Effect of combined therapies including nutrition and physical exercise in advanced cancer patients: A pooled analysis.

Background and aims: Although many cancer patients suffer from malnutrition or cancer cachexia, there is no standard of care so far due to limited intervention trials. Pooled data from two combined trials were analyzed regarding nutritional status and survival time. Materials and methods: Data from two trials with advanced cancer patients were included. In both trials, patients in the intervention group received at least three times nutritional counseling and supervised training sessions. Patients in the control group continued being treated according to usual care. Nutritional status was measured using BMI, body composition and handgrip strength. Survival time was analyzed using the Cox proportional hazard model with the period between the beginning of the trial and death as underlying time scale. Results: 68 men (61.8%) and 42 women (38.2%) were randomized either to the intervention (n = 56) or the control (n = 54) group. The inter-group difference for changes in BMI and body composition was not statistically significant after 3 months. Handgrip strength improved significantly from 34.4 ± 10.2 kg to 36.3 ± 9.9 kg at 3 months in the intervention compared to 33.9 ± 9.2 kg to 34.9 ± 9.1 kg in the control group (p = 0.006). The analysis of survival time showed no inter-group difference for all patients. A detailed analysis for different diagnoses showed that in patients with lung cancer, the covariates "CRP value," "days from first diagnosis to randomization" as well as "gender" were significantly associated with survival time. Patients with higher CRP value had a shorter survival time and female patients had a shorter survival time than male patients in our analysis. In addition, patients with pancreatic cancer randomized to the control group had a 20% shorter survival time than those in the intervention group (p = 0.048). Conclusion: The pooled analysis showed a significant improvement of handgrip strength in advanced cancer patients through the implementation of a combined therapy. Handgrip strength is of prognostic significance in hospitalized patients due to its association with mortality and morbidity. However, no improvements in further tests were detected. There is great need for further investigations examining the effect of nutritional and exercise therapy on survival time with focus on different cancer diagnoses.

Influence of weekday of admission and level of distress on length of hospital stay in patients with low back pain: a retrospective cohort study.

BACKGROUND: Low back pain (LBP) is often a complex problem requiring interdisciplinary management to address patients' multidimensional needs. Providing inpatient care for patients with LBP in primary care hospitals is a challenge. In this setting, interdisciplinary LBP management is often unavailable during weekends. Delays in therapeutic procedures may result in a prolonged length of hospital stay (LoS). The impact of delays on LoS might be strongest in patients reporting high levels of psychological distress. Therefore, this study investigates the influence of weekday of admission and distress on LoS of inpatients with LBP. METHODS: This retrospective cohort study was conducted between 1 February 2019 and 31 January 2020. In part 1, a negative binomial model was fitted to LoS with weekday of admission as a predictor. In part 2, the same model included weekday of admission, distress level, and their interaction as covariates. Planned contrast was used in part 1 to estimate the difference in log-expected LoS between group 1 (admissions Friday/Saturday) and the reference group (admissions Sunday-Thursday). In part 2, the same contrast was used to estimate the corresponding difference in (per-unit) distress trends. RESULTS: We identified 173 patients with LBP. The mean LoS was 7.8 days (SD = 5.59). Patients admitted on Friday (mean LoS = 10.3) and Saturday (LoS = 10.6) had longer stays, but not those admitted on Sunday (LoS = 7.1). Analysis of the weekday effect and planned contrast showed that admission on Friday or Saturday was associated with a significant increase in LoS (log ratio = 0.42, 95% CI = 0.21 to 0.63). A total of 101 patients (58%) returned questionnaires, and complete data on distress were available from 86 patients (49%). According to the negative binomial model for LoS and the planned contrast, the distress effect on LoS was significantly influenced (difference in slopes = 0.816, 95% CI = 0.03 to 1.60) by dichotomic weekdays of admission (Friday/Saturday vs. Sunday-Thursday). CONCLUSIONS: Delays in interdisciplinary LBP management over the weekend may prolong LoS. This may particularly affect patients reporting high levels of distress. Our study provides a platform to further explore whether interdisciplinary LBP management addressing patients' multidimensional needs reduces LoS in primary care hospitals.

NRS-2002 components, nutritional score and severity of disease score, and their association with hospital length of stay and mortality.

