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.

Omega-3 Polyunsaturated Fatty Acids and Stroke Burden.

Stroke is a major leading cause of death and disability worldwide. N-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid and docosahexaenoic acid have potent anti-inflammatory effects, reduce platelet aggregation, and regress atherosclerotic plaques. Since the discovery that the Greenland Eskimo population, whose diet is high in marine n-3 PUFAs, have a lower incidence of coronary heart disease than Western populations, numerous epidemiological studies to explore the associations of dietary intakes of fish and n-3 PUFAs with cardiovascular diseases, and large-scale clinical trials to identify the benefits of treatment with n-3 PUFAs have been conducted. In most of these studies the incidence and mortality of stroke were also evaluated mainly as secondary endpoints. Thus, a systematic literature review regarding the association of dietary intake of n-3 PUFAs with stroke in the epidemiological studies and the treatment effects of n-3 PUFAs in the clinical trials was conducted. Moreover, recent experimental studies were also reviewed to explore the molecular mechanisms of the neuroprotective effects of n-3 PUFAs after stroke.

The cost-effectiveness of omega-3 polyunsaturated fatty acids - The Australian healthcare perspective.

OBJECTIVES: To examine the cost-effectiveness of a triglyceride lowering medication-icosapent ethyl added on to statin from Australian healthcare system perspective. METHODS: A Markov-model was developed using data from the pivotal trial of icosapent ethyl in a secondary prevention population. Probabilities of CVD events were derived and extrapolated from the published Kaplan-Meier curve using a valid algorithm. Management cost of CVD, health-related quality of life, and background non-CVD mortality were extracted from publicly available sources. Acquisition cost of icosapent ethyl from the United States was used in the current analysis. Australian patients with histories of CVD were modelled for a 25 year time horizon and costs and benefits were discounted. Sensitivity analyses (SA) were undertaken. Value of perfect information (VPI) was quantified. RESULTS: Treatment with icosapent ethyl was associated with both higher costs and benefits (i.e. quality-adjusted life year [QALY] and life year [LY]), resulting in an incremental cost-effectiveness ratio (ICER) of AUD59,036/QALY or AUD54,358/LY. Using the often quoted willingness-to-pay (WTP)/QALY of AUD50,000/QALY, icosapent ethyl was not considered cost-effective. SA showed that time horizon, drug cost, and discount rate were the key drivers of the ICER. Total monetary VPI for icosapent ethyl was over AUD15 million over 5 years. CONCLUSIONS: Patients with established CVD in whom level of triglycerides is high would benefit from the treatment using icosapent ethyl, however, it is not a cost-effective from an Australian healthcare system perspective. The government may consider subsidising this medication given the clinical need but at a discounted acquisition cost.

Cost analysis of Omega-3 supplementation in critically ill patients with sepsis.

INTRODUCTION: Nutritional supplement of omega-3 fatty acids have been proposed to improve clinical outcomes in critically ill patients. While previous work have demonstrated that omega-3 supplementation in patients with sepsis is associated with reduced ICU and hospital length of stay, the financial impact of this intervention is unknown. OBJECTIVE: Perform a cost analysis to evaluate the impact of omega-3 supplementation on ICU and hospital costs. METHODS: We extracted data related to ICU and hospital length of stay from the individual studies reported in a recent systematic review. The Cochrane Collaboration tool was used to assess the risk of bias in these studies. Average daily ICU and hospital costs per patient were obtained from a cost study by Kahn et al. We estimated the ICU and hospital costs by multiplying the mean length of stay by the average daily cost per patient in ICU or Hospital. Adjustments for inflation were made according to the USD annual consumer price index. We calculated the difference between the direct variable cost of patients with omega-3 supplementation and patients without omega-3 supplementation. 95% confidence intervals were estimated using bootstrap re-sampling procedures with 1000 iterations. RESULTS: A total of 12 RCT involving 925 patients were included in this cost analysis. Septic patients supplemented with omega-3 had both lower mean ICU costs ($15,274 vs. $18,172) resulting in $2897 in ICU savings per patient and overall hospital costs ($17,088 vs. $19,778), resulting in $2690 in hospital savings per patient. Sensitivity analyses were conducted to investigate the impact of different study methods on the LOS. The results were still consistent with the overall findings. CONCLUSION: Patients with sepsis who received omega-3 supplementation had significantly shorter LOS in the ICU and hospital, and were associated with lower direct variable costs than control patients. The 12 RCTs used in this analysis had a high risk of bias. Large-scaled, high-quality, multi-centered RCTs on the effectiveness of this intervention is recommended to improve the quality of the existing evidence.

