Protein is an important component of nutritional support predicting complications in malnourished hospitalised patients - Details of our previous randomised controlled trial (RCT).

BACKGROUND AND AIMS: Nutritional support can be an effective tool to avoid and reduce malnutrition. However, it is unclear which component, i.e. nutrient, is most efficient. With the present analysis we define the most important predictors of the body weight change and the complication incidence during hospitalisation. METHODS: Data of our previous randomised controlled nutritional trail was analysed according to per-protocol. A factor analysis was performed using binary logistic and multiple linear regression analyses with the outcome variables "complication yes/no" and "body weight change", respectively. RESULTS: Repeated measure ANOVA revealed a highly significant intervention effect for both protein and caloric intake (p < 0.001) after 5 and 10 days of intervention. Patients of the intervention group (IG; n = 59) were able to keep their body weight in contrast to control group (CG; n = 59) patients (68.3 (15.5) kg vs. 64.4 (15.8) kg, p = 0.003). The mean plasma ascorbic acid level was higher in IG than in CG at discharge (47.2 (26.8) µmol/l vs. 34.1 (24.2) µmol/l, p = 0.005). The number of patients suffering from in-hospital complications was lower in IG than in CG (4/59 vs. 13/59, p = 0.034). Positive effects on the antibiotic therapies for infectious complications (1/58 vs. 8/59, p = 0.032), the SF-36 physical summary scale (37 (11) % vs. 33 (9), p = 0.039) and the readmission rates (26/54 vs. 43/58, p = 0.019) were recorded. The mean protein intake predicted the chance of having a complication whereas the body weight change was best predicted by the mean caloric intake. CONCLUSIONS: Caloric and protein intake are important predictors of complications and the change in body weight, respectively. In contrast, age and disease severity did not influence the outcome in our nutritional trial.

Budget impact of parenteral iron treatment of iron deficiency: methodological issues raised by using real-life data.

OBJECTIVES: Iron deficiency is common in pregnancy, postpartum, inflammatory bowel disease, chronic kidney disease, chronic heart failure, heavy uterine bleeding, cancer and following surgery. We estimate the budget impact (BI) on the Swiss mandatory health insurance associated with substituting iron sucrose (standard) with ferric carboxymaltose (new treatment) using real-life data. METHODS: Resource use was based on recent primary data (Polyquest Prescriber Analysis, Anemia Patient Record Study in Switzerland). Personnel costs were estimated using the Swiss Tarmed fee-for-service reimbursement system. Drug costs and costs of materials used were based on official tariffs (Spezialitätenliste, MiGeL). Actual IMS sales data of both products were used to verify the BI model (1 CHF ≈ 1 USD, Jan 2013). RESULTS: Ferric carboxymaltose was associated with cost savings of 30-44 % per patient per treatment cycle compared to iron sucrose. Costs per 200/500/1,000 mg total dosage treatment cycle were CHF 101/210/420 for ferric carboxymaltose and CHF 144/375/721 for iron sucrose. This results in cost savings of CHF 22-31 million across all indications in 2009. Savings were driven by personnel cost reductions (application time and number of applications). Sensitivity analyses confirmed these cost savings, even for the higher application costs of ferric carboxymaltose, with minimum savings of CHF 17 million per year. CONCLUSIONS: Treating iron deficiency involves substantial costs to the Swiss MHI which may be reduced by substituting iron sucrose with ferric carboxymaltose. The use of real-life data raises methodological questions about the fundamental compatibility of this data with the conceptual framework of BI analysis.

Symptom-modifying effect of chondroitin sulfate in knee osteoarthritis: a meta-analysis of randomized placebo-controlled trials performed with structum(®).

