Depression and Time to Knee Arthroplasty Among Adults Who Have Knee Osteoarthritis.

BACKGROUND: Depression is common in osteoarthritis (OA) and is associated with poor outcomes following total knee arthroplasty (TKA). Depression can increase pain sensitivity and may be related to an increased likelihood of TKA. METHODS: Nationally distributed electronic health record data from 2010 to 2018 were used to identify eligible patients (n = 9,466) who had knee OA and were 45 to 80 years of age. Cox proportional hazard models were computed to estimate the association between depression and incident TKA for all patients and by age group (45 to 54, 55 to 64, and 65 to 80 years of age). Confounding was controlled using entropy balancing. Sensitivity analyses determined if the association between depression and TKA differed when depression occurred in the 12 months occurring 90, 60, 30, and 0 days lag time before TKA. RESULTS: The mean age of the sample was 63 (range, 45 to 80), 64.0% were women, 83.3% were White race, and approximately 50% resided in the Midwest. There was no association between depression and incident TKA (hazard ratio = 0.97; confidence interval = 0.81 to 1.16]). Results did not differ in age-stratified analyses. Sensitivity analyses revealed a higher percentage of TKA among depressed versus nondepressed patients (24.2 versus 21.6%; P = .028) when the patient's depression diagnosis was established in the 12 months with no lag time before TKA. CONCLUSIONS: Patients who have knee OA and comorbid depression, compared to those who have only knee OA, do not have an increased likelihood of TKA. The multifactorial, complex decision to obtain TKA does not appear to be influenced by depression, but depression is a common comorbidity.

Prevalence and Predictors of Depression in Women with Osteoarthritis: Cross-Sectional Analysis of Nationally Representative Survey Data.

Osteoarthritis (OA) is the most common joint disease in the US and can increase the risk of depression. Both depression and OA disproportionately affect women, yet this study is one of few on depression prevalence, treatment across age groups, and predictors in women with OA. Data were extracted from the 2011-March 2020 National Health and Nutrition Examination Survey (NHANES). Women aged ≥ 45 years with self-reported osteo- or degenerative arthritis were included. Outcomes were depression (assessed with PHQ-9) and treatment (self-reported pharmacotherapy and mental health services). Logistic regression was used to examine associations between age group, covariates, and outcomes. Overall, depression prevalence was 8%, with higher proportions among those 45-64 years old. Aging was associated with reduced odds of depression (Age 65-79: OR 0.68 (95% CI: 0.52-0.89); Age 80+: OR 0.49 (95% CI: 0.33-0.74); vs. Age 45-54). Of those with a positive depression screen, 21.6% documented some form of treatment. Age group was not statistically different between those treated and those not treated. Women aged 45-64 with osteoarthritis may be at increased risk of depression, and most are not treated. As depression is related to increased pain and risk of rehospitalization, future research should prioritize interventions to increase uptake of depression treatment.

Primary Care Research: Looking Back and Moving Forward With Reflections on NAPCRG's First 50 Years.

NAPCRG celebrated 50 years of leadership and service at its 2022 meeting. A varied team of primary care investigators, clinicians, learners, patients, and community members reflected on the organization's past, present, and future. Started in 1972 by a small group of general practice researchers in the United States, Canada, and the United Kingdom, NAPCRG has evolved into an international, interprofessional, interdisciplinary, and intergenerational group devoted to improving health and health care through primary care research. NAPCRG provides a nurturing home to researchers and teams working in partnership with individuals, families, and communities. The organization builds upon enduring values to create partnerships, advance research methods, and nurture a community of contributors. NAPCRG has made foundational contributions, including identifying the need for primary care research to inform primary care practice, practice-based research networks, qualitative and mixed-methods research, community-based participatory research, patient safety, practice transformation, and partnerships with patients and communities. Landmark documents have helped define classification systems for primary care, responsible research with communities, the central role of primary care in health care systems, opportunities to revitalize generalist practice, and shared strategies to build the future of family medicine. The future of health and health care depends upon strengthening primary care and primary care research with stronger support, infrastructure, training, and workforce. New technologies offer opportunities to advance research, enhance care, and improve outcomes. Stronger partnerships can empower primary care research with patients and communities and increase commitments to diversity and quality care for all. NAPCRG offers a home for all partners in this work.

Construction of an Administrative Osteoarthritis Severity Index.

