Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable, with 99% overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.

Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer.

BACKGROUND: Adipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy. For this reason, we assessed the expression of the lipolysis-associated genes and proteins in subcutaneous adipose tissue (SAT) of gastrointestinal (GI) cancer patients compared to controls to verify their involvement in cancer, among different types of GI cancers, and in cachexia. METHODS: We considered patients with GI cancer (gastric, pancreatic, and colorectal) at their first diagnosis, with/without cachexia, and controls with benign diseases. We collected SAT and total RNA was extracted and ATGL, HSL, PPARα, and MCP1 were analyzed by qRT-PCR. Western blot was performed to evaluate CGI-58, PLIN1 and PLIN5. RESULTS: We found higher expression of ATGL and HSL in GI cancer patients with respect to controls (p ≤ 0.008) and a trend of increase for PPARα (p = 0.055). We found an upregulation of ATGL in GI cancer patients with cachexia (p = 0.033) and without cachexia (p = 0.017) vs controls. HSL was higher in patients with cachexia (p = 0.020) and without cachexia (p = 0.021), compared to controls. ATGL was upregulated in gastric cancer vs controls (p = 0.014) and higher HSL was found in gastric (p = 0.008) and in pancreatic cancer (p = 0.033) vs controls. At the protein level, we found higher CGI-58 in cancer vs controls (p = 0.019) and in cachectic vs controls (p = 0.029), as well as in gastric cancer vs controls (p = 0.027). CONCLUSION: In our cohort of GI cancer patients, we found a modulation in the expression of genes and proteins involved in lipolysis, and differences were interestingly detected according to cancer type.

Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the etiologic criterion for inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified-Delphi review. A multi-round review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable with 99 % overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (mg/dL or mg/L) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgement based upon underlying diagnosis or condition, clinical signs, or CRP.

Standardization of Body Composition Status in Patients with Advanced Urothelial Tumors: The Role of a CT-Based AI-Powered Software for the Assessment of Sarcopenia and Patient Outcome Correlation.

BACKGROUND: Sarcopenia is a well know prognostic factor in oncology, influencing patients' quality of life and survival. We aimed to investigate the role of sarcopenia, assessed by a Computed Tomography (CT)-based artificial intelligence (AI)-powered-software, as a predictor of objective clinical benefit in advanced urothelial tumors and its correlations with oncological outcomes. METHODS: We retrospectively searched patients with advanced urothelial tumors, treated with systemic platinum-based chemotherapy and an available total body CT, performed before and after therapy. An AI-powered software was applied to CT to obtain the Skeletal Muscle Index (SMI-L3), derived from the area of the psoas, long spine, and abdominal muscles, at the level of L3 on CT axial images. Logistic and Cox-regression modeling was implemented to explore the association of sarcopenic status and anthropometric features to the clinical benefit rate and survival endpoints. RESULTS: 97 patients were included, 66 with bladder cancer and 31 with upper-tract urothelial carcinoma. Clinical benefit outcomes showed a linear positive association with all the observed body composition variables variations. The chances of not experiencing disease progression were positively associated with ∆_SMI-L3, ∆_psoas, and ∆_long spine muscle when they ranged from ~10-20% up to ~45-55%. Greater survival chances were matched by patients achieving a wider ∆_SMI-L3, ∆_abdominal and ∆_long spine muscle. CONCLUSIONS: A CT-based AI-powered software body composition and sarcopenia analysis provide prognostic assessments for objective clinical benefits and oncological outcomes.

Assessment of renal microcirculation in biopsy-proven tubulointerstitial nephritis in patients with and without glomerular disease: the role of resistive index.

BACKGROUND: Renal resistive index (RRI) measured by Doppler sonography is a marker of microvascular status and it is associated with changes in renal function. Aim of the study was to assess RRI in biopsy-proven tubulointerstitial nephritis (TIN) in patients with and without glomerular disease. METHODS: 132 consecutive patients underwent to native renal biopsy with diagnosis of isolated TIN or in association with glomerulonephritis. Estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion and renal ecocolorDoppler ultrasonography with RRI assessment were performed at time of enrollment. RESULTS: Patients with isolated-TIN had significantly higher RRI than both patients with non-immunoglobulin A glomerulonephritis (non-IgA-TIN) [0.73 (0.68-0.77) vs 0.64 (0.60-0.67), p < 0.001] and patients with IgA nephropathy (IgAN) [0.73 (0.68-0.77) vs 0.66 (0.60-0.71), p < 0.01]. Patients with isolated-TIN had mainly RRI ≥ 0.70 (n = 15, 65.2%) with the respect to patients with non-IgA-TIN (n = 7, 12.3%) and patients with IgAN (n = 17, 32.7%). A negative linear correlation was found between RRI and hemoglobin (r = 0.233, p < 0.01) and between RRI and eGFR (r = 0.537, p < 0.001). CONCLUSION: Tubulointerstitial damage is the most accurate histological lesion that correlates with eGFR and renal impairment. RRI can be a useful parameter to detect tubulointerstitial lesions.