OBJECTIVE: To perform a meta-analysis of randomized double-blind placebo-controlled clinical trials to assess the efficacy of a specific chondroitin sulfate preparation (Structum®, Laboratoires Pierre Fabre, Castres; France) as a symptom-modifying drug in osteoarthritis (OA) of the knee. METHODS: A Medline search was conducted up to October 2010 and two articles reporting two trials were identified; one additional trial was identified through contacting the producer of Structum®. There was no evidence of heterogeneity across the trials and results were pooled using a fixed effects model. RESULTS: Pooled results demonstrated a modest, but significant effect of Structum® (1 g daily) over placebo on the reduction of pain during activity following a treatment period of 3-6 months of 6 mm (95% confidence interval (CI) -9.50, -1.72, p=0.005) on the visual analog scale (VAS) and a reduction in the algo-functional Index (AFI) by a weighted mean difference of -0.73 (95% CI -1.28 to -0.18, p=0.01). In addition, the pooled analysis demonstrated a statistically significant increase in OMERACT-OARSI responders in the Structum®-treated patients by 20% (RR of 1.20 (95% CI 1.06 to 1.36, p=0.003)), compared to placebo. CONCLUSION: These results demonstrate that this chondroitin sulfate preparation (Structum®) is effective on symptoms in patients with OA of the knee compared to placebo, and may therefore have a role in the management of patients with knee osteoarthritis of Kellgren-Lawrence grades II and III.

Effects of a preconditioning oral nutritional supplement on pig livers after warm ischemia.

Background. Several approaches have been proposed to pharmacologically ameliorate hepatic ischemia/reperfusion injury (IRI). This study was designed to evaluate the effects of a preconditioning oral nutritional supplement (pONS) containing glutamine, antioxidants, and green tea extract on hepatic warm IRI in pigs. Methods. pONS (70 g per serving, Fresenius Kabi, Germany) was dissolved in 250 mL tap water and given to pigs 24, 12, and 2 hrs before warm ischemia of the liver. A fourth dose was given 3 hrs after reperfusion. Controls were given the same amount of cellulose with the same volume of water. Two hours after the third dose of pONS, both the portal vein and the hepatic artery were clamped for 40 min. 0.5, 3, 6, and 8 hrs after reperfusion, heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), portal venous flow (PVF), hepatic arterial flow (HAF), bile flow, and transaminases were measured. Liver tissue was taken 8 hrs after reperfusion for histology and immunohistochemistry. Results. HR, MAP, CVP, HAF, and PVF were comparable between the two groups. pONS significantly increased bile flow 8 hrs after reperfusion. ALT and AST were significantly lower after pONS. Histology showed significantly more severe necrosis and neutrophil infiltration in controls. pONS significantly decreased the index of immunohistochemical expression for TNF-α, MPO, and cleaved caspase-3 (P < 0.001). Conclusion. Administration of pONS before and after tissue damage protects the liver from warm IRI via mechanisms including decreasing oxidative stress, lipid peroxidation, apoptosis, and necrosis.

Plant polyphenols attenuate hepatic injury after hemorrhage/resuscitation by inhibition of apoptosis, oxidative stress, and inflammation via NF-kappaB in rats.

PURPOSE: Oxidative stress and inflammation contribute to hepatic injury after hemorrhage/resuscitation (H/R). Natural plant polyphenols, i.e., green tea extract (GTE) possess high anti-oxidant and anti-inflammatory activities in various models of acute inflammation. However, possible protective effects and feasible mechanisms by which plant polyphenols modulate pro-inflammatory, apoptotic, and oxidant signaling after H/R in the liver remain unknown. Therefore, we investigated the effects of GTE and its impact on the activation of NF-kappaB in the pathogenesis of hepatic injury induced by H/R. METHODS: Twenty-four female LEWIS rats (180-250 g) were fed a standard chow (ctrl) or a diet containing 0.1% polyphenolic extracts (GTE) from Camellia sinensis starting 5 days before H/R. Rats were hemorrhaged to a mean arterial pressure of 30 ± 2 mmHg for 60 min and resuscitated (H/R and GTE H/R groups). Control groups (sham, ctrl, and GTE) underwent surgical procedures without H/R. Two hours after resuscitation, tissues were harvested. RESULTS: Plasma alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increased 3.5-fold and fourfold, respectively, in vehicle-treated rats as compared to GTE-fed rats. Histopathological analysis revealed significantly decreased hepatic necrosis and apoptosis in GTE-fed rats after H/R. Real-time PCR showed that GTE diminished gene expression of pro-apoptotic caspase-8 and Bax, while anti-apoptotic Bcl-2 was increased after H/R. Hepatic oxidative (4-hydroxynonenal) and nitrosative (3-nitrotyrosine) stress as well as systemic IL-6 level and hepatic IL-6 mRNA were markedly reduced in GTE-fed rats compared with controls after H/R. Plant polyphenols also decreased the activation of both JNK and NFκB. CONCLUSIONS: Taken together, GTE application blunts hepatic damage, apoptotic, oxidative, and pro-inflammatory changes after H/R. These results underline the important roles of JNK and NF-kappaB in inflammatory processes after H/R and the beneficial impact of plant polyphenols in preventing their activation.