OBJECTIVE: Electronic health record (EHR) databases are a powerful resource to investigate clinical trajectories of osteoarthritis (OA). There are no existing EHR tools to evaluate risk for knee arthroplasty (KA). We developed an OA severity index (OASI) using EHR data and demonstrate the index's association with time to KA. METHODS: This retrospective cohort study used 2010-2018 nationally distributed Optum EHR data. Eligible patients were 45 to 80 years old with a new diagnosis of knee OA in 2011-2012 and no prior KA. The OASI was a sum of first instance of x-ray imaging, advanced imaging, intra-articular injection, nonsteroidal anti-inflammatory drugs, and opioids. Principal components analysis index (PCI) score was also explored. Extended Cox proportional hazard models assessed time-dependent OASI and time to KA. RESULTS: Among 16,675 eligible patients, 12.7% underwent KA. Median follow-up time was 72 months. Adjusted OASI models showed each additional event almost doubled the risk for KA (adjusted hazard ratio = 1.80, 95% confidence interval: 1.75-1.86). Similar results were observed for PCI. CONCLUSION: The sum OASI performs well identifying patients who would undergo KA and offers simplicity versus the PCI. Although replication in other cohorts is recommended, the OASI appears to be a novel and valid means to measure clinical OA severity in research studies using large EHR-based cohorts.

Characteristics of Patients with Non-Cancer Pain and Perceived Severity of COVID-19 Related Stress.

Synopsis Patients with non-cancer pain reported increased pain and pain interference during the first months of the COVID-19 pandemic. We determined if pain, prescription opioid use, and comorbidities were associated with perceived COVID-19-related stress as the pandemic peaked. Analysis of survey data revealed that depression/anxiety, pain severity, and pain interference were most strongly and consistently associated with greater stress due to COVID-19 related changes in lifestyle, worsening of emotional/mental health and worsening pain. Identifying specific stressful experiences that most impacted patients with non-cancer pain may help target public health and treatment interventions. Background: During the first months of the COVID-19 pandemic, patients with chronic pain reported increased pain severity and interference. This study measured the association between pain, prescription opioid use, and comorbidities with perceived COVID-19-related stress as the pandemic peaked in the United States. Methods: From 9/2020 to 3/2021, the first 149 subjects from a prospective cohort study of non-cancer pain, completed a survey which contained the Complementary and Integrative Research (CAIR) Pandemic Impact Questionnaire (C-PIQ). Respondents also reported whether the pandemic has contributed to their pain or opioid use. Bivariate comparisons explored patient characteristics with each CAIR domain. Results: Respondents mean age was 54.6 (±11.3) years, 69.8% were female, 64.6% were White. Respondent characteristics were not associated with reading/watching/thinking about the pandemic or with worry about health. Depression/anxiety (p=0.003), using any prescription opioid in the prior three months (p=0.009), higher morphine milligram equivalent used (p=0.005), higher pain severity (p=0.011), and higher pain interference (p=0.0004) were all positively and significantly associated with moderate to severe stress due to COVID-19 related lifestyle changes. Depression/anxiety, pain severity, and pain interference were positively associated with COVID-19-related worsening emotional/mental health. Depression/anxiety were significantly (p<0.0001) associated with reporting that the pandemic made their pain worse. Conclusion: Depression, anxiety, pain severity, and pain interference were most strongly and consistently associated with COVID-19 changes in way of life, worsening of emotional/mental health, and worsening pain. Identifying specific stressful experiences that most impacted patients with noncancer pain may inform public health and treatment interventions.

Increased Smoking Cessation Among Veterans With Large Decreases in Posttraumatic Stress Disorder Severity.

