regarding response to a nutritional intervention while providing similar prognostic information regarding mortality at short and long terms. METHODS: We reanalyzed data of 2028 patients included in the Swiss-wide multicenter, randomized controlled trial EFFORT (Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial) comparing individualized nutritional support with usual care nutrition in medical inpatients. The primary endpoint was 30-d all-cause mortality. RESULTS: Although stratifying patients by high compared with low NRS score showed no difference in response to nutritional support, patients with high adapted NRS showed substantial benefit, whereas patients with low adapted NRS showed no survival benefit [adjusted hazard ratio: 0.55 [95% confidence interval (CI): 0.37, 0.80]] compared with 1.17 (95% CI: 0.70, 1.93), a finding that was significant in an interaction analysis [coefficient: 0.48 (95% CI: 0.25, 0.94), P = 0.031]. A similar effect regarding treatment response was found when stratifying patients on the basis of MNA compared with the adapted MNA. Regarding the prognostic performance, both original scores were slightly superior in predicting mortality than the adapted scores. CONCLUSIONS: Adapting the NRS and MNA by including nutritional parameters only improves their ability to predict response to a nutrition intervention, but slightly reduces their overall prognostic performance. Scores dependent on disease severity may best be considered prognostic scores, whereas nutritional risk scores not including parameters reflecting disease severity may indeed improve a more personalized treatment approach for nourishment interventions. The trial was registered at clinicaltrials.gov as NCT02517476.

Association of Glutamine and Glutamate Metabolism with Mortality among Patients at Nutritional Risk-A Secondary Analysis of the Randomized Clinical Trial EFFORT.

Glutamine and its metabolite glutamate serve as the main energy substrates for immune cells, and their plasma levels drop during severe illness. Therefore, glutamine supplementation in the critical care setting has been advocated. However, little is known about glutamine metabolism in severely but not critically ill medical patients. We investigated the prognostic impact of glutamine metabolism in a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled trial comparing individualized nutritional support to usual care in patients at nutritional risk. Among 234 patients with available measurements, low plasma levels of glutamate were independently associated with 30-day mortality (adjusted HR 2.35 [95% CI 1.18-4.67, p = 0.015]). The impact on mortality remained consistent long-term for up to 5 years. No significant association was found for circulating glutamine levels and short- or long-term mortality. There was no association of glutamate nor glutamine with malnutrition parameters or with the effectiveness of nutritional support. This secondary analysis found glutamate to be independently prognostic among medical inpatients at nutritional risk but poorly associated with the effectiveness of nutritional support. In contrast to ICU studies, we found no association between glutamine and clinical outcome.

Association of admission cortisol levels with outcomes and treatment response in patients at nutritional risk : A secondary analysis of a randomized clinical trial.

INTRODUCTION: Cortisol is a metabolically active stress hormone that may play a role in the pathogenesis of malnutrition. We studied the association between admission cortisol levels and nutritional parameters, disease severity, and response to nutritional support among medical inpatients at nutritional risk. METHODS: Admission cortisol was measured in a subset of 764 patients participating in the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a multicentre, randomized-controlled trial that compared individualized nutritional support with usual nutritional care. RESULTS: Overall, mean cortisol levels were 570 (± 293) nmol/L and significantly higher in patients with high nutritional risk (NRS ≥ 5) and in patients reporting loss of appetite. Cortisol levels in the highest quartile (> 723 nmol/l) were associated with adverse outcomes including mortality at 30 days and 5 years (adjusted HR 2.31, [95%CI 1.47 to 3.62], p = 0.001 and 1.51, [95%CI 1.23 to 1.87], p < 0.001). Nutritional treatment tended to be more effective regarding mortality reduction in patients with high vs. low cortisol levels (adjusted OR of nutritional support 0.54, [95%CI 0.24 to 1.24] vs. OR 1.11, [95%CI 0.6 to 2.04], p for interaction = 0.134). This effect was most pronounced in the subgroup of patients with severe malnutrition (NRS 2002 ≥ 5, p for interaction = 0.047). CONCLUSION: This secondary analysis of a randomized nutritional trial suggests that cortisol levels are linked to nutritional and clinical outcome among multimorbid medical patients at nutritional risk and may help to improve risk assessment, as well as response to nutritional treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Changes in serum albumin concentrations over 7 days in medical inpatients with and without nutritional support. A secondary post-hoc analysis of a randomized clinical trial.

