Omega-3 Polyunsaturated Fatty Acids are not associated with Peripheral Artery Disease in a Meta-Analysis from the Multi-Ethnic Study of Atherosclerosis and Atherosclerosis Risk in Communities Study Cohorts.

BACKGROUND: Research suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce. OBJECTIVES: We evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts. METHODS: Omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured at baseline for all MESA (n = 6495) and Minnesota ARIC participants (n = 3612). Incident clinical PAD events (MESA n = 106; ARIC n = 149) identified primarily through ICD discharge codes were assessed through follow-up of each cohort. Associations between omega-3 PUFAs (EPA, DHA, and EPA+DHA) and incident PAD were modeled in MESA and ARIC as quartiles and continuously using Cox proportional hazards regression, respectively. A fixed-effects meta-analysis was conducted to evaluate associations in the 2 cohorts combined. RESULTS: In the fully adjusted model, in 10,107 participants, no significant associations were observed between EPA, DHA, or EPA+DHA, and incident PAD modeled as quartiles or continuously for either MESA or ARIC cohorts separately or in the meta-analysis after a follow-up of approximately 15 y. CONCLUSION: This study is consistent with previous literature indicating that the beneficial effects of omega-3 PUFAs on the markers of ASCVD may not translate to a clinically meaningful decrease in PAD risk.

An umbrella review and meta-analysis of renin-angiotensin system drugs use and COVID-19 outcomes.

BACKGROUND: Despite the availability of extensive literature on the effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) on COVID-19 outcomes, the evidence is still controversial. We aimed to provide a comprehensive assessment of the effect of ACEIs/ARBs on COVID-19-related outcomes by summarising the currently available evidence. METHODS: An umbrella review was conducted using Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 1 February 2021. Systematic reviews with meta-analysis that evaluated the effect of ACEIs/ARBs on COVID-19-related clinical outcomes were eligible. Studies' quality was appraised using the AMSTAR 2 Critical Appraisal Tool. Data were analysed using the random-effects modelling including several subgroup analyses. Heterogenicity was assessed using I2 statistic. The study protocol was registered in PROSPERO (CRD42021233398) and reported using PRISMA guidelines. RESULTS: Overall, 47 reviews were eligible for inclusion. Out of the nine COVID-19 outcomes evaluated, there was significant associations between ACEIs/ARBs use and each of death (OR = 0.80, 95%CI = 0.75-0.86; I2  = 51.9%), death/ICU admission as composite outcome (OR = 0.86, 95%CI = 0.80-0.92; I2  = 43.9%), severe COVID-19 (OR = 0.86, 95%CI = 0.78-0.95; I2  = 68%) and hospitalisation (OR = 1.23, 95%CI = 1.04-1.46; I2  = 76.4%). The significant reduction in death/ICU admission, however, was higher among studies which presented adjusted measure of effects (OR = 0.63, 95%CI = 0.47-0.84) and were of moderate quality (OR = 0.74, 95%CI = 0.63-0.85). CONCLUSIONS: Collective evidence from observational studies indicate a good quality evidence on the significant association between ACEIs/ARBs use and reduction in death and death/ICU admission, but poor-quality evidence on both reducing severe COVID-19 and increasing hospitalisation. Our findings further support the current recommendations of not discontinuing ACEIs/ARBs therapy in patients with COVID-19.

OMEGA-3 FATTY ACIDS ARE ASSOCIATED WITH DECREASED PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY: A Combined Analysis of MESA and GOLDR Cohorts.

PURPOSE: Inflammation is associated with diabetic retinopathy development and progression, and previous studies have demonstrated that omega-3 polyunsaturated fatty acids have anti-inflammatory properties. Therefore, the goal of this study was to determine if omega-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are associated with decreased risk and severity of retinopathy in individuals with type 2 diabetes. METHODS: In a combined population of 1,356 individuals with type 2 diabetes from the Multi-Ethnic Study of Atherosclerosis and Genetics of Latino Diabetic Retinopathy cohorts, odds ratios using logistic regression were determined to assess the association between polyunsaturated fatty acids and retinopathy. RESULTS: In 1,356 participants with type 2 diabetes, individuals in the fourth quartile of DHA were 17% less likely to have retinopathy compared with the first quartile ( P = 0.009, CI: 0.72-0.95). Secondary analysis revealed 38% lower severity of retinopathy in individuals in the fourth quartile compared with the first quartile of DHA ( P = 0.006; CI: 0.44-0.87) and EPA + DHA ( P = 0.004; CI: 0.44-0.85). No significant associations were observed between EPA and retinopathy. CONCLUSION: DHA is inversely associated with the presence and severity of diabetic retinopathy. Increased intake of dietary sources of DHA may provide some protection against retinopathy in individuals with type 2 diabetes and warrants more research as a preventative option.

