Validation of alopecia coding in US claims data among women of childbearing age.

BACKGROUND: Accurately identifying alopecia in claims data is important to study this rare medication side effect. OBJECTIVES: To develop and validate a claims-based algorithm to identify alopecia in women of childbearing age. METHODS: We linked electronic health records from a large healthcare system in Massachusetts (Mass General Brigham) with Medicaid claims data from 2016 through 2018 to identify all women aged 18 to 50 years with an ICD-10 code for alopecia, including alopecia areata, androgenic alopecia, non-scarring alopecia, or cicatricial alopecia, from a visit to the MGB system. Using eight predefined algorithms to identify alopecia in Medicaid claims data, we randomly selected 300 women for whom we reviewed their charts to validate the alopecia diagnosis. Positive predictive values (PPVs) were computed for the primary algorithm and seven algorithm variations, stratified by race. RESULTS: Out of 300 patients with at least 1 ICD-10 code for alopecia in the Medicaid claims, 286 had chart-confirmed alopecia (PPV = 95.3%). The algorithm requiring two diagnosis codes plus one prescription claim for alopecia treatment identified 55 patients (PPV = 100%). The algorithm requiring 1 diagnosis code for alopecia plus 1 procedure claim for intralesional triamcinolone injection identified 35 patients (PPV = 100%). Across all 8 algorithms tested, the PPV varied between 95.3% and 100%. The PPV for alopecia ranged from 94% to 100% in White and 96%-100% in 48 non-White women. The exact date of alopecia onset was difficult to determine in charts. CONCLUSION: At least one recorded ICD-10 code for alopecia in claims data identified alopecia in women of childbearing age with high accuracy.

Incidence of fibrosing colonopathy with pancreatic enzyme replacement therapy in patients with cystic fibrosis.

BACKGROUND: High daily doses of pancreatic enzyme replacement therapy (PERT) were historically associated with risk of fibrosing colonopathy (FC) in people with cystic fibrosis (pwCF), leading to development of PERT dosing guidelines and reformulated products. This study quantified incidence of FC in pwCF treated with PERT following those measures. METHODS: This large prospective cohort study included eligible pwCF enrolled in the Cystic Fibrosis Foundation Patient Registry with ≥1 clinic visit in 2012-2014 and follow-up through 2020. Data on PERT exposure, demographics, and medical history were collected. Clinical data, imaging, and histopathology of suspected cases were examined by an independent adjudication panel of physicians familiar with this complication. RESULTS: Base Study Population included 26,025 pwCF who contributed 155,814 person-years [mean (SD) 6.0 (2.0) years] of follow-up. Over 7.8 years, 29 pwCF had suspected FC; three cases were confirmed by adjudication, 22 cases were confirmed as not FC, and four cases were indeterminate. There were 22,161 pwCF exposed to any PERT, with mean PERT use time of 5.583 person-years and mean daily dose of 8328 U lipase per kg per day. All three confirmed cases and four indeterminate cases of FC occurred during current use of PERT. Incidence rates per 1000 person-years exposed were 0.0242 (95 % CI [0.0050, 0.0709]) for confirmed FC and 0.0566 (95 % CI [0.0227, 0.1166]) for indeterminate or confirmed FC. CONCLUSIONS: The incidence of FC in pwCF is very low in the era of current treatment guidelines and more stringent quality standards for PERT products.

Development and Validation of ICD-10-CM-based Algorithms for Date of Last Menstrual Period, Pregnancy Outcomes, and Infant Outcomes.

INTRODUCTION AND OBJECTIVE: Validation studies of algorithms for pregnancy outcomes based on International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes are important for conducting drug safety research using administrative claims databases. To facilitate the conduct of pregnancy safety studies, this exploratory study aimed to develop and validate ICD-10-CM-based claims algorithms for date of last menstrual period (LMP) and pregnancy outcomes using medical records. METHODS: Using a mother-infant-linked claims database, the study included women with a pregnancy between 2016-2017 and their infants. Claims-based algorithms for LMP date utilized codes for gestational age (Z3A codes). The primary outcomes were major congenital malformations (MCMs) and spontaneous abortion; additional secondary outcomes were also evaluated. Each pregnancy outcome was identified using a claims-based simple algorithm, defined as presence of ≥ 1 claim for the outcome. Positive predictive values (PPV) and 95% confidence intervals (CI) were calculated. RESULTS: Overall, 586 medical records were sought and 365 (62.3%) were adjudicated, including 125 records each for MCMs and spontaneous abortion. Last menstrual period date was validated among maternal charts procured for pregnancy outcomes and fewer charts were adjudicated for the secondary outcomes. The median difference in days between LMP date based on Z3A codes and adjudicated LMP date was 4.0 (interquartile range: 2.0-10.0). The PPV of the simple algorithm for spontaneous abortion was 84.7% (95% CI 78.3, 91.2). The PPV for the MCM algorithm was < 70%. The algorithms for the secondary outcomes pre-eclampsia, premature delivery, and low birthweight performed well, with PPVs > 70%. CONCLUSIONS: The ICD-10-CM claims-based algorithm for spontaneous abortion performed well and may be used in pregnancy studies. Further algorithm refinement for MCMs is needed. The algorithms for LMP date and the secondary outcomes would benefit from additional validation in a larger sample.

A prospective analysis of red blood cell membrane polyunsaturated fatty acid levels and risk of non-Hodgkin lymphoma.

Published studies report inconsistent associations of polyunsaturated fatty acid (PUFA) intake with non-Hodgkin lymphoma (NHL) risk. We conducted a nested case-control study in Nurses' Health Study and Health Professionals Follow-Up Study participants to evaluate a hypothesis of inverse association of pre-diagnosis red blood cell (RBC) membrane PUFA levels with risk of NHL endpoints. We confirmed 583 NHL cases and matched 583 controls by cohort/sex, age, race and blood draw date/time. We estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL endpoints using logistic regression. RBC PUFA levels were not associated with all NHL risk; cis 20:2n-6 was associated with follicular lymphoma risk (OR [95% CI] per one standard deviation increase: 1.35 [1.03-1.77]), and the omega-6/omega-3 PUFA ratio was associated with diffuse large B-cell lymphoma risk (2.33 [1.23-4.43]). Overall, PUFA did not demonstrate a role in NHL etiology; the two unexpected positive associations lack clear biologic explanations.

Interdisciplinary model-informed drug development for extending duration of elagolix treatment in patients with uterine fibroids.

AIM: Elagolix, a gonadotropin-releasing hormone receptor antagonist, was recently approved for heavy menstrual bleeding associated with uterine fibroids (UF, Oriahnn) at a dose of 300 mg twice daily (BID) in combination with add-back therapy (oestradiol 1 mg/norethindrone acetate 0.5 mg [E2/NETA] once daily) for 24 months use. The limited duration of treatment is related to elagolix dose- and duration-dependent decrease in oestrogen that is mechanistically linked to changes in bone mineral density (BMD). The work herein supported the extended treatment duration of 24 months. METHODS: An integrated exposure-response and epidemiological modelling framework of elagolix effects on femoral neck BMD (FN-BMD), informed by real-world data and phase 3 clinical trials data, was developed to predict the time course and magnitude of changes in BMD and its relation to risk of bone fracture in women with UF. RESULTS: Model results indicated that women treated with elagolix 300 mg BID + E2/NETA in the long term (ie, >24 months) may experience less than 1% loss in FN-BMD per year, relative to placebo. The exposure-response model simulations and clinical risk factors were used to estimate 10-year risk of fractures using the clinically validated Fracture Risk Assessment Tool (FRAX). The impact of elagolix 300 mg BID + E2/NETA treatment on the 10-year risk of hip or major osteoporotic fractures estimated from the FRAX model was minimal compared to that of placebo. CONCLUSION: The elagolix