INTRODUCTION: Improvement in posttraumatic stress disorder (PTSD) is associated with better health behavior such as better medication adherence and greater use of nutrition and weight loss programs. However, it is not known if reducing PTSD severity is associated with smoking cessation, a poor health behavior common in patients with PTSD. AIMS AND METHODS: Veterans Health Affairs (VHA) medical record data (2008-2015) were used to identify patients with PTSD diagnosed in specialty care. Clinically meaningful PTSD improvement was defined as ≥20 point PTSD Checklist (PCL) decrease from the first PCL ≥50 and the last available PCL within 12 months and at least 8 weeks later. The association between clinically meaningful PTSD improvement and smoking cessation within 2 years after baseline among 449 smokers was estimated in Cox proportional hazard models. Entropy balancing controlled for confounding. RESULTS: On average, patients were 39.4 (SD = 12.9) years of age, 86.6% were male and 71.5% were white. We observed clinically meaningful PTSD improvement in 19.8% of participants. Overall, 19.4% quit smoking in year 1 and 16.6% in year 2. More patients with versus without clinically meaningful PTSD improvement stopped smoking (n = 36, cumulative incidence = 40.5% vs. 111, cumulative incidence = 30.8%, respectively). After controlling for confounding, patients with versus without clinically meaningful PTSD improvement were more likely to stop smoking within 2 years (hazard ratio = 1.57; 95% confidence interval: 1.04-2.36). CONCLUSIONS: Patients with clinically meaningful PTSD improvement were significantly more likely to stop smoking. Further research should determine if targeted interventions are needed or whether improvement in PTSD symptoms is sufficient to enable smoking cessation. IMPLICATIONS: Patients with PTSD are more likely to develop chronic health conditions such as heart disease and diabetes. Poor health behaviors, including smoking, partly explain the risk for chronic disease in this patient population. Our results demonstrate that clinically meaningful PTSD improvement is followed by greater likelihood of smoking cessation. Thus, PTSD treatment may enable healthier behaviors and reduce risk for smoking-related disease.

PTSD symptom improvement and smoking cessation among a sample of veterans.

Context: Poor health behaviors are common in persons with posttraumatic stress disorder (PTSD). PTSD symptom improvement has been followed by better health behaviors such as medication adherence and use of nutrition, weight loss, and substance abuse treatment programs. Whether PTSD improvement is associated with smoking cessation is uncertain. Objective: To determine if patients with, compared to without, clinically meaningful improvement (≥20 points vs. <20 points) in PTSD Checklist (PCL) scores are more likely to stop smoking. Study Design: Retrospective cohort using entropy balancing to control for confounding in Cox proportional hazard models overall and stratified by depression and alcohol abuse/dependence. Dataset: Veterans Health Affairs (VHA) medical record data from 2008-2015. Population studied: Patients aged 18-70 years with PTSD who had ≥ 1 visit to PTSD specialty care with a PCL score ≥50, at least one PCL score from ≥8 weeks to 12 months following first PCL≥50 ('exposure year'), and persistent smokers in the exposure year (n=449). Index date is the end of the exposure year. Intervention/Instrument: Change from first to last PCL score in exposure year classified as clinically meaningful vs. less than clinically meaningful improvement (≥20 point decrease vs. <20 point decrease). Outcome measures. Time to smoking cessation as documented in VHA administrative medical record data in the 2-years after index. Follow-up time was measured as months from index to either smoking cessation or censoring. Results: Overall, patients were 39.4 (±12.9) years old, 71.5% white, 86.6% male, 19.8% had a clinically meaningful PCL score decrease, and 32.7% quit smoking in the 2-years after index. After entropy weighting, PCL decrease ≥ 20 vs. < 20 was associated with a 57% increased likelihood of smoking cessation (HR=1.57; 95% CI=1.04-2.36). The relationship of PTSD improvement with smoking cessation was similar in patients with vs. without depression and with and without alcohol abuse/dependence. Among patients who quit smoking, about half remained non-smokers in the 12-months after initial quit date. Conclusions: A clinically meaningful reduction in PTSD symptoms was associated with smoking cessation in the 2-years after PTSD improvement. Not all patients with PTSD have access to PTSD treatment modalities that integrate smoking cessation therapy; however, PTSD treatment alone may improve patient self-efficacy and enable smoking cessation.

Consumption of High-Oleic Soybean Oil Improves Lipid and Lipoprotein Profile in Humans Compared to a Palm Oil Blend: A Randomized Controlled Trial.