ASSOCIATION OF PLASMA ω-3 FATTY ACIDS WITH EARLY AGE-RELATED MACULAR DEGENERATION IN THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS.

PURPOSE: To examine the association between omega-3 polyunsaturated fatty acids, docosahexaenoic acid, and eicosapentaenoic acid and age-related macular degeneration (AMD) in the Multi-Ethnic Study of Atherosclerosis cohort. METHODS: Multi-Ethnic Study of Atherosclerosis is a multicenter, prospective cohort study designed to identify risk factors for cardiovascular disease in four ethnic groups. Six thousand eight hundred and fourteen participants of White, African American, Hispanic/Latino, and Chinese descent, aged 45-84 years, were recruited, with those found to have cardiovascular disease excluded. Our study population included all Multi-Ethnic Study of Atherosclerosis participants with baseline polyunsaturated fatty acid measurements and retinal photography at Examination 5 (n = 3,772). Fundus photographs were assessed for AMD using a standard grading protocol. Relative risk regression (log link) determined associations between polyunsaturated fatty acid levels and AMD. RESULTS: There was a significant association between increasing docosahexaenoic acid levels and increasing docosahexaenoic acid + eicosapentaenoic acid levels with reduced risk for early AMD (n = 214 participants with early AMD, of which n = 99 (46.3%) are non-White). Eicosapentaenoic acid levels alone were not significantly associated with AMD. CONCLUSION: Our analysis suggests increasing levels of docosahexaenoic acid are associated with reduced risk for early AMD in a multiethnic cohort. This represents the first racially diverse study demonstrating an association between omega-3 polyunsaturated fatty acids and AMD risk.

Changes of Plasma Phospholipid Fatty Acids Profiles in Pregnancy in Relation to the Diagnosis and Treatment of Gestational Diabetes Mellitus.

BACKGROUND: Plasma phospholipid fatty acids (FAs) in early and mid-pregnancy have been prospectively related to gestational diabetes mellitus (GDM) risk. Yet, changes of FAs following GDM diagnosis and treatment and their implications for glucose metabolism and control remain understudied. METHODS: From the Eunice Kennedy Shriver National Institute Child Health and Human Development Fetal Growth Studies-Singleton Cohort of 2802 pregnant women, we ascertained 85 GDM cases using the Carpenter and Coustan criteria and 85 non-GDM controls after exclusion. Using plasma collected before (23-31 weeks) and after GDM diagnosis (33-39 weeks), we quantified 25 saturated, poly- and monounsaturated FAs levels. We estimated the fold change of FAs before and after GDM diagnosis, using multiple linear mixed models adjusting for confounders. RESULTS: Eight FAs showed significant fold changes from the baseline values (23-31 weeks) among GDM cases as compared to women without GDM. Five FAs showed reduced fold changes [myristic acid (14:0): ß: -0.22 (95% CI: -0.30, -0.14), palmitic acid (16:0): ß: -0.02 (95% CI: -0.04, -0.01), cis-palmitoleic acid (16:1n7): ß: -0.15 (95% CI: -0.24, -0.05), alpha-linolenic acid (18:3n3): ß: -0.19 (95% CI: -0.31, -0.07], and dihomo-gamma-linoleic acid (20:3n6): ß:-0.16; 95% CI: -0.21, -0.11)], whereas 3 showed increases [heptadecanoic acid (17:0): ß: 0.17 (95% CI: 0.11, 0.22), cis-vaccenic acid (18:1n7): ß: 0.06 (95% CI: 0.03, 0.10), and arachidonic acid (20:4n6): ß: 0.10 (95% CI: 0.06, 0.13)]. CONCLUSIONS: Our study identified 8 FAs with unique patterns of change before and after GDM diagnosis that differed significantly between women with and without GDM. Our findings may shed light on the role of FA metabolism in the pathophysiology and disease management and progression of GDM. CLINICAL TRIAL REGISTRY: NCT00912132.

