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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.
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Fragilidad , Desnutrición , Sarcopenia , Humanos , Sarcopenia/diagnóstico por imagen , Sarcopenia/terapia , Sarcopenia/complicaciones , Fragilidad/complicaciones , Pacientes Internos , Desnutrición/diagnóstico , Desnutrición/terapia , Desnutrición/complicaciones , Apoyo Nutricional , Pronóstico , Tomografía Computarizada por Rayos XRESUMEN
Importance: Whether interprofessional collaboration is effective and safe in decreasing hospital length of stay remains controversial. Objective: To evaluate the outcomes and safety associated with an electronic interprofessional-led discharge planning tool vs standard discharge planning to safely reduce length of stay among medical inpatients with multimorbidity. Design, Setting, and Participants: This multicenter prospective nonrandomized controlled trial used interrupted time series analysis to examine medical acute hospitalizations at 82 hospitals in Switzerland. It was conducted from February 2017 through January 2019. Data analysis was conducted from March 2021 to July 2022. Intervention: After a 12-month preintervention phase (February 2017 through January 2018), an electronic interprofessional-led discharge planning tool was implemented in February 2018 in 7 intervention hospitals in addition to standard discharge planning. Main Outcomes and Measures: Mixed-effects segmented regression analyses were used to compare monthly changes in trends of length of stay, hospital readmission, in-hospital mortality, and facility discharge after the implementation of the tool with changes in trends among control hospitals. Results: There were 54â¯695 hospitalizations at intervention hospitals, with 27â¯219 in the preintervention period (median [IQR] age, 72 [59-82] years; 14â¯400 [52.9%] men) and 27â¯476 in the intervention phase (median [IQR] age, 72 [59-82] years; 14â¯448 [52.6%] men) and 438â¯791 at control hospitals, with 216â¯261 in the preintervention period (median [IQR] age, 74 [60-83] years; 109â¯770 [50.8%] men) and 222â¯530 in the intervention phase (median [IQR] age, 74 [60-83] years; 113â¯053 [50.8%] men). The mean (SD) length of stay in the preintervention phase was 7.6 (7.1) days for intervention hospitals and 7.5 (7.4) days for control hospitals. During the preintervention phase, population-averaged length of stay decreased by -0.344 hr/mo (95% CI, -0.599 to -0.090 hr/mo) in control hospitals; however, no change in trend was observed among intervention hospitals (-0.034 hr/mo; 95% CI, -0.646 to 0.714 hr/mo; difference in slopes, P = .09). Over the intervention phase (February 2018 through January 2019), length of stay remained unchanged in control hospitals (slope, -0.011 hr/mo; 95% CI, -0.281 to 0.260 hr/mo; change in slope, P = .03), but decreased steadily among intervention hospitals by -0.879 hr/mo (95% CI, -1.607 to -0.150 hr/mo; change in slope, P = .04, difference in slopes, P = .03). Safety analyses showed no change in trends of hospital readmission, in-hospital mortality, or facility discharge over the whole study time. Conclusions and Relevance: In this nonrandomized controlled trial, the implementation of an electronic interprofessional-led discharge planning tool was associated with a decline in length of stay without an increase in hospital readmission, in-hospital mortality, or facility discharge. Trial Registration: isrctn.org Identifier: ISRCTN83274049.