BACKGROUND: Malnutrition is a substantial issue in hospitals, leading to prolonged length of hospital stay, increased perioperative morbidity and increased mortality. There are several validated screening tools for malnutrition, one of which is the Nutritional Risk Screening 2002 (NRS). It screens patients based on recent weight loss, reduction of recent food intake, body mass index (BMI), severity of disease and age. Higher NRS scores have been shown to be negatively associated with patients’ outcomes such as increased morbidity and mortality. OBJECTIVES: The aim of the study was to evaluate how the two NRS components Nutritional Score (NS) and Severity of Disease Score (SDS) are associated with patients’ length of hospital stay and mortality. METHODS: All patients admitted to the medical department of a large community hospital in Switzerland were screened for malnutrition using the nutrition screening NRS during the years 2014 to 2017. Data on patients’ NRS, primary diagnosis, number of secondary diagnoses, mortality, length of stay (LOS), discharge, sex and age were collected. The association between the NRS components and LOS/mortality was estimated using a linear mixed-effects regression model and a logistic regression model, respectively, with adjustment for confounders (age, sex, comorbidity, diagnosis group, mode of discharge and year of hospitalisation). RESULTS: The evaluation of the outcomes of 21,855 hospitalisations demonstrated that the NS was associated with an increment in the LOS of 5.5–12.3% per score point, depending on the diagnosis group. An increase in the SDS by one point was associated with an increase in the LOS of 2.2–11.3%. The odds for all-cause in-hospital mortality were increased by 44.1% (95% confidence interval [CI] 33.7–55.2%) per point in the NS, and by 73% (95% CI 57.5–90.1%) per point in the SDS. CONCLUSIONS: Increases in both components of the NRS are associated with longer LOS. The NS has a slightly stronger impact on LOS compared to the SDS and its effect is dependent on the patient’s diagnosis group. Increases in the SDS are linked to a higher mortality than increases in the NS.

Effect of a leucine-rich supplement in combination with nutrition and physical exercise in advanced cancer patients: A randomized controlled intervention trial.

BACKGROUND & AIMS: Branched-chain amino acids and specifically leucine stimulate protein synthesis and may overcome an anabolic resistance in malnourished and cachectic cancer patients. Therefore, we hypothesized that the addition of a leucine-rich supplement to a multimodal therapy improves physical function in advanced cancer patients. METHODS: This single center, randomized trial examined a multimodal therapy over 12 weeks in patients with advanced cancer. The intervention group received a leucine-rich supplement in combination with a nutrition and physical exercise program. Patients in the control group received standard care. Primary endpoint was physical function measured with the short physical performance battery (SPPB). Secondary endpoints were further physical performance tests, nutritional status, dietary intake, fatigue, quality of life (QoL) and clinical course. All parameters were evaluated at baseline, after three and at six months. RESULTS: 23 women and 29 men with an average age of 63.1 ± 10.3 (range 30-81) years and BMI of 25.4 ± 4.7 kg/m2 were randomized either to the intervention (n = 27) or control (n = 25) group. Patients in the intervention group joined a mean of 28.4 ± 7.4 training sessions (78.8%), 3.2 ± 0.6 nutritional counselling sessions (106.7%) and consumed on average 85.4 ± 33.2 supplements (71.2%). Inter-group comparison showed no significant difference in the primary endpoint SPPB after three (p = 0.184, 95% CI: -1.43, 0.29) and six months (p = 0.986, 95% CI: -0.87, 0.89). However, the secondary endpoint handgrip strength improved significantly from 35.8 ± 9.8 kg at baseline to 37.6 ± 10.0 kg at three months in the intervention group compared to 35.7 ± 8.8 kg at baseline to 34.0 ± 10.1 kg at three months in the control group (p < 0.001, 95% CI: -6.03, -1.97). The inter-group difference for changes in the further secondary endpoints nutritional status, dietary intake, fatigue, QoL and clinical course showed a trend towards an improvement in the intervention group, however, the differences were not significant after three and six months. CONCLUSIONS: The present trial demonstrated a good adherence to the multimodal therapy as well as a significant improvement of handgrip strength in patients with advanced cancer. In addition, the clinical course data underlined the safety of the program. However, we failed to show significant improvements in further physical performance tests, especially our primary outcome factor SPPB as well as nutritional status, fatigue or QoL.