Plasma ω-3 and ω-6 PUFA Concentrations and Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Current literature examining the prospective relation of circulating omega-3 (n-3) and omega-6 (n-6) PUFAs and atrial fibrillation (AF) is limited to predominantly white populations. OBJECTIVES: We investigated the association of circulating n-3 and n-6 PUFAs with incident AF in participants from the Multi-Ethnic Study of Atherosclerosis. METHODS: A total of 6229 participants (mean age = 62 y; 53% female; 39% white, 27% black, 22% Hispanic, and 12% Chinese) who were free of baseline AF and with plasma phospholipid PUFAs measured at baseline using GC were prospectively followed for the development of AF. Incident AF was ascertained using International Classification of Diseases-9 codes from hospital discharge records and Medicare claims data with follow-up through 2014. Multivariable Cox proportional hazards regression analysis was performed to determine the risk of incident AF. RESULTS: During a median follow-up of 12.9 y, 813 (13%) participants developed AF. Each higher SD increment in arachidonic acid (AA; 20:4n-6) concentrations was associated with an 11% decreased risk of incident AF (HR: 0.89; 95% CI: 0.82, 0.96). Similarly, higher overall n-6 PUFA concentrations were also associated with a reduced AF risk (HR per SD increment: 0.93; 95% CI: 0.87, 1.00). Although no significant overall associations were observed for any individual n-3 PUFAs, higher circulating concentrations of DHA (22:6n-3) and EPA (20:5n-3) were associated with a decreased AF risk in blacks and Hispanics (DHA only) but not whites or Chinese Americans. CONCLUSIONS: In a multiethnic cohort of individuals free of baseline cardiovascular disease, higher plasma concentrations of n-6 PUFAs, particularly AA, were associated with a reduced risk of incident AF. Important differences in AF risk were also noted across race/ethnicity for the n-3 PUFAs DHA and EPA.

Plasma phospholipid n-3 and n-6 polyunsaturated fatty acids in relation to cardiometabolic markers and gestational diabetes: A longitudinal study within the prospective NICHD Fetal Growth Studies.

BACKGROUND: Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM). METHODS AND FINDINGS: Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15-26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42-0.96; P = 0.042) and 33% (0.67; 95% CI 0.45-0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10-14 and DGLA at GWs 10-14 and 15-26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15-26 was associated with a 45% (0.55; 95% CI 0.37-0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (

A Prospective Study of Leukocyte Telomere Length and Risk of Gestational Diabetes in a Multiracial Cohort.

BACKGROUND: Short telomere length (TL), an indicator of cellular aging and oxidative stress, has been implicated in glucose homeostasis. Additionally, studies have illustrated that the association of TL with health outcomes may vary by age. Yet, data on the association between TL and gestational diabetes mellitus (GDM) are sparse and the potential effect modification by age remains unknown. METHODS: We prospectively investigated TL in early pregnancy in relation to the subsequent GDM risk in a case-control study of 93 women with GDM and 186 randomly selected controls matched on age, race/ethnicity, and gestational weeks at blood collection. TL was measured using blood samples collected at 10-14 gestational weeks and reported as the T/S ratio, a ratio of telomere repeat length T to copy number of a single copy gene S. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusted for major risk factors. RESULTS: Overall, TL was not significantly associated with GDM risk. The TL-GDM association was significantly modified by age (Pinteraction = 0.02). Shorter TL in early pregnancy was associated with an increased GDM risk among women <30 years old (adjusted OR comparing the shortest vs. longest tertile: 3.1, 95% CI = 1.2, 8.1), but not associated with GDM risk among women ≥30 years. CONCLUSION: Our findings suggest that TL in early pregnancy may be implicated in GDM development, particularly among younger women.

A longitudinal study of iron status during pregnancy and the risk of gestational diabetes: findings from a prospective, multiracial cohort.