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Registros Electrónicos de Salud , Alta del Paciente , Anciano , Femenino , Hospitales , Humanos , Tiempo de Internación , Masculino , Multimorbilidad , Estudios ProspectivosRESUMEN
BACKGROUND & AIMS: Screening for malnutrition upon hospital admission is the first crucial step for proper nutritional assessment and treatment. While several nutritional screening and assessment instruments exist, there is a lack of head-to-head validation of these instruments. We studied the ability of five different nutrition screening and assessment instruments to predict 1-year mortality and response to nutritional treatment in participants of the EFFORT randomized trial. METHODS: In this secondary analysis of a Swiss-wide multicenter, randomized clinical trial comparing individualized nutritional support with usual care nutrition in medical inpatients, we prospectively classified patients as low, intermediate, and high nutritional risk based on five nutritional screening and assessment instruments (NRS 2002, SGA, SNAQ, MNA and MUST). RESULTS: Overall mortality at 1-year in the 1866 included patients was 30.4%. There were significant correlations and a significant concordance between all instruments with r-values ranging from 0.23 to 0.55 and kappa values ranging from 0.10 to 0.36. While high nutritional risk was associated with higher mortality in all instruments, SGA and MNA showed the strongest association with adjusted odds ratios of 3.17 (95%CI, 2.18 to 4.61, p < 0.001) and 3.45 (95%CI, 2.28 to 5.22, p < 0.001). When comparing mortality in intervention group patients to control group patients stratified by severity of malnutrition, there was overall no clear trend towards more benefit in patients with more severe malnutrition, with NRS 2002 and SGA showing the most pronounced relationship between the severity of malnutrition and reduction in mortality as a response to nutritional support. CONCLUSION: Among all five screening and assessment instruments, higher nutritional risk was associated with higher risk for mortality and adverse clinical outcome, but not with more or less treatment response from nutritional support with differences among scores. Adding more specific parameters to these instruments is important when using them to decide for or against nutritional support interventions in an individual patient. TRIAL REGISTRATION: ClinicalTrials.gov NCT02517476.
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Desnutrición , Evaluación Nutricional , Humanos , Pacientes Internos , Desnutrición/complicaciones , Desnutrición/diagnóstico , Desnutrición/terapia , Estado Nutricional , Apoyo NutricionalRESUMEN
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.
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Liderazgo , Desnutrición , Adulto , Hospitalización , Humanos , Desnutrición/complicaciones , Desnutrición/diagnóstico , Desnutrición/terapia , Evaluación Nutricional , Estado Nutricional , Apoyo NutricionalRESUMEN
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.
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OBJECTIVES: Malnutrition is highly prevalent in patients with aging-related vulnerability defined by very old age (≥80 y), physical frailty or cognitive impairment, and increases the risks for morbidity and mortality. The effects of individualized nutritional support for patients with aging-related vulnerability in the acute hospital setting on mortality and other clinical outcomes remains understudied. METHODS: For 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 analyzed data of patients at a nutritional risk (Nutritional Risk Screening 2002 score ≥3 points) with aging-related vulnerability, randomized to receive protocol-guided individualized nutritional support to reach specific protein and energy goals (intervention group) or routine hospital food (control group). The primary endpoint was all-cause 30-d mortality. RESULTS: Of the 881 patients with aging-related vulnerability, 23.4% presented with a frailty syndrome, 81.8% were age ≥80 y and 15.3% showed cognitive impairment. Patients with aging-related vulnerability receiving individualized nutritional support compared with routine hospital food showed a >50% reduction in the risk of 30-day mortality (60 of 442 [13.6%] versus 31 of 439 [7.1%]; odds ratio: 0.48; 95% confidence interval, 0.31-0.76; P = 0.002). Significant improvements were also found for long-term mortality at 180 days, as well as functional outcomes and quality of life measures. CONCLUSIONS: Malnourished patients with aging-related vulnerability show a significant and clinically relevant reduction in the risk of mortality and other adverse clinical outcomes after individualized in-hospital nutritional support compared to routine hospital nutrition. These data support the early screening of patients with aging-related vulnerability for nutritional risk, followed by a nutritional assessment and implementation of individualized nutritional interventions.