Green tea extract ameliorates reperfusion injury to rat livers after warm ischemia in a dose-dependent manner.

SCOPE: Polyphenolic constituents of green tea (Camellia sinensis) have been shown to be potent scavengers of reactive oxygen species (ROS). Thus, this study was designed to assess its effects after liver ischemia-reperfusion. METHODS AND RESULTS: Fasted Sprague-Dawley rats were gavaged with different concentrations of green tea extract (GTE) 2 h before 90 min of warm ischemia of the left lateral liver lobe (30% of liver). Controls were given the same volume of Ringer's solution. A preparation of pentobarbital sodium (intraperitoneal) and ketamine (intramuscular) was used for anesthesia. After reperfusion, transaminases, liver histology, hepatic microcirculation, and both phagocytosis of latex bead particles as well as the expression of tumor necrosis alpha (TNF-α) to index cellular activation were investigated. Furthermore, the expression of superoxide dismutase (Mn-SOD) was assessed. After 90 min of warm ischemia aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) increased dramatically to 1946 ± 272/3244 ± 757 U/L, 1680 ± 134/2080 ± 379 U/L, and 7857 ± 1851/2036 ± 1193 U/L at 2/6 h, respectively. GTE (200 mg/kgbody weight) significantly prevented this increase in a dose-dependent manner by 21-51% at 2 h and 29-34% at 6 h, respectively. Histology confirmed the protective effects while both TNF-α expression and phagocytosis of latex beads by Kupffer cells (KCs) were significantly reduced. GTE intake significantly increased the expression of manganese superoxide dismutase. In vivo microscopy revealed improved acinar and sinusoidal perfusion after GTE. CONCLUSION: Preconditioning with a single oral dose of GTE ameliorates ischemia-reperfusion injury in liver. Decreased cellular activation and improved microcirculation are the proposed mechanisms.

The use of high-dose melatonin in liver resection is safe: first clinical experience.

Experimental data suggest that melatonin decreases inflammatory changes after major liver resection, thus positively influencing the postoperative course. To assess the safety of a preoperative single dose of melatonin in patients undergoing major liver resection, a randomized controlled double-blind pilot clinical trial with two parallel study arms was designed at the Department of General and Transplantation Surgery, Ruprecht-Karls-University, Heidelberg. A total of 307 patients, who were referred for liver surgery, were screened. One hundred and thirteen patients, for whom a major liver resection (≥3 segments) was scheduled, were eligible. Sixty-three eligible patients refused to participate, and therefore, 50 patients were randomized. A preoperative single dose of melatonin (50 mg/kg BW) dissolved in 250 mL of milk was administered through the gastric tube after the intubation for general anesthesia. Controls were given the same amount of microcrystalline cellulose. Primary endpoint was safety. Secondary endpoints were postoperative complications. Melatonin was effectively absorbed with serum concentrations of 1142.8 ± 7.2 ng/mL (mean ± S.E.M.) versus 0.3 ± 7.8 ng/mL in controls (P < 0.0001). Melatonin treatment resulted in lower postoperative transaminases over the study period (P = 0.6). There was no serious adverse event in patients after melatonin treatment. A total of three infectious complications occurred in either group. A total of eight noninfectious complications occurred in five control patients, whereas three noninfectious complications occurred in three patients receiving preoperative melatonin (P = 0.3). There was a trend toward shorter ICU stay and total hospital stay after melatonin treatment. Therefore, a single preoperative enteral dose of melatonin is effectively absorbed and is safe and well tolerated in patients undergoing major liver surgery.

Effects of green tea catechins on the pro-inflammatory response after haemorrhage/resuscitation in rats.

