Handling Missing Data in Health Economics and Outcomes Research (HEOR): A Systematic Review and Practical Recommendations.

BACKGROUND: Missing data in costs and/or health outcomes and in confounding variables can create bias in the inference of health economics and outcomes research studies, which in turn can lead to inappropriate policies. Most of the literature focuses on handling missing data in randomized controlled trials, which are not necessarily always the data used in health economics and outcomes research. OBJECTIVES: We aimed to provide an overview on missing data issues and how to address incomplete data and report the findings of a systematic literature review of methods used to deal with missing data in health economics and outcomes research studies that focused on cost, utility, and patient-reported outcomes. METHODS: A systematic search of papers published in English language until the end of the year 2020 was carried out in PubMed. Studies using statistical methods to handle missing data for analyses of cost, utility, or patient-reported outcome data were included, as were reviews and guidance papers on handling missing data for those outcomes. The data extraction was conducted with a focus on the context of the study, the type of missing data, and the methods used to tackle missing data. RESULTS: From 1433 identified records, 40 papers were included. Thirteen studies were economic evaluations. Thirty studies used multiple imputation with 17 studies using multiple imputation by chained equation, while 15 studies used a complete-case analysis. Seventeen studies addressed missing cost data and 23 studies dealt with missing outcome data. Eleven studies reported a single method while 20 studies used multiple methods to address missing data. CONCLUSIONS: Several health economics and outcomes research studies did not offer a justification of their approach of handling missing data and some used only a single method without a sensitivity analysis. This systematic literature review highlights the importance of considering the missingness mechanism and including sensitivity analyses when planning, analyzing, and reporting health economics and outcomes research studies.

Use of Metformin and Survival in Patients with Hepatocellular Carcinoma (HCC) Undergoing Liver Directed Therapy: Analysis of a Nationwide Cancer Registry.

BACKGROUND: Examine the association of metformin use and overall survival (OS) in patients with HCC undergoing image-guided liver-directed therapy (LDT): ablation, transarterial chemoembolization (TACE), or Yttrium-90 radioembolization (Y90 RE). METHODS: Using National Cancer Institute Surveillance, Epidemiology, and End Results registry and Medicare claims databases between 2007 and 2016, we identified patients ≥ 66 years who underwent LDT within 30 days of HCC diagnosis. Patients with liver transplant, surgical resection, and other malignancies were excluded. Metformin use was identified by at least two prescription claims within 6 months before LDT. OS was measured by time between first LDT and death or last Medicare observation. Comparisons were performed between both all and diabetic patients on and not on metformin. RESULTS: Of 2746 Medicare beneficiaries with HCC undergoing LDT, 1315 (47.9%) had diabetes or diabetes-related complications. Among all and diabetic patients, 433(15.8%) and 402 (30.6%) were on metformin respectively. Median OS was greater for patients on metformin (19.6 months, 95% CI 17.1-23.0) vs those not (16.0 months, 15.0-16.9; p = 0.0238). Patients on metformin had lower risk of death undergoing ablation (HR 0.70; 0.51-0.95; p = 0.0239) and TACE (HR 0.76, 0.66-0.87; p = 0.0001), but not Y90 RE (HR1.22, 0.89-1.69; p = 0.2231). Among diabetics, OS was greater for those on metformin vs those not (HR 0.77, 0.68-0.88; p < 0.0001). Diabetic patients on metformin had longer OS undergoing TACE (HR 0.71, 0.61-0.83; p < 0.0001), but not ablation (HR 0.74, 0.52-1.04; p = 0.0886) or Y90 RE (HR 1.26, 0.87-1.85; p = 0.2217). CONCLUSION: Metformin use is associated with improved survival in HCC patients undergoing TACE and ablation.

Out-of-Pocket Expenditures for Imaging Examinations: Perspectives From National Patient Surveys Over Two Decades.