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Pacientes Internos , Desnutrición , Anciano , Envejecimiento , Anciano Frágil , Hospitalización , Humanos , Desnutrición/terapia , Estado Nutricional , Apoyo Nutricional , Calidad de VidaRESUMEN
BACKGROUND: Patients with chronic kidney disease (CKD) are at substantial risk of malnutrition, which negatively affects clinical outcomes. We investigated the association of kidney function assessed at hospital admission and effectiveness of nutritional support in hospitalized medical patients at risk of malnutrition. METHODS: This is a secondary analysis of an investigator-initiated, randomized-controlled, Swiss multicenter trial (EFFORT) that compared individualised nutritional support with usual hospital food on clinical outcomes. We compared effects of nutritional support on mortality in subgroups of patients stratified according to kidney function at the time of hospital admission (estimated glomerular filtration rates [eGFR] <15, 15-29, 30-59, 60-89 and ≥ 90 ml/min/1.73 m2). RESULTS: We included 1943 of 2028 patients (96%) from the original trial with known admission creatinine levels. Admission eGFR was a strong predictor for the beneficial effects of nutritional support in regard to lowering of 30-day mortality. Patients with an eGFR <15, 15-29 and 30-59 had the strongest mortality benefit (odds ratios [95%CI] of 0.24 [0.05 to 1.25], 0.37 [0.14 to 0.95] and 0.39 [0.21 to 0.75], respectively), while patients with less severe impairment in kidney function had a less pronounced mortality benefits (p for interaction 0.001). A similar stepwise association of kidney function and response to nutritional support was found also for other secondary outcomes. CONCLUSION: In medical inpatients at nutritional risk, admission kidney function was a strong predictor for the response to nutritional therapy. Initial kidney function may help to individualize nutritional support in the future by identification of patients with most clinical benefit. CLINICAL TRIAL REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT02517476.
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Riñón/fisiología , Encuestas Nutricionales , Estado Nutricional , Insuficiencia Renal Crónica/fisiopatología , Anciano , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Masculino , Desnutrición/etiología , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Deterioration of nutritional status during hospitalization in patients with chronic heart failure increases mortality. Whether nutritional support during hospitalization reduces these risks, or on the contrary, may be harmful due to an increase in salt and fluid intake, remains unclear. OBJECTIVES: The purpose of this trial was to study the effect of nutritional support on mortality in patients hospitalized with chronic heart failure who are at nutritional risk. METHODS: A total of 645 patients with chronic heart failure (36% [n = 234] with acute decompensation) participated in the investigator-initiated, open-label EFFORT (Effect of early nutritional support on Frailty, Functional Outcomes and Recovery of malnourished medical inpatients) trial. Patients were randomized to protocol-guided individualized nutritional support to reach energy, protein, and micronutrient goals (intervention group) or standard hospital food (control group). The primary endpoint was all-cause mortality at 30 days. RESULTS: Mortality over 180 days increased with higher severity of malnutrition (odds ratio per 1-point increase in Nutritional Risk Screening 2002 score: 1.65; 95% confidence interval [CI]: 1.21 to 2.24; p = 0.001). By 30 days, 27 of 321 intervention group patients (8.4%) died, compared with 48 of 324 (14.8%) control group patients (odds ratio: 0.44; 95% CI: 0.26 to 0.75; p = 0.002). Patients at high nutritional risk showed the most benefit from nutritional support. Mortality effects remained significant at 180-day follow-up. Intervention group patients also had a lower risk for major cardiovascular events at 30 days (17.4% vs. 26.9%; odds ratio: 0.50; 95% CI: 0.34 to 0.75; p = 0.001). CONCLUSIONS: Among hospitalized patients with chronic heart failure at high nutritional risk, individualized nutritional support reduced the risk for mortality and major cardiovascular events compared with standard hospital food. These data support malnutrition screening upon hospital admission followed by an individualized nutritional support strategy in this vulnerable patient population. (Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial [EFFORT]; NCT02517476).
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Insuficiencia Cardíaca/mortalidad , Hospitalización , Apoyo Nutricional , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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.
