Branched Chain Amino Acid Supplementation to a Hypocaloric Diet Does Not Affect Resting Metabolic Rate but Increases Postprandial Fat Oxidation Response in Overweight and Obese Adults after Weight Loss Intervention.

BACKGROUND: Branched chain amino acids (BCAA) supplementation is reported to aid in lean mass preservation, which may in turn minimize the reduction in resting metabolic rate (RMR) during weight loss. Our study aimed to examine the effect of BCAA supplementation to a hypocaloric diet on RMR and substrate utilization during a weight loss intervention. METHODS: A total of 111 Chinese subjects comprising 55 males and 56 females aged 21 to 45 years old with BMI between 25 and 36 kg/m2 were randomized into three hypocaloric diet groups: (1) standard-protein (14%) with placebo (CT), (2) standard-protein with BCAA, and (3) high-protein (27%) with placebo. Indirect calorimetry was used to measure RMR, carbohydrate, and fat oxidation before and after 16 weeks of dietary intervention. RESULTS: RMR was reduced from 1600 ± 270 kcal/day to 1500 ± 264 kcal/day (p < 0.0005) after weight loss, but no significant differences in the change of RMR, respiratory quotient, and percentage of fat and carbohydrate oxidation were observed among the three diet groups. Subjects with BCAA supplementation had an increased postprandial fat (p = 0.021) and decreased postprandial carbohydrate (p = 0.044) oxidation responses compared to the CT group after dietary intervention. CONCLUSIONS: BCAA-supplemented standard-protein diet did not significantly attenuate reduction of RMR compared to standard-protein and high-protein diets. However, the postprandial fat oxidation response increased after BCAA-supplemented weight loss intervention.

Facilitators of and barriers to implementing a traditional Chinese medicine collaborative model of care for axial spondyloarthritis: a qualitative study.

BACKGROUND: Conventional therapy may be inadequate for many patients with axial spondyloarthritis (axSpA). Traditional Chinese medicine (TCM) may be a viable alternative, but its effectiveness for axSpA is unknown. We are currently conducting a pragmatic randomised controlled trial (RCT) to investigate the effectiveness of a TCM collaborative model of care (TCMCMC), which combines usual rheumatologic care with acupuncture for patients with axSpA. This nested qualitative sub-study aims to identify facilitators of and barriers to the implementation of the TCMCMC. METHODS: We conducted individual in-depth interviews with participants who had completed the acupuncture regimen to elicit opinions on the facilitators of and barriers to the implementation of the TCMCMC. The interviews were transcribed and analysed using thematic analysis. RESULTS: Twelve participants were included, with data saturation occurring after 10 interviews. The analysis revealed both a number of important 'facilitators' and 'barriers'. Facilitators to the implementation of the TCMCMC included effectiveness of TCM to relieve symptoms, inadequacy of conventional treatment and positive social perceptions of TCM. Barriers included scepticism towards TCM, inability of TCM to provide instant relief, needle-related discomfort, variable effectiveness of TCM influenced by physicians' skills and experience and the high cost of TCM. Recommendations to overcome barriers included further patient education about TCM. CONCLUSION: Policymakers should take into account the various feasibility factors identified in this study when developing and implementing a TCMCMC. TRIAL REGISTRATION NUMBER: NCT03420404 (ClinicalTrials.gov).

Branched-Chain Amino Acid Supplementation Does Not Preserve Lean Mass or Affect Metabolic Profile in Adults with Overweight or Obesity in a Randomized Controlled Weight Loss Intervention.