Nutrition in Gastrointestinal Disease: Liver, Pancreatic, and Inflammatory Bowel Disease.

Liver, pancreatic, and inflammatory bowel diseases are often associated with nutritional difficulties and necessitate an adequate nutritional therapy in order to support the medical treatment. As most patients with non-alcoholic fatty liver disease are overweight or obese, guidelines recommend weight loss and physical activity to improve liver enzymes and avoid liver cirrhosis. In contrast, patients with alcoholic steatohepatitis or liver cirrhosis have a substantial risk for protein depletion, trace elements deficiency, and thus malnutrition. Patients with chronic pancreatitis and patients with inflammatory bowel disease have a similar risk for malnutrition. Therefore, it clearly is important to screen these patients for malnutrition with established tools and initiate adequate nutritional therapy. If energy and protein intake are insufficient with regular meals, oral nutritional supplements or artificial nutrition, i.e., tube feeding or parenteral nutrition, should be used to avoid or treat malnutrition. However, the oral route should be preferred over enteral or parenteral nutrition. Acute liver failure and acute pancreatitis are emergencies, which require close monitoring for the treatment of metabolic disturbances. In most patients, energy and protein requirements are increased. In acute pancreatitis, the former recommendation of fasting is obsolete. Each disease is discussed in this manuscript and special recommendations are given according to the pathophysiology and clinical routine.

Effects of nutrition and physical exercise intervention in palliative cancer patients: A randomized controlled trial.

BACKGROUND & AIMS: Cancer cachexia is multifactorial and should be targeted using a multimodal form of intervention. The purpose of the present trial was to test the effects of a combined nutrition and physical exercise program on cancer patients with metastatic or locally advanced tumors of the gastrointestinal and lung tracts. METHODS: Patients were randomized into two groups: One group received a minimum of three standardized individual nutritional counselling sessions and participated in a 60-min exercise program twice a week. The second group received their usual care. The intervention spanned a period of three months. Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0), physical performance (hand-grip strength, 6-min walk test, timed sit-to-stand test and 1 repetition maximum leg press), nutritional status (body weight, bioelectrical impedance analysis), dietary intake (three-day dietary record) and clinical data (unexpected hospital days, performance status) were tested at baseline and after three and six months. RESULTS: In total, 18 women and 40 men (mean age 63, range 32-81) with metastatic or locally advanced tumors of the gastrointestinal (n = 38) and lung (n = 20) tracts were included. Median adherence to the supervised exercise program was 75%. The median number of individual nutritional counselling sessions was 3.0 (range 0-7 sessions). Post intervention, no difference in global health status/quality of life (overall QoL) was observed. Intervention was superior to UC for the patient-rated symptom scale regarding nausea and vomiting (p = 0.023) and protein intake (p = 0.01). No statistical differences were observed for energy intake, nutritional status and physical performance. CONCLUSIONS: The results show good adherence to a combined nutrition and exercise program. The multimodal intervention did not improve overall QoL, but contributed to an adequate protein intake and to the general well-being of the patient by reducing nausea and vomiting.

Are Four Simple Questions Able to Predict Weight Loss in Outpatients With Metastatic Cancer? A Prospective Cohort Study Assessing the Simplified Nutritional Appetite Questionnaire.

BACKGROUND: Severe weight loss is directly responsible for up to one-fifth of all cancer deaths and has a major impact on quality of life. The simplified nutritional appetite questionnaire (SNAQ) was validated to predict weight loss within 6 mo in community-dwelling adults and nursing home residents. METHODS: We prospectively assessed the SNAQ in 133 palliative cancer outpatients. The SNAQ predictions were validated after 3 and 6 mo with the observed weight change. In addition, the treating oncologists gave their predictions concerning future weight loss according to their clinical judgment. RESULTS: A significant weight loss of 5% of the original body weight within 6 mo occurred in 20 (24%) of the 133 patients. The SNAQ predicted weight loss with a sensitivity of 0.38 and a specificity of 0.66 (P-value 0.81). The treating oncologists predicted weight loss with a sensitivity of 0.67 and a specificity of 0.7 (P-value 0.002). CONCLUSION: The SNAQ does not represent a useful tool to predict impending weight loss in palliative cancer outpatients. The predictions of the treating oncologists were more reliable than those from the SNAQ, but remain poor. Better methods to predict weight loss in this patient group are therefore required.