PURPOSE: Using national surveys, we longitudinally studied imaging costs-and specifically those paid out-of-pocket (OOP) by patients-over two decades. METHODS: Using 2000 to 2019 Medical Expenditure Panel Survey data, we identified all imaging-focused encounters (mammography, radiography, ultrasonography, and CT and MR [surveyed together in Medical Expenditure Panel Survey]) and calculated mean overall and OOP encounter costs. Effects of sociodemographic, personal, and clinical factors were measured using logistic regression and generalized linear modeling. RESULTS: We identified 102,717 patients (mean 45.6 years; 64.8% female; 58.8% White) undergoing 229,010 imaging-focused encounters. Between 2000 and 2019, mean costs of mammography, radiography, and ultrasonography increased 14.5%, 24.5%, and 40% and total mean cost of CT or MR decreased by 15.1%. OOP costs were incurred by 51%. Overall mean OOP costs increased 89.8% from 2000 to 2019. Mean OOP costs for mammography decreased by 32.9%; mean OOP costs for radiography, ultrasonography, and CT or MR increased 81%, 123.2%, and 61%, respectively. Patients were less likely to incur OOP costs when older, of racial and ethnic minorities, female, or recipients of public only (versus private) insurance. Among those with OOP costs, the presence of comorbidities, lack of insurance, younger age, and history of cancer significantly increased OOP costs. CONCLUSION: Mean overall patient OOP costs for imaging examinations increased significantly and substantially over the last two decades. Lack of insurance, younger age, history of cancer, and other comorbidities were associated with higher OOP costs. As diagnostic imaging utilization increases, patient financial hardship considerations merit further attention.

Length of Stay, Cost, and Outcomes related to Traumatic Subdural Hematoma in inpatient setting in the United States.

OBJECTIVE: In the US, the prevalence of traumatic subdural hematoma (TSDH) continues to increase. Using a nationally representative sample of discharge records of patients with TSDH, the study objectives were to estimate trend in number of TSDH cases, surgical management, inpatient cost, length of stay (LOS), mortality rate, and complication rate; and to identify the association of sociodemographic, clinical and hospital characteristics with complications and mortality. METHOD: We identified patients with a primary diagnosis of TSDH from the National Inpatient Sample (NIS) database from 2010 to 2017. Quarterly and monthly trends were estimated using interrupted time series design. Multivariate logistic regressions measured association between various factors and inpatient death and complications. RESULTS: Number of cases, mean LOS, rate of complication increased. Proportion of patients undergoing surgery, mean inpatient cost, inpatient mortality decreased. Mean inpatient cost was $23,182.40 and LOS was 6.41 days. Odds of inpatient death and complications increased with injury severity score and comorbid conditions requiring use of anticoagulants. Odds of inpatient death were highest among those ≥85 years old and in south and northeast region. CONCLUSION: Given the increase in prevalence of TSDH in USA, additional resources should be allocated toward improving patient outcomes and lowering healthcare costs.

Trends and variations in utilization and costs of radiotherapy for prostate cancer: A SEER medicare analysis from 2007 through 2016.

OBJECTIVE: To assess recent changes and disparities in utilization and costs of radiotherapy in Medicare beneficiaries with prostate cancer. METHODS: Surveillance, Epidemiology and End Results (SEER) -Medicare linked data from 2006-2016 were used to identify continuously enrolled Medicare beneficiaries with a first-time diagnosis of prostate cancer who, within 12 months of diagnosis, underwent at least one radiotherapy related service. Trends in the utilization of different radiotherapy techniques over time, yearly changes in per-patient costs of radiotherapy, and effect of socio-demographic and clinical characteristics on total cost were measured. Per patient annual costs, annual incidence of prostate cancer, and utilization of radiotherapy were used to estimate total costs of radiotherapy to the Medicare program. RESULTS: For Medicare beneficiaries with a first-time diagnosis of prostate cancer, the utilization of intensity modulated radiation therapy (IMRT), proton therapy, and stereotactic body radiation therapy (SBRT) increased 23.62%, 0.74% and 1.61% respectively (p <0.0001) while brachytherapy decreased 17.04% (p <0.0001). Cost per beneficiary decreased $340.24 (95% CI: $136.05 - $544.43) annually (p = 0.0065). Age, registry region, and Gleason score were all associated with expenditures. The total cost to the Medicare program was estimated at US $1.16 billion in the year 2016. DISCUSSION: In Medicare beneficiaries with prostate cancer treated with radiotherapy, IMRT is the primary mode of treatment. Utilization of brachytherapy decreased significantly despite the efficacy and cost-effectiveness. Although per patient costs have decreased, the share of patient responsibility remained unaltered across years. The current costs to Medicare of radiotherapy for newly diagnosed prostate cancer patients is substantial.