Guidance for assessment of the muscle mass phenotypic criterion for the Global Leadership Initiative on Malnutrition diagnosis of malnutrition.

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic- and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition.

Guidance for assessment of the muscle mass phenotypic criterion for the Global Leadership Initiative on Malnutrition (GLIM) diagnosis of malnutrition.

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic- and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition.

Cost-Effectiveness of Parenteral Nutrition Containing ω-3 Fatty Acids in Hospitalized Adult Patients From 5 European Countries and the US.

BACKGROUND: ω-3 Fatty acid (FA)-containing parenteral nutrition (PN) is associated with improvements in patient outcomes and with reductions in hospital length of stay (HLOS) vs standard PN regimens (containing non-ω-3 FA lipid emulsions). We present a cost-effectiveness analysis of ω-3 FA-containing PN vs standard PN in 5 European countries (France, Germany, Italy, Spain, UK) and the US. METHODS: This pharmacoeconomic model was based on estimates of ω-3 efficacy reported in a recent meta-analysis and data from country-specific sources. It utilized a probabilistic discrete event simulation model to compare ω-3 FA-containing PN with standard PN in a population of critically ill and general ward patients. The influence of model parameters was evaluated using probabilistic and deterministic sensitivity analyses. RESULTS: Overall costs were reduced with ω-3 FA-containing PN in all 6 countries compared with standard PN, ranging from €1741 (±€1284) in Italy to €5576 (±€4193) in the US. Expenses for infections and HLOS were lower in all countries for ω-3 FA-containing PN vs standard PN, with the largest cost differences for both in the US (infection: €825 ± €4001; HLOS: €4879 ± €1208) and the smallest savings in the UK for infections and in Spain for HLOS (€63 ± €426 and €1636 ± €372, respectively). CONCLUSION: This cost-effectiveness analysis in 6 countries demonstrates that the superior clinical efficacy of ω-3 FA-containing PN translates into significant decreases in mean treatment cost, rendering it an attractive cost-saving alternative to standard PN across different healthcare systems.

Omega-3 fatty acid-containing parenteral nutrition in ICU patients: systematic review with meta-analysis and cost-effectiveness analysis.

BACKGROUND: Omega-3 (ω-3) fatty acid (FA)-containing parenteral nutrition (PN) is associated with significant improvements in patient outcomes compared with standard PN regimens without ω-3 FA lipid emulsions. Here, we evaluate the impact of ω-3 FA-containing PN versus standard PN on clinical outcomes and costs in adult intensive care unit (ICU) patients using a meta-analysis and subsequent cost-effectiveness analysis from the perspective of a hospital operating in five European countries (France, Germany, Italy, Spain, UK) and the US. METHODS: We present a pharmacoeconomic simulation based on a systematic literature review with meta-analysis. Clinical outcomes and costs comparing ω-3 FA-containing PN with standard PN were evaluated in adult ICU patients eligible to receive PN covering at least 70% of their total energy requirements and in the subgroup of critically ill ICU patients (mean ICU stay > 48 h). The meta-analysis with the co-primary outcomes of infection rate and mortality rate was based on randomized controlled trial data retrieved via a systematic literature review; resulting efficacy data were subsequently employed in country-specific cost-effectiveness analyses. RESULTS: In adult ICU patients, ω-3 FA-containing PN versus standard PN was associated with significant reductions in the relative risk (RR) of infection (RR 0.62; 95% CI 0.45, 0.86; p = 0.004), hospital length of stay (HLOS) (- 3.05 days; 95% CI - 5.03, - 1.07; p = 0.003) and ICU length of stay (LOS) (- 1.89 days; 95% CI - 3.33, - 0.45; p = 0.01). In critically ill ICU patients, ω-3 FA-containing PN was associated with similar reductions in infection rates (RR 0.65; 95% CI 0.46, 0.94; p = 0.02), HLOS (- 3.98 days; 95% CI - 6.90, - 1.06; p = 0.008) and ICU LOS (- 2.14 days; 95% CI - 3.89, - 0.40; p = 0.02). Overall hospital episode costs were reduced in all six countries using ω-3 FA-containing PN compared to standard PN, ranging from €-3156 ± 1404 in Spain to €-9586 ± 4157 in the US. CONCLUSION: These analyses demonstrate that ω-3 FA-containing PN is associated with statistically and clinically significant improvement in patient outcomes. Its use is also predicted to yield cost savings compared to standard PN, rendering ω-3 FA-containing PN an attractive cost-saving alternative across different health care systems. STUDY REGISTRATION: PROSPERO CRD42019129311.