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Fuerza de la Mano , Pacientes Internos , Desnutrición/complicaciones , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Terapia Nutricional , Estado Nutricional , Apoyo Nutricional , Oportunidad Relativa , Resultado del TratamientoRESUMEN
BACKGROUND: In polymorbid patients with bronchopulmonary infection, malnutrition is an independent risk factor for mortality. There is a lack of interventional data investigating whether providing nutritional support during the hospital stay in patients at risk for malnutrition presenting with lower respiratory tract infection lowers mortality. METHODS: For this secondary analysis of a randomized clinical trial (EFFORT), we analyzed data of a subgroup of patients with confirmed lower respiratory tract infection from an initial cohort of 2028 patients. Patients at nutritional risk (Nutritional Risk Screening [NRS] score ≥3 points) were randomized to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group). The primary endpoint of this analysis was all-cause 30-day mortality. RESULTS: We included 378 of 2028 EFFORT patients (mean age 74.4 years, 24% with COPD) into this analysis. Compared to usual care hospital nutrition, individualized nutritional support to reach caloric and protein goals showed a similar beneficial effect of on the risk of mortality in the subgroup of respiratory tract infection patients as compared to the main EFFORT trial (odds ratio 0.47 [95%CI 0.17 to 1.27, p = 0.136] vs 0.65 [95%CI 0.47 to 0.91, p = 0.011]) with no evidence of a subgroup effect (p for interaction 0.859). Effects were also similar among different subgroups based on etiology and type of respiratory tract infection and for other secondary endpoints. CONCLUSION: This subgroup analysis from a large nutrition support trial suggests that patients at nutritional risk as assessed by NRS 2002 presenting with bronchopulmonary infection to the hospital likely have a mortality benefit from individualized inhospital nutritional support. The small sample size and limited statistical power calls for larger nutritional studies focusing on this highly vulnerable patient population. CLINICAL TRIAL REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT02517476.
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Desnutrición/dietoterapia , Desnutrición/epidemiología , Apoyo Nutricional/métodos , Infecciones del Sistema Respiratorio/epidemiología , Anciano , Estudios de Cohortes , Comorbilidad , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Suiza/epidemiologíaRESUMEN
BACKGROUND: Among medical inpatients at risk of malnutrition, the use of individualized nutritional support during the hospital stay was found to reduce complications and improve mortality at short-term. We evaluated clinical outcomes at 6-months follow-up. METHODS: We randomly assigned 2028 patients to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or hospital food as usual (control group) during the hospital stay. The intervention was discontinued at hospital discharge and further nutritional support was based on the discretion of the treating team. We had complete follow-up information of 1995 patients (98%), which were included in the final analysis. The primary endpoint was all-cause mortality at 6-months. Prespecified secondary end points included non-elective hospital readmissions, functional outcome and quality of life. RESULTS: At 6-month, 231 of 994 (23.2%) intervention group patients had died compared to 246 of 999 (24.6%) control group patients, resulting in a hazard ratio for death of 0.90 (95%CI 0.76 to 1.08, p = 0.277). Compared to control patients, intervention group patients had similar rates of hospital readmission (27.3% vs. 27.6%, HR 1.00 (95%CI 0.84 to 1.18), p = 0.974), falls (11.2% vs. 10.9%, HR 0.96 (95%CI 0.72 to 1.27), p = 0.773) and similar quality of life and activities of daily living scores. INTERPRETATION: While individualized nutritional support during the hospital stay significantly reduced short-term mortality, there was no legacy effect on longer term outcomes. Future trials should investigate whether continuation of nutritional support after hospital discharge reduces the high malnutrition-associated mortality rates in this vulnerable patient population. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02517476.