BACKGROUND: Serum albumin concentrations are frequently used to monitor nutritional therapy in the hospital setting but supporting studies are largely lacking. Within this secondary analysis of a randomized nutritional trial (EFFORT), we assessed whether nutritional support affects short-term changes in serum albumin concentrations and whether an increase in albumin concentration has prognostic implications regarding clinical outcome and response to treatment. METHODS: We analyzed patients with available serum albumin concentrations at baseline and day 7 included in EFFORT, a Swiss-wide multicenter randomized clinical trial that compared individualized nutritional therapy with usual hospital food (control group). RESULTS: Albumin concentrations increased in 320 of 763 (41.9%) included patients (mean age 73.3 years (SD ± 12.9), 53.6% males) with no difference between patients receiving nutritional support and controls. Compared with patients that showed a decrease in albumin concentrations over 7 days, those with an increase had a lower 180-day mortality [74/320 (23.1%) vs. 158/443 (35.7%); adjusted odds ratio 0.63, 95% CI 0.44 to 0.90; p = 0.012] and a shorter length of hospital stay [11.2 ± 7.3 vs. 8.8 ± 5.6 days, adjusted difference -2.2 days (95%CI -3.1 to -1.2)]. Patients with and without a decrease over 7 days had a similar response to nutritional support. CONCLUSION: Results from this secondary analysis indicate that nutritional support did not increase short-term concentrations of albumin over 7 days, and changes in albumin did not correlate with response to nutritional interventions. However, an increase in albumin concentrations possibly mirroring resolution of inflammation was associated with better clinical outcomes. Repeated in-hospital albumin measurements in the short-term is, thus, not indicated for monitoring of patients receiving nutritional support but provides prognostic information. TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Association between prealbumin, all-cause mortality, and response to nutrition treatment in patients at nutrition risk: Secondary analysis of a randomized controlled trial.

BACKGROUND: Because of the shorter half-life as compared with albumin, serum prealbumin concentrations have been proposed to be useful nutrition biomarkers for the assessment of patients at nutrition risk. In a post hoc analysis of patients at nutrition risk from a randomized controlled nutrition trial, we tested the hypothesis that (1) prealbumin is associated with higher all-cause 180-day mortality rates and that (2) individualized nutrition support compared with usual-care nutrition more effectively improves survival at 30 days in patients with low prealbumin levels compared with patients with normal prealbumin levels. METHODS: We performed a prespecified cohort study in patients included in the pragmatic, Swiss, multicenter randomized controlled EFFORT trial comparing the effects of individualized nutrition support with usual care. We studied low prealbumin concentrations (<0.17 g/L) in a subgroup of 517 patients from one participating center. RESULTS: A total of 306 (59.2%) patients (mean age 71.9 years, 53.6% men) had low admission prealbumin levels (<0.17 g/L). There was a significant association between low prealbumin levels and mortality at 180 days (115/306 [37.6%] vs 47/211 [22.3%], fully adjusted hazard ratio [HR]=1.59, 95% CI 1.11-2.28; P = 0.011). Prealbumin levels significantly improved the prognostic value of the Nutritional Risk Screening total score regarding mortality prediction at short- and long-term. The difference in mortality between patients receiving individualized nutrition support and usual-care nutrition was similar for patients with low prealbumin levels compared with patients with normal prealbumin levels (HR=0.90 [95% CI=0.51-1.59] vs HR=0.88 [95% CI=0.35-2.23]) with no evidence for interaction (P = 0.823). CONCLUSION: Among medical inpatients at nutrition risk, low admission prealbumin levels correlated with different nutrition markers and higher mortality risk, but patients with low or high prealbumin levels had a similar benefit from nutrition support. Further studies should identify nutrition markers that help further personalize nutrition interventions.

