scholarly journals Pre-diagnostic plasma metabolomics and the risk of exfoliation glaucoma

2021 ◽  
Author(s):  
Jae Hee Kang ◽  
Oana A Zeleznik ◽  
Lisa Frueh ◽  
Jessica Lasky-Su ◽  
A. Heather Eliassen ◽  
...  
Keyword(s):  
Family History ◽  
Enrichment Analysis ◽  
Health Study ◽  
Plasma Metabolites ◽  
Blood Draw ◽  
Standard Deviation Increase ◽  
Exfoliation Glaucoma ◽  
Metabolite Set Enrichment Analysis ◽  
Eye Exams

Objective: To identify pre-diagnostic plasma metabolomic biomarkers associated with risk of exfoliation glaucoma (XFG). Methods: We conducted a metabolomic study using a 1:1 matched nested case-control study design within the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Participants provided blood samples in 1989-'90 (NHS) and 1993-'95 (HPFS); we identified 205 participants who newly developed XFG during follow-up to 2018 (average time to diagnosis from blood draw=11.8 years); XFG was confirmed with medical record review. We profiled plasma metabolites using liquid chromatography-mass spectrometry and identified 379 known metabolites that passed quality control checks. Metabolites were transformed using probit scores for normality. We used multivariable-adjusted logistic regression adjusting for matching factors (such as age, residential latitude, season and time of blood draw), glaucoma family history and other covariates. Metabolite Set Enrichment Analysis was used to identify metabolite classes associated with risk of XFG. Number of effective tests (NEF) and False Discovery Rate (FDR) were used to adjust for multiple comparisons. Results: Mean age of cases (n=205) at diagnosis was 71 years; 84% were women and >99% were Caucasian; matched controls (n=205) all reported eye exams as of the matched cases' index date. A total of 33 metabolites were nominally significantly associated with XFG risk (p<0.05) and 4 metabolite classes were significantly associated (FDR<0.05). Overall, adverse associations were observed for the classes of lysophosphatidylcholines (FDR=0.02) and phosphatidylethanolamine plasmalogens (FDR=0.004). Inverse associations were observed for triglycerides (FDR<0.001) and steroid and steroid derivatives (FDR=0.03); in particular, the multivariable-adjusted odds ratio for XFG risk associated with each 1 standard deviation increase in plasma cortisone levels was 0.49 (95% CI=0.32-0.74; NEF=0.05). Results did not differ materially by time between blood draw and diagnosis, latitude of residence (< or ≥41°N latitude), age (< or ≥60 years), sex or glaucoma family history. Conclusions: Four broad classes of metabolites (including steroids such as cortisone and 3 lipid classes) in pre-diagnostic plasma collected almost a decade before diagnosis were associated with XFG risk; these results should be confirmed in future studies.

Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012632
Author(s):  
Kjetil Bjornevik ◽  
Eilis J. O'Reilly ◽  
Samantha Molsberry ◽  
Laurence N. Kolonel ◽  
Loic Le Marchand ◽  
...  
Keyword(s):  
Light Chain ◽  
Conditional Logistic Regression ◽  
Disease Diagnosis ◽  
Health Study ◽  
Plasma Samples ◽  
Blood Draw ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Rate Ratios

Objective:To assess whether plasma neurofilament light chain (NfL) levels are elevated before ALS diagnosis and to evaluate whether pre-diagnostic NfL levels are associated with metabolic alterations.Methods:We conducted a matched case-control study nested in three large prospective US cohorts (the Nurses’ Health Study, the Health Professionals Follow-up Study, and the Multiethnic Cohort Study), and identified 84 individuals who developed ALS during follow-up and had available plasma samples prior to disease diagnosis. For each ALS case, we randomly selected controls from those who were alive at the time of the case diagnosis and matched on birth year, sex, race/ethnicity, fasting status, cohort, and time of blood draw. We measured NfL in the plasma samples and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for ALS, adjusting for body mass index, smoking, physical activity, and urate levels.Results:Higher NfL levels were associated with a higher ALS risk in plasma samples collected within 5 years of the ALS diagnosis (RR per 1 standard deviation [SD] increase: 2.68, 95% CI: 1.18-6.08), but not in samples collected further away from the diagnosis (RR per 1 SD increase 1.16, 95% CI: 0.78-1.73). A total of 21 metabolites were correlated with pre-diagnostic NfL levels in ALS cases (p < 0.05), but none of these remained significant after multiple comparison adjustments.Conclusions:Plasma NfL levels were elevated in pre-diagnostic ALS cases, indicating that NfL may be a useful biomarker already in the earliest stages of the disease.Classification of Evidence:This study provides Class II evidence that plasma NfL levels are elevated in pre-diagnostic ALS patients.

scholarly journals Anxiety, Depression, and Colorectal Cancer Survival: Results from Two Prospective Cohorts

2020 ◽  
Vol 9 (10) ◽  
pp. 3174
Author(s):  
Claudia Trudel-Fitzgerald ◽  
Shelley S. Tworoger ◽  
Xuehong Zhang ◽  
Edward L. Giovannucci ◽  
Jeffrey A. Meyerhardt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fixed Effects ◽  
Cox Regression ◽  
Sensitivity Analyses ◽  
Disease Stage ◽  
Health Study ◽  
Anxiety And Depression ◽  
Depression Symptoms ◽  
Standard Deviation Increase

Given the unalterable nature of most risk factors for colorectal cancer (CRC) survival (e.g., disease stage), identifying modifiable determinants is critical. We investigated whether anxiety and depression were related to CRC survival using data from the Nurses’ Health Study (NHS) and Health Professional Follow-up Study (HPFS). Participants who received a CRC diagnosis and provided information about anxiety (nNHS = 335; nHPFS = 232) and depression (nNHS = 893; nHPFS = 272) within 4 years of diagnosis were included. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) of overall mortality, while controlling for covariates (sociodemographics, cancer characteristics, and lifestyle factors). Pooled risk estimates were derived from fixed effects meta-analyses of the cohorts. Among 1732 CRC patients, 814 deaths occurred during the 28-year follow-up. Each 1 standard deviation increase in anxiety or depression symptoms was associated with a similar 16% higher mortality risk (anxiety: 95% CI = 1.05–1.29; depression: 95% CI = 1.07–1.26). Comparable results were observed across all sensitivity analyses (introducing a 1-year lag, restricting to CRC-related mortality, considering potential behavioral pathways) and stratified models (cancer stage, sex). Our findings suggest greater anxiety and depression symptoms can not only impede adherence to healthy habits and reduce quality of life in cancer patients but could also be a marker for accelerated CRC progression.

scholarly journals A prospective analysis of circulating plasma metabolomics and ovarian cancer risk

2019 ◽  
Author(s):  
Oana A. Zeleznik ◽  
A. Heather Eliassen ◽  
Peter Kraft ◽  
Elizabeth M. Poole ◽  
Bernard Rosner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Risk ◽  
Enrichment Analysis ◽  
Structural Features ◽  
Plasma Metabolites ◽  
Ovarian Cancer Risk ◽  
Statistical Association ◽  
Metabolite Set Enrichment Analysis ◽  
Health Studies ◽  
Serous Tumors

AbstractWe assessed the association of pre-diagnostic plasma metabolites (N=420) with ovarian cancer risk. We included 252 cases and 252 matched controls from the Nurses’ Health Studies. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing the 90th-10thpercentile in metabolite levels, using permutation tests to account for testing multiple correlated hypotheses. Weighted gene co-expression network analysis (WGCNA) modules (n=10) and metabolite set enrichment analysis (MSEA; n=23) were also evaluated. Pseudouridine had the strongest statistical association with ovarian cancer risk overall (OR=2.56, 95%CI=1.48-4.45; p=0.001/adjusted-p=0.15). C36:2 phosphatidylcholine (PC) plasmalogen had the strongest statistical association with lower risk (OR=0.11, 95%CI=0.03-0.35; p<0.001/adjusted-p=0.06) and pseudouridine with higher risk (OR=9.84, 95%CI=2.89-37.82; p<0.001/adjusted-p=0.07) of non-serous tumors. Seven WGCNA modules and 15 classes were associated with risk at FDR≤0.20. Triacylglycerols (TAGs) showed heterogeneity by tumor aggressiveness (case-only heterogeneity-p<0.0001). TAG association with risk overall and serous tumors differed by acyl carbon content and saturation. Pseudouridine may be a novel risk factor for ovarian cancer. TAGs may also be important, particularly for rapidly fatal tumors, with associations differing by structural features. Validation in independent prospective studies and complementary experimental work to understand biological mechanisms is needed.

Abstract MP54: Circulating Prolactin Concentrations and Risk of Type 2 Diabetes in US Women

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Jun Li ◽  
Megan S Rice ◽  
Tianyi Huang ◽  
Sue Hankinson ◽  
Charles Clevenger ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Menopausal Status ◽  
Health Study ◽  
Blood Collection ◽  
Plasma Prolactin ◽  
Inverse Association ◽  
Total Plasma ◽  
Blood Draw

Background: Prolactin, a multifunctional hormone, is involved in regulating insulin sensitivity and glucose homeostasis in experimental and cross-sectional human studies. However, whether circulating levels of prolactin are associated with risk of type 2 diabetes (T2D) remains unclear. Methods: We analyzed the prospective relationship between circulating prolactin levels and T2D risk in in the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII) with up to 22 years of follow-up. Total plasma prolactin was measured using immunoassay in 8,637 women free of T2D and cardiovascular disease at baseline blood collection (NHSI: 1989-1990; NHSII: 1996-1999) and a subset of 1,017 NHS women who provided a second blood sample in 2000-2002. In addition, baseline bioactive prolactin levels were measured in a subset of 2,658 women using the Nb2 lymphoma cell bioassay. We calculated hazard ratios (HRs) using Cox regressions. Results: A total of 701 incident T2D cases were documented during 159,517 person-years of follow-up. Circulating prolactin levels were inversely associated with T2D risk; the multivariable HR comparing the highest with the lowest quartile of prolactin levels was 0.71 (95% confidence interval, 0.54-0.93; P trend =0.02). The associations were similar by menopausal status and risk factors ( P >0.70 for interaction). Additional adjustment for sex hormones, growth factors, adipokine, and inflammatory markers did not alter the results. The association of bioactive prolactin with T2D risk was suggestively stronger than that of total prolactin (comparable HR=0.56 vs. 0.82 among the 2,658 women). The inverse association of total plasma prolactin with incident T2D waned linearly with time, with a significant association observed during the first 9 years after blood draw. Conclusion: High circulating prolactin level was independently associated with lower risk of T2D in women. Our findings are consistent with experimental evidence, supporting a possible protective role for prolactin in the pathogenesis of T2D.

scholarly journals Epigenome-wide association study using prediagnostic bloods identifies a new genomic region (near TMEM204 and IFT140) associated with pancreatic cancer risk

2020 ◽  
Author(s):  
Dominique S. Michaud ◽  
Mengyuan Ruan ◽  
Devin C. Koestler ◽  
Dong Pei ◽  
Carmen J. Marsit ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dna Methylation ◽  
Study Design ◽  
Peripheral Blood ◽  
Association Studies ◽  
Health Study ◽  
Blood Collection ◽  
Blood Draw ◽  
Prospective Study Design

AbstractBackgroundEpigenome-wide association studies (EWAS) using peripheral blood have identified specific sites of DNA methylation associated with risk of various cancers and may hold promise to identify novel biomarkers of risk; however, few studies have been performed for pancreatic cancer and none using a prospective study design.MethodsUsing a nested case-control study design, incident pancreatic cancer cases and matched controls were identified from participants who provided blood at baseline in three prospective cohort studies (Nurses’ Health Study, Health Professionals Follow-up Study and Physicians’ Health Study). DNA methylation levels were measured in DNA extracted from leukocytes using the Illumina MethylationEPIC array. Average follow-up period for this analysis was 13 years.ResultsA region in chromosome 16 near genesTMEM204 and IFT140 was identified as being differentially methylated in cases and controls. For some CpGs in the region, the associations were stronger with shorter time to diagnosis (e.g., OR= 5.95, 95% CI = 1.52-23.12, for top vs bottom quartile, for <5 years between blood draw and cancer diagnosis) but associations remained significantly higher even when cases were diagnosed over 10 years after blood collection. Statistically significant differences in DNA methylation levels were also observed in the gastric secretion pathway using GSEA analysis.ConclusionsChanges in DNA methylation in peripheral blood may mark alterations in metabolic or immune pathways (potentially including alterations in immune subtypes) that play a role in pancreatic cancer. Identifying new biological pathways in carcinogenesis of pancreatic cancer using EWAS approach could provide new opportunities for improving treatment and prevention.

scholarly journals Prevalence and determinants of diabetes and prediabetes in southwestern Iran: the Khuzestan comprehensive health study (KCHS)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sanam Hariri ◽  
Zahra Rahimi ◽  
Nahid Hashemi-Madani ◽  
Seyyed Ali Mard ◽  
Farnaz Hashemi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Waist Circumference ◽  
Multinomial Logistic Regression ◽  
Fasting Blood Glucose ◽  
Health Study ◽  
Khuzestan Province ◽  
Logistic Regression Models ◽  
Relative Risks ◽  
Southwestern Iran

Background The Middle East and North Africa (MENA) is postulated to have the highest increase in the prevalence of diabetes by 2030; however, studies on the epidemiology of diabetes are rather limited across the region, including in Iran. Methods This study was conducted between 2016 and 2018 among Iranian adults aged 20 to 65 years residing in Khuzestan province, southwestern Iran. Diabetes was defined as the fasting blood glucose (FBG) level of 126 mg/dl or higher, and/or taking antidiabetic medications, and/or self-declared diabetes. Prediabetes was defined as FBG 100 to 125 mg/dl. Multinomial logistic regression models were used to examine the association of multiple risk factors that attained significance on the outcome. Results Overall, 30,498 participants were recruited; the mean (±SD) age was 41.6 (±11.9) years. The prevalence of prediabetes and diabetes were 30.8 and 15.3%, respectively. We found a similar prevalence of diabetes in both sexes, although it was higher among illiterates, urban residents, married people, and smokers. Participants aged 50–65 and those with Body Mass Index (BMI) 30 kg/m2 or higher were more likely to be affected by diabetes [RR: 20.5 (18.1,23.3) and 3.2 (3.0,3.6)]. Hypertension [RR: 5.1 (4.7,5.5)], waist circumference (WC) equal or more than 90 cm [RR: 3.6 (3.3,3.9)], and family history [RR: 2.3 (2.2,2.5)] were also significantly associated with diabetes. For prediabetes, the main risk factors were age 50 to 65 years [RR: 2.6 (2.4,2.8)], BMI 30 kg/m2 or higher [RR: 1.9 (1.8,2.0)], hypertension and WC of 90 cm or higher [RR: 1.7 (1.6,1.8)]. The adjusted relative risks for all variables were higher in females than males, with the exception of family history for both conditions and waist circumference for prediabetes. Conclusions Prediabetes and diabetes are prevalent in southwestern Iran. The major determinants are older age, obesity, and the presence of hypertension. Further interventions are required to escalate diabetes prevention and diagnosis in high-risk areas across Iran.

scholarly journals AB1065 VISIT COMPLIANCE IN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER: RESULTS FROM A GAZI UNIVERSITY FMF COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1822.1-1822
Author(s):  
R. Bilici Salman ◽  
A. Avanoğlu Güler ◽  
H. Satiş ◽  
H. Karadeniz ◽  
H. Babaoglu ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Family History ◽  
Familial Mediterranean Fever ◽  
Predictive Factors ◽  
Severity Score ◽  
Comorbid Disease ◽  
Rheumatology Clinic ◽  
Mediterranean Fever ◽  
One Year

Background:Follow-up in all rheumatologic patients is critical, particularly Familial Mediterranean Fever (FMF). Current recommendations for all experts by the EULAR state that patients with FMF should be evaluated 6-monthly intervals to monitore the character and frequency of the attacks and the acute phase response. Disease-related complications such as amyloidosis can beasymptomaticand need only a careful follow-up.Objectives:to quantify this phenomenon and to find predictive factors of visit compliance in patients with FMF.Methods:The study included 474 adult patients with a diagnosis of FMF who followed at the outpatient rheumatology clinic of tertiary university hospital, from January 2018 to December 2018. . Demographic, socioeconomic data, familiy history, comorbid disease, medication history, characteristics, the International Severity Score for FMF (ISSF),autoinflammatory disease damage index (ADDI) were recorded. Visit compliance was defined as the presence of two visits in the outpatient rheumatology clinic for FMF last one year for the purposes set out in EULAR suggestion.Those who had fewer than two visits in the last one year were considered noncompliant.Results:230 (48.5%) were compliant while 244 (51.5 %) patients were noncompliant with their rheumatology visit. Both compliant and noncompliant patients had similar median age and disease duration. Female sex and being married was increased the visit compliance.The results of the logistic regression model exploring factors associated with compliance indicated that presence of family history in parents, absence of family history in sibling, treatment with biologic agents, other drug using,presence of more than 2 attacks except fever and adequate medical care were important predictors of visit compliance.Conclusion:In conclusion, if FMF patients visit compliance increase, their functionality, medication adherence and quality of life will increase and flares and complication of disease can decrease. Thus, we highlight some recommendations for FMF specialist, patients and health care providers to improve outcomes.Table 2.Multivariate logistic regression analysis for predictive factors of visit compliance of the patients with FMF, n=430Adj. OR%95 CI**pFamily history in parents(positive history vs negative)1,81,0-3,10.03Family history in sibling(negative history vs positive)1,91,2-3,10.004Comorbid disease status1,30,7-2,50.32Treatment(anakinra&canakinumab vs colchicine)3,71,7-8,20.001Drug using(other drugs vs FMF drugs)2,21,1-4,40.01More than 2 attacks except fever2,31,2-4,00.004Chronic peripheral arthritis2,30,8-6,60.10Proteinuria2,20,7-6,70.14Adequate medical care1,91,2-3,10.003Number of index flare within last 12-month0,90,9-1,00.38ISSF severity score0,80,7-1,10,30Disclosure of Interests:None declared

scholarly journals Longitudinal Event-Level Sexual Risk and Substance Use among Gay, Bisexual, and Other Men Who Have Sex with Men

2021 ◽  
Vol 18 (6) ◽  
pp. 3183
Author(s):  
Jordan M. Sang ◽  
Zishan Cui ◽  
Paul Sereda ◽  
Heather L. Armstrong ◽  
Gbolahan Olarewaju ◽  
...  
Keyword(s):  
Substance Use ◽  
Sexual Risk ◽  
Health Study ◽  
Anal Sex ◽  
Study Objective ◽  
Condomless Anal Sex ◽  
Gamma Hydroxybutyrate ◽  
Sex With Men ◽  
Hiv Negative

(1) Background: Condomless anal sex and substance use are associated with STI risk among gay, bisexual, and other men who have sex with men (gbMSM). Our first study objective was to describe event-level sexual risk and substance use trends among gbMSM. Our second study objective was to describe substances associated with event-level sexual risk. (2) Methods: Data come from the Momentum Health Study in Vancouver, British Columbia and participants were recruited from 2012–2015, with follow-up until 2018. Stratified by self-reported HIV status, we used generalized estimating equations to assess trends of sexual event-level substance use and assessed interactions between substance use and time period on event-level higher risk sex defined as condomless anal sex with an HIV serodifferent or unknown status partner. (3) Results: Event-level higher risk anal sex increased across the study period among HIV-negative/unknown (baseline prevalence: 13% vs. study end prevalence: 29%) and HIV-positive gbMSM (baseline prevalence: 16% vs. study end prevalence: 38%). Among HIV-negative/unknown gbMSM, event-level erectile drug use increased, while alcohol use decreased over the study period. Overall, interactions between substance use and time on higher risk anal sex were not statistically significant, regardless of serostatus. However, we found a number of time-specific significant interactions for erectile drugs, poppers, Gamma-hydroxybutyrate (GHB), crystal methamphetamine and ecstasy/MDMA use among HIV-negative/unknown gbMSM. (4) Conclusion: Significant differences in substance use trends and associated risks exist and are varied among gbMSM by serostatus. These findings provide a more comprehensive understanding of the effects of event-level substance use on sexual risk through longitudinal follow-up of nearly six years.

scholarly journals Association of oral contraceptives and tubal ligation with risk of early natural menopause

2021 ◽  
Author(s):  
C R Langton ◽  
B W Whitcomb ◽  
A C Purdue-Smithe ◽  
L L Sievert ◽  
S E Hankinson ◽  
...  
Keyword(s):  
Oral Contraceptives ◽  
Proportional Hazards ◽  
Reproductive Factors ◽  
Cox Proportional Hazards ◽  
Tubal Ligation ◽  
Health Study ◽  
Early Menopause ◽  
Natural Menopause ◽  
Increased Risk

Abstract STUDY QUESTION What is the association of oral contraceptives (OCs) and tubal ligation (TL) with early natural menopause? SUMMARY ANSWER We did not observe an association of OC use with risk of early natural menopause; however, TL was associated with a modestly higher risk. WHAT IS KNOWN ALREADY OCs manipulate hormone levels, prevent ovulation, and may modify the rate of follicular atresia, while TL may disrupt the blood supply to the ovaries. These mechanisms may be associated with risk of early menopause, a condition associated with increased risk of cardiovascular disease and other adverse health outcomes. STUDY DESIGN, SIZE, DURATION We examined the association of OC use and TL with natural menopause before the age of 45 years in a population-based study within the prospective Nurses’ Health Study II (NHSII) cohort. Participants were followed from 1989 to 2017 and response rates were 85-90% for each cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants included 106 633 NHSII members who were premenopausal and aged 25-42 years at baseline. Use, duration and type of OC, and TL were measured at baseline and every 2 years. Menopause status and age were assessed every 2 years. Follow-up continued until early menopause, age 45 years, hysterectomy, oophorectomy, death, cancer diagnosis, or loss to follow-up. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs adjusted for lifestyle, dietary, and reproductive factors. MAIN RESULTS AND THE ROLE OF CHANCE Over 1.6 million person-years, 2579 members of the analytic cohort experienced early natural menopause. In multivariable models, the duration, timing, and type of OC use were not associated with risk of early menopause. For example, compared with women who never used OCs, those reporting 120+ months of OC use had an HR for early menopause of 1.01 (95% CI, 0.87-1.17; P for trend=0.71). TL was associated with increased risk of early menopause (HR = 1.17, 95% CI, 1.06-1.28). LIMITATIONS, REASONS FOR CAUTION Our study population is homogenous with respect to race and ethnicity. Additional evaluation of these relations in more diverse populations is important. WIDER IMPLICATIONS OF THE FINDINGS To our knowledge, this is the largest study examining the association of OC use and TL with early natural menopause to date. While TL was associated with a modest higher risk of early menopause, our findings do not support any material hazard or benefit for the use of OCs. STUDY FUNDING/COMPETING INTEREST(S) The study was sponsored by UO1CA176726 and R01HD078517 from the National Institutes of Health and Department of Health and Human Services. The work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have no competing interests to report. TRIAL REGISTRATION NUMBER N/A

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