National Utilization, Survival, and Costs Analysis of Treatment Options for Stage I Non-Small Cell Lung Cancer: A SEER-Medicare Database Analysis.

RATIONALE AND OBJECTIVES: To compare utilization, outcomes, and costs of surgery, radiation therapy, and percutaneous ablation for the treatment of stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Using 2006-2016 Medicare-linked Surveillance, Epidemiology, and End Results (SEER) databases, stage I NSCLC patients who underwent surgery, radiotherapy, or percutaneous ablation were identified using relevant billing codes. National utilization rates were determined. Overall survival for treatment arms were compared using log-rank test and Cox-proportional hazard modeling. Mean direct costs for each treatment strategy during the first year after diagnosis were compared using Analysis of Variance. RESULTS: A total of 15,847 Stage I NSCLC patients were identified; mean age at diagnosis was 75.5 years (minimum age = 66 years) and 59.2% were female. A total of 10,732 patients (67.7%) underwent only surgery, 5013 (31.6%) only radiotherapy, and 102 (0.6%) only ablation. Utilization of surgery and ablation decreased while radiotherapy utilization increased from 2007 to 2015 (p < 0.0001). Compared to the ablation group, overall survival was greater for the surgery group (HR: 0.7, 95% CI of HR: 0.6-0.9, p = 0.0047) and lower for the radiotherapy group (HR: 1.4, 95% CI of HR: 1.1-1.8, p = 0.002). The mean first year cost of therapy for ablation = $11,976) was significantly less (p < 0.05) than for radiotherapy ($15,447) and surgery ($22,669). CONCLUSION: In Medicare patients with stage I NSCLC, the utilization of radiation therapy has increased and surgery has declined, while utilization of percutaneous ablation has remained uniformly low. Although overall survival is best for surgery, then ablation, and then radiation therapy, first year treatment costs are lowest for ablation.

Impact of novel systemic therapies on the first-year costs of care for melanoma among Medicare beneficiaries.

BACKGROUND: Since 2011, the therapeutic landscape of melanoma has changed dramatically because of the adoption of immune checkpoint inhibitor and targeted therapies. The authors sought to quantify the effects of these changes on short-term treatment costs by comparing the first-year cancer-attributable costs in novel (2011-2015) and historical (2004-2010) treatment eras. METHODS: The authors estimated the first-year cancer-attributable and out-of-pocket (OOP) costs by cancer stage at diagnosis by using a case-control approach. Patients aged ≥67 years with melanoma results were used to calculate the total direct costs of treatment during the first year after the diagnosis of melanoma in the US Medicare population older than 65 years. Costs were reported in 2018 dollars. RESULTS: Costs increased with the stage at diagnosis. Average first-year cancer-attributable costs per patient for stage IV patients increased significantly by 61.7% from $45,952 to $74,297 after the adoption of novel treatments. Per-patient OOP responsibility decreased by almost 30.8% across all stages of cancer but increased by 16.5% for stage IV patients from 2004 ($7646) to 2015 ($8911). The total direct cost of treatment for persons with melanoma older than 65 years increased by $16.03 million (4.93%) from $324.68 million in 2010 to $340.71 million in 2015. The largest increase in yearly total cost, $23.64 million (56.53%), was observed among stage IV patients. CONCLUSIONS: The direct cost of melanoma increased significantly in the Medicare population, particularly for advanced-stage disease. Prevention and early detection initiatives may reduce the economic burden of melanoma.

Survey of Pharmacists' Knowledge of Connecticut's Medical Cannabis Program.