Association of CT-based diagnosis of sarcopenia with prognosis and treatment response in patients at risk of malnutrition - A secondary analysis of the Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) trial.

BACKGROUND & AIM: CT-derived measures of muscle mass may help to identify patients with sarcopenia. We investigated the prognostic significance of CT-derived sarcopenia and muscle attenuation with nutritional markers, clinical outcomes and response to nutritional support in medical in-patients at nutritional risk. METHOD: Within this secondary analysis of the randomized-controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) comparing individualized nutritional support with usual care nutrition in medical inpatients, we investigated associations of CT-based sarcopenia and muscle attenuation at the level L3 with different nutritional and clinical outcomes, and the response to the nutritional intervention. The primary composite endpoint was adverse clinical outcome within 30 days of hospital admission. RESULTS: We included 573 of 2028 EFFORT patients with available CT scans, of which 68.4% met the CT-based definition of sarcopenia and 72.9% had low muscle attenuation. In multivariate analysis, low skeletal muscle index was associated with higher nutritional risk (coefficient per NRS class -0.94 (95%CI -1.87 to -0.01) p = 0.049) and higher risk for adverse clinical outcomes (adjusted odds ratio 1.59 (95% CI 1.06 to 2.38), p = 0.024). Low muscle attenuation was also associated with adverse clinical outcome (adjusted odds ratio 1.67 (95%CI 1.08 to 2.58), p = 0.02). Nutritional support tended to be more effective in reducing mortality in non-sarcopenic patients compared to patients with CT-based sarcopenia (p for interaction 0.058). CONCLUSIONS: Within a population of medical patients at nutritional risk, CT-based sarcopenia and muscle attenuation were associated with several nutritional parameters and predicted adverse clinical outcomes. Information from CT scans, thus may help to better characterize these patients, and may be helpful in guiding therapeutic interventions.

Prevalence of Micronutrient Deficiencies in Patients Hospitalized with COVID-19: An Observational Cohort Study.

BACKGROUND: A higher risk for severe clinical courses of coronavirus disease 2019 (COVID-19) has been linked to deficiencies of several micronutrients. We therefore studied the prevalence of deficiencies of eight different micronutrients in a cohort of hospitalized COVID-19-patients. METHODS: We measured admission serum/plasma levels of vitamins A, B12, D, and E, as well as folic acid, zinc, selenium, and copper in 57 consecutively admitted adult patients with confirmed COVID-19 and analyzed prevalence of micronutrient deficiencies and correlations among micronutrient levels. Further, we studied associations of micronutrient levels with severe disease progression, a composite endpoint consisting of in-hospital mortality and/or need for intensive care unit (ICU) treatment with logistic regression. RESULTS: Median age was 67.0 years (IQR 60.0, 74.2) and 60% (n = 34) were male. Overall, 79% (n = 45) of patients had at least one deficient micronutrient level and 33% (n = 19) had ≥3 deficiencies. Most prevalent deficiencies were found for selenium, vitamin D, vitamin A, and zinc (51%, 40%, 39%, and 39%, respectively). We found several correlations among micronutrients with correlation coefficients ranging from r = 0.27 to r = 0.42. The strongest associations with lower risk for severe COVID-19 disease progression (adjusted odds ratios) were found for higher levels of vitamin A (0.18, 95% CI 0.05-0.69, p = 0.01), zinc (0.73, 95% CI 0.55-0.98, p = 0.03), and folic acid (0.88, 95% CI 0.78-0.98, p = 0.02). CONCLUSIONS: We found a high prevalence of micronutrient deficiencies in mostly older patients hospitalized for COVID-19, particularly regarding selenium, vitamin D, vitamin A, and zinc. Several deficiencies were associated with a higher risk for more severe COVID-19 courses. Whether supplementation of micronutrients is useful for prevention of severe clinical courses or treatment of COVID-19 warrants further research.