Partially hydrogenated oils (PHO) have been removed from the food supply due to adverse effects on risk for coronary heart disease (CHD). High-oleic soybean oils (HOSBO) are alternatives that provide functionality for different food applications. The objective of this study was to determine how consumption of diets containing HOSBO compared to other alternative oils, with similar functional properties, modifies LDL cholesterol (LDLc) and other risk factors and biomarkers of CHD. A triple-blind, crossover, randomized controlled trial was conducted in humans (n = 60) with four highly-controlled diets containing (1) HOSBO, (2) 80:20 blend of HOSBO and fully hydrogenated soybean oil (HOSBO+FHSBO), (3) soybean oil (SBO), and (4) 50:50 blend of palm oil and palm kernel oil (PO + PKO). Before and after 29 days of feeding, lipids/lipoproteins, blood pressure, body composition, and markers of inflammation, oxidation, and hemostasis were measured. LDLc, apolipoprotein B (apoB), NonHDL-cholesterol (HDLc), ratios of total cholesterol (TC)-to-HDLc and LDLc-to-HDL cholesterol, and LDL particle number and small LDL particles concentration were lower after HOSBO and HOSBO+FHSBO compared to PO (specific comparisons p < 0.05). Other than TC:HDL, there were no differences in lipid/lipoprotein markers when comparing HOSBO+FHSBO with HOSBO. LDLc and apoB were higher after HOSBO compared to SBO (p < 0.05). PO + PKO increased HDLc (p < 0.001) and apolipoprotein AI (p < 0.03) compared to HOSBO and HOSBO+FHSBO. With the exception of lipid hydroperoxides, dietary treatments did not affect other CHD markers. HOSBO, and blends thereof, is a PHO replacement that results in more favorable lipid/lipoprotein profiles compared to PO + PKO (an alternative fat with similar functional properties).

Preanalytical Sample Handling Conditions and Their Effects on the Human Serum Metabolome in Epidemiologic Studies.

Many epidemiologic studies use metabolomics for discovery-based research. The degree to which sample handling may influence findings, however, is poorly understood. In 2016, serum samples from 13 volunteers from the US Department of Agriculture's Beltsville Human Nutrition Research Center were subjected to different clotting (30 minutes/120 minutes) and refrigeration (0 minutes/24 hours) conditions, as well as different numbers (0/1/4) and temperatures (ice/refrigerator/room temperature) of thaws. The median absolute percent difference (APD) between metabolite levels and correlations between levels across conditions were estimated for 628 metabolites. The potential for handling artifacts to induce false-positive associations was estimated using variable hypothetical scenarios in which 1%-100% of case samples had different handling than control samples. All handling conditions influenced metabolite levels. Across metabolites, the median APD when extending clotting time was 9.08%. When increasing the number of thaws from 0 to 4, the median APD was 10.05% for ice and 5.54% for room temperature. Metabolite levels were correlated highly across conditions (all r's ≥ 0.84), indicating that relative ranks were preserved. However, if handling varied even modestly by case status, our hypotheticals showed that results can be biased and can result in false-positive findings. Sample handling affects levels of metabolites, and special care should be taken to minimize effects. Shorter room-temperature thaws should be preferred over longer ice thaws, and handling should be meticulously matched by case status.

Which aspects of neighbourhood environment are most associated with meeting physical activity recommendations in American adults: an NHIS study.

OBJECTIVES: To investigate which perceived neighbourhood characteristics are most strongly linked with adequate physical activity (PA) in a nationally representative sample of adults in the USA. DESIGN: Cross-sectional. SETTING: USA via 2015 National Health Interview Survey Data. PARTICIPANTS: A group of 28 697 non-institutionalised adults with complete data. PRIMARY OUTCOME MEASURES: Meeting PA was defined as 150 min/week of moderate to vigorous activity. RESULTS: The population had a mean age of 49.6 (±18.3) years and was 51.3% female and 66.2% non-Hispanic white. In adjusted, weighted analysis, places to walk and relax was mostly strongly associated with meeting PA recommendations (OR=1.40 (95% CI 1.27 to 1.54)). Other elements associated with meeting PA were presence of bus or transit stops to walk to and presence of movies, libraries or churches to walk to (OR=1.12 (95% CI 1.03 to 1.23) and OR=1.19 (95% CI 1.08 to 1.31), respectively). CONCLUSIONS: In this analysis, the characteristic most strongly associated with PA was presence of places to walk and relax. Identifying communities that may lack amenities such as this, like a park, may help direct community investment to enhance structures that encourage activity.

Neighborhood built and social environment and meeting physical activity recommendations among mid to older adults with joint pain.