Introduction: Over the last few years, a growth in research and interest in medical cannabis (most often referred to as medical marijuana) use have occurred nationally. Medical cannabis has become a treatment option for disease conditions, such as epilepsy, wasting syndrome associated with AIDs, and post-traumatic stress disorder, when traditional medication is ineffective. Objectives: The objectives were to identify knowledge deficits of the medical cannabis program (MCP) in Connecticut among Connecticut pharmacists and the impact of MCP on Connecticut pharmacy practice and concerns Connecticut pharmacists have regarding medical cannabis use. Methods: A cross-sectional survey through an online platform, Google forms, was administered for 2 months (October 15, 2017-December 15, 2017). An e-mail containing the link to the survey was e-mailed to all pharmacists whose e-mail addresses were available from the State of Connecticut's Commission of Pharmacy database (n = 6182). Of those with available e-mail addresses, only 5653 pharmacists received the e-mail; the others were rejected upon receipt of our e-mail. Our survey consists of 16 items related to pharmacist demo- graphic information, knowledge assessment, impact on pharmacists' practice, and concerns stemming from medical cannabis. Results: Only 51 (15.2%) respondents believed that Connecticut MCP would impact their practice. Only 39 (11.6%) respondents selected the two correct requirements for patient registration and correctly identified the wrong choices. Only 81 (24.2%) respondents identified the correct approved dose (maximum allowable monthly amount of 2.5 ounces) of medical cannabis. Sixty-eight (20.2%) respondents correctly identified all three approved conditions and all other incorrect conditions. Sixty-five (19.40%) respondents correctly identified all roles of dispensary pharmacists. Majority of respondents, 243 (72.5%), expressed their concern about federal laws regarding cannabis. A total of 98 (29.3%) respondents thought that they were knowledgeable enough about the side effects of medical cannabis to provide appropriate counseling to patients. Conclusion: Overall, the results of our survey found that Connecticut licensed pharmacists had lack of complete and accurate knowledge regarding the state's MCP. As more states legalize medical cannabis, it will be imperative that education of pharmacists and other health care professionals about the MCP and the clinical use of cannabis occur.

Assessment of structured classroom debate to teach an antimicrobial stewardship elective course.

BACKGROUND AND PURPOSE: The main aim of this study was to evaluate the effect of a structured classroom debate format on teaching antimicrobial stewardship. EDUCATIONAL ACTIVITY AND SETTING: An active learning approach using a debate format was implemented to engage students in infectious diseases concepts to further develop critical thinking skills. This was a one-group, pre- and posttest design conducted in third year pharmacy students enrolled at the Philadelphia College of Osteopathic Medicine School of Pharmacy Georgia campus. A ten-item assessment survey was used prior to and after the course to evaluate student knowledge. Student perception of skill development was assessed by a survey using a five-point Likert scale. The skills assessed included critical thinking, communication, public speaking, research/drug information, and teamwork. FINDINGS: Thirty-three students participated in the six debates over the course of the semester. There was a statistically significant increase in post-knowledge assessment mean score (75%) compared to pre-knowledge assessment mean score (45%). The post-course survey showed improved confidence in perception of skills in all of the areas assessed. SUMMARY: The structured classroom debate format has a positive association with increasing students' knowledge level and perception of skills assessed.

Variation in prostate surgery costs and outcomes in the USA: robot-assisted versus open radical prostatectomy.

AIM: To compare perioperative complications, inpatient cost and length of stay between robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) using National Inpatient Sample data from 2010 to 2015. PATIENTS & METHODS: A total of 69,009 records with RARP or ORP were analyzed using multivariate logistic regression and generalized linear models. RESULTS: The RARP had superior perioperative outcomes at a higher cost (adjusted mean difference = 2956; 95% CI: $2822-$3090) and shorter length of stay (mean difference = 0.85; 95% CI: 0.81-0.89) compared with ORP. Mean cost of RARP was lowest in urban teaching, private invest-own, high volume and northeast region hospitals and highest for black men. CONCLUSION: Compared with ORP, RARP had significantly better perioperative outcomes at a higher cost.

Impact of atrial fibrillation on inpatient cost for ischemic stroke in the USA.