Validation of modified GLIM criteria to predict adverse clinical outcome and response to nutritional treatment: A secondary analysis of a randomized clinical trial.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) recently suggested specific criteria to standardize the diagnosis of malnutrition. There is need for validation of these criteria regarding response to nutrition treatment. Our aim was to validate modified GLIM (mGLIM) criteria among medical inpatients at risk of disease related malnutrition for prediction of outcome and response to nutritional therapy. METHODS: This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a multicenter randomized controlled trial conducted between April 2014 and February 2018. Adult medical inpatients at nutritional risk (Nutrition Risk Score 2002 ≥ 3 points) were randomly assigned to receive nutritional therapy according to an algorithm based on individualized nutritional requirements (intervention group) or standard hospital food (control group). We included all participants with available information regarding mGLIM criteria. The primary outcome was adverse clinical outcome, which was a composite of 30-day all-cause mortality, ICU-admission, rehospitalization rate, major complications and decline in functional status. RESULTS: Of 1917 eligible participants at nutritional risk, 1181 (61.6%) met the diagnosis of malnutrition based on mGLIM criteria. The incidence of adverse clinical outcome was significantly higher in mGLIM-positive participants compared with mGLIM-negative participants [330/1181 (27.9%) versus 140/736 (19.0%); multivariable adjusted odds ratio [OR] 1.53; 95% CI 1.22-1.93; p < 0.001]. Regarding the effect of nutritional therapy, the reduction in adverse clinical outcomes was higher in mGLIM-positive participants [180/581 (31.0%) vs. 150/600 (25.0%), OR 0.69; 95% CI 0.53-0.9, p = 0.007], compared with mGLIM-negative participants [75/379 (19.8%) versus 65/357 (18.2%), OR 0.95; 95% CI 0.65-1.40, p = 0.797], a finding that was, however, not significant in interaction analysis (p for interaction = 0.217). CONCLUSION: Data from this secondary analysis of a multicenter randomized trial involving medical inpatients at nutritional risk validate the strong prognostic value of mGLIM criteria regarding adverse clinical outcomes and other long-term outcomes. However, further research is needed to improve the ability of GLIM criteria to predict therapeutic response to nutritional interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Admission serum albumin concentrations and response to nutritional therapy in hospitalised patients at malnutrition risk: Secondary analysis of a randomised clinical trial.

BACKGROUND: Historically, admission serum albumin concentrations have been considered useful biochemical markers for nutrition assessment. However, there is a lack of randomised trial data investigating whether low albumin concentrations are helpful for identifying patients benefitting from nutritional support. METHODS: This study was a secondary analysis of the EFFORT trial, a Swiss-wide multicentre, randomised controlled trial comparing individualised nutritional support with usual care nutrition in medical inpatients from April 1, 2014, to February 1, 2018. 1389 of 2028 patients at nutritional risk with available albumin concentrations on admission were included. The primary endpoint was all-cause mortality within 30 and 180 days. Patients were stratified into groups of low or normal albumin based on the albumin cut-off of 30 g/L. ClinicalTrials.gov number, NCT02517476. FINDINGS: 1389 patients (mean age, 73.1 (SD 3.5) years; 747 (53.8%) men) were included and 676 (48.7%) had low serum albumin concentrations at admission (<30 g/L). Mortality at 180 days was significantly increased in the low albumin group compared with patients with normal albumin concentrations (219/676 (32.4%) vs. 162/713 (22.7%), fully adjusted HR 1.4, 95%CI 1.11 to 1.77, p = 0.005]. Effects of nutritional support on 30-day mortality were similar for patients with low compared to patients with normal albumin concentrations (HR 0.68, 95%CI 0.44 to 1.05 vs. HR 0.70, 95%CI 0.41 to 1.20), with no evidence for a subgroup effect (p for interaction=0.97). INTERPRETATION: Based on this secondary analysis of a randomised trial, low admission serum albumin concentrations in hospitalised, non-critically ill, medical patients at nutritional risk had prognostic implications and indicated higher mortality risk but were not helpful in selecting patients for nutritional interventions. FUNDING: The Swiss National Science Foundation (SNSF) (PP00P3_150531) and the Research Council of the Kantonsspital Aarau (1410.000.058 and 1410.000.044) provided funding for the EFFORT trial.

