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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).
Wunderle, C, Siegenthaler, J, Seres, D, Owen-Michaane, M, Tribolet, P, Stanga, Z, Mueller, B, Schuetz, P
The American journal of clinical nutrition. 2024;(3):800-808
Abstract
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.
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Selenium Supplementation in Patients with Hashimoto Thyroiditis:A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Huwiler, VV, Maissen-Abgottspon, S, Stanga, Z, Mühlebach, S, Trepp, R, Bally, L, Bano, A
Thyroid : official journal of the American Thyroid Association. 2024
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Hashimoto Thyroiditis (HT) is a disease of the thyroid gland, which can result in insufficient production of thyroid hormone. Thyroid hormone is responsible for numerous functions within the body, such as weight regulation and energy production. Selenium is a nutrient that is used in the body to make thyroid hormones and low levels have been seen in patients with HT. Selenium supplementation has been researched previously, but inconsistent results have been shown. This systematic review and meta-analysis of 35 and 32 randomised control trials respectively, aimed to determine the effect of selenium supplementation on HT. The results showed that selenium supplementation favourably influenced thyroid hormones and oxidative stress, without affecting inflammation, but only if individuals were not receiving thyroid hormone replacement therapy. Adverse events were similar between the supplementation and control groups. It was concluded that selenium supplementation is a safe and effective therapy for individuals with HT who are not receiving hormone replacement therapy. This study could be used by healthcare professionals to recommend selenium supplementation as a way to balance thyroid hormones and alleviate the effects of HT.
Abstract
Background: Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; I2 = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; I2 = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; I2 = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; I2 = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. Conclusions: In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.
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The influence of patients' nutritional risk, nutritional status, and energy density in MEDPass versus conventional administration of oral nutritional supplements - A secondary analysis of a randomized controlled trial.
Schläppi, K, Reber, E, Schönenberger, KA, Stanga, Z, Kurmann, S
The journal of nutrition, health & aging. 2024;28(3):100170
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Older people and those admitted to hospital are at a higher risk for malnutrition. Nutritional supplements may be able to prevent malnutrition. However, there are a lack of guidelines on the optimal timing of administration and dosage, leading to reduced effects and poor compliance. This sub-analysis of a randomised control trial aimed to determine the effect of an administration method called the Medication Pass Nutritional Supplement Program (MEDPass), on older and hospitalised individuals, which focuses on nutrient supplementation three to four times per day. The results showed that of the 202 individuals included, the MEDPass administration method of supplementation had no effect on energy intake, protein intake, body weight, appetite, nausea, handgrip strength, weight, or compliance to medication compared to if supplementation was taken in the conventional manner with meals. It was concluded that the MEDPass mode of delivering nutritional supplements was not superior to the standard method of delivery. This study could be used by healthcare professionals to understand that without guidelines on when to take nutritional supplementation, some individuals may not be benefitting. However, the MEDPass method of delivery may not optimise supplementation.
Abstract
OBJECTIVES The clinical influence of nutritional risk, nutritional status, and energy density of oral nutritional supplements (ONS) in MEDPass versus conventional administration of ONS is currently unknown. The aim of this analysis was to examine whether these variables have an impact on clinical outcomes. METHODS Secondary analysis of the intention to treat dataset of the randomized controlled MEDPass Trial in geriatric and medical inpatients. Patients in the intervention group received 4 × 50 ml ONS during the medication rounds (MEDPass mode), while those in the control group received ONS in a non-standardized manner. The examined endpoints included energy and protein coverage, ONS intake, handgrip strength (HGS), weight, appetite nausea and 30-day mortality. Three subgroup analyses for NRS 2002 total score (3, 4 or 5-7 points), NRS 2002 impaired nutritional status score (0, 1, 2 or 3 points) and energy density of the ONS (1.5 kcal/mL or 2 kcal/mL) were performed using linear and logistic regression with interaction and mixed effect models. RESULTS The data of 202 patients (103 women and 99 men) at nutritional risk (NRS total 2002 score ≥3), mean (SD) age 82.2 (6.5) years were included. There was no significant difference between the groups in the primary endpoint energy coverage in all three subgroup analyses. There were also no significant differences between the groups in the secondary endpoints of protein coverage, ONS intake, HGS, weight, appetite, nausea, and 30-day mortality. CONCLUSION The MEDPass mode of ONS administration was not superior to the conventional mode of administration in this study. ONS with high energy density (≥2 kcal/mL) should be offered since current evidence shows a tendency towards improved appetite, increased ONS and increased energy intake.
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Red blood cell distribution width (RDW) - A new nutritional biomarker to assess nutritional risk and response to nutritional therapy?
Haenggi, E, Kaegi-Braun, N, Wunderle, C, Tribolet, P, Mueller, B, Stanga, Z, Schuetz, P
Clinical nutrition (Edinburgh, Scotland). 2024;(2):575-585
Abstract
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.
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Should handgrip strength be considered when choosing the administration mode of oral nutritional supplements in geriatric patients? A secondary analysis of the MEDPass Trial.