BACKGROUND: Atrial fibrillation is a significant risk factor for ischemic stroke and increases cost of treatment. AIMS: To estimate the incremental inpatient cost and length of stay due to atrial fibrillation among adults hospitalized with a primary diagnosis of ischemic stroke after controlling for sociodemographic, clinical, and hospital characteristics in a nationally representative discharge record of US population. METHODS: Hospital discharge records with a primary diagnosis of ischemic stroke were identified from the National Inpatient Sample data for the years 2010-2013. Generalized linear model with log link and least-square means were utilized to estimate the incremental inpatient cost and length of stay in ischemic stroke due to atrial fibrillation after controlling for sociodemographic, clinical, and hospital characteristics. RESULTS: Among 434,544 hospital discharge records with a primary diagnosis of ischemic stroke, 90,190 (20.76%) discharge records had a secondary diagnosis of atrial fibrillation. The average inpatient cost for all discharge records with a primary diagnosis of ischemic stroke was (mean = $13,072, median = $9270.87) significantly (p < 0.0001) higher compared to all discharge records without ischemic stroke (mean = $12,543.07, median = $7517.13). The mean length of stay for all records was 4.55 days (95% CI = 4.53-4.56). Among those identified with ischemic stroke, adjusted mean inpatient cost was higher by $2829 (95% CI = $2708-$2949) and mean length of stay was greater by 0.85 (95% CI = 0.81-0.89) for those with atrial fibrillation compared to those without. CONCLUSIONS: The presence of atrial fibrillation was associated with increased inpatient cost and length of stay among patients diagnosed with ischemic stroke. Increased inpatient cost and length of stay call for a more comprehensive patient care approach including targeted interventions among adults diagnosed with ischemic stroke and atrial fibrillation, which could potentially reduce the overall cost in this population.

Cost-Effectiveness and Budget Impact of Lumacaftor/Ivacaftor in the Treatment of Cystic Fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a chronic, progressive, genetic disease affecting more than 30,000 people in the United States and 70,000 people globally. The goals of treatment are to slow disease progression, reduce pulmonary exacerbations, relieve chronic symptoms, and improve the patient's quality of life. Lumacaftor/ivacaftor is a new therapy for CF that has demonstrated good clinical outcomes, including improved absolute percentage predicted forced expiratory volume in 1 second (FEV1%). However, given the high cost of therapy, there is a need to evaluate the overall value of lumacaftor/ivacaftor in CF management. OBJECTIVES: To (a) conduct a cost-effectiveness analysis (CEA) of lumacaftor/ivacaftor to understand the overall effectiveness of the drug compared with its costs and (b) conduct a budget impact analysis (BIA) to understand the potential financial effect of introducing a new drug in a health plan. METHODS: Two static decision models were developed using Microsoft Excel to evaluate the cost-effectiveness and budget impact of lumacaftor/ivacaftor over a 1-year time frame from a payer perspective. Model inputs included drug costs (wholesale acquisition costs), drug monitoring schedules (package inserts), drug monitoring costs (Centers for Medicare & Medicaid physician fee schedule and published literature), FEV1% predicted and pulmonary exacerbation values (clinical trials), and cost to treat pulmonary exacerbations (published literature). The outcomes in the CEA included total cost of therapy; average cost-effectiveness ratio (ACER), defined as cost per FEV1% predicted; and incremental cost-effectiveness ratio (ICER), defined as the difference in the ratio of cost per FEV1% predicted of lumacaftor/ivacaftor and placebo. Outcomes in the BIA included total budget impact; cost per member per month (PMPM), defined as total budget impact per hypothetical plan population; and cost per treated member per month (PTMPM), defined as total budget impact per target CF population. All costs were adjusted to 2016 dollars, and one-way sensitivity analyses were conducted to test the model robustness given uncertainty in model inputs and study assumptions. RESULTS: The annual cost of therapy per patient for lumacaftor/ivacaftor was $379,780. The ACER for lumacaftor/ivacaftor was $151,912, while the ICER for lumacaftor/ivacaftor compared with placebo was $95,016 per FEV1% predicted. The annual total budget impact due to the inclusion of lumacaftor/ivacaftor on the health plan formulary was $266,046. The PMPM cost was $0.02 and the PTMPM cost was $6.21. CONCLUSIONS: In patients with CF, lumacaftor/ivacaftor has demonstrated better clinical effectiveness compared with placebo alongside an increased drug acquisition cost. However, the therapy may be a viable alternative to existing standard therapy over a short time horizon. Health care payers, both private and public, need to evaluate the cost-effectiveness and the financial effect when considering expansion of new drug coverage in CF management. DISCLOSURES: No outside funding supported this study. Covvey and Kamal have received research funding from Novartis Pharmaceuticals. Covvey, Giannetti, and Kamal have received research funding from the College of Psychiatric and Neurologic Pharmacists. Kamal serves as a consultant to the Lynx Group (Cranbury, NJ) and Manticore Consulting Group (Scottsdale, AZ). Mukherjee has nothing to disclose. A related poster abstract was presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; March 27-30, 2017; Denver, CO.