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Hospitalización , Desnutrición/prevención & control , Estado Nutricional , Apoyo Nutricional , Accidentes por Caídas , Actividades Cotidianas , Anciano , Proteínas en la Dieta/administración & dosificación , Ingestión de Energía , Femenino , Humanos , Masculino , Mortalidad , Readmisión del Paciente , Calidad de Vida , Factores de RiesgoRESUMEN
Importance: Inflammation is a key driver of malnutrition during illness and is often accompanied by metabolic effects, including insulin resistance and reduction of appetite. However, it still remains unclear if inflammation influences the response to nutritional support among patients with disease-related malnutrition. Objective: To examine whether patients' baseline inflammatory status is associated with the effect of nutritional support on 30-day mortality. Design, Setting, and Participants: 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 randomized clinical trial conducted in 8 Swiss hospitals from April 2014 to February 2018. A total of 1950 participants who had C-reactive protein measurements at the time of admission were included in this secondary analysis. Data analysis was conducted between June and July 2019. Interventions: Hospitalized patients at risk for malnutrition were randomly assigned to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group). Main Outcomes and Measures: The primary end point was 30-day mortality. Based on C-reactive protein levels at admission, patients were stratified into groups with low, moderate, or high inflammation (<10 mg/L, 10-100 mg/L, and >100 mg/L, respectively). Results: A total of 1950 patients (median [interquartile range] age, 75 [65-83] years; 1025 [52.6%] men) were included; 533 (27.3%) had low levels of inflammation, 894 (45.9%) had moderate levels of inflammation, and 523 (26.8%) had high levels of inflammation. Compared with the control group, patients receiving nutritional support showed a significant reduction in 30-day mortality, regardless of C-reactive protein level (adjusted odds ratio, 0.61; 95% CI, 0.43-0.86; P = .005). In the subgroup of patients with high inflammation, there was no beneficial effect of nutritional support (adjusted odds ratio, 1.32; 95% CI, 0.70-2.50; P = .39), providing evidence that inflammation has a significant modifying association (P for interaction = .005). Conclusions and Relevance: Based on this secondary analysis of a multicenter randomized trial, a patient's admission inflammatory status was associated with their response to nutritional support. If validated in future clinical trials, nutritional support may need to be individualized based on a patient's initial presentation and markers of inflammation. These results may also help to explain some of the heterogeneity in treatment effects of nutrition seen in previous critical care trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02517476.
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Proteína C-Reactiva/metabolismo , Desnutrición/sangre , Desnutrición/terapia , Apoyo Nutricional , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Hospitalización , Humanos , Inflamación , Masculino , Desnutrición/mortalidad , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: The Nutritional Risk Screening 2002 (NRS 2002) identifies patients at risk of malnutrition. We studied the prognostic implications of this score with regard to short-term and long-term clinical outcomes in a well-characterised cohort of medical inpatients from a previous trial. METHODS: This is a secondary analysis of an investigator-initiated, prospective randomised controlled multicenter trial in Switzerland (EFFORT) that compared the effects of an individualised nutritional support intervention with standard of care. We investigated associations between admission NRS and several short-term and long-term outcomes using multivariable regression analyses. RESULTS: Of the 2028 patients, 31% had an NRS of 3, 38% of 4 and 31% of ≥5 points, and 477 (24%) died during the 180 days of follow-up. For each point increase in NRS, we found a stepwise increase in risk of 30-day mortality (adjusted Hazard Ratio (HR) 1.22 (95% CI 1.00 to 1.48), p = 0.048) and 180-day mortality (adjusted HR 1.37 (95% CI 1.22 to 1.55), p < 0.001). NRS was associated with length of hospital stay (adjusted difference of 0.60 days per NRS point increase, 95%CI 0.23 to 0.97, p = 0.002) and functional outcomes at 180 days (adjusted decrease in Barthel index of -4.49 points per NRS point increase, 95%CI -6.54 to -2.45, p < 0.001). In a subgroup analysis, associations of NRS and short-term adverse outcomes were less pronounced in patients receiving nutritional support (intervention group) compared to control group patients (adjusted HR for 30-day mortality 1.12 [95%CI 0.83 to 1.52, p = 0.454] vs. 1.33 [95%CI 1.02 to 1.72, p = 0.032]). CONCLUSION: The NRS is a strong and independent risk score for malnutrition-associated mortality and adverse outcomes over 180 days. Our data provide strong evidence that the nutritional risk, however, is modifiable and can be reduced by the provision of adequate nutritional support.
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Desnutrición/diagnóstico , Tamizaje Masivo , Evaluación Nutricional , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Tiempo de Internación , Masculino , Desnutrición/mortalidad , Desnutrición/terapia , Persona de Mediana Edad , Mortalidad , Apoyo Nutricional , Readmisión del Paciente , Medicina de Precisión , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Nivel de Atención , SuizaRESUMEN
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% (nâ=â482). 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, Pâ=â.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, Pâ=â.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, Pâ=â.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.