Early combined parenteral and enteral nutrition for pancreaticoduodenectomy - Retrospective cohort analysis.

BACKGROUND: Suggested guidelines for nutritional support after pancreaticoduodenectomy are still controversial. Recent evidence suggests that combining enteral nutrition (EN) with parenteral nutrition (PN) improves outcome. For ten years, patients have been treated with Early Combined Parenteral and Enteral Nutrition (ECPEN) after PD. The aim of this study was to report on rationale, safety, effectiveness and outcome associated with this method. METHODS: Consecutive PD performed between 2003 and 2012 were analyzed retrospectively. Early EN and PN was standardized and started immediately after surgery. EN was increased to 40 ml/h (1 kcal/ml) over 24 h, while PN was supplemented based on a daily energy target of 25 kcal/kg. Standard enteral and parenteral products were used. RESULTS: Sixty-nine patients were nutritionally supplemented according to ECPEN. The median coverage of kcal per patients related to the total caloric requirements during the entire hospitalization (nutrition balance) was 93.4% (range: 100%-69.3%). The nutritional balance in patients with needle catheter jejunostomy (NCJ) was significantly higher than in the group with nasojejunal tube (97.1% vs. 91.6%; p < 0.0001). Mortality rate was 5.8%, while major complications (Clavien-Dindo 3-5) occurred in 21.7% of patients. Neither the presence of preoperative malnutrition nor the application of preoperative immunonutrition was associated with postoperative clinical outcome. CONCLUSION: This is the first European study of ECPEN after PD. ECPEN is safe and, especially in combination with NCJ, provides comprehensive coverage of caloric requirements during the postoperative phase. Clinical controlled trials are needed to investigate potential benefits of complete energy supplementation during the early postoperative phase after PD.

[Epidemiology of malnutrition]. / Die Epidemiologie der Mangelernährung.

The World Health Organisation classifies malnutrition worldwide as the greatest threat to public health. An expert report of the Council of Europe clearly showed that malnutrition in hospitalised patients is a real existing problem in all European countries, including Switzerland. According to the literature, malnutrition is prevalent in 20 - 60 % of patients on hospital admission. Malnutrition increases with age and is found more and more in obese subjects. Unintentional weight loss is the main feature of disease-related malnutrition in normalweight and obese individuals. The nutritional problem in obese persons manifests itself through nutrient imbalances and micronutrient deficiency. The cause for nutritional deficiencies is a hypercaloric diet with its energy - dense, but qualitative low - value foods. Depending on the extent of obesity, certain micronutrients are to be critically evaluated. It has been proven that for instance the vitamin D and iron metabolism are pathologically impaired by the increased fatty tissue. In Switzerland, the proportion of people under 20 years has decreased from 40.7 % (1900) to 20.6 % (2011), whereas in the elderly over 64 years, an increase from 5.8 % to 17.2 % has been recorded. In the very elderly people over 80 years, the increase from 0.5 % to 4.8 % has been particularly pronounced. Because malnutrition increases with age, it will be an important issue in the future and hospitals, nursing homes and home care will be particularly affected.

Influence of a nutritional intervention on dietary intake and quality of life in cancer patients: a randomized controlled trial.

OBJECTIVE: Weight loss is common in patients with malignant tumors and it can adversely affect quality of life and survival. The aim of the present study was to investigate the effects of a nutritional intervention in cancer patients in an outpatient setting. METHODS: Cancer outpatients (N = 58) who were classified as undernourished or at high risk for undernutrition by the Nutritional Risk Screening 2002 tool were randomized into two groups. One group (n = 30) received standardized individual nutritional therapy, including counseling by a dietitian, food fortification, and oral nutritional supplements if required. The second group (n = 28) received standard care. The nutritional intervention lasted 3 mo. Dietary intake (3-d dietary record), nutritional status (body weight), physical functioning (performance status, hand-grip strength) and quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0) were assessed at baseline and after 6 wk and 3 mo. An additional follow-up assessment was carried out 3 mo post-intervention. RESULTS: Nutritional intervention led to a significantly higher average energy and protein intake in the nutritional therapy group (+379 kcal; 95% confidence interval [CI], 117-642; P = 0.007, respectively; +10.4 g; 95% CI, 2.3-18.5; P = 0.016). However, the increased dietary intake was not associated with improvements in nutritional status, physical functioning, or quality of life. CONCLUSIONS: Individual nutritional counseling significantly and positively influenced energy and protein intake, but did not improve nutritional or physical outcome or quality of life. These results indicate that nutritional therapy alone is of limited efficacy in cancer patients whose nutritional status has already deteriorated.