Arthritis is a leading cause of disability in the United States, with the most efficacious treatments being physical activity (PA). Arthritis patients are less likely to meet PA recommendations and the neighborhood environment may play a role. This study examines the effect of neighborhood walkability and social cohesion on PA among arthritis patients in a sample of US adults. This cross-sectional study used 2015 National Health Interview Survey data. Eligible participants were age ≥45 years, had arthritis, recent leg-joint pain and complete data. Walkability was based on 6 questions regarding amenities and destinations that promote walking. Social cohesion was based on 4 validated questions. Meeting PA was defined as 150 min/week. Chi-squared testing and logistic regression determined associations between neighborhood environment and PA, including interaction between social cohesion and walkability. The final unweighted sample included 3,826 participants with mean age 64.6 years (SE = 0.26), 61.8% female and 78.1% non-Hispanic White. In adjusted, weighted analysis, not, slightly, and moderately-walkable neighborhoods all had lower odds of meeting PA recommendations verses highly-walkable neighborhood (OR = 0.61[95% CI 0.41-0.92], OR = 0.65[95% CI 0.50-0.85], OR = 0.75[95% CI 0.59-0.97], respectively). Social cohesion was independently associated with decreased odds of meeting PA guidelines (p = 0.003). No interaction with walkability was found (p = 0.405). Less than a highly-walkable neighborhood and lower social cohesion were independently associated with decreased odds of meeting PA recommendations among adults with arthritis and recent joint pain. Since walking is one of the most effective treatments for arthritis, clinicians should be sensitive to barriers patients may perceive to walking.

Combined effect of posttraumatic stress disorder and prescription opioid use on risk of cardiovascular disease.

AIM: Prescription opioid analgesic use (OAU) is associated with increased risk of cardiovascular disease (CVD). OAU is more common in patients with than without posttraumatic stress disorder (PTSD), and PTSD is associated with higher CVD risk. We determined whether PTSD and OAU have an additive or multiplicative association with incident CVD. METHODS AND RESULTS: Veterans Health Affairs patient medical record data from 2008 to 2015 was used to identify 2861 patients 30-70 years of age, free of cancer, CVD and OAU for 12 months before index date. We defined a four-level exposure variable: 1) no PTSD/no OAU, 2) OAU alone, 3) PTSD alone and 4) PTSD+OAU. Cox proportional hazard models estimated the association between the exposure variable and incident CVD. The mean age was 49.0 (±11.0), 85.7% were male and 58.3% were White, 34.4% had no PTSD/no OAU, 32.9% had PTSD alone, 10.6% had OAU alone, and 22.1% had PTSD+OAU. Compared with patients with no PTSD/no OAU, those with PTSD alone were not at increased risk of incident CVD (hazard ratio = 0.82; 95% confidence interval (CI): 0.63-1.17); however, OAU alone and PTSD+OAU were both significantly associated with incident CVD (hazard ratio = 1.99; 95% CI:1.36-2.92 and hazard ratio = 2.20; 95% CI: 1.61-3.02). There was no significant additive or multiplicative PTSD and OAU association with incident CVD. CONCLUSION: OAU is associated with nearly a two-fold increased risk of CVD in patients with and without PTSD. Despite no additive or multiplicative interaction effects, the high prevalence of OAU in PTSD may represent a novel contributor to the elevated CVD burden among patients with PTSD.

The association between depression and type of treatments received for chronic low back pain.

BACKGROUND: Depression is associated with receipt of opioids in non-cancer pain. OBJECTIVES: To determine whether the receipt of opioid therapy modifies the relationship of depression and use of multiple non-opioid pain treatments. METHODS: Patients (n = 320) with chronic low back pain (CLBP) were recruited from family medicine clinics and completed questionnaires that measured use of home remedies, physical treatments requiring a provider and non-opioid medication treatments. A binary variable defined use (yes/no) of all three non-opioid treatment categories. Depression (yes/no) was measured with the PHQ-2. The use of opioids (yes/no) was determined by medical record abstraction. Unadjusted and adjusted logistic regression models, stratified on opioid use, estimated the association between depression and use of all three non-opioid treatments. RESULTS: Participants were mostly female (71.3%), non-white (57.5%) and 69.4% were aged 18 to 59 years. In adjusted analyses stratified by opioid use, depression was not significantly associated with using three non-opioid treatments (OR = 2.20; 95% CI = 0.80-6.07) among non-opioid users; but among opioid users, depression was significantly associated with using three non-opioid treatments (OR = 3.21; 95% CI: 1.14-8.99). These odds ratios were not significantly different between opioid users and non-users (P = 0.609). CONCLUSION: There is modest evidence to conclude that patients with CLBP and comorbid depression, compared with those without depression, were more likely to try both opioid and non-opioid pain treatments. Non-response to other pain treatments may partly explain why depression is associated with greater prescription opioid use.