Clinical trials with multiple endpoints can establish a correlation, but not (yet) causality, between dietary supplementation with omega-3 fatty acids and keratoconjunctivitis sicca.

AIM: We review clinical evidence of therapeutic efficacy and effectiveness of omega-3 fatty acids (omega-3s) in keratoconjunctivitis sicca, colloquially known as dry eye disease. In doing so, we identify relevant literature to address the following questions: (1) What definitive guidance can clinical evidence offer eye physicians and their patients? (2) What aspects of omega-3 supplementation lack definitive evidence, and how might economic assessments help? METHODS: A targeted and systematic search strategy based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was designed in this study for refereed clinical trials of omega-3s in dry eye treatment. Four key databases were accessed. Records were filtered through a three-step process using predetermined inclusion criteria. Data was extracted for experimental design, sample population characteristics, content of test and control groups, symptoms and associated opthalmologic conditions, diagnostic measures, patient health outcomes, adverse events, and model time horizon. RESULTS: A total of 219 records were initially identified, of which 21 prospective clinical trials, with a total of 2,973 participants, were admitted for review. Clinical evidence indicates that daily oral supplementation with omega-3s statistically correlates with dry eye treatment in the general symptomatic population as well as induced sub-populations. Reported adverse events are minimal. These trials nonetheless exhibit considerable heterogeneity in clinical endpoints, particularly as a result of the multi-factorial character of dry eye as well as continuous advances in scientific knowledge and technology. Their findings and recommendations appear to be of limited external validity. And causal inferences are needed, but difficult to establish. These have encouraged and sustained wide variations in ophthalmologic practice and normative decision-making. CONCLUSIONS: Comparability of omega-3 therapeutic efficacy and effectiveness remains a major challenge in dry eye disease management. Notwithstanding its multi-factorial character, addressing prevailing methodological and empirical issues in clinical trials will help reduce knowledge gaps and normative choices among eye physicians and patients alike. In this regard, pharmacoeconomics offers a useful and robust toolset through which analysis of cost-minimization, cost-effectiveness, and cost-utility as well as meta-analysis can be comparatively pursued. Blending measures of costs and outcomes puts in perspective the heterogeneity of clinical endpoints in keratoconjunctivitis sicca.

A review of economic evaluations for beneficial health outcomes of micronutrient and long-chain omega-3 fatty acid supplementation.

A comprehensive review of the literature identified 13 papers exploring economic evaluations of supplementation with micronutrients or long-chain omega-3 fatty acids in developed countries. Evidence of efficacy included single-study-based estimates and estimates based on published meta-analyses or data synthesis. Results suggest that supplementation with specific micronutrients or long-chain omega-3 fatty acids for specific health outcomes, and targeted at particular population groups, may be cost-effective or deliver cost savings for health care providers. While the quality of the analyses was variable and some authors reported considerable uncertainty of the results, the approaches adopted were in the main conservative. This suggests that investigating the potential economic impact of supplementation, particularly where there is good evidence of efficacy and predicted clinical benefit, is informative. Economic evaluations may also be useful to assess whether further nutritional research into particular health outcomes is a good investment of funds.

Omega-3 fatty acids (ῳ-3 fatty acids) in epilepsy: animal models and human clinical trials.

INTRODUCTION: There is growing interest in alternative and nutritional therapies for drug resistant epilepsy. ῳ-3 fatty acids such as fish or krill oil are widely available supplements used to lower triglycerides and enhance cardiovascular health. ῳ-3 fatty acids have been studied extensively in animal models of epilepsy. Yet, evidence from randomized controlled clinical trials in epilepsy is at an early stage. AREAS COVERED: This report focuses on the key ῳ-3 fatty acids DHA and EPA, their incorporation into the lipid bilayer, modulation of ion channels, and mechanisms of action in reducing excitability within the central nervous system. This paper presents pre-clinical evidence from mouse, rat, and canine models, and reports the efficacy of n-3 fatty acids in randomized controlled clinical trials. An English language search of PubMed and Google scholar for the years 1981-2016 was performed for animal studies and human randomized controlled clinical trials. Expert commentary: Basic science and animal models provide a cogent rationale and substantial evidence for a role of ῳ-3 fatty acids in reducing seizures. Results in humans are limited. Recent Phase II RCT evidence suggests that low to moderate dose of ῳ-3 fatty acids reduce seizures; however, larger multicenter randomized trials are needed to confirm or refute the evidence. The safety, health effects, low cost and ease of use make ῳ-3 fatty acids an intriguing alternative therapy for drug resistant epilepsy. Though safety of profile is excellent, the human data is not yet sufficient to support efficacy in drug resistant epilepsy at this time.