Pharmacoeconomics of Parenteral Nutrition with ω-3 Fatty Acids in Hospitalized Adults.

The inclusion of ω-3 fatty acids as part of parenteral nutrition is associated with clinical benefits such as a reduced likelihood of infectious complications and shorter hospital and intensive care unit (ICU) stays. As healthcare resources are limited, pharmacoeconomic analyses have been performed, typically modeling studies, using cost and outcomes data to investigate the cost-effectiveness of parenteral nutrition regimens including ω-3 fatty acids from fish oil compared with standard parenteral nutrition without such ω-3 fatty acids. This review covers pharmacoeconomic studies encompassing Italian, French, German, and UK hospitals for ICU and non-ICU hospitalized patients, and for ICU patients in China. The results show that the use of parenteral nutrition including ω-3 fatty acids more than offsets any additional acquisition costs in all national scenarios investigated to date, indicating that parenteral nutrition including ω-3 fatty acids is a clinically and economically beneficial strategy compared with standard parenteral nutrition.

Patient access to oral nutritional supplements: Which policies count?

OBJECTIVES: Oral nutritional supplements (ONS) represent a cost-effective method for treating malnutrition. The aim of this study was to investigate the effects of public policies on patient access to ONS, using the Italian regionalized health care system as a case study, subsequently compared with the centralized British National Health Service. METHODS: Regional policies in the nine largest Italian regions and British policies were gathered through a literature review; interviews with officers responsible for clinical nutrition policies at the regional level in Italy were also conducted. Total ONS regional sales in Italy were gathered from industry sources. RESULTS: Regulation by Italian regions focused on patient access and local prescribing issues (facilities and specialists allowed to prescribe reimbursed ONS, clinical pathways for malnutrition or disease-related malnutrition, length of prescriptions, and distribution of ONS). British policies focused on organizational issues (clinical governance through multidisciplinary Nutrition Support Teams, Nutrition Steering Committees and Clinical Commissioning Groups), education and referral by health care professionals. Neither per capita reimbursed ONS expenditure nor the proportion covered by public funds seem dependent on policies implemented at the regional level in Italy. There is no cutting-edge evidence that British policies produced broader diffusion of ONS, but they appear to have standardized their use within a more homogenous framework. CONCLUSION: As no clear relation between regional policies and variation in patient access to ONS emerges in Italy, national policies should be encouraged to enhance awareness of malnutrition among health care professionals and encourage the diffusion of multidisciplinary nutrition teams in health care organizations.

Effectiveness and efficacy of nutritional therapy: A systematic review following Cochrane methodology.

BACKGROUND & AIMS: Disease-related malnutrition has deleterious consequences on patients' outcome and healthcare costs. The demonstration of improved outcome by appropriate nutritional management is on occasion difficult. The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed the Nutrition Education Study Group (ESPEN-NESG) to increase recognition of nutritional knowledge and support in health services. METHODS: To obtain the best available evidence on the potential effects of malnutrition on morbidity, mortality and hospital stay; cost of malnutrition; effect of nutritional treatment on outcome parameters and pharmaco-economics of nutritional therapy, a systematic review of the literature was performed following Cochrane methodology, to answer the following key questions: Q1) Is malnutrition an independent predictive factor for readmission within 30 days from hospital discharge? Q2) Does nutritional therapy reduce the risk of readmission within 30 days from hospital discharge? Q3) Is nutritional therapy cost-effective/does it reduce costs in hospitalized patients? and Q4) Is nutritional therapy cost effective/does it reduce costs in outpatients? RESULTS: For Q1 six of 15 identified observational studies indicated that malnutrition was predictive of re-admissions, whereas the remainder did not. For Q2 nine randomized controlled trials and two meta-analyses gave non-conclusive results whether re-admissions could be reduced by nutritional therapy. Economic benefit and cost-effectiveness of nutritional therapy was consistently reported in 16 identified studies for hospitalized patients (Q3), whereas the heterogeneous and limited corresponding data on out-patients (Q4) indicated cost-benefits in some selected sub-groups. CONCLUSIONS: This result of this review supports the use of nutritional therapy to reduce healthcare costs, most evident from large, homogeneous studies. In general, reports are too heterogeneous and overall of limited quality for conclusions on impact of malnutrition and its treatment on readmissions.