Plant polyphenols, i.e. green tea extract (GTE), possess high antioxidative and anti-inflammatory capacity, thus being protective in various models of acute inflammation. However, their anti-inflammatory effect and a feasible mechanism in haemorrhage/resuscitation (H/R)-induced liver injury remain unknown. We investigated the effects of GTE and the role of NF-κB in the pathogenesis of liver injury induced by H/R, and their effects on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration. Female Lewis rats were fed a standard chow diet (control, ctrl) or a diet containing 0·1 % polyphenolic GTE for five consecutive days before H/R. Rats were haemorrhaged to a mean arterial pressure of 30 (sem 2) mmHg for 60 min and resuscitated. Control groups (sham_ctrl and sham_GTE) underwent surgical procedures without H/R. At 2 h after resuscitation, tissues were harvested. Serum alanine aminotransferase (ALT) and IL-6 were measured. Hepatic necrosis, ICAM-1 expression and polymorphonuclear leucocyte (PMNL) infiltration were assessed. Hepatic expression of IκBα (phospho) was measured. H/R induced strong liver damage with increased necrosis and serum ALT levels. Compared with both sham groups, inflammatory markers (serum IL-6 and hepatic PMNL infiltration) were elevated after H/R (P < 0·05). Also, H/R increased IκBα phosphorylation. GTE administration markedly (P < 0·05) decreased serum ALT and IL-6 levels, hepatic necrosis as well as PMNL infiltration and the expression of ICAM-1 and phosphorylated IκBα compared with H/R. In conclusion, we observed that NF-κB activation plays an important role in the pathogenesis of liver injury after H/R through the up-regulation of hepatic ICAM-1 expression and subsequent PMNL infiltration. GTE pre-treatment prevents liver damage in this model of acute inflammation through a NF-κB-dependent mechanism.

Short-term individual nutritional care as part of routine clinical setting improves outcome and quality of life in malnourished medical patients.

BACKGROUND & AIMS: Strategies to treat malnutrition lack practicability in the hospital setting. The present study aimed at developing and evaluating a routinely manageable concept for an improved nutritional care of malnourished in-hospital patients. METHODS: A randomized controlled intervention study was conducted. 132 risk patients defined by Nutritional Risk Screening 2002, were randomized to individualised nutrition support (intervention group [n = 66]) or standard hospital care (control group [n = 66]). Body weight, plasma vitamin levels, quality of life, complications, antibiotic therapies, readmissions and mortality were assessed. RESULTS: Nutrition interventions led to higher intakes (mean [standard deviation]) in energy (1553 [341] kcal vs. 1115 [381] kcal, p < 0.001) and protein (65.4 [16.4] g vs. 43.9 [17.2] g, p < 0.001). Intervention patients (n = 66) kept their body weight in comparison to control patients (n = 66; 0.0 [2.9] kg vs. -1.4 [3.2] kg, p = 0.008). Positive effects on plasma ascorbic acid level (46.7 [26.7] µmol/l vs. 34.1 [24.2] µmol/l, p = 0.010), SF-36 function summary scale (37 [11] % vs. 32 [9] %, p = 0.030), number of complications (4/66 vs. 13/66, p = 0.035), antibiotic therapies (1/66 vs. 8/66, p = 0.033) and readmissions (17/64 vs. 28/61, p = 0.027) were recorded. CONCLUSIONS: Malnourished patients profit from nutrition support regarding nutrition status and quality of life. They have fewer complications, need fewer antibiotics and are less often re-hospitalised.

Trends and stabilization up to 2022 in overweight and obesity in Switzerland, comparison to France, UK, US and Australia.

In Switzerland a rapid increase in the total overweight population (BMI > or = 25) from 30.3% to 37.3% and in the obese segment (BMI > or = 30) from 5.4% to 8.1% was observed between 1992 and 2007. The objective of this study is to produce a projection until 2022 for the development of adult overweight and obesity in Switzerland based on four National Health Surveys conducted between 1992 and 2007. Based on the projection, these prevalence rates may be expected to stabilize until 2022 at the 2007 level. These results were compared with future projections estimated for France, UK, US and Australia using the same model.

Melatonin protects from hepatic reperfusion injury through inhibition of IKK and JNK pathways and modification of cell proliferation.