Effect of the addition of chia's by-product on the composition of fatty acids in hamburgers through chemometric methods.

BACKGROUND: Hamburger is a meat-based food that is easy to prepare and is widely consumed. It can be enriched using different ingredients, such as chia's by-product, which is rich in omega-3. Chemometrics is a very interesting tool to assess the influence of ingredients in the composition of foods. A complete factorial design 2(2) (two factors in two levels) with duplicate was performed to investigate the influence of the factors (1) concentration of textured soy proteins (TSP) and (2) concentration of chia flour partially defatted (CFPD) as a partial replacement for the bovine meat and porcine fat mix in hamburgers. RESULTS: The results of proximal composition, lipid oxidation, fatty acids sums, ratios, and nutritional indexes were used to propose statistical models. The factors TSP and CFPD were significant, and the increased values contributed to improve the composition in fatty acids, crude protein, and ash. Principal components analysis distinguished the samples with a higher content of chia. In desirability analysis, the highest level of TSP and CFPD was described as the optimal region, and it was not necessary to make another experimental point. CONCLUSION: The addition of chia's by-product is an alternative to increase the α-linolenic contents and to obtain nutritionally balanced food.

Grocery store podcast about omega-3 fatty acids influences shopping behaviors: a pilot study.

OBJECTIVES: To determine whether listening to a podcast about omega-3 fatty acids (n-3s) while grocery shopping increased shoppers' awareness about and purchases of seafood and other foods rich in n-3s. METHODS: Repeated-measures design with a convenience sample (n = 56) of grocery shoppers who listened to the podcast while shopping. Pre- and postintervention semistructured interviews were conducted. The Theory of Reasoned Action was the study's framework. RESULTS: Shoppers were primarily females (mean age, 41 ± 15.3 years). Their perceived ability to buy [t(55) = 6.27, P < .0001] and perceived importance regarding buying [t(55) = 3.38, P < .01] n-3-rich foods improved significantly. At least 1 n-3 rich food (mean, 1.5 ± 0.8) was purchased by 30%, and 79% planned future purchases. CONCLUSION AND IMPLICATIONS: Podcasts may effectively communicate nutrition information. More research with a larger sample size is needed to evaluate the effects of the podcast on long-term changes in shopping behavior.

Stability of omega-3 LC-PUFA-rich photoautotrophic microalgal oils compared to commercially available omega-3 LC-PUFA oils.

Microalgae are the primary producers of omega-3 LC-PUFA, which are known for their health benefits. Their oil may thus be a potential alternative for fish oil. However, oxidative and hydrolytic stability of omega-3 LC-PUFA oils are important parameters. The purpose of this work was therefore to evaluate these parameters in oils from photoautotrophic microalgae (Isochrysis, Phaeodactylum, Nannochloropsis gaditana, and Nannochloropsis sp.) obtained with hexane/isopropanol (HI) and hexane (H) and compare them with commercial omega-3 LC-PUFA oils. When the results of both the primary and secondary oxidation parameters were put together, it was clear that fish, tuna, and heterotrophic microalgae oil are the least oxidatively stable oils, whereas krill oil and the microalgae oils performed better. The microalgal HI oils were shown to be more oxidatively stable than the microalgal H oils. The hydrolytic stability was shown not to be a problem during the storage of any of the oils.

Marine by-product phospholipids as booster of medicinal compounds.

Marine phospholipids are defined as phospholipids containing docosahexaenoic acid (DHA) or eicosapentaenoic acid that would be more effective than fish oil, which is mostly composed of triacylglycerol, in exerting health benefits. Marine phospholipids would boost the effect of both the health-beneficial hydrophilic and the hydrophobic compounds such as cell differentiators, anticancer compounds, and antiobesity compounds. When marine phospholipids are served as liposomal drinks, they would be more effective than adding into solid foods or feeds. As long as the liposome bilayer is basically composed of marine phospholipids, they would promote the encapsulated functional compounds. And this is the principal advantage of choosing marine phospholipids as liposomal membrane. Bioconversion of marine phospholipid would also be advantageous in delivering DHA into the desired tissue. For example, lysophosphatidylserine obtained through phospholipase D-mediated transphosphatidylation and phospholipase A1 or sn-1 positional specific lipase-mediated partial hydrolysis seemed to be the most effective chemical form in delivering DHA into brain.