Economy matters to fight against malnutrition: Results from a multicenter survey.

BACKGROUND AND AIM: Malnutrition represents a serious health care threat, as it increases morbidity, mortality and health care cost. The effective screening and treatment with enteral (EN) or parenteral (PN) nutrition are the key elements of the policy called Optimal Nutrition Care for All (ONCA). The study tried to analyze the impact of the state's economy on the implementation of EN and PN to define its role in ONCA. MATERIAL AND METHODS: an international survey in twenty two European countries was performed between January and December 2014. An electronic questionnaire was distributed to 22 representatives of clinical nutrition (PEN) societies. The questionnaire comprised questions regarding country economy, reimbursement, education and the use EN and PN. Return rate was 90.1% (n = 20). RESULTS: EN and PN were used in all countries surveyed (100%), but to different extent. The country's income significantly influenced the reimbursement for EN and PN (p < 0.05). It was also associated with the overall use of tube feeding and PN (p = 0.05), but not with the use of oral nutritional supplements (p = 0.165). The use of both, EN and PN at hospitals was not depended on the economy (p > 0.05). Education was actively carried out in all countries, however the teaching at the pre-graduate level was the least widespread, and also correlated with the country income (p = 0.042). CONCLUSIONS: Results indicated that economic situation influences all aspects of ONCA, including education and treatment. The reimbursement for EN and PN seemed to be the key factor of effective campaign against malnutrition.

Mini-Nutritional Assessment, Malnutrition Universal Screening Tool, and Nutrition Risk Screening Tool for the Nutritional Evaluation of Older Nursing Home Residents.

INTRODUCTION: Malnutrition plays a major role in clinical and functional impairment in older adults. The use of validated, user-friendly and rapid screening tools for malnutrition in the elderly may improve the diagnosis and, possibly, the prognosis. The aim of this study was to assess the agreement between Mini-Nutritional Assessment (MNA), considered as a reference tool, MNA short form (MNA-SF), Malnutrition Universal Screening Tool (MUST), and Nutrition Risk Screening (NRS-2002) in elderly institutionalized participants. METHODS: Participants were enrolled among nursing home residents and underwent a multidimensional evaluation. Predictive value and survival analysis were performed to compare the nutritional classifications obtained from the different tools. RESULTS: A total of 246 participants (164 women, age: 82.3 ± 9 years, and 82 men, age: 76.5 ± 11 years) were enrolled. Based on MNA, 22.6% of females and 17% of males were classified as malnourished; 56.7% of women and 61% of men were at risk of malnutrition. Agreement between MNA and MUST or NRS-2002 was classified as "fair" (k = 0.270 and 0.291, respectively; P < .001), whereas the agreement between MNA and MNA-SF was classified as "moderate" (k = 0.588; P < .001). Because of the high percentage of false negative participants, MUST and NRS-2002 presented a low overall predictive value compared with MNA and MNA-SF. Clinical parameters were significantly different in false negative participants with MUST or NRS-2002 from true negative and true positive individuals using the reference tool. For all screening tools, there was a significant association between malnutrition and mortality. MNA showed the best predictive value for survival among well-nourished participants. CONCLUSIONS: Functional, psychological, and cognitive parameters, not considered in MUST and NRS-2002 tools, are probably more important risk factors for malnutrition than acute illness in geriatric long-term care inpatient settings and may account for the low predictive value of these tests. MNA-SF seems to combine the predictive capacity of the full version of the MNA with a sufficiently short time of administration.

Nutritional assessment and therapy in COPD: a European Respiratory Society statement.