BACKGROUND: Branched-chain amino acid (BCAA) supplementation has been shown to increase muscle mass or prevent muscle loss during weight loss. OBJECTIVE: We aimed to investigate the effects of a BCAA-supplemented hypocaloric diet on lean mass preservation and insulin sensitivity. METHODS: A total of 132 Chinese adults (63 men and 69 women aged 21-45 y, BMI 25-36 kg/m2) were block randomly assigned by gender and BMI into 3 hypocaloric diet (deficit of 500 kcal/d) groups: standard-protein (14%) with placebo (control, CT) or BCAA supplements at 0.1 g · kg-1 body weight · d-1 (BCAA) or high-protein (27%) with placebo (HP). The subjects underwent 16 wk of dietary intervention with provision of meals and supplements, followed by 8 wk of weight maintenance with provision of supplements only. One-way ANOVA analysis was conducted to analyze the primary (lean mass and insulin sensitivity) and secondary outcomes (anthropometric and metabolic parameters) among the 3 groups. Paired t-test was used to analyze the change in each group. RESULTS: The 3 groups demonstrated similar significant reductions in body weight (7.97%), fat mass (13.8%), and waist circumference (7.27%) after 16 wk of energy deficit. Lean mass loss in BCAA (4.39%) tended to be lower than in CT (5.39%) and higher compared with HP (3.67%) (P = 0.06). Calf muscle volume increased 3.4% in BCAA and intramyocellular lipids (IMCLs) decreased in BCAA (17%) and HP (18%) (P < 0.05) over 16 wk. During the 8 wk weight maintenance period, lean mass gain in BCAA (1.03%) tended to be lower compared with CT (1.58%) and higher than in HP (-0.002%) (P = 0.04). Lean mass gain differed significantly between CT and HP (P = 0.03). Insulin sensitivity and metabolic profiles did not differ among the groups throughout the study period. CONCLUSIONS: BCAA supplementation does not preserve lean mass or affect insulin sensitivity in overweight and obese adults during weight loss. A higher protein diet may be more advantageous for lean mass preservation.

Exploring the implementation of the Community for Successful Ageing (ComSA)program in Singapore: lessons learnt on program delivery for improving BioPsychoSocial health.

BACKGROUND: The Community for Successful Ageing (ComSA) program has implemented overlapping BioPsychoSocial (BPS) components as part of a Community Development (CD) grassroots and volunteer-led initiative. Implementation of such multi-component programming is influenced by known program characteristics including novelty, complexity and observability as well as related organizational factors. As such, we explored ComSA CD's implementation from the organizational perspective, seeking to inform program improvements. METHODS: We conducted four focus groups with program staff, partners and trainers (total N = 21 participants). Findings were analysed using an interpretative approach and synthesized into a line of argument informing lessons learnt. RESULTS: An implementation framework was identified. It is guided by considering the influence of known program characteristics across major themes, representing three core implementation stages. These and supporting sub-themes are elaborated in turn: 1) Creating commitment toward the program was challenged by novelty and at times a lack of shared understanding of ComSA CD, particularly relating to the S component. Overall, cohesion within organizational contexts and having a strong rapport with the community (ability to engage) were needed to persuade volunteers and participants to commit to the program. 2) Coordination and resource allocation were influenced by the complexity of interconnecting BPS components - requiring aligning communication between partners and adapting the BPS sequence, given the separated management structure of program trainers. Efficiency of resource utilization was constrained by the ability to pool and match resources given the limited manpower and community partners who worked-in-silo due to a KPI-centric culture. 3) Collaborative program monitoring and appraisal increased observability of the program's benefits, but depended on partners' prior commitment. Despite appreciating its holistic BPS programming, dropout rate was used as a way to gauge program success, which has limited interpretability. Occasional uncertainty about the program value contributed to concerns about duplicating existing ageing programs, particularly those related to the B component. CONCLUSION: Lessons learnt for improving BPS programming include (1) eliciting better participants' buy-in and shared program vision, (2) increasing adaptability of BPS sequence and building a culture of shared values for working together (3) and developing comprehensive monitoring systems for program appraisal.

Theory and Design of the Community for successful ageing (ComSA) program in Singapore: connecting BioPsychoSocial health and quality of life experiences of older adults.