Sociodemographic Determinants of Out-of-Pocket Expenditures for Patients Using Prescription Drugs for Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that has a substantial economic impact on patients. Patients with RA are at an increased risk for disability and for loss of income. The inclusion of biologic drugs in RA therapy has increased the cost of treatment. Little is known about the relationship between sociodemographic characteristics and the out-of-pocket (OOP) expenditures for prescription drugs for patients with RA, including biologics, disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and analgesics. OBJECTIVES: To explore the relationship between sociodemographic characteristics, personal characteristics, and OOP expenditures associated with RA prescription medications. A secondary objective was to measure the average OOP expenditures for different therapeutic classes of RA medications, including biologics, DMARDs, NSAIDs, corticosteroids, and analgesics. METHODS: In this retrospective analysis of Medical Expenditure Panel Survey (MEPS) data from 2009 to 2012, we identified a patient sample of 1090 adults with RA, which represented approximately 9.71 million patients in the MEPS database. The total OOP expenditure was calculated based on the OOP expenditure for each prescription drug corresponding to an individual. Patient variables included age, race, sex, insurance status, number of comorbid conditions, region, area of living, annual family income, and marital status. Logistic regression and generalized linear models were used for analysis. The mean OOP expenditure for therapeutic classes was estimated using nonparametric percentiles from 1000 cluster bootstrap estimates. RESULTS: Overall, the mean annual OOP expenditure was $273.99 (95% confidence interval [CI], $197.07-$364.75). The OOP expenditures were lower for privately insured (0.31; 95% CI, 0.21-0.45) patients and publicly insured (0.18; 95% CI, 0.12-0.27) patients versus uninsured patients, and for poor (0.60; 95% CI, 0.43-0.84) and low-income (0.69; 95% CI, 0.49-0.97) patients versus high-income patients. The mean annual OOP expenditure decreased with age (0.98; 95% CI, 0.97-0.99), was lower (0.73; 95% CI, 0.58-0.92) for male patients than for female patients, and increased with the presence of comorbidities (1.16; 95% CI, 1.07-1.25). The average annual OOP expenditure was highest for biologics ($2556.73), followed by DMARDs ($89.37). The average annual OOP expenditures were $27.97, $52.36, and $72.51 for corticosteroids, NSAIDs, and narcotic analgesics, respectively. CONCLUSIONS: Age, sex, race, income level, insurance status, and comorbidity status significantly affected patient OOP expenditure. Higher OOP expenditures among the uninsured, female patients, patients with low income levels, and patients with several comorbidities could adversely affect RA therapy. The use of expensive biologics needs to be monitored to reduce prescription-related cost-sharing among patients with RA.

Solvent-free lipase-catalyzed preparation of diacylglycerols.

Various methods have been applied for the enzymatic preparation of diacylglycerols that are used as dietary oils for weight reduction in obesity and related disorders. Interesterification of rapeseed oil triacylglycerols with commercial preparations of monoacylglycerols, such as Monomuls 90-O18, Mulgaprime 90, and Nutrisoft 55, catalyzed by immobilized lipase from Rhizomucor miehei (Lipozyme RM IM) in vacuo at 60 degrees C led to extensive (from 60 to 75%) formation of diacylglycerols. Esterification of rapeseed oil fatty acids with Nutrisoft, catalyzed by Lipozyme RM in vacuo at 60 degrees C, also led to extensive (from 60 to 70%) formation of diacylglycerols. Esterification of rapeseed oil fatty acids with glycerol in vacuo at 60 degrees C, catalyzed by Lipozyme RM and lipases from Thermomyces lanuginosus (Lipozyme TL IM) and Candida antarctica (lipase B, Novozym 435), also provided diacylglycerols, however, to a lower extent (40-45%). Glycerolysis of rapeseed oil triacylglycerols with glycerol in vacuo at 60 degrees C, catalyzed by Lipozyme TL and Novozym 435, led to diacylglycerols to the extent of

Stereospecific incorporation of palmitoyl, oleoyl and linoleoyl moieties into adipose tissue triacylglycerols of rats results in constant sn-1:sn-2:sn-3 in rats fed rapeseed, olive, conventional or high oleic sunflower oils, but not in those fed coriander oil.