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Anciano Frágil/estadística & datos numéricos , Fragilidad/mortalidad , Desnutrición/mortalidad , Deficiencia de Vitamina D/mortalidad , Deficiencia de Vitamina D/terapia , Anciano , Anciano de 80 o más Años , Suplementos Dietéticos , Femenino , Fragilidad/sangre , Fragilidad/complicaciones , Humanos , Pacientes Internos/estadística & datos numéricos , Masculino , Desnutrición/sangre , Desnutrición/complicaciones , Prevalencia , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Vitamina D/análogos & derivados , Vitamina D/sangre , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/complicaciones , Vitaminas/uso terapéuticoRESUMEN
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.
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Benchmarking/normas , Afecciones Crónicas Múltiples/terapia , Adolescente , Adulto , Anciano , Ensayos Clínicos como Asunto , Investigación sobre la Eficacia Comparativa , Atención a la Salud/estadística & datos numéricos , Prestación Integrada de Atención de Salud/normas , Hospitalización/estadística & datos numéricos , Humanos , Relaciones Interprofesionales , Tiempo de Internación/estadística & datos numéricos , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Alta del Paciente/normas , Readmisión del Paciente/normas , Transferencia de Pacientes/normas , Ensayos Clínicos Pragmáticos como Asunto , Estudios Prospectivos , Calidad de la Atención de Salud , Asignación de Recursos , Adulto JovenRESUMEN
BACKGROUND: Guidelines recommend the use of nutritional support during hospital stays for medical patients (patients not critically ill and not undergoing surgical procedures) at risk of malnutrition. However, the supporting evidence for this recommendation is insufficient, and there is growing concern about the possible negative effects of nutritional therapy during acute illness on recovery and clinical outcomes. Our aim was thus to test the hypothesis that protocol-guided individualised nutritional support to reach protein and caloric goals reduces the risk of adverse clinical outcomes in medical inpatients at nutritional risk. METHODS: The Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) is a pragmatic, investigator-initiated, open-label, multicentre study. We recruited medical patients at nutritional risk (nutritional risk screening 2002 [NRS 2002] score ≥3 points) and with an expected length of hospital stay of more than 4 days from eight Swiss hospitals. These participants were randomly assigned (1:1) to receive either protocol-guided individualised nutritional support to reach protein and caloric goals (intervention group) or standard hospital food (control group). Randomisation was done with variable block sizes and stratification according to study site and severity of malnutrition using an interactive web-response system. In the intervention group, individualised nutritional support goals were defined by specialist dietitians and nutritional support was initiated no later than 48 h after admission. Patients in the control group received no dietary consultation. The composite primary endpoint was any adverse clinical outcome defined as all-cause mortality, admission to intensive care, non-elective hospital readmission, major complications, and decline in functional status at 30 days, and it was measured in all randomised patients who completed the trial. This trial is registered with ClinicalTrials.gov, number NCT02517476. FINDINGS: 5015 patients were screened, and 2088 were recruited and monitored between April 1, 2014, and Feb 28, 2018. 1050 patients were assigned to the intervention group and 1038 to the control group. 60 patients withdrew consent during the course of the trial (35 in the intervention group and 25 in the control group). During the hospital stay, caloric goals were reached in 800 (79%) and protein goals in 770 (76%) of 1015 patients in the intervention group. By 30 days, 232 (23%) patients in the intervention group experienced an adverse clinical outcome, compared with 272 (27%) of 1013 patients in the control group (adjusted odds ratio [OR] 0·79 [95% CI 0·64-0·97], p=0·023). By day 30, 73 [7%] patients had died in the intervention group compared with 100 [10%] patients in the control group (adjusted OR 0·65 [0·47-0·91], p=0·011). There was no difference in the proportion of patients who experienced side-effects from nutritional support between the intervention and the control group (162 [16%] vs 145 [14%], adjusted OR 1·16 [0·90-1·51], p=0·26). INTERPRETATION: In medical inpatients at nutritional risk, the use of individualised nutritional support during the hospital stay improved important clinical outcomes, including survival, compared with standard hospital food. These findings strongly support the concept of systematically screening medical inpatients on hospital admission regarding nutritional risk, independent of their medical condition, followed by a nutritional assessment and introduction of individualised nutritional support in patients at risk. FUNDING: The Swiss National Science Foundation and the Research Council of the Kantonsspital Aarau, Switzerland.