BACKGROUND: Despite the emphasis on holistic health promotion in community programs for older people, few studies explicitly consider how BioPsychoSocial (BPS) health elements are interconnected and function to improve Quality of Life (QoL). The Community for Successful Ageing (ComSA) program in Singapore focuses on Community Development (CD) initiatives for older people, accounting for BPS theory in its design and content. Biological (B) health is conceived as physiological and cognitive functioning and related biological self-care; Psychological (P) health as feelings of life satisfaction, and Social health (S) as perceived social support and civic engagement. Furthermore, three overlapping sub-constructs are theorized to connect these elements. Namely Bio-Psychological (BP) health in terms of self-perceptions of ageing; the Psycho-Social (PS) aspects of interpersonal communication; and the Socio-Communal (SC) health in terms of civic engagement. BPS health is conceived as distinct from QoL, defined as composed of control, autonomy, self-realisation and pleasure (measured by CASP-19) of the older person. We examined 1) interconnections of BPS constructs and related sub-constructs and 2) their associations with QoL to inform a practical, applied program theory. METHODS: A baseline survey (n = 321) of program participants (Mean = 70 years, SD = 8.73). All continuous variables were binarized as 'high' if the scores were above the median. Multivariate logistic regression was used to assess 1) the adjusted effect of each BPS construct on CASP-19, and 2) the odds of scoring high on one BPS construct with the odds of scoring high on a related sub-construct (e.g. B and BP health). RESULTS: The strongest relationship with QoL was markedly with BP self-perceptions of ageing (OR = 4.07, 95%CI = 2.21-7.49), followed by P life satisfaction (OR = 3.66, 95%CI = 2.04-6.57), PS interpersonal communication (OR = 2.42, 95%CI = 1.23-4.77), SC civic engagement (OR = 1.94, 95%CI = 1.05-3.57), and S social support (OR = 1.89, 95%CI = 1.06-3.38). Core B, P and S health were closely associated with their sub-constructs. CONCLUSION: ComSA CD is tightly coupled to its proposed program theory. It offers classes to improve B self-care and BP self-perceptions of ageing, group-based guided autobiography to improve P life-satisfaction and PS interpersonal communication, and community initiatives that encourage seniors to solve community issues. This holistic approach is likely to enhance ageing experiences and QoL.

Retrospective evaluation of healthcare utilisation and mortality of two post-discharge care programmes in Singapore.

OBJECTIVE: To evaluate the impact on healthcare utilisation frequencies and charges, and mortality of a programme for frequent hospital utilisers and a programme for patients requiring high acuity post-discharge care as part of an integrated healthcare model. DESIGN: A retrospective quasi-experimental study without randomisation where patients who received post-discharge care interventions were matched 1:1 with unenrolled patients as controls. SETTING: The National University Health System (NUHS) Regional Health System (RHS), which was one of six RHS in Singapore, implemented the NUHS RHS Integrated Interventions and Care Extension (NICE) programme for frequent hospital utilisers and the NUHS Transitional Care Programme (NUHS TCP) for high acuity post-discharge care. The programmes were supported by the Ministry of Health in Singapore, which is a city-state nation located in Southeast Asia with a 5.6 million population. PARTICIPANTS: Linked healthcare administrative data, for the time period of January 2013 to December 2016, were extracted for patients enrolled in NICE (n=554) or NUHS TCP (n=270) from June 2014 to December 2015, and control patients. INTERVENTIONS: For both programmes, teams conducted follow-up home visits and phone calls to monitor and manage patients' post-discharge. PRIMARY OUTCOME MEASURES: One-year pre- and post-enrolment healthcare utilisation frequencies and charges of all-cause inpatient admissions, emergency admissions, emergency department attendances, specialist outpatient clinic (SOC) attendances, total inpatient length of stay and mortality rates were compared. RESULTS: Patients in NICE had lower mortality rate, but higher all-cause inpatient admission, emergency admission and emergency department attendance charges. Patients in NUHS TCP did not have lower mortality rate, but had higher emergency admission and SOC attendance charges. CONCLUSIONS: Both NICE and NUHS TCP had no improvements in 1 year healthcare utilisation across various setting and metrics. Singular interventions might not be as impactful in effecting utilisation without an overhauling transformation and restructuring of the hospital and healthcare system.

Traditional Chinese medicine (TCM) collaborative care for patients with axial spondyloarthritis (AcuSpA): protocol for a pragmatic randomized controlled trial.