Branched-chain amino acid supplementation during a 100-km ultra-marathon--a randomized controlled trial.

Ultra-marathon running is supposed to increase the parameters of skeletal muscle damage and impair renal function. The purpose of this study was to investigate the effect of branched-chain amino acid supplementation on skeletal muscle damage and renal function during a 100-km ultra-marathon. Twenty-eight athletes were randomly divided into two groups, one group using branched-chain amino acid supplementation (BCAA) and a control group (CON). The athletes in the BCAA group were supplemented with a total of 50 g of an amino acid concentrate including 20 g of BCAA. The intake of energy, antioxidants and parameters of both skeletal muscle damage and renal function were determined. Race time was not different between BCAA and CON when controlled for the personal best time in a 100-km ultra-marathon. Neither the intake of energy and antioxidants nor the parameters of skeletal muscle damage and renal function were different between BCAA and CON. We concluded that BCAA-supplementation before and during a 100-km ultra-marathon had no effect on performance, skeletal muscle damage or renal function.

No effect of short-term amino acid supplementation on variables related to skeletal muscle damage in 100 km ultra-runners - a randomized controlled trial.

BACKGROUND: The purpose of this study was to investigate the effect of short-term supplementation of amino acids before and during a 100 km ultra-marathon on variables of skeletal muscle damage and muscle soreness. We hypothesized that the supplementation of amino acids before and during an ultra-marathon would lead to a reduction in the variables of skeletal muscle damage, a decrease in muscle soreness and an improved performance. METHODS: Twenty-eight experienced male ultra-runners were divided into two groups, one with amino acid supplementation and the other as a control group. The amino acid group was supplemented a total of 52.5 g of an amino acid concentrate before and during the 100 km ultra-marathon. Pre- and post-race, creatine kinase, urea and myoglobin were determined. At the same time, the athletes were asked for subjective feelings of muscle soreness. RESULTS: Race time was not different between the groups when controlled for personal best time in a 100 km ultra-marathon. The increases in creatine kinase, urea and myoglobin were not different in both groups. Subjective feelings of skeletal muscle soreness were not different between the groups. CONCLUSIONS: We concluded that short-term supplementation of amino acids before and during a 100 km ultra-marathon had no effect on variables of skeletal muscle damage and muscle soreness.

Prevalence of exercise-associated hyponatremia in male ultraendurance athletes.

OBJECTIVE: The prevalence of exercise-associated hyponatremia (EAH) has mainly been investigated in marathoners and Ironman triathletes. The aim of this study was to investigate the prevalence of EAH in male ultraendurance athletes in other disciplines, such as ultraswimming, ultracycling, and ultramarathon running. DESIGN: Observational field study. SETTING: "Marathon Swim" in Lake Zurich, the "Swiss Cycling Marathon," the "Swiss Bike Masters," the "100-km Lauf Biel," and the "Swiss Jura Marathon." PARTICIPANTS: Fifteen ultraswimmers, 28 ultra-road cyclists, 37 ultra-mountain bikers, 95 ultramarathoners, and 25 mountain ultramarathoners. MAIN OUTCOME MEASURES: Changes in body mass, plasma sodium, urinary specific gravity, and hematocrit were measured. The athletes recorded their intake of fluids. RESULTS: Two swimmers (13%), 3 road cyclists (10.7%), no mountain bikers (0%), 5 ultramarathoners (5%), and 2 mountain ultramarathoners (8%) developed EAH. In the mountain bikers (r = -0.41) and the 100-km ultramarathoners (r = -0.52), fluid intake was significantly and negatively related to race time. In the mountain ultramarathoners, fluid consumption increased during the race. CONCLUSIONS: The prevalence of EAH was no higher in ultraendurance athletes compared with existing reports on marathoners and Ironman triathletes. Of the 200 investigated ultraendurance athletes, 12 finishers (6%) developed EAH.