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Desnutrición/prevención & control , Apoyo Nutricional/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Atención Dirigida al Paciente/métodos , Enfermedad Aguda/epidemiología , Anciano , Anciano de 80 o más Años , Enfermedad Crónica/epidemiología , Comorbilidad , Ingestión de Energía , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Medición de RiesgoRESUMEN
BACKGROUND: Adrenal hormone metabolite levels are altered in acute illnesses such as community-acquired pneumonia (CAP). Our aim was to investigate associations of sex and mineralocorticoid hormone metabolites with short- and long-term mortality and severity of CAP in male and female patients. METHODS: We prospectively followed 285 patients (60.4% male, mean age 71 years) with CAP from a previous multicenter trial. At baseline, levels of different metabolites of sex hormones and mineralocorticoids were measured by liquid chromatography coupled to tandem mass spectrometry. We calculated Cox regression models adjusted for age and comorbidities. RESULTS: All-cause mortality was 5.3% after 30 days and increased to 47.4% after 6 years. In males, high levels of dihydrotestosterone were associated with higher 6-year mortality (adjusted HR 2.84, 95%CI 1.15-6.99, p = 0.023), whereas high levels of 17-OH-progesterone were associated with lower 6-year mortality (adjusted HR 0.72, 95%CI 0.54-0.97, p = 0.029). Testosterone levels in males correlated inversely with inflammatory markers (CRP rho = - 0.39, p < 0.001; PCT rho = - 0.34, p < 0.001) and disease severity as assessed by the Pneumonia severity index (PSI) (rho = - 0.23, p = 0.003). No similar association was found for female patients. CONCLUSION: Whereas in males with CAP, sex and mineralocorticoid hormone metabolite levels correlated with inflammation, disease severity and long-term survival, no similar association was found for females. Further study of sex and mineralocorticoid hormones in acute illness could generate predictive signatures with implementation in clinical practice.
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Dihidrotestosterona/sangre , Neumonía/sangre , Neumonía/mortalidad , Caracteres Sexuales , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Neumonía/diagnóstico , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de TiempoRESUMEN
BACKGROUND: Oxidative stress is a modifiable risk-factor in infection causing damage to human cells. As an adaptive response, cells catabolize Tyrosine to 3-Nitrotyrosine (Tyr-NO2) by nitrosylation. We investigated whether a more efficient reduction in oxidative stress, mirrored by a lowering of Tyrosine, and an increase in Tyr-NO2 and the Tyrosine/Tyr-NO2 ratio was associated with better clinical outcomes in patients with community-acquired pneumonia (CAP). METHODS: We measured Tyrosine and Tyr-NO2 in CAP patients from a previous randomized Swiss multicenter trial. The primary endpoint was adverse outcome defined as death or ICU admission within 30-days; the secondary endpoint was 6-year mortality. RESULTS: Of 278 included CAP patients, 10.4% experienced an adverse outcome within 30 days and 45.0% died within 6 years. After adjusting for the pneumonia Severity Index [PSI], BMI and comorbidities, Tyrosine nitrosylation was associated with a lower risk for short-term adverse outcome and an adjusted OR of 0.44 (95% CI 0.20 to 0.96, p = 0.039) for Tyr-NO2 and 0.98 (95% CI 0.98 to 0.99, p = 0.043) for the Tyrosine/Tyr-NO2 ratio. There were no significant associations for long-term mortality over six-years for Tyr-NO2 levels (adjusted hazard ratio 0.81, 95% CI 0.60 to 1.11, p = 0.181) and Tyrosine/Tyr-NO2 ratio (adjusted hazard ratio 1.00, 95% CI 0.99 to 1.00, p = 0.216). CONCLUSIONS: Tyrosine nitrosylation in our cohort was associated with better clinical outcomes of CAP patients at short-term, but not at long term. Whether therapeutic modulation of the Tyrosine/Tyr-NO2 pathway has beneficial effects should be evaluated in future studies. TRIAL REGISTRATION: ISRCTN95122877. Registered 31 July 2006.