Effect of micronutrient supplementation in addition to nutritional therapy on clinical outcomes of medical inpatients: results of an updated systematic review and meta-analysis.

BACKGROUND: There is increasing evidence from randomized controlled trials showing that different types of nutritional support interventions improve clinical outcomes in malnourished medical inpatients. Whether trials using micronutrient supplementation in addition to nutritional therapy are superior to trials without micronutrient supplementation remains unclear. METHODS: This is a secondary analysis of a systematic search and meta-analysis. We searched Cochrane Library, MEDLINE, and EMBASE electronic database from inception to December 15, 2020, for randomized controlled trials comparing the nutritional support interventions vs. usual care on all-cause mortality (primary endpoint) of medical inpatients with nutritional risk. We stratified trials based on whether or not micronutrient supplementation was used as part of the nutritional strategy. RESULTS: We included 23 randomized controlled trials (5 trials with and 18 trials without micronutrient supplementation) with a total of 6745 patients. Overall, mortality was significantly lower in patients receiving nutritional support compared to control group patients with an odds ratio of 0.74 (95% CI 0.59-0.94, p = 0.01). There was no difference between trials with and without micronutrient supplementation on mortality (odds ratio 0.70 (95% CI 0.46-1.08) vs. 0.77 (95% CI 0.57-1.04), I2 = 0%, p for subgroup difference = 0.73). Similarly, no differences in effect were found regarding non-elective readmissions and length of hospital stay. CONCLUSIONS: While nutritional support reduces mortality and improves other clinical outcomes, we did not find evidence that trials using micronutrient supplementation in addition to nutritional therapy were superior to trials with no supplementation. The role of micronutrient supplementation in addition to nutritional support needs further research.

Value of handgrip strength to predict clinical outcomes and therapeutic response in malnourished medical inpatients: Secondary analysis of a randomized controlled trial.

BACKGROUND: Disease-related malnutrition is associated with loss of muscle mass and impaired functional status. Handgrip strength (HGS) has been proposed as an easy-to-use tool to assess muscle strength in clinical practice. OBJECTIVES: We investigated the prognostic implications of HGS in patients at nutritional risk with regard to clinical outcomes and response to nutritional support. METHODS: This was a secondary analysis of the randomized controlled, multicenter, Effect of Early Nutritional Support on Frailty, Functional Outcome, and Recovery of Malnourished Medical Inpatients Trial, which compared the effects of individualized nutritional support with usual hospital food in medical inpatients at nutritional risk. Our primary endpoint was 30-d all-cause mortality. The association between sex-specific HGS and clinical outcomes was investigated using multivariable regression analyses, adjusted for randomization, age, weight, height, nutritional risk, admission diagnosis, comorbidities, interaction terms, and study center. We used interaction terms to investigate possible effect modification regarding the nutritional support intervention. RESULTS: Mean ± SD HGS in the 1809 patients with available handgrip measurement was 17.0 ± 7.1 kg for females and 28.9 ± 11.3 kg for males. Each decrease of 10 kg in HGS was associated with increased risk of 30-d mortality (female: adjusted OR: 2.11; 95% CI: 1.23, 3.62, P = 0.007; male: adjusted OR: 1.44; 95% CI: 1.07, 1.93, P = 0.015) and 180-d mortality (female: adjusted OR: 1.45; 95% CI: 1.0, 2.10, P = 0.048; male: adjusted OR: 1.55; 95% CI: 1.28, 1.89, P < 0.001). Individualized nutritional support was most effective in reducing mortality in patients with low HGS (adjusted OR: 0.29; 95% CI: 0.10, 0.82 in patients in the ≤10th percentile compared with OR: 0.98; 95% CI: 0.66, 1.48 in patients in the >10th percentile; P for interaction = 0.026). CONCLUSIONS: In medical inpatients at nutritional risk, HGS provided significant prognostic information about expected mortality and complication risks and helps to identify which patients benefit most from nutritional support. HGS may thus improve individualization of nutritional therapy.This trial was registered at clinicaltrials.gov as NCT02517476.