Uhlmann, K, Reber, E, Schonenberger, KA, Stanga, Z, Kurmann, S
Nutrition (Burbank, Los Angeles County, Calif.). 2024;:112429
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OBJECTIVE It is important to individualize nutrition therapy and to identify whether certain patient groups benefit from a specific intervention such as oral nutritional supplements (ONS). This study investigated whether patients with weak handgrip strength (HGS) benefit better from ONS administration in the Medication Pass Nutritional Supplement Program (MEDPass) mode regarding the individual coverage of energy and protein requirements throughout their hospitalization. METHODS A secondary analysis of the intention-to-treat data set of the randomized controlled MEDPass trial was conducted. Weak HGS was defined as <27 kg for men and <16 kg for women. Linear mixed-effect models adjusted for the stratification factors energy density of ONS and nutritional risk screening 2002 score were used to address the aim of the study. RESULTS We included 188 participants. Energy and protein coverage did not differ between the patients with weak or normal HGS depending on ONS administration mode (P = 0.084, P = 0.108). Patients with weak HGS and MEDPass administration mode tended to have the lowest energy and protein coverage (estimated mean, 77.2%; 95% confidence interval [CI], 69.3%-85% and estimated mean, 95.1%; 95% CI, 85.3%-105%, respectively). Patients with weak HGS and conventional ONS administration had the highest energy and protein coverage (estimated mean, 90%; 95% CI, 82.8%-97.2% and estimated mean, 110.2%; 95% CI, 101.3%-119%, respectively). CONCLUSION No clear recommendations regarding the mode of ONS administration depending on HGS can be made. In clinical practice, appetite and satiety in patients with weak HGS should be monitored, and the ONS administration mode should be adjusted accordingly.
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Association of leucine and other branched chain amino acids with clinical outcomes in malnourished inpatients: a secondary analysis of the randomized clinical trial EFFORT.
Wunderle, C, Ciobanu, C, Ritz, J, Tribolet, P, Neyer, P, Bernasconi, L, Stanga, Z, Mueller, B, Schuetz, P
European journal of clinical nutrition. 2024
Abstract
BACKGROUND The essential branched-chain amino acids leucine, isoleucine and valine are considered anabolic and stimulate protein synthesis in the muscles as well in the liver. They also promote muscle recovery and contribute to glucose homeostasis. Recent studies in critically ill patients have demonstrated that depletion of plasma leucine is associated with increased mortality, but data in the non-critical care setting is lacking. METHODS This secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT), investigated the impact of leucine, isoleucine, and valine metabolism on clinical outcomes. The primary endpoint was 180-day all-cause mortality. RESULTS Among 238 polymorbid patients with available metabolite measurements, low serum leucin levels were associated with a doubled risk of 180-day all-cause mortality in a fully adjusted regression model (adjusted HR 2.20 [95% CI 1.46-3.30], p < 0.001). There was also an association with mortality for isoleucine (1.56 [95% CI 1.03-2.35], p = 0.035) and valine (1.69 [95% CI 1.13-2.53], p = 0.011). When comparing effects of nutritional support on mortality in patients with high and low levels of leucine, there was no evidence of significant differences in effectiveness of the intervention. The same was true for isoleucine and valine. CONCLUSION Our data suggest that depletion of leucine, isoleucine, and valine among malnourished polymorbid patients is associated with increases in long-term mortality. However, patients with low metabolite levels did not show a pronounced benefit from nutritional support. Further research should focus on the clinical effects of nutritional support in patients with depleted stores of essential branched-chain amino acids. CLINICAL TRIAL REGISTRATION clinicaltrials.gov as NCT02517476 (registered 7 August 2015).
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Prognostic implications of the arginine metabolism in patients at nutritional risk: A secondary analysis of the randomized EFFORT trial.
Stumpf, F, Wunderle, C, Ritz, J, Bernasconi, L, Neyer, P, Tribolet, P, Stanga, Z, Mueller, B, Bischoff, SC, Schuetz, P
Clinical nutrition (Edinburgh, Scotland). 2024;(3):660-673
Abstract
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).
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Sex differences in clinical presentation, treatment response, and side effects of nutritional therapy among patients at nutritional risk: a secondary analysis of the randomized clinical trial EFFORT.