Reactive oxygen species (ROS) are involved in pathophysiology of ischemia/reperfusion injury. Melatonin is a potent scavenger of ROS. Thus, this study was designed to elucidate its effects in a combined hepatic warm ischemia and resection model. The right lateral and caudate lobes (32% of liver volume) of Sprague-Dawley rats underwent warm ischemia for 30 min followed by reperfusion and subsequent resection of the nonischemic liver tissue. Some rats were gavaged with 50 mg/kg melatonin 2 hr before the onset of experiments. Controls received the same volume of microcrystalline cellulose. Survival, transaminases, histology, flow cytometry, inducible nitric oxide synthase (iNOS) expression, and activation of signal transduction pathways [c-Jun N-terminal kinase (JNK), cJUN, IkappaB kinase alpha (IKKalpha), proliferating cell nuclear antigen (PCNA), and Ki67] were assessed for hepatic injury, oxidative stress, and cell proliferation. Melatonin significantly improved animal survival and decreased transaminase levels, the indices for necrosis, liver damage, leukocyte infiltration, and iNOS expression. In parallel, the expression of IKKalpha, JNK1, and cJUN decreased by 35-50% after melatonin (P < 0.05). At the same time, melatonin reduced the expression of both PCNA and Ki67 in liver (P < 0.05). Melatonin is hepatoprotective most likely via mechanisms including inhibition of IKK and JNK pathways and regulation of cell proliferation.

Cost analysis of parenteral nutrition regimens in the intensive care unit: three-compartment bag system vs multibottle system.

BACKGROUND: Parenteral nutrition (PN) can be administered with separate bottles or as commercially prepared all-in-one systems. The aim of this study was to evaluate the overall cost of PN using the 3-compartment bag vs standard multibottle system. METHODS: Overall costs of hospital PN were calculated from expenditures (solutions, consumable items, and staff costs). Time that staff spent preparing the PN was measured to determine personnel costs; bottom-up costing was used to assign a monetary value. Standard treatment algorithms of a 10-day course of PN for a standard 70-kg patient were specified for both systems. One-way sensitivity analyses were performed to test the robustness of the model's conclusions. RESULTS: The daily total cost of the 3-compartment bag system was euro42.26 per patient whereas the total cost of the separate bottle system was euro51.62, resulting in a cost saving of euro9.36 per patient with the 3-compartment bag system. For 10 days of treatment, PN costs euro422.51 per patient for the 3-compartment system vs euro516.16 for the multibottle system. Sensitivity analyses showed that the difference in costs between the 2 systems was maintained in the face of changes in patients' nutrition requirements and personnel costs. CONCLUSIONS: The costs associated with PN using a 3-compartment bag system were lower than those associated with a multibottle system. Given the established therapeutic equivalence of the 2 systems, this study shows the 3-compartment bag system to be the system of choice to reduce costs.

PORTAL: pilot study on the safety and tolerance of preoperative melatonin application in patients undergoing major liver resection: a double-blind randomized placebo-controlled trial.

BACKGROUND: Major surgical procedures facilitate systemic endotoxinemia and formation of free radicals with subsequent inflammatory changes that can influence the postoperative course. Experimental data suggest that preoperative supraphysiological doses of melatonin, a potent immuno-modulator and antioxidant, would decrease postoperative infectious and non-infectious complications induced by major abdominal surgery. METHODS/DESIGN: A randomized controlled double blind single center clinical trial with two study arms comprising a total of 40 patients has been designed to assess the effects of a single preoperative dose of melatonin before major liver resection. Primary endpoints include the determination of safety and tolerance of the regimen as well as clinical parameters reflecting pathophysiological functions of the liver. Furthermore, data on clinical outcome (infectious and non-infectious complications) will be collected as secondary endpoints to allow a power calculation for a randomized clinical trial aiming at clinical efficacy. DISCUSSION: Based on experimental data, this ongoing clinical trial represents an advanced element of the research chain from bench to bedside in order to reach the highest level of evidence-based clinical facts to determine if melatonin can improve the general outcome after liver resection. TRIAL REGISTRATION: EudraCT200600530815.

Uncertainty in decision-making: value of additional information in the cost-effectiveness of lifestyle intervention in overweight and obese people.