Nutritional risk is a predictor for long-term mortality: 5-Year follow-up of the EFFORT trial.

BACKGROUND AND AIMS: The nutritional risk screening (NRS 2002) is a validated screening tool for malnutrition. This study aims to investigate the prognostic value of the NRS 2002 and its individual components regarding long-term mortality and adverse outcomes in a well-characterized cohort of medical inpatients. METHODS: We performed a 5-year follow-up investigation of patients included in the investigator-initiated, prospective, randomized controlled multicenter EFFORT trial that evaluated the effects of individualized nutritional intervention vs. standard hospital food. We used multivariable cox regression analyses adjusted for randomisation arm, study centre, comorbidities and main admission diagnosis to investigate associations between NRS 2002 total scores at time of hospital admission and several long-term outcomes. RESULTS: We had confirmed mortality data over the mean follow-up time of 3.2 years in 1874 from the initial cohort of 2028 EFFORT patients. Mortality showed a step-wise increase in patients with NRS 3 (289/565 [51.2%]) and NRS 4 (355/717 [49.6%]) to 59.5% (353/593) in patient with NRS≥5 corresponding to an adjusted Hazard Ratio (HR) of 1.28 (95%CI 1.15 to 1.42, p ≤ 0.001) for mortality after one year and 1.13 (95%CI 1.05 to 1.23, p = 0.002) for the overall time period. All individual components of NRS including disease severity, food intake, weight loss and BMI provided prognostic information regarding long-term mortality risk. CONCLUSION: Nutritional risk mirrored by a NRS 2002 total score is a strong and independent predictor of long-term mortality and morbidity in polymorbid medical inpatients particularly in patients with high nutritional risk with an NRS ≥5 points.

Vitamin D deficiency is highly prevalent in malnourished inpatients and associated with higher mortality: A prospective cohort study.

The impact of vitamin D deficiency on the recovery of patients with malnutrition remains undefined. Our aim was to study the prevalence of vitamin D deficiency in a well-characterized cohort of patients with malnutrition and its association with outcomes.Within this secondary analysis of a randomized controlled trial, we examined the association of vitamin D deficiency and adverse clinical outcomes over a follow-up of 180 days in hospitalized patients at risk for malnutrition. We measured 25-hydroxyvitamin D levels upon admission and defined Vitamin D deficiency when levels were <50nmol/l. The primary endpoint was 180-day mortality.The prevalence of vitamin D deficiency in our cohort of 828 patients was 58.2% (n = 482). Patients with vitamin D deficiency had increased 180-day mortality rates from 23.1% to 29.9% (odds ratio 1.42, 95% confidence interval [CI] 1.03-1.94, P = .03). When adjusting the analysis for demographics, comorbidities, and randomization, this association remained significant for the subgroup of patients not receiving vitamin D treatment (adjusted odds ratio 1.63, 95% CI 1.01-2.62, P = .04). There was no significantly lower risk for mortality in the subgroup of vitamin D deficient patients receiving vitamin D treatment compared to not receiving treatment (adjusted odds ratio 0.74, 95% CI 0.48-1.13, P = .15).Vitamin D deficiency is highly prevalent in the population of malnourished inpatients and is negatively associated with long-term mortality particularly when patients are not receiving vitamin D treatment. Our findings suggest that malnourished patients might benefit from vitamin D screening and treatment in case of deficiency.

Association of Nutritional Support With Clinical Outcomes Among Medical Inpatients Who Are Malnourished or at Nutritional Risk: An Updated Systematic Review and Meta-analysis.