BACKGROUND: Axial spondyloarthritis (AxSpA) is a chronic disease which results in fatigue, pain, and reduced quality of life (QoL). Traditional Chinese medicine (TCM), especially acupuncture, has shown promise in managing pain. Although a TCM collaborative model of care (TCMCMC) has been studied in cancer, there are no randomized controlled trials investigating TCM in AxSpA. Therefore, we will conduct a pragmatic trial to determine the clinical effectiveness, safety, and cost-effectiveness of TCMCMC for patients with AxSpA. We define TCMCMC as standard TCM history taking and physical examination, acupuncture, and TCM non-pharmacological advice and communications with rheumatologists in addition to usual rheumatologic care. The purpose of this paper is to describe the rationale for and methodology of this trial. METHODS/DESIGN: This pragmatic randomized controlled trial will recruit 160 patients who are diagnosed with AxSpA and have inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs). Simple randomization to usual rheumatologic care or the intervention (TCMCMC) with a 1:1 allocation ratio will be used. Ten 30-min acupuncture sessions will be provided to patients assigned to the TCMCMC arm. All participants will continue to receive usual rheumatologic care. The primary endpoint - spinal pain - will be evaluated at week 6. Secondary endpoints include clinical, quality of life, and economic outcome measures. Patients will be followed up for up to 52 weeks, and adverse events will be documented. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of a TCMCMC for patients with AxSpA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03420404 . Registered on 14 February 2018.

A systematic review of the clinical application of data-driven population segmentation analysis.

BACKGROUND: Data-driven population segmentation analysis utilizes data analytics to divide a heterogeneous population into parsimonious and relatively homogenous groups with similar healthcare characteristics. It is a promising patient-centric analysis that enables effective integrated healthcare interventions specific for each segment. Although widely applied, there is no systematic review on the clinical application of data-driven population segmentation analysis. METHODS: We carried out a systematic literature search using PubMed, Embase and Web of Science following PRISMA criteria. We included English peer-reviewed articles that applied data-driven population segmentation analysis on empirical health data. We summarized the clinical settings in which segmentation analysis was applied, compared and contrasted strengths, limitations, and practical considerations of different segmentation methods, and assessed the segmentation outcome of all included studies. The studies were assessed by two independent reviewers. RESULTS: We retrieved 14,514 articles and included 216 articles. Data-driven population segmentation analysis was widely used in different clinical contexts. 163 studies examined the general population while 53 focused on specific population with certain diseases or conditions, including psychological, oncological, respiratory, cardiovascular, and gastrointestinal conditions. Variables used for segmentation in the studies are heterogeneous. Most studies (n = 170) utilized secondary data in community settings (n = 185). The most common segmentation method was latent class/profile/transition/growth analysis (n = 96) followed by K-means cluster analysis (n = 60) and hierarchical analysis (n = 50), each having its advantages, disadvantages, and practical considerations. We also identified key criteria to evaluate a segmentation framework: internal validity, external validity, identifiability/interpretability, substantiality, stability, actionability/accessibility, and parsimony. CONCLUSIONS: Data-driven population segmentation has been widely applied and holds great potential in managing population health. The evaluations of segmentation outcome require the interplay of data analytics and subject matter expertise. The optimal framework for segmentation requires further research.

Assessing the validity of a data driven segmentation approach: A 4 year longitudinal study of healthcare utilization and mortality.