Gender-Stratified Prevalence of Psychiatric and Pain Diagnoses in a Primary Care Patient Sample with Fibromyalgia.

OBJECTIVE: Comorbid psychiatric and pain-related conditions are common in patients with fibromyalgia. Most studies in this area have used data from patients in specialty care and may not represent the characteristics of fibromyalgia in primary care patients. We sought to fill gaps in the literature by determining if the association between psychiatric diagnoses, conditions associated with chronic pain, and fibromyalgia differed by gender in a primary care patient population. DESIGN: Retrospective cohort. SETTING AND SUBJECTS: Medical record data obtained from 38,976 patients, ≥18 years of age with a primary care encounter between July 1, 2008, to June 30, 2016. METHODS: International Classification of Diseases-9 codes were used to define fibromyalgia, psychiatric diagnoses, and conditions associated with chronic pain. Unadjusted associations between patient demographics, comorbid conditions, and fibromyalgia were computed using binary logistic regression for the entire cohort and separately by gender. RESULTS: Overall, 4.6% of the sample had a fibromyalgia diagnosis, of whom 76.1% were women. Comorbid conditions were more prevalent among patients with vs without fibromyalgia. Depression and arthritis were more strongly related to fibromyalgia among women (odds ratio [OR] = 2.80, 95% confidence interval [CI] = 2.50-3.13; and OR = 5.19, 95% CI = 4.62-5.84) compared with men (OR = 2.16, 95% CI = 1.71-2.71; and (OR = 3.91, 95% CI = 3.22-4.75). The relationship of fibromyalgia and other diagnoses did not significantly differ by gender. CONCLUSIONS: Except for depression and arthritis, the burden of comorbid conditions in patients with fibromyalgia is similar in women and men treated in primary care. Fibromyalgia comorbidities in primary care are similar to those found in specialty care.

Disability Benefits and Change in Prescription Opioid Dose.

Among chronic low back pain (CLBP) patients, workers' compensation is associated with longer term prescription opioid analgesic use (OAU). The aim was to study the association between receiving Social Security Disability Insurance (SSDI) benefits and course of OAU. This prospective cohort study utilized data from primary care patients diagnosed with non-cancer CLBP. The outcomes were morphine equivalent dose (MED) - categorized as no OAU, 1-50mg MED, or >50mg MED - and change in MED over time using mixed multinomial logistic regression models. Covariates included sociodemographics, pain severity, pain management characteristics, continuity of care with their physician, health-related quality of life, number of comorbid health conditions, obesity, depression, and anxiety. In adjusted analysis, SSDI vs. non-SSDI patients were more likely to be receiving >50mg MED vs. no OAU at baseline (OR = 10.19; 95% CI:1.51-68.83). Differences in OAU trajectory between SSDI groups were nonsignificant (P = 0.204). Collection of SSDI benefits was an independent predictor of higher MED at baseline and persistently higher MED during 2 years of follow-up. Providers should consider the risk of persistent, high-dose opioid use in patients receiving SSDI benefits.

Phytosterols and their derivatives: Structural diversity, distribution, metabolism, analysis, and health-promoting uses.

Phytosterols (plant sterols) occur in the cells of all plants. They are important structural components that stabilize the biological membranes of plants. Sterols can occur in the "free" unbound form or they can be covalently bound via an ester or glycosidic bond. Since our previous 2002 review on phytosterols and phytosterol conjugates, phytosterol glucosides have been found to be important structural components in the lipid rafts of the plasma membrane of plant cells, where they are thought to be essential to the function of plasma membrane enzymes and perhaps other proteins. Phytosterols also serve as precursors in the synthesis of important bioactive compounds such as steroidal saponins, steroidal glycoalkaloids, phytoecdysteroids, and brassinosteroids. Methods for the analysis of phytosterols range from traditional gas chromatography of free phytosterols to modern sophisticated forms of mass spectrometry which have been used for the new field of sterol lipidomics, sometimes called "sterolomics." Phytosterol-enriched functional foods first appeared about twenty years ago and many clinical studies have confirmed the low density lipoprotein (LDL) cholesterol-lowering properties of various types of phytosterols. In recent years additional clinical studies and more than ten important meta-analyses have provided insights to better understand the cholesterol-lowering and other biological effects of plant sterols.