No fluid overload in male ultra-runners during a 100 km ultra-run.

We investigated the change in body composition and hydration status in 27 male ultra-runners during a 100 km ultra-run. The athletes drank fluids ad libitum during the run; intake of calories, fluids, and electrolytes during performance were determined. Body mass decreased by 1.9 kg, haematocrit decreased, plasma [Na(+)] remained unchanged, and urinary specific gravity and plasma volume increased. Fluid intake was 0.52 (0.18) L/h and was related to running speed (r = 0.50; p = 0.0081). Δ body mass was associated with total fluid intake during the race (r = 0.49, p = 0.0095). Sodium intake amounted to 425 (478) mg/h and potassium intake to 140 (179) mg/h. Sodium and potassium intake were not related to either postrace concentration or change in plasma concentration. Sodium intake, however, was related to Δ urinary sodium concentration (r = 0.45, p = 0.0227). The increase in plasma volume was significantly and negatively related to both postrace plasma [Na(+)] (r = - 0.42, p = 0.0278) and the postrace potassium-to-sodium ratio in urine (r = - 0.44, p = 0.0218). To conclude, we found no fluid overload in these ultra-runners, the increase in plasma volume was most probably due to a stimulation of the renin-angiotensin-aldosterone system (RAAS) since sodium intake was not related to both the change in plasma [Na(+)] or postrace plasma [Na(+)].

Maintained total body water content and serum sodium concentrations despite body mass loss in female ultra-runners drinking ad libitum during a 100 km race.

We investigated in 11 female ultra-runners during a 100 km ultra-run, the association between fluid intake and prevalence of exercise-associated hyponatremia in a cross-sectional study. Athletes drank ad libitum and recorded their fluid intake. They competed at 8.0 (1.0) km/h and finished within 762 (91) min. Fluid intake was 4.1 (1.3) L during the race, equal to 0.3 (0.1) L/h. Body mass decreased by 1.5 kg (p< 0.01); pre race body mass was related to speed in the race (r = -0.78, p< 0.05); and change (Delta) in body mass was not associated with speed in the race. Change in body mass was positively (r = 0.70; p< 0.05), and Delta urinary specific gravity negatively (r = -0.67; p< 0.05), correlated to Delta percent total body water. Changes in body mass were not related to fluid intake during the race. Fluid intake was not correlated to running speed and showed no association with either Delta percent total body water nor Delta [Na] in plasma. Fluid intake showed no relationship with both Delta haematocrit and Delta plasma volume. No exercise-associated hyponatremia occurred. Female ultra- runners consuming fluids ad libitum during the race experienced no fluid overload, and ad libitum drinking protects against exercise-associated hyponatremia. The reported higher incidence of exercise-associated hyponatremia in women is not really a gender effect but due to women being more prone to overdrink.

Nutritional counseling improves quality of life and nutrient intake in hospitalized undernourished patients.

OBJECTIVE: Up to 60% of hospitalized patients are undernourished. We studied the impact of nutritional therapy on quality of life and food intake. METHODS: Undernourished patients were randomized into two groups. The nutritional therapy group (NT group) received individual nutritional counseling and interventions, including oral nutritional supplements if appropriate, by a dietitian. The oral nutritional supplement group (ONS group) received oral nutritional supplements in addition to hospital meals without further instruction or counseling. Study duration was 10 to 15 d. At baseline and before discharge (time point 1) we measured energy and protein intakes and quality of life. Quality of life was measured again 2 mo after discharge (time point 2). RESULTS: Energy and protein intakes increased between baseline and time point 1 in both groups (P=0.001). The NT group (n=18) met the energy requirements at time point 1 by 107% and of protein by 94%, the ONS group (n=18) by 90% and 88%, respectively. Hospital meals alone did not cover the requirements. From baseline to time point 1, quality of life increased in both groups. Quality of life increased further in the NT group from time point 1 to time point 2 (P=0.016), but not in the ONS group. CONCLUSION: Both interventions caused a significant increase in energy and protein intakes and quality of life. In the NT group every patient received an efficacious individualized intervention. In contrast, the 7 of 18 patients in the ONS group who did not consume ONS had no intervention at all. Therefore, undernourished patients should be counseled individually by a dietitian.