Cost implications of alternative sources of (n-3) fatty acid consumption in the United States.

The Dietary Guidelines for Americans 2010 provides authoritative advice on what Americans should eat to stay healthy. These guidelines provide a quantitative recommendation to consume 250 mg/d of (n-3) fatty acids (also known as omega-3 fatty acids). To achieve this goal, Americans would need to more than triple the amount of EPA and DHA currently consumed. This paper assessed the cost implications of increased levels of EPA and DHA from marine and nonmarine food sources using data from the 2007-2008 NHANES, USDA nutrient data base, and the USDA Center for the Nutrition Policy and Promotion food price data. Stearidonic acid (SDA)-enhanced soybean oil is a lower cost alternative to commonly consumed marine food as a source of EPA. In addition, given that SDA-enhanced soybean oil is intended to be used as an ingredient in a variety of products, this may enable consumers to increase consumption of EPA through commonly consumed foods.

A multi-country health economic evaluation of highly concentrated N-3 polyunsaturated fatty acids in secondary prevention after myocardial infarction.

BACKGROUND: Patients who survive an acute myocardial infarction (MI) are at an increased risk of subsequent major cardiovascular events and (often sudden) cardiac death. The use of highly concentrated and purified omega-3 polyunsaturated fatty acids (n-3 PUFAs), in addition to standard secondary prevention after MI, results in a significant reduction in the risk of sudden death versus no n-3 PUFAs. This study assessed the cost effectiveness of adding n-3 PUFAs to the current secondary prevention treatment versus standard prevention alone after acute MI in five countries: Australia, Belgium, Canada, Germany and Poland. METHODS: Based on the clinical outcomes of GISSI-P (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico - Prevenzione) [MI, stroke, revascularisation rate and mortality], a decision model was built in DataProtrade mark. The implications of adding n-3 PUFAs to standard treatment in patients aged 59 years with a recent history of MI were analysed from the healthcare payer's perspective. The time horizon was 3.5 years (identical to GISSI-Prevenzione) but the effects on life expectancy through avoidance of cardiac events were calculated lifelong. Event costs were based on literature data. Life expectancy data for survivors of cardiac disease were taken from the Saskatchewan database and then adjusted by country. Results are expressed as extra cost (Euro) per life-year gained (LYG). Annual discounting of 5% was applied to health effects and costs. RESULTS: Treatment with highly concentrated n-3 PUFAs yielded between 0.261 (Poland) and 0.284 (Australia) LYG, at an additional cost of 787 Euros(Canada) to 1,439 Euros(Belgium). The ICER varied between 2,788 Euros(Canada) and 5,097 Euros(Belgium) per LYG. Sensitivity analyses on effectiveness, cost of complications and discounting proved the robustness of the results. A second-order Monte Carlo simulation based on the 95% confidence intervals obtained from GISSI-P suggests that highly concentrated n-3 PUFAs are cost effective in 93% of simulations in Poland and in >98% of simulations in the other countries, assuming the country-specific societal willingness-to-pay threshold. Total costs were considerably increased by including healthcare costs incurred during the remaining life-years, but this had no impact on the ICER-based treatment recommendation. CONCLUSIONS: Adding highly concentrated n-3 PUFAs to standard treatment in the secondary prevention of MI appears to be cost effective versus standard treatment alone in the five countries studied.

Highly purified omega-3 polyunsaturated fatty acids are effective as adjunct therapy for secondary prevention of myocardial infarction.

Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione was the first large randomized trial to produce evidence that a pharmaceutical preparation of highly purified omega-3 polyunsaturated fatty acids (PUFAs), administered as an adjunct to other accepted interventions, had a favorable effect on hard clinical end-points in post-myocardial infarction patients. Much of the 20% all-cause mortality benefit recorded during the study could be attributed to a 45% reduction in sudden death--a fatal outcome that traditionally has proved resistant to medical intervention. These results were obtained with an omega-3 PUFA dose of 1 g/day, which is much lower than was routinely being used at the time the study was initiated (e.g. 4 g/day for hypertriglyceridemia). One consequence of this low-dose regimen was that the tolerability profile of omega-3 PUFAs during GISSI-Prevenzione was considered highly satisfactory, with low adverse event incidence rates and low rates of discontinuation due to adverse events. Time-course analysis established that much of the survival benefit of omega-3 PUFA treatment in GISSI-Prevenzione was realized during the early months of the trial. The beneficial effects of omega-3 PUFA treatment were observed on top of standard, secondary pharmacological prevention therapy like anti-platelet agents, statins, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors. The benefits of omega-3 PUFA therapy were also apparent in patients at all standards of adherence to a healthy diet and may have been augmented in patients with the best dietary profile. Patients with diabetes mellitus (approximately 15% of the study cohort) appeared to benefit from omega-3 PUFAs to at least the same extent as the general study population; the treatment effect on sudden death was progressively more pronounced as left ejection fraction declined. Cost-effectiveness analyses undertaken from a third-party payer perspective for Italy revealed that the cost of low-dose treatment with highly purified omega-3 PUFAs was approximately Euro 25,000 per life-year gained.