BACKGROUND: Segmentation of heterogeneous patient populations into parsimonious and relatively homogenous groups with similar healthcare needs can facilitate healthcare resource planning and development of effective integrated healthcare interventions for each segment. We aimed to apply a data-driven, healthcare utilization-based clustering analysis to segment a regional health system patient population and validate its discriminative ability on 4-year longitudinal healthcare utilization and mortality data. METHODS: We extracted data from the Singapore Health Services Electronic Health Intelligence System, an electronic medical record database that included healthcare utilization (inpatient admissions, specialist outpatient clinic visits, emergency department visits, and primary care clinic visits), mortality, diseases, and demographics for all adult Singapore residents who resided in and had a healthcare encounter with our regional health system in 2012. Hierarchical clustering analysis (Ward's linkage) and K-means cluster analysis using age and healthcare utilization data in 2012 were applied to segment the selected population. These segments were compared using their demographics (other than age) and morbidities in 2012, and longitudinal healthcare utilization and mortality from 2013-2016. RESULTS: Among 146,999 subjects, five distinct patient segments "Young, healthy"; "Middle age, healthy"; "Stable, chronic disease"; "Complicated chronic disease" and "Frequent admitters" were identified. Healthcare utilization patterns in 2012, morbidity patterns and demographics differed significantly across all segments. The "Frequent admitters" segment had the smallest number of patients (1.79% of the population) but consumed 69% of inpatient admissions, 77% of specialist outpatient visits, 54% of emergency department visits, and 23% of primary care clinic visits in 2012. 11.5% and 31.2% of this segment has end stage renal failure and malignancy respectively. The validity of cluster-analysis derived segments is supported by discriminative ability for longitudinal healthcare utilization and mortality from 2013-2016. Incident rate ratios for healthcare utilization and Cox hazards ratio for mortality increased as patient segments increased in complexity. Patients in the "Frequent admitters" segment accounted for a disproportionate healthcare utilization and 8.16 times higher mortality rate. CONCLUSION: Our data-driven clustering analysis on a general patient population in Singapore identified five patient segments with distinct longitudinal healthcare utilization patterns and mortality risk to provide an evidence-based segmentation of a regional health system's healthcare needs.

Rhythm-centred music making in community living elderly: a randomized pilot study.

BACKGROUND: Quality of life has become an important aspect in the measurement of the health of an individual as the population ages. Rhythm-centred music making (RMM) has been shown to improve physical, psychological and social health. The purpose of this study was to explore the effects of RMM on quality of life, depressive mood, sleep quality and social isolation in the elderly. METHODS: A randomised controlled trial with cross over was conducted. 54 participants were recruited with 27 participants in each arm. In phase 1, group A underwent the intervention with group B as the control. In phase 2, group B underwent the intervention with group A as the control. The intervention involved 10 weekly RMM sessions. Patient related outcome data which included European Quality of Life-5 Dimensions (EQ5D), Geriatric Depression Scale (GDS), Pittsburg Sleep Quality Index (PSQI) and Lubben Social Network Scale (LSNS) scores were collected before the intervention, at 11th and at the 22nd week. RESULTS: A total of 31 participants were analyzed at the end of the study. The mean age was 74.65 ± 6.40 years. In analysing the change in patient related outcome variables as a continuous measure, participation in RMM resulted in a non-significant reduction in EQ5D by 0.004 (95% CI: -0.097,0.105), GDS score by 0.479 (95% CI:-0.329,1.287), PSQI score by 0.929 (95% CI:- 0.523,2.381) and an improvement in LSNS by 1.125 (95% CI:-2.381,0.523). In binary analysis, participation in RMM resulted in a 37% (OR = 1.370, 95% CI: 0.355,5.290), 55.3% (OR = 1.553, 95% CI: 0.438,5.501), 124.1% (OR = 2.241, 95% CI = 0.677,7.419) and 14.5% (OR = 1.145, 95% CI = 0.331,3.963) non-significant increase in odds of improvement in EQ5D, GDS, PSQI and LSNS scores respectively. CONCLUSION: Participation in RMM did not show any statistically significant difference in the quality of life of the participants. It is however, an interesting alternative tool to use in the field of integrative medicine. Moving forward, a larger study could be performed to investigate the effects of RMM on the elderly with an inclusion of a qualitative component to evaluate effects of RMM that were not captured by quantitative indicators. TRIAL REGISTRATION: This trial was retrospectively registered. This trial was registered in the Australian New Zealand Clinical Trials Registry under trial number ACTRN12616001281482 on 12 September 2016.

Long-chain polyunsaturated fatty acid status during pregnancy and maternal mental health in pregnancy and the postpartum period: results from the GUSTO study.