AIMS/HYPOTHESIS: The aim of this study was to prospectively and longitudinally investigate maternal iron status during early to mid-pregnancy, and subsequent risk of gestational diabetes mellitus (GDM), using a comprehensive panel of conventional and novel iron biomarkers. METHODS: A case-control study of 107 women with GDM and 214 controls (matched on age, race/ethnicity and gestational week during blood collection) was conducted within the the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort (2009-2013), a prospective and multiracial pregnancy cohort. Plasma hepcidin, ferritin and soluble transferrin receptor (sTfR) were measured and sTfR:ferritin ratio was derived, twice before GDM diagnosis (gestational weeks 10-14 and 15-26) and at weeks 23-31 and 33-39. GDM diagnosis was ascertained from medical records. Adjusted ORs (aORs) for GDM were estimated using conditional logistic regression analysis, adjusting for demographics, prepregnancy BMI and other major risk factors. RESULTS: Hepcidin concentrations during weeks 15-26 were 16% higher among women with GDM vs controls (median 6.4 vs 5.5 ng/ml; p = 0.02 ), and were positively associated with GDM risk; the aOR (95% CI) for highest vs lowest quartile was 2.61 (1.07, 6.36). Ferritin levels were also positively associated with GDM risk; the aOR (95% CI) for highest vs lowest quartile was 2.43 (1.12, 5.28) at weeks 10-14 and 3.95 (1.38, 11.30) at weeks 15-26. The sTfR:ferritin ratio was inversely related to GDM risk; the aOR (95% CI) for highest vs lowest quartile was 0.33 (0.14, 0.80) at weeks 10-14 and 0.15 (0.05, 0.48) at weeks 15-26. CONCLUSIONS/INTERPRETATION: Our findings suggest that elevated iron stores may be involved in the development of GDM from as early as the first trimester. This raises potential concerns for the recommendation of routine iron supplementation among iron-replete pregnant women.

Repeated versus single measurement of plasma omega-3 fatty acids and risk of heart failure.

PURPOSE: Studies have previously examined the relation between a single measure of plasma fatty acids and risk of heart failure. However, it is unclear whether the use of repeated measures of fatty acids over time is required for the assessment of omega-3 fatty acids heart failure relation. METHODS: Using a nested case-control design, this ancillary study used 421 cases and 421 matched controls from the Physicians' Health Study to assess the variability of plasma phospholipid fatty acids over time and compare the results of omega-3 fatty acids heart failure associations using a single versus repeated measurements of plasma phospholipid fatty acids. Plasma omega-3 fatty acids were measured at baseline (1982) and approximately 15 years later using gas chromatography. RESULTS: Spearman's correlation coefficients between baseline and follow-up measures of α-linolenic acid (ALA), EPA, DPA, and DHA were 0.20, 0.45, 0.28, and 0.50, respectively, in the control series. Multivariable adjusted odds ratios for heart failure per standard deviation higher plasma ALA were 0.98 (95% CI 0.85-1.13) when using baseline ALA and 0.86 (95% CI 0.74-1.01) when using the average of baseline and follow-up ALA measurements. Corresponding odds ratios for total long chain omega-3 FAs (EPA + DHA + DPA) were 0.87 (0.73-1.03) and 0.88 (0.75-1.04). CONCLUSIONS: Our data demonstrate modest correlation between measurements of plasma phospholipid fatty acids spaced by 15 years. A single measurement of plasma phospholipid fatty acids appears reasonable to estimate the risk of heart failure over long-term follow-up.

Impact and Implementation of an Early Years Fundamental Motor Skills Intervention for Children 4-5 Years.

Fundamental motor skills (FMS) are the cornerstone of a child's motor development, but concerns remain on the current level of FMS competencies, and intervention is required. This evaluation investigated if a targeted Early Years FMS intervention, delivered by a specialist physical education (PE) provider, improved the FMS of 4-5-year-old children across multiple sites. METHODS: The Early Years FMS intervention ran for 18 weeks, 1 h/week, using a standardised programme of activities to develop FMS competencies across 219 children from 15 schools in the Midlands, UK. An adapted assessment was employed as a measure of FMS, assessing locomotor, object control, and stability skills at weeks 1, 9, and 18. The FMS were each rated as green = competent, amber = working towards, or red = not meeting the standards of the skill. A description of key programme implementation characteristics was described. FINDINGS: Statistically significant increases in FMS competencies were achieved for 80% of participants at 18 weeks. Key implementation characteristics for the intervention included consistent staffing, a standardised programme, and a variety of pedagogical approaches delivered by specialist PE staff. CONCLUSION: This evaluation provided important insights into the effectiveness and implementation of the Early Years FMS intervention to improve FMS competencies in children aged 4-5 years.

Professional-Facing Digital Health Solutions for the Care of Patients With Chronic Pain: Protocol for a Systematic Scoping Review.

BACKGROUND: Chronic pain is a highly prevalent condition and one of the most common reasons why people seek health care. As a result, chronic pain has a significant personal and economic burden. The COVID-19 pandemic has aggravated the situation for patients with chronic pain through increased risk factors (eg, anxiety or depression) as well as decreased access to health care. Digital health solutions to support people with chronic pain are becoming increasingly popular. Most of the research has focused on patient-facing digital health solutions, although it is clear that the involvement of health and care professionals is crucial in chronic pain care. Certainly, digital health solutions intended for the use of health and care professionals in the care of patients with chronic pain (ie, professional facing) exist, for example, for clinical decision support; however, no review has investigated the studies reporting these interventions. OBJECTIVE: The overall aim of this scoping review is to identify the available professional-facing digital health solutions for the purpose of chronic pain management. The objectives of this review are to investigate the components, target populations, and user settings of the available professional-facing digital solutions; health and care professionals' perspectives on using digital health solutions (if reported); the methods in which the digital health solutions are developed; and the outcomes of using professional-facing digital health solutions. METHODS: Databases including MEDLINE, Embase, CINAHL, PsycInfo, and Inspec will be searched for studies reporting professional-facing digital health solutions for chronic pain care, using a comprehensive search strategy developed for each of the specific databases. A total of 2 independent reviewers will screen the titles and abstracts for review inclusion and then conduct full-text screening. Any conflicts in study inclusion will be resolved by a third reviewer at each stage of the screening process. Following data extraction and quality assessment, a qualitative content analysis of the results will be conducted. This review will identify the available professional-facing digital health solutions for chronic pain management. The results of this review are likely to be heterogeneous in terms of content (ie, the digital solutions will serve a variety of purposes, settings, target populations, etc) and methods (ie, experimental and nonexperimental designs). RESULTS: The review is expected to finish in March 2024 and published in the summer of 2024. CONCLUSIONS: This protocol outlines the need for a scoping review to identify professional-facing digital health solutions for the management of chronic pain. Results from this review will contribute to the growing field of research into the utility of digital health for chronic pain management. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51311.

Physical Activity and High-Sensitivity C-Reactive Protein in Pregnancy: Does It Matter during Leisure or Work?

INTRODUCTION: Physical activity (PA), regardless of domain, is recommended for pregnant individuals in clinical guidelines, but limited evidence is available for work-related PA. This study aimed to examine the associations of occupational (OPA) and leisure-time PA (LTPA) with plasma high-sensitivity C-reactive protein (hs-CRP), a risk marker for adverse pregnancy outcomes, among pregnant individuals. METHODS: This longitudinal study included 257 workers in the fetal growth cohort. OPA/LTPA and hs-CRP were measured in each trimester. OPA/LTPA was divided into high and low groups by the median level. Multivariable linear regressions were applied to estimate the adjusted geometric mean differences of hs-CRP (mg·L-1) comparing high versus low OPA/LTPA in each trimester and the changes in OPA/LTPA over pregnancy. RESULTS: OPA was positively associated with hs-CRP (high: 5.14 vs low: 3.59; P value: 0.001) in the first trimester, particularly for standing/walking or walking fast, regardless of carrying things. LTPA was negatively associated with hs-CRP in the second (high: 3.93 vs low: 5.08; 0.02) and third trimesters (high: 3.30 vs low: 4.40; 0.046). Compared with the low OPA + high LTPA group, hs-CRP was higher in both the high OPA + high LTPA and high OPA + low LTPA groups in the first trimester, and in the high OPA + low LTPA group only in the third trimester. The change in OPA during pregnancy was positively associated with hs-CRP, whereas the change in LTPA was negatively associated with hs-CRP from the second to the third trimester. CONCLUSIONS: In pregnant individuals, LTPA was negatively associated with hs-CRP, whereas OPA was positively associated with hs-CRP. More research on OPA's health impact among pregnant individuals is needed, and guidelines may consider the potential unfavorable influence of OPA on pregnant individuals.

Maternal plasma phospholipid polyunsaturated fatty acids in early pregnancy and thyroid function throughout pregnancy: a longitudinal study.

BACKGROUND: Evidence has indicated that polyunsaturated fatty acids (PUFAs)-enriched diet could reduce inflammation because of thyroid autoimmunity in vivo, and therefore, enhance thyroid function. OBJECTIVES: We investigated whether early pregnancy plasma phospholipid PUFAs could benefit maternal thyroid function across pregnancy, which is critical to fetal brain development and growth in pregnancy. METHODS: Within the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort, we collected plasma samples longitudinally from 214 subjects [107 with gestational diabetes mellitus (GDM) matched with 107 controls] with a singleton pregnancy. We measured 11 PUFAs at early pregnancy (10-14 wk) and 5 thyroid biomarkers at 10-14, 15-26, 23-31, and 33-39 wk, including free thyroxine (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone, antithyroid peroxidase, and antithyroglobulin. Associations of PUFAs with thyroid function biomarkers and relative risk (RR) of gestational hypothyroidism (GHT) during pregnancy were assessed using generalized linear mixed models and modified Poisson regression, respectively. RESULTS: After sample weighting because of subjects with GDM over-representing in the analytic sample with biomarkers, eicosapentaenoic acid (EPA) at early pregnancy was associated with a reduction of 0.24 pmol/L (95% confidence intervals: -0.31, -0.16) in fT3 across gestation per standard deviation (SD) increment, whereas docosahexaenoic acid (DHA) at early pregnancy was associated with an increment of 0.04 ng/dL (0.02, 0.05) in fT4 across gestation per SD increment. Furthermore, EPA and docosatetraenoic acid (DTA) were associated with lower risks of persistent GHT (EPA-RR: 0.13; 0.06, 0.28; DTA-RR: 0.24; 0.13, 0.44) per SD increment. All significant associations remained robust in sensitivity analysis and multiple testing. CONCLUSIONS: Certain plasma phospholipid PUFAs were associated with optimal levels of thyroid biomarkers and even lower risk of GHT throughout pregnancy, which might be potentially targeted for maternal thyroid regulation in early pregnancy. CLINICAL TRIAL REGISTRY: This trial was registered at https://beta. CLINICALTRIALS: gov/study/NCT00912132?distance=50&term=NCT00912132&rank=1 as NCT00912132.

Antidepressants: A content analysis of healthcare providers' tweets.

Background: Antidepressants are the primary treatment for depression, and social support from social media may offer another support route. Whilst Twitter has become an interactive platform for healthcare providers and their patients, previous studies found low engagement of healthcare providers when discussing antidepressants on Twitter. This study aims to analyse the Twitter posts of healthcare providers related to antidepressants and to explore the healthcare providers' engagement and their areas of interest. Method: Tweets within a 10-day period were collected through multiple searches with a list of keywords within Twitter. The results were filtered against several inclusion criteria, including a manual screening to identify healthcare providers. A content analysis was conducted on eligible tweets where correlative themes and subthemes were identified. Key findings: Healthcare providers contributed 5.9% of the antidepressant-related tweets (n = 770/13,005). The major clinical topics referred to in the tweets were side effects, antidepressants for the treatment of COVID-19, and antidepressant studies of psychedelics. Nurses posted more tweets sharing personal experiences with commonly negative attitudes, in contrast to physicians. Links to external webpages were commonly used among healthcare providers, especially users representing healthcare organisations. Conclusions: A relatively low proportion of healthcare providers' engagement on Twitter regarding antidepressants (5.9%) was identified, with a minimal increase throughout the COVID-19 pandemic when compared to previous studies. The major clinical topics referred to in the tweets were side effects, antidepressants for the treatment of COVID-19 and antidepressant studies of psychedelics, which have been made publicly available. In general, the findings confirmed that social media platforms are a mechanism by which healthcare providers, organisations and students support patients, share information about adverse drug effects, communicate personal experiences, and share research. It is plausible that this could impact the belief and behaviours of people with lived experience of depression who may see these tweets.

Identifying the important outcomes to measure for pharmacy-led, clinical services within primary care: A nominal group technique approach.

BACKGROUND: The introduction of clinical pharmacy services is part of a multi-disciplinary approach to reduce pressure on primary care. Ascertaining the impact of clinical pharmacists in general practice is vital to ensure intended benefits are achieved. However, this is complicated by poor quality evidence, multiple interventions, and a lack of agreement regarding outcome measures. OBJECTIVES: To develop an outcomes framework for clinical pharmacy services delivered in Scottish general practice using a consensus methodology. METHODS: A modified nominal group technique (NGT) was conducted using Microsoft Teams and Qualtrics. This involved a pre-NGT questionnaire, silent generation of ideas, round robin, discussions, ranking, and a final consensus exercise. A selective sampling strategy recruited experienced pharmacists from Scottish health regions. NGT ranking results were used to signify relative importance of the outcome areas. NGT discussions underwent inductive thematic analysis to explore key areas considered. RESULT: Overall, 13 (median: 24 years of experience) pharmacists participated, representing 11 of 14 Scottish regions. In total, 21 outcome areas, derived from the literature and a pre-NGT questionnaire, were considered during the NGT ranking exercise. Consensus identified five important outcome areas: Patient Experience, Medication Related Adverse Events, Cost-Effectiveness, Medication Optimisation, and Health Related Quality of Life. Thematic analysis highlighted the importance of the outcome framework's target audience, factors influencing the interpretation of outcomes, and the feasibility of the associated outcome measures. CONCLUSIONS: The five key outcome areas will facilitate evidence-based decisions regarding service delivery. Future work should develop a measurement plan, involving routinely collected sources of outcomes data. The feasibility of collecting outcomes in the real-world context should be considered, identifying measures which are easy to collect within existing data infrastructures. This paper describes a replicable method to gain consensus for a national approach to data collection from a strong theoretical basis using an online methodology.

Early Pregnancy Maternal Plasma Phospholipid Saturated Fatty Acids and Fetal Growth: Findings from a Multi-Racial/Ethnic Birth Cohort in US.

Saturated fatty acids (SFAs) during pregnancy are associated with disrupted metabolic programming among offspring at birth and later growth. We examined plasma phospholipid SFAs in early pregnancy and fetal growth throughout pregnancy. We enrolled 321 pregnant women from the NICHD Fetal Growth Studies-Singleton Cohort at gestational weeks 8-13. Ultrasonogram schedules were randomly assigned to capture weekly fetal growth. We measured plasma phospholipid SFAs at early pregnancy using blood samples and modeled fetal growth trajectories across tertiles of SFAs with cubic splines using linear mixed models after full adjustment. We then compared pairwise weekly fetal growth biometrics referencing the lowest tertile in each SFA using the Wald test. We found that even-chain and very long even-chain SFAs were inversely associated, whereas odd-chain SFAs were positively associated with fetal weight and size. Compared with the lowest tertile, the highest tertile of pentadecanoic acid (15:0) had a greater fetal weight and size, starting from week 13 until late pregnancy (at week 39: 3429.89 vs. 3269.08 g for estimated fetal weight; 328.14 vs. 323.00 mm for head circumference). Our findings could inspire future interventions using an alternative high-fat diet rich in odd-chain SFAs for optimal fetal growth.

Plasma Amino Acids in Early Pregnancy and Midpregnancy and Their Interplay With Phospholipid Fatty Acids in Association With the Risk of Gestational Diabetes Mellitus: Results From a Longitudinal Prospective Cohort.

OBJECTIVE: We prospectively evaluated plasma amino acids (AAs) in early pregnancy and midpregnancy and their interplay with phospholipid fatty acids (FAs) in association with gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS: From a longitudinal pregnancy cohort of 2,802 individuals, concentrations of 24 plasma AAs at 10-14 and 15-26 gestational weeks (GW) were assessed among 107 GDM case subjects and 214 non-GDM control subjects. We estimated adjusted odds ratios (OR) and 95% CI for the associations of plasma AAs and the joint associations of plasma AAs and phospholipid FAs with GDM risk, adjusting for risk factors including age, prepregnancy BMI, and family history of diabetes. RESULTS: Glycine at 10-14 GW was inversely associated with GDM (adjusted OR [95% CI] per SD increment: 0.55 [0.39-0.79]). Alanine, aspartic acid, and glutamic acid at 10-14 GW were positively associated with GDM (1.43 [1.08-1.88], 1.41 [1.11-1.80], and 1.39 [0.98-1.98]). At 15-26 GW, findings for glycine, alanine, aspartic acid, and the glutamine-to-glutamic acid ratio were consistent with the directions observed at 10-14 GW. Isoleucine, phenylalanine, and tyrosine were positively associated with GDM (1.64 [1.19-2.27], 1.15 [0.87-1.53], and 1.56 [1.16-2.09]). All P values for linear trend were <0.05. Several AAs and phospholipid FAs were significantly and jointly associated with GDM. For instance, the lowest risk was observed among women with higher glycine and lower even-chain saturated FAs at 10-14 GW (adjusted OR [95% CI] 0.15 [0.06, 0.37]). CONCLUSIONS: Plasma AAs may be implicated in GDM development starting in early pregnancy. Associations of AAs with GDM may be enhanced in the copresence of phospholipid FA profile.

n-6 fatty acid biomarkers and incident atrial fibrillation: an individual participant-level pooled analysis of 11 international prospective studies.

BACKGROUND: The presence of atrial fibrillation (AF) is associated with an over 2-fold increased risk of stroke, heart failure, and cardiovascular mortality. Long chain n-6 PUFAs have been suggested to have a variety of beneficial biologic effects that may reduce AF development; however, prior studies evaluating this relationship are limited. OBJECTIVES: We prospectively evaluated the association between circulating levels of linoleic acid (LA) and arachidonic acid (AA) with incident AF. METHODS: We used participant-level data from a global consortium of 11 prospective cohort studies with measurements of LA and AA in adults (aged ≥18 y). Participating studies conducted de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcomes, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 41,335 participants, 6173 incident cases of AF were ascertained, with median follow-up time of 14 y. In multivariable analysis, per interquintile range (difference between the 10th and 90th percentiles for each fatty acid), circulating n-6 levels were not associated with incident AF. For LA, the hazard ratio per interquintile range was 0.96 (95% confidence interval [CI]: 0.89, 1.04), and for AA, 1.02 (95% CI: 0.94, 1.10), with little evidence of heterogeneity between cohorts. Associations were similarly nonsignificant across subgroups of age, race, and biomarker fraction. CONCLUSIONS: Biomarkers of n-6 fatty acids including LA and AA are not associated with incident AF. These findings suggest that overall effects of n-6 PUFAs on influencing AF development are neutral.

Development of a primary care pharmacy outcomes framework: An umbrella literature review.

BACKGROUND: An aging population and rising multi-morbidity has shifted healthcare provision from secondary to primary care. Pharmacy-led services have been introduced to support this. The development of an outcomes framework for these services would facilitate conclusions to be drawn on their effectiveness. OBJECTIVES: To identify outcomes used to evaluate pharmacy-led medication therapy and disease management services within primary care settings to develop an outcomes framework for future studies. METHODS: An umbrella literature review was conducted. MEDLINE, EMBASE, The Cochrane Library and PsycINFO were searched in June 2020 to identify relevant articles. Eligible reviews were those including studies published from 2010 onwards which reported on the outcomes of pharmacy-led medication therapy and disease management services within primary care, excluding community pharmacy settings. Data were extracted and a content analysis, guided by the ECHO model, stratified the outcomes into four areas: economic, clinical, humanistic and service. RESULTS: Twenty-four reviews covering 52 unique studies were identified. Pharmacy-led services included: medication reviews (n=24, 46.2%), disease and therapy management (n=17, 32.7%), educational services (n=6, 11.5%), medicines reconciliation (n=3, 5.8%), and medication compliance support (n=1, 1.9%). Services were commonly targeted towards endocrine (n=23, 44.2%) or cardiovascular diseases (n=20, 38.5%). Outcomes most commonly explored were clinical (n=38, 73.1%) and service outcomes (n=37, 71.2%), followed by humanistic (n=23, 44.2%) and economic outcomes (n=13, 25.0%). Overall, 17 sub-categories of outcomes were identified; common sub-categories were: disease indicators [clinical]; medication use and healthcare utilisation [service]; adherence to medicines [humanistic]; and healthcare costs [economic]. CONCLUSIONS: The findings informed the development of an outcomes framework to guide the evaluation of medication therapy and disease management services, and facilitate international standardised outcome measures within primary care pharmacy to be developed. This could help offer vital evidence on the effectiveness of these services to ensure the pharmacy workforce is working optimally to support primary care.