Importance: Malnutrition affects a considerable proportion of the medical inpatient population. There is uncertainty regarding whether use of nutritional support during hospitalization in these patients positively alters their clinical outcomes. Objective: To assess the association of nutritional support with clinical outcomes in medical inpatients who are malnourished or at nutritional risk. Data Sources: For this updated systematic review and meta-analysis, a search of the Cochrane Library, MEDLINE, and Embase was conducted from January 1, 2015, to April 30, 2019; the included studies were published between 1982 and 2019. Study Selection: A prespecified Cochrane protocol was followed to identify trials comparing oral and enteral nutritional support interventions with usual care and the association of these treatments with clinical outcomes in non-critically ill medical inpatients who were malnourished. Data Extraction and Synthesis: Two reviewers independently extracted data and assessed risk of bias; data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was mortality. The secondary outcomes included nonelective hospital readmissions, length of hospital stay, infections, functional outcome, daily caloric and protein intake, and weight change. Results: A total of 27 trials (n = 6803 patients) were included, of which 5 (n = 3067 patients) were published between 2015 and 2019. Patients receiving nutritional support compared with patients in the control group had significantly lower rates of mortality (230 of 2758 [8.3%] vs 307 of 2787 [11.0%]; odds ratio [OR], 0.73; 95% CI, 0.56-0.97). A sensitivity analysis suggested a more pronounced reduction in the risk of mortality in recent trials (2015 or later) (OR, 0.47; 95% CI, 0.28-0.79) compared with that in older studies (OR, 0.94; 95% CI, 0.72-1.22), in patients with established malnutrition (OR, 0.52; 95% CI, 0.34-0.80) compared with that in patients at nutritional risk (OR, 0.85; 95% CI, 0.62-1.18), and in trials with high protocol adherence (OR, 0.67; 95% CI, 0.54-0.84) compared with that in trials with low protocol adherence (OR, 0.88; 95% CI, 0.44-1.76). Nutritional support was also associated with a reduction in nonelective hospital readmissions (14.7% vs 18.0%; risk ratio, 0.76; 95% CI, 0.60-0.96), higher energy intake (mean difference, 365 kcal; 95% CI, 272-458 kcal) and protein intake (mean difference, 17.7 g; 95% CI, 12.1-23.3 g), and weight increase (0.73 kg; 95% CI, 0.32-1.13 kg). No significant differences were observed in rates of infections (OR, 0.86; 95% CI, 0.64-1.16), functional outcome (mean difference, 0.32; 95% CI, -0.51 to 1.15), and length of hospital stay (mean difference, -0.24; 95% CI, -0.58 to 0.09). Conclusions and Relevance: This study's findings suggest that despite heterogeneity and varying methodological quality among trials, nutritional support was associated with improved survival and nonelective hospital readmission rates among medical inpatients who were malnourished and should therefore be considered when treating this population.

Integrative hospital treatment in older patients to benchmark and improve outcome and length of stay - the In-HospiTOOL study.

BACKGROUND: A comprehensive in-hospital patient management with reasonable and economic resource allocation is arguably the major challenge of health-care systems worldwide, especially in elderly, frail, and polymorbid patients. The need for patient management tools to improve the transition process and allocation of health care resources in routine clinical care particularly for the inpatient setting is obvious. To address these issues, a large prospective trial is warranted. METHODS: The "Integrative Hospital Treatment in Older patients to benchmark and improve Outcome and Length of stay" (In-HospiTOOL) study is an investigator-initiated, multicenter effectiveness trial to compare the effects of a novel in-hospital management tool on length of hospital stay, readmission rate, quality of care, and other clinical outcomes using a time-series model. The study aims to include approximately 35`000 polymorbid medical patients over an 18-month period, divided in an observation, implementation, and intervention phase. Detailed data on treatment and outcome of polymorbid medical patients during the in-hospital stay and after 30 days will be gathered to investigate differences in resource use, inter-professional collaborations and to establish representative benchmarking data to promote measurement and display of quality of care data across seven Swiss hospitals. The trial will inform whether the "In-HospiTOOL" optimizes inter-professional collaboration and thereby reduces length of hospital stay without harming subjective and objective patient-oriented outcome markers. DISCUSSION: Many of the current quality-mirroring tools do not reflect the real need and use of resources, especially in polymorbid and elderly patients. In addition, a validated tool for optimization of patient transition and discharge processes is still missing. The proposed multicenter effectiveness trial has potential to improve interprofessional collaboration and optimizes resource allocation from hospital admission to discharge. The results will enable inter-hospital comparison of transition processes and accomplish a benchmarking for inpatient care quality.