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Infecciones Comunitarias Adquiridas/epidemiología , Admisión del Paciente/estadística & datos numéricos , Neumonía/epidemiología , Tirosina/análogos & derivados , Tirosina/sangre , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/metabolismo , Infecciones Comunitarias Adquiridas/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Redes y Vías Metabólicas , Persona de Mediana Edad , Mortalidad , Neumonía/diagnóstico , Neumonía/metabolismo , Neumonía/mortalidad , Pronóstico , Factores de Riesgo , Suiza/epidemiología , Factores de Tiempo , Tirosina/metabolismoRESUMEN
OBJECTIVES: The gut, microflora-dependent metabolite trimethylamine-N-oxide (TMAO) has emerged as a dietary-associated risk factor for incident cardiovascular events. Chronic obstructive pulmonary disease (COPD) is a prevalent disease worldwide with a high associated risk for cardiovascular disease and death due to an infectious cause. AIMS: To study whether TMAO is predictive for adverse clinical outcomes in patients with exacerbated COPD. METHODS: A total of 189 patients with COPD exacerbation were prospectively followed for a median of 6.1 y. TMAO plasma levels at the time of emergency department admission were measured by liquid chromatography coupled with tandem mass spectrometry. Cox and linear regression models were used to investigate associations of TMAO with all-cause mortality and different comorbidities. RESULTS: All-cause mortality was 55.6% after 6 y. The deceased patients showed significantly higher median admission TMAO (µmol/L) levels compared with survivors (3.9 [interquartile range: 2.3-7.1] versus 2.9 [interquartile range: 1.8-4.7]; P = 0.01), which resulted in an unadjusted hazard ratio of 1.8 ([95% confidence interval: 1.2-3.0], P = 0.01). This association was no longer significant after multivariate adjustment. Median TMAO levels were similar in nonpneumonic and pneumonic COPD exacerbation. Higher age, higher body mass index, diabetes mellitus, and chronic kidney disease were predictors for increased plasma TMAO levels in linear regression analysis. CONCLUSIONS: Increased circulating TMAO levels per se were associated with long-term all-cause mortality in patients with COPD independent of type of exacerbation. However, this association was largely explained by comorbidities and age. Whether TMAO levels can additionally be influenced by nutritional interventions should be addressed in future studies.
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Microbioma Gastrointestinal , Metilaminas/sangre , Mortalidad , Enfermedad Pulmonar Obstructiva Crónica/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Factores de Riesgo , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: The release of hormones from the adrenal gland is vital in acute and chronic illnesses such as chronic obstructive pulmonary disease (COPD) involving recurrent exacerbations. Using a metabolomic approach, we aim to investigate associations of different adrenal hormone metabolites with short- and long-term mortality in COPD patients. METHODS: We prospectively followed 172 COPD patients (median age 75 years, 62% male) from a previous Swiss multicenter trial. At baseline, we measured levels of a comprehensive spectrum of adrenal hormone metabolites, including glucocorticoid, mineralocorticoid and androgen hormones by liquid chromatography coupled with tandem mass spectrometry (MS). We calculated Cox regression models adjusted for gender, age, comorbidities and previous corticosteroid therapy. RESULTS: Mortality was 6.4% after 30 days and increased to 61.6% after 6 years. Higher initial androgen hormones predicted lower long-term mortality with significant results for dehydroepiandrosterone (DHEA) [adjusted hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.70-0.98; p=0.026] and dehydroepiandrosterone sulfate (DHEA-S) (adjusted HR, 0.68; 95% CI, 0.50-0.91; p=0.009). An activation of stress hormones (particularly cortisol and cortisone) showed a time-dependent effect with higher levels pointing towards higher mortality at short term, but lower mortality at long term. Activation of the mineralocorticoid axis tended to be associated with increased short-term mortality (adjusted HR of aldosterone, 2.76; 95% CI, 0.79-9.65; p=0.111). CONCLUSIONS: Independent of age, gender, corticosteroid exposure and exacerbation type, adrenal hormones are associated with mortality at short and long term in patients with COPD exacerbation with different time-dependent effects of glucocorticoids, androgens and mineralocorticoids. A better physiopathological understanding of the causality of these effects may have therapeutic implications.