A multi-country health-economic evaluation of highly concentrated n-3 polyunsaturated fatty acids in the secondary prevention after myocardial infarction.

Patients who survive an acute myocardial infarction (MI) are at increased risk of subsequent major cardiovascular events and cardiac (often sudden) death. The use of highly concentrated and purified omega-3 polyunsaturated fatty acids (n-3 PUFAs), in addition to standard secondary prevention after MI, results in a significant reduction in the risk of sudden death. This study assessed the cost-effectiveness of adding n-3 PUFAs to the current secondary prevention treatment after acute MI in 5 countries: Australia, Belgium, Canada, Germany, Poland. Based on the clinical outcomes of GISSI-Prevenzione (MI, stroke, revascularisation rate and mortality), a decision-model was built in DataPROTM. The implications of adding n-3 PUFAs to standard treatment in patients with a recent history of MI were analysed from the health care payer's perspective. The time horizon was 3.5 years (identical to GISSI-Prevenzione). Event costs were based on literature data. Life expectancy data for survivors of cardiac disease were taken from the Saskatchewan database and then country-adjusted. Results are expressed as extra cost (Euro) per life-year gained (LYG). Annual discounting of 5% was applied to health effects and costs. Treatment with highly concentrated n-3 PUFAs yielded between 0.260 (Poland) and 0.284 (Australia) LYG, at an additional cost of Euro 807 (Canada) to Euro 1,451 (Belgium). The incremental cost-effectiveness ratio (ICER) varied between Euro 2,867 (Canada) and Euro 5,154 (Belgium) per LYG. Sensitivity analyses on effectiveness, cost of complications and discounting proved the robustness of the results. A 2nd order Monte Carlo simulation based on the 95% CIs obtained from GISSI showed that highly concentrated n-3 PUFAs are cost-effective in more than 99% of patients (assuming societal willingness to pay threshold of Euro 20,000/LYG). Including health care costs incurred during the remaining life-years considerably increased total costs, but had no impact on the ICER-based treatment recommendation. Adding highly concentrated n-3 PUFAs to standard treatment in the secondary prevention after MI appears to be cost-effective in the 5 countries studied.

Cost-effectiveness analysis of n-3 polyunsaturated fatty acids (PUFA) after myocardial infarction: results from Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI)-Prevenzione Trial.

OBJECTIVE: To estimate the cost effectiveness of treatment with n-3 polyunsaturated fatty acids (PUFA) for secondary prevention after myocardial infarction (MI). DESIGN AND SETTING: The cost-effectiveness analysis of n-3 PUFA treatment after MI was based on morbidity and mortality data and the use of resources obtained prospectively during the 3.5 year follow-up period of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI)-Prevenzione study. The cost-effectiveness analysis took into account the incremental number of life-years gained and the incremental costs for hospital admissions, diagnostic tests and drugs, applying a 5% discount rate. The value for money of n-3 PUFA treatment was assessed using the cost-effectiveness ratio and the number needed to treat (NNT) approach. PERSPECTIVE: Third-party payer. MAIN OUTCOME MEASURES AND RESULTS: The incremental cost-effectiveness ratio for n-3 PUFA in the basecase scenario was 24,603 euro (EUR, 1999 values) per life-year gained (95% confidence interval: 22,646 to 26,930). Sensitivity analysis included the analysis of extremes, producing estimates varying from EUR15,721 to EUR52,524 per life-year gained. 172 patients would need to be treated per year with n-3 PUFA, at an annual cost of EUR68,000, in order to save 1 patient. This is comparable with the NNT value, and associated annual cost for simvastatin, but less costly than that for pravastatin. CONCLUSIONS: The cost effectiveness of long term treatment with n-3 PUFA is comparable with other drugs recently introduced in the routine care of secondary prevention after MI. Since the clinical benefit provided by n-3 PUFA is additive, this therapy should be added to the established routine practice, with additive costs.