Wunderle, C, Suter, SS, Endner, N, Haenggi, E, Kaegi-Braun, N, Tribolet, P, Stanga, Z, Mueller, B, Schuetz, P
The American journal of clinical nutrition. 2024
Abstract
BACKGROUND Considering sex-specific factors has become an increasingly recognized area for research and practice, in the field of clinical nutrition, there is insufficient evidence regarding differences in clinical presentation, treatment response, and side effects of nutritional therapy among female and male patients. OBJECTIVES We hypothesized that the clinical presentation, response to nutritional therapy, and side effects from the intervention would differ in the two sexes. METHODS This secondary analysis investigated differences among female and male patients at risk for malnutrition regarding initial presentation, clinical outcomes, and treatment response in patients included in 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. RESULTS Of 2028 patients included in the trial, 964 were females and 1064 were males. The nutritional history and clinical presentation of female patients was different: they consumed less food and had a greater loss of appetite than the male population. Male patients had higher risk for mortality at 180 d [27% compared with 19%; adjusted hazards ratio (HR): 1.35; 95% CI: 1.12, 1.63] and further adverse clinical outcomes. However, there was no difference in the effect of nutritional support on mortality among female and male patients (HR: 0.76; 95% CI: 0.45, 1.27, compared with HR: 0.81; 95% CI: 0.54, 1.21, respectively; P-interaction = 0.939). CONCLUSIONS Results of this multicenter randomized trial suggest that multimorbid female inpatients have a different clinical presentation and are more prone to loss of appetite and reduced daily dietary intake than male inpatients. Importantly, the favorable response to nutritional interventions was similar in both sexes. This trial was registered at clinicaltrials.gov as NCT02517476.
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Nutritional support in hospitalised patients with diabetes and risk for malnutrition: a secondary analysis of an investigator-initiated, Swiss, randomised controlled multicentre trial.
Keller, B, Wunderle, C, Tribolet, P, Stanga, Z, Kaegi-Braun, N, Mueller, B, Schuetz, P
BMJ open. 2024;(8):e084754
Abstract
OBJECTIVES The main objective of this study was to investigate the effects of nutritional support on mortality in hospitalised patients with diabetes and nutritional risk participating in the Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) trial. DESIGN Secondary analysis of a Swiss-wide multicentre, randomised controlled trial. PARTICIPANTS Patients with diabetes and risk for malnutrition. INTERVENTIONS Individualised nutritional support versus usual care. PRIMARY OUTCOME MEASURE 30-day all-cause mortality. RESULTS Of the 2028 patients included in the original trial, 445 patients were diagnosed with diabetes and included in this analysis. In terms of efficacy of nutritional therapy, there was a 25% lower risk for mortality in patients with diabetes receiving nutritional support compared with controls (7% vs 10%, adjusted HR 0.75 (95% CI 0.39 to 1.43)), a finding that was not statistically significant but similar to the overall trial effects with no evidence of interaction (p=0.92). Regarding safety of nutritional therapy, there was no increase in diabetes-specific complications associated with nutritional support, particularly there was no increase in risk for hyperglycaemia (adjusted OR 0.97, 95% CI 0.56 to 1.67 p=0.90). CONCLUSION Patients with diabetes and malnutrition in the hospital setting have a particularly high risk for adverse outcomes and mortality. Individualised nutritional support reduced mortality in this secondary analysis of a randomized trial, but this effect was not significant calling for further large-scale trials in this vhighly ulnerable patient population. TRIAL REGISTRATION NUMBER NCT02517476.
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Muscle matters: Prognostic implications of malnutrition and muscle health parameters in patients with cancer. A secondary analysis of a randomised trial.
Olpe, T, Wunderle, C, Bargetzi, L, Tribolet, P, Laviano, A, Stanga, Z, Prado, CM, Mueller, B, Schuetz, P
Clinical nutrition (Edinburgh, Scotland). 2024;(9):2255-2262
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BACKGROUND Low muscle mass and malnutrition are independently associated with an increased risk of adverse outcomes in patients with cancer. However, it is not yet clear which parameter is most indicative of these risks. This study investigates the prognostic significance of different parameters reflecting malnutrition and muscle health in a well-characterised oncology population at nutritional risk. METHODS This preplanned secondary analysis included patients with cancer from a Swiss-wide, randomised-controlled nutritional trial. We investigated associations among malnutrition markers (i.e., malnutrition diagnosis based on modified Global Leadership Initiative on Malnutrition (GLIM) criteria, albumin concentration) and muscle health markers (i.e., hand grip strength, computed tomography (CT)-based muscle mass and radiodensity) with 180-day all-cause mortality (primary outcome). RESULTS We included 269 patients with a main admission diagnosis of cancer and available CT scans. In a mutually adjusted model, four parameters contributed to risk assessment including modified malnutrition diagnosis (GLIM) (HR 1.78 (95%CI 1.17 to 2.69), p = 0.007, AUC 0.58), low albumin concentration (HR 1.58 (95%CI 1.08 to 2.31), p = 0.019, AUC 0.62), low handgrip strength (HR 2.05 (95%CI 1.43 to 2.93), p = 0.001, AUC 0.62) and low muscle radiodensity (HR 1.39 (95%CI 0.90 to 2.16), p = 0.139, AUC 0.63). Combining these parameters resulted in a model with high prognostic power regarding 180-day mortality (overall AUC 0.71). CONCLUSIONS In this study of inpatients with cancer at nutritional risk, several malnutrition and muscle health parameters emerged as independent prognostic indicators for mortality. The use of these parameters may improve risk stratification and guide nutritional interventions in this vulnerable population. TRIAL REGISTRATION ClinicalTrials.gov, number NCT02517476.