Nutrition and metabolism have been the topic of extensive scientific research in chronic obstructive pulmonary disease (COPD) but clinical awareness of the impact dietary habits, nutritional status and nutritional interventions may have on COPD incidence, progression and outcome is limited. A multidisciplinary Task Force was created by the European Respiratory Society to deliver a summary of the evidence and description of current practice in nutritional assessment and therapy in COPD, and to provide directions for future research. Task Force members conducted focused reviews of the literature on relevant topics, advised by a methodologist. It is well established that nutritional status, and in particular abnormal body composition, is an important independent determinant of COPD outcome. The Task Force identified different metabolic phenotypes of COPD as a basis for nutritional risk profile assessment that is useful in clinical trial design and patient counselling. Nutritional intervention is probably effective in undernourished patients and probably most when combined with an exercise programme. Providing evidence of cost-effectiveness of nutritional intervention is required to support reimbursement and thus increase access to nutritional intervention. Overall, the evidence indicates that a well-balanced diet is beneficial to all COPD patients, not only for its potential pulmonary benefits, but also for its proven benefits in metabolic and cardiovascular risk.

Cost-effectiveness of omega-3 fatty acid supplements in parenteral nutrition therapy in hospitals: a discrete event simulation model.

BACKGROUND & AIMS: A recent meta-analysis showed that supplementation of omega-3 fatty acids in parenteral nutrition (PN) regimens is associated with a statistically and clinically significant reduction in infection rate, and length of hospital stay (LOS) in medical and surgical patients admitted to the ICU and in surgical patients not admitted to the ICU. The objective of this present study was to evaluate the cost-effectiveness of the addition of omega-3 fatty acids to standard PN regimens in four European countries (Italy, France, Germany and the UK) from the healthcare provider perspective. METHODS: Using a discrete event simulation scheme, a patient-level simulation model was developed, based on outcomes from the Italian ICU patient population and published literature. Comparative efficacy data for PN regimens containing omega-3 fatty acids versus standard PN regimens was taken from the meta-analysis of published randomised clinical trials (n = 23 studies with a total of 1502 patients), and hospital LOS reduction was further processed in order to split the reduction in ICU stay from that in-ward stays for patients admitted to the ICU. Country-specific cost data was obtained for Italian, French, German and UK healthcare systems. Clinical outcomes included in the model were death rates, nosocomial infection rates, and ICU/hospital LOS. Probabilistic and deterministic sensitivity analyses were undertaken to test the reliability of results. RESULTS: PN regimens containing omega-3 fatty acids were more effective on average than standard PN both in ICU and in non-ICU patients in the four countries considered, reducing infection rates and overall LOS, and resulting in a lower total cost per patient. Overall costs for patients receiving PN regimens containing omega-3 fatty acids were between €14 144 to €19 825 per ICU patient and €5484 to €14 232 per non-ICU patient, translating into savings of between €3972 and €4897 per ICU patient and savings of between €561 and €1762 per non-ICU patient. Treatment costs were completely offset by the reduction in hospital stay costs and antibiotic costs. Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: These results suggest that the supplementation of PN regimens with omega-3 fatty acids would be cost effective in Italian, French, German and UK hospitals.

Effectiveness and cost-effectiveness of supplemental glutamine dipeptide in total parenteral nutrition therapy for critically ill patients: a discrete event simulation model based on Italian data.

INTRODUCTION: The supplementation of alanyl-glutamine dipeptide in critically ill patients necessitating total parenteral nutrition (TPN) improves clinical outcomes, reducing mortality, infection rate, and shortening intensive care unit (ICU) hospital lengths of stay (LOSs), as compared to standard TPN regimens. METHODS: A Discrete Event Simulation model that incorporates outcomes rates from 200 Italian ICUs for over 60,000 patients, alanyl-glutamine dipeptide efficacy data synthesized by means of a Bayesian random effects meta-analysis, and national cost data has been developed to evaluate the alternatives from the cost perspective of the hospital. Simulated clinical outcomes are death and infection rates in ICU, death rate in general ward, and hospital LOSs. Sensitivity analyses are performed by varying all uncertain parameter values in a plausible range. RESULTS: The internal validation process confirmed the accuracy of the model in replicating observed clinical data. Alanyl-glutamine dipeptide on average results more effective and less costly than standard TPN: reduced mortality rate (24.6% ± 1.6% vs. 34.5% ± 2.1%), infection rate (13.8% ± 2.9% vs. 18.8% ± 3.9%), and hospital LOS (24.9 ± 0.3 vs. 26.0 ± 0.3 days) come at a lower total cost per patient (23,409 ± 3,345 vs. 24,161 ± 3,523 Euro).Treatment cost is completely offset by savings on ICU and antibiotic costs. Sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: Alanyl-glutamine dipeptide is expected to improve clinical outcomes and to do so with a concurrent saving for the Italian hospital.