We report the stereospecific (sn-1, sn-2, sn-3) distribution of fatty acids in subcutaneous adipose tissue triacylglycerols of male weaned Wistar rats fed either a standard diet or diets containing, in addition to 20 g corn oil/kg feed, 120 g/kg feed, each, of canola-type rapeseed oil, olive oil, conventional or high oleic sunflower oil or high petroselinic coriander oil for 10 wk. The regiospecific distribution of the major acyl moieties in the sn-1 (3) vs. sn-2 positions of the adipose tissue triacylglycerols broadly reflected that of the dietary oils. The saturated palmitoyl and stearoyl moieties were more abundant in the sn-1 and sn-3 positions compared with the sn-2 position of the adipose tissue triacylglycerols, and both occurred at a higher proportion in the sn-1 than in the sn-3 position. Oleoyl moieties were abundant in all the three positions of the adipose tissue triacylglycerols, whereas petroselinoyl moieties were more abundant in the sn-1 and sn-3 positions compared with the sn-2 position. Linoleoyl moieties occurred predominantly in the sn-2 position compared with the sn-1 and sn-3 positions of the adipose tissue triacylglycerols; however, they were more abundant in the sn-3 than in the sn-1 position. Despite widely varying proportions of the palmitoyl, oleoyl and linoleoyl moieties at the three positions of the dietary triacylglycerols, the ratios of each of these acyl moieties at the sn-1, sn-2, and sn-3 positions in adipose tissue triacylglycerols were essentially constant for all groups, with the exception of the group fed coriander oil, indicating a rigid stereospecific incorporation.

The composition of the major molecular species of adipose tissue triacylglycerols of rats reflects those of dietary rapeseed, olive and sunflower oils.

We report the composition of constituent fatty acids and molecular species of adipose tissue triacylglycerols of male weaned Wistar rats fed diets containing, in addition to 20 g corn oil/kg feed, 120 g per kg feed canola-type rapeseed oil, olive oil or conventional sunflower oil for 10 wk. The composition of fatty acids and molecular species of the triacylglycerols of subcutaneous, epididymal and perirenal adipose tissues did not differ among groups (P > 0.01), broadly reflecting the corresponding compositions of the dietary oils. The major molecular species of dietary triacylglycerols, especially trioleoylglycerol (OOO) and linoleoyl-dioleoylglycerols (LOO) in the rapeseed oil and olive oil diets, dioleoyl-palmitoylglycerols (OOP) in the olive oil diet, dilinoleoyl-oleoylglycerols (LLO) in the rapeseed oil and sunflower oil diets, and dilinoleoyl-palmitoylglycerols (LLP), linoleoyl-oleoyl-palmitoylglycerols (LOP) as well as trilinoleoylglycerol (LLL) in the sunflower oil diet were also prominent constituents of the corresponding adipose tissue triacylglycerols. On the other hand, predominant molecular species containing alpha-linolenoyl (Ln) moieties, e.g., alpha-linolenoyl-linoleoyl-oleoylglycerols (LnLO) and alpha -linolenoyl-dioleoylglycerols (LnOO) from the rapeseed oil diet were not prominent constituents of rat adipose tissue triacylglycerols, whereas LOP from rapeseed oil and olive oil diets and OOP from rapeseed oil and sunflower oil diets were distinctly enriched in the corresponding adipose tissues. Most of the minor molecular species of the dietary triacylglycerols from all the three diets were distinctly present in the corresponding adipose tissues. Thus, despite numerous biochemical processes involved in the metabolism of dietary triacylglycerols, a substantial proportion of the molecular species of adipose tissue triacylglycerols containing linoleoyl (L), oleoyl (O) and palmitoyl (P) moieties resemble those of dietary triacylglycerols.