OBJECTIVE: Studies have demonstrated a relationship between lower omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) status and anxiety and depression. It is uncertain whether similar associations occur in pregnant women, when anxiety and depression could have long-term effects on the offspring. We examined the associations between plasma LC-PUFA status during pregnancy and perinatal mental health. METHOD: At 26-28 weeks' gestation, plasma LC-PUFAs were measured in mothers of the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort study, who were recruited between June 2009 and September 2010. Maternal symptoms of anxiety and depression were assessed with the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3 months' postpartum. The STAI-state subscale was used as a continuous measure of current anxiety, while EPDS scores ≥ 15 during pregnancy or ≥ 13 postpartum were indicative of symptoms of probable depression. RESULTS: In adjusted regression analyses (n = 698), lower plasma total omega-3 PUFA concentrations (ß = -6.49 STAI-state subscale scores/unit increase of omega-3 fatty acid; 95% CI, -11.90 to -1.08) and higher plasma omega-6:omega-3 PUFA ratios (ß = 6.58 scores/unit increase of fatty acid ratio; 95% CI, 1.19 to 12.66), specifically higher arachidonic acid (AA):docosahexaenoic acid, AA:eicosapentaenoic acid, and AA:docosapentaenoic acid ratios, were associated with increased antenatal anxiety (P < .05 for all), but not postpartum anxiety. There was no association between plasma PUFAs and perinatal probable depression. CONCLUSIONS: No association was found with probable depression in pregnancy or postpartum. Lower plasma omega-3 fatty acids and higher omega-6:omega-3 fatty acid ratios were associated with higher antenatal anxiety, but not postpartum anxiety. Replication in other studies is needed to confirm the findings and determine the direction of causality. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01174875.

Cost-effectiveness of aspirin adjuvant therapy in early stage colorectal cancer in older patients.

BACKGROUND & AIMS: Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older. METHODS: Two five-state Markov models were constructed separately for Stage I and II colorectal cancer using TreeAge Pro 2014. Two hypothetical cohorts of 10,000 individuals at a starting age of 65 years and with colorectal cancer in remission were put through the models separately. Cost-effectiveness of aspirin was evaluated against no treatment (Stage I and II) and capecitabine (Stage II) over a 20-year period from the United States societal perspective. Extensive one-way sensitivity analyses and multivariable Probabilistic Sensitivity Analyses (PSA) were performed. RESULTS: In the base case analyses, aspirin was cheaper and more effective compared to other comparators in both stages. Sensitivity analyses showed that no treatment and capecitabine (Stage II only) can be cost-effective alternatives if the utility of taking aspirin is below 0.909, aspirin's annual fatal adverse event probability exceeds 0.57%, aspirin's relative risk of disease progression is 0.997 or more, or when capecitabine's relative risk of disease progression is less than 0.228. Probabilistic Sensitivity Analyses (PSA) further showed that aspirin could be cost-effective 50% to 80% of the time when the willingness-to-pay threshold was varied from USD 20,000 to USD 100,000. CONCLUSION: Even with a modest treatment benefit, aspirin is likely to be cost-effective in Stage I and II colorectal cancer, thus suggesting a potential unique role in secondary prevention in this group of patients.

The V227A polymorphism at the PPARA locus is associated with serum lipid concentrations and modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentrations in Chinese women.

Peroxisome proliferators activated receptor alpha (PPARalpha) regulates the transcription of several proteins involved in human lipoprotein metabolism. We screened the PPARA locus for polymorphisms in 20 unrelated subjects from each of three ethnic groups (Chinese, Malays and Asian Indians). Only the V227A polymorphism was observed. We genotyped 4248 subjects (2899 Chinese, 761 Malay and 588 Asian Indians) and found allele frequencies for the A227 allele of 0.04 in Chinese, 0.006 in Malays and 0.003 in Asian Indians. We examined the associations between this polymorphism and serum lipid concentrations in Chinese. In women, but not in men, the presence of the A227 allele was associated with lower serum concentrations of total cholesterol [5.38mmol/l (95%CI: 5.22-5.54) versus 5.21mmol/l (95%CI: 4.99-5.43), p=0.047] and triglycerides [1.19mmol/l (95%CI: 1.10-1.28) versus 1.09mmol/l (95%CI: 0.98-1.21), p=0.048]. We also found that the V227A polymorphism modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentration (p-value for interaction=0.049). Our findings implicate PPARalpha in the lipid lowering associated with diets high in PUFA and suggests that genetic variation at the PPARA locus may determine the lipid response to changes in PUFA intake.