Management and prevention of refeeding syndrome in medical inpatients: An evidence-based and consensus-supported algorithm.

OBJECTIVES: Refeeding syndrome (RFS) can be a life-threatening metabolic condition after nutritional replenishment if not recognized early and treated adequately. There is a lack of evidence-based treatment and monitoring algorithm for daily clinical practice. The aim of the study was to propose an expert consensus guideline for RFS for the medical inpatient (not including anorexic patients) regarding risk factors, diagnostic criteria, and preventive and therapeutic measures based on a previous systematic literature search. METHODS: Based on a recent qualitative systematic review on the topic, we developed clinically relevant recommendations as well as a treatment and monitoring algorithm for the clinical management of inpatients regarding RFS. With international experts, these recommendations were discussed and agreement with the recommendation was rated. RESULTS: Upon hospital admission, we recommend the use of specific screening criteria (i.e., low body mass index, large unintentional weight loss, little or no nutritional intake, history of alcohol or drug abuse) for risk assessment regarding the occurrence of RFS. According to the patient's individual risk for RFS, a careful start of nutritional therapy with a stepwise increase in energy and fluids goals and supplementation of electrolyte and vitamins, as well as close clinical monitoring, is recommended. We also propose criteria for the diagnosis of imminent and manifest RFS with practical treatment recommendations with adoption of the nutritional therapy. CONCLUSION: Based on the available evidence, we developed a practical algorithm for risk assessment, treatment, and monitoring of RFS in medical inpatients. In daily routine clinical care, this may help to optimize and standardize the management of this vulnerable patient population. We encourage future quality studies to further refine these recommendations.

Vitamin D Deficiency Strongly Predicts Adverse Medical Outcome Across Different Medical Inpatient Populations: Results From a Prospective Study.

Vitamin D deficiency has been associated with several adverse outcomes mainly in the outpatient setting. The objective of this study was to examine the prevalence of vitamin D deficiency and its association with risk of adverse clinical outcomes in a large prospective cohort of medical inpatients.We collected clinical data and measured 25(OH)D levels in adult medical patients upon hospital admission and followed them for 30 days. Regression analyses adjusted for age, gender, comorbidities, and main medical diagnosis were performed to study the effect of vitamin D deficiency on several hospital outcomes.Of 4257 included patients, 1510 (35.47%) had 25(OH)D levels of 25 to 50 nmol/L (vitamin D insufficiency) and 797 (18.72%) had levels of <25nmol/L (severe deficiency). Vitamin D insufficiency and severe deficiency were associated (OR/HR, 95%CI) with an increased risk of 30-day mortality (OR 1.70, 1.22-2.36 and 2.70, 1.22-2.36) and increased length of stay (HR 0.88, 0.81-0.97 and 0.72, 0.65-0.81). Severe deficiency was associated with risk of falls (OR 1.77, 1.18-2.63), impaired Barthel index (OR 1.80, 1.42-2.28), and impairment in quality of life. Most associations remained robust after multivariate adjustment and in subgroups stratified by gender, age, comorbidities, and main diagnoses (P for interaction >0.05).In this comprehensive and large medical inpatient cohort, vitamin D deficiency was highly prevalent and strongly associated with adverse clinical outcome. Interventional research is urgently needed to prove the effect of vitamin D supplementation on these outcomes.