OBJECTIVES: To quantify the uncertainty in the cost-effectiveness of lifestyle intervention versus standard care in overweight and obese people in Switzerland and to determine if further research is necessary based on current information. There has been an increasing interest in using value of information analysis in medical decision-making to quantify the uncertainty in decision-making, and to identify the need for further research. METHODS: Value of information analysis was applied on a probabilistic cost-effectiveness model to evaluate the uncertainty by calculating the patient expected value of perfect information (EVPI), population EVPI, and partial EVPI. The costs were expressed in Swiss Francs (CHF), price year 2006. RESULTS: Overall, the EVPI was higher in overweight than in obese people. The maximum population EVPI was CHF 6.8 million in overweight people and CHF 3.2 million in moderate obese people, representing the upper limit on costs associated with decision uncertainty. The partial EVPI estimated a higher uncertainty in the model parameters such as utilities, body mass index, cardiovascular risk factors, and systolic blood pressure in overweight and moderate obese subjects. CONCLUSIONS: The EVPI analysis indicates that there is some uncertainty regarding the choice between lifestyle intervention and standard care. The parameter EVPI suggests that if further research is commissioned, this should focus on the effectiveness of lifestyle intervention on cardiovascular risk factors and utilities.

Early enteral supplementation with key pharmaconutrients improves Sequential Organ Failure Assessment score in critically ill patients with sepsis: outcome of a randomized, controlled, double-blind trial.

OBJECTIVE: To assess the safety and efficacy of an early enteral pharmaconutrition supplement containing glutamine dipeptides, antioxidative vitamins and trace elements, and butyrate in critically ill, septic patients. DESIGN: A prospective, randomized, controlled, double-blind clinical trial. SETTING: Adult intensive care unit in a university hospital. PATIENTS: Fifty-five critically ill, septic patients requiring enteral feeding. INTERVENTIONS: Patients received either an enteral supplement (500 mL of Intestamin, Fresenius Kabi) containing conditionally essential nutrients or a control solution via the nasogastric route for up to 10 days. Inclusion occurred within 24 hrs of intensive care unit admission. Additionally, patients received enteral feeding with an immunonutrition formula (experimental group) or standard formula (control group) initiated within 48 hrs after enrollment. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed by daily total Sequential Organ Failure Assessment (SOFA) score over the 10-day study period in both patient groups. Patients receiving the experimental supplement showed a significantly faster decline in the regression slopes of delta daily total SOFA score over time compared with control. The difference between the regression coefficients of the two slopes was significant irrespective of the level of analysis: intent to treat -0.32 vs. -0.14, p < .0001; per protocol -0.34 vs. -0.14, p < .0001; and completers (patients receiving > or = 80% of the calculated caloric target over a period of 6 days), -0.26 vs. -0.16, p = .0005. Vitamin C, as a marker of supplement absorption, increased from 10.6 (1.9-159.4) micromol/L (normal range 20-50 micromol/L) on day 1 to 58.7 (5.4-189.9) micromol/L by day 3 (p = .002) in the intervention group but remained below the normal range in the control group 17.0 (2.8-78.5) on day 1 and 14.3 (2.4-179.6) on day 3. Serum levels of glycine, serine, arginine, ornithine, vitamin E, and beta-carotene all increased significantly with treatment in the supplementation group. CONCLUSIONS: In medical patients with sepsis, early enteral pharmaconutrition with glutamine dipeptides, vitamin C and E, beta-carotene, selenium, zinc, and butyrate in combination with an immunonutrition formula results in significantly faster recovery of organ function compared with control.

PROUD: effects of preoperative long-term immunonutrition in patients listed for liver transplantation.

BACKGROUND: Patients with end stage liver disease are characteristically malnourished which is associated with poor outcome. Formulas enriched with arginine, omega-3 fatty acids, and nucleotides, "immunonutrients", potentially improve their nutritional status. This study is designed to evaluate the clinical outcome of long-term "immunonutrition" of patients with end-stage liver disease while on the waiting list for liver transplantation. METHODS/DESIGN: A randomized controlled double blind multi-center clinical trial with two parallel groups comprising a total of 142 newly registered patients for primary liver transplantation has been designed to assess the safety and efficacy of the long-term administration of ORAL IMPACT, an "immunonutrient" formula, while waiting for a graft. Patients will be enrolled the day of registration on the waiting list for liver transplantation. Study ends on the day of transplantation. Primary endpoints include improved patients' nutritional and physiological status, as measured by mid-arm muscle area, triceps skin fold thickness, grip strength, and fatigue score, as well as patients' health related quality of life. Furthermore, patients will be followed for 12 postoperative weeks to evaluate anabolic recovery after transplantation as shown by reduced post-transplant mechanical ventilation, hospital stay, wound healing, infectious morbidities (pneumonia, intraabdominal abscess, sepsis, line sepsis, wound infection, and urinary tract infection), acute and chronic rejection, and mortality. DISCUSSION: Formulas enriched with arginine, omega-3 fatty acids, and nucleotides have been proven to be beneficial in reducing postoperative infectious complications and length of hospital stay among the patients undergoing elective gastrointestinal surgery. Possible mechanisms include downregulation of the inflammatory responses to surgery and immune modulation rather than a sole nutritional effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT00495859.

Meta-analysis of the efficacy of a single dose of phenylephrine 10 mg compared with placebo in adults with acute nasal congestion due to the common cold.

BACKGROUND: Although nonprescription oral phenylephrine 10 mg has been judged "generally recognized as safe and effective" by the US Food and Drug Administration (FDA), its efficacy as a nasal decongestant has been questioned. OBJECTIVE: This study assessed available data on the efficacy of oral phenylephrine 10 mg as a nasal decongestant. METHODS: Three sources were used to identify potentially relevant publications--the bibliography of the phenylephrine section of the 1976 FDA monograph on over-the-counter cold, cough, allergy, bronchodilator, and antiasthmatic products; a 2004 Cochrane Review of nasal decongestants for the common cold; and a search of MEDLINE from 1966 through January 2007 using the term phenylephrine nasal. To be included in the analyses, studies had to have a single-dose, randomized, placebo-controlled design; involve an orally administered product in which phenylephrine 10 mg was the sole active ingredient; enroll patients with acute nasal congestion due to the common cold; evaluate nasal airway resistance (NAR) as the efficacy end point; and have sufficient data in the study report to allow reanalysis and/or meta-analysis of phenylephrine 10 mg versus placebo. Reanalysis of individual studies and fixed-effects and random-effects meta-analyses were performed. Statistical significance at 30 and 60 minutes after dosing (the primary time points) and a >or=20% reduction in NAR from baseline were considered indicative of a clinically meaningful difference. RESULTS: Fifteen potentially relevant studies were identified, of which 8 met the inclusion criteria. Data from 7 crossover studies involving a total of 113 subjects were reanalyzed and then pooled for meta-analysis; results from the initial phase of the eighth study, a parallel-group trial involving 50 subjects, were included in the reanalysis of individual studies but not in the meta-analyses. Significant differences in favor of phenylephrine were seen in 4 of the 8 studies (P or=20% with phenylephrine. CONCLUSION: These meta-analyses of 7 crossover studies and the reanalysis of a parallel-group study support the effectiveness of a single oral dose of phenylephrine 10 mg as a decongestant in adults with acute nasal congestion associated with the common cold.

Preoperative immunonutrition suppresses perioperative inflammatory response in patients with major abdominal surgery-a randomized controlled pilot study.

BACKGROUND/AIM: Perioperative administration of immunoenriched diets attenuates the perioperative inflammatory response and reduces postoperative infection complications. However, many questions still remain unresolved in this area, such as the length of diet administration, diet composition, and the mechanisms involved. We performed an open, randomized, triple-arm study comparing the effect of two perioperative feeding regimens with a postoperative one. METHODS: 46 candidates for major elective surgery for malignancy in the upper gastrointestinal tract were randomized to drink preoperatively either 1 L of an immunoenriched formula (Impact) for 5 days (IEF group) or 1 L of Impact plus (Impact enriched with glycine) for 2 days (IEF plus group). The same product as the patient received preoperatively was given to both groups for 7 days postoperatively. In the control group (CON group), patients only received Impact for 7 days postoperatively; there was no preoperative treatment. The main outcome measures were postoperative C-reactive protein (CRP) serum levels. RESULTS: In the two preoperatively supplemented groups (treatment groups), perioperative endotoxin levels, CRP (postoperative day 7), and TNF-alpha (postoperative days 1 and 3) levels were significantly lower compared to the CON group (p < .01). Furthermore, the length of postoperative IMU/ICU stay (Impact 1.9 +/- 1.3 days; Impact plus 2.2 +/- 1.1 days; control group 5.9 +/- 0.8 days) and length of hospital stay (Impact 19.7 +/- 2.3 days; Impact plus 20.1 +/- 1.3 days; control group 29.1 +/- 3.6 days) were both reduced in the treatment groups compared to the control group. Infectious complications (Impact 2/14 (14%); Impact plus 5/17 (29%); control group 10/15 (67%)) also showed a trend toward reduction in the treatment groups. CONCLUSIONS: Perioperative administration of an immunoenriched diet significantly reduces systemic perioperative inflammation and postoperative complications in patients undergoing major abdominal cancer surgery, when compared with postoperative diet administration alone. A shortened preoperative feeding regimen of 2 days with Impact enriched with glycine (Impact plus) was as effective as Impact administered for 5 days preoperatively.

A German national prevalence study on the cost of intensive care: an evaluation from 51 intensive care units.

INTRODUCTION: Intensive care unit (ICU) costs account for up to 20% of a hospital's costs. We aimed to analyse the individual patient-related cost of intensive care at various hospital levels and for different groups of disease. METHODS: Data from 51 ICUs all over Germany (15 primary care hospitals and 14 general care hospitals, 10 maximal care hospitals and 12 focused care hospitals) were collected in an observational, cross-sectional, one-day point prevalence study by two external study physicians (January-October 2003). All ICU patients (length of stay > 24 hours) treated on the study day were included. The reason for admission, severity of illness, surgical/diagnostic procedures, resource consumption, ICU/hospital length of stay, outcome and ICU staffing structure were documented. RESULTS: Altogether 453 patients were included. ICU (hospital) mortality was 12.1% (15.7%). The reason for admission and the severity of illness differed between the hospital levels of care, with a higher amount of unscheduled surgical procedures and patients needing mechanical ventilation in maximal care hospital and focused care hospital facilities. The mean total costs per day were euro 791 +/- 305 (primary care hospitals, euro 685 +/- 234; general care hospitals, euro 672 +/- 199; focused care hospitals, euro 816 +/- 363; maximal care hospitals, euro 923 +/- 306), with the highest cost in septic patients (euro 1,090 +/- 422). Differences were associated with staffing, the amount of prescribed drugs/blood products and diagnostic procedures. CONCLUSION: The reason for admission, the severity of illness and the occurrence of severe sepsis are directly related to the level of ICU cost. A high fraction of costs result from staffing (up to 62%). Specialized and maximum care hospitals treat a higher proportion of the more severely ill and most expensive patients.

Prevention and treatment of obesity with lifestyle interventions: review and meta-analysis.

OBJECTIVE: To assess the mid- to long-term effectiveness of lifestyle interventions in the prevention and treatment of obesity. METHODS: A systematic literature review with meta-analysis was performed. Electronic databases, reference lists, books and reports covering topic of obesity were searched. The included studies were randomized clinical trials of lifestyle interventions in overweight and obese subjects that had a minimum observation period of one year. Outcomes evaluated were measurements of body weight, body mass index, waist circumference, systolic and diastolic blood pressure, blood lipids: total cholesterol, low density lipoprotein, high density lipoprotein, triglyceride, blood glucose control: two-hour plasma glucose, fasting plasma glucose, and glycosylated haemoglobin. RESULTS: Thirteen studies have been selected in the prevention and seventeen in the treatment of obesity. Compared with standard care, lifestyle intervention reduced significantly body weight, body mass index, waist circumference, blood pressure, blood lipids and blood glucose in overweight and obese people. The favorable effects were maintained up to three years. CONCLUSIONS: Lifestyle interventions were efficacious in the mid- to long-term prevention and treatment of obesity leading to a significant reduction in body weight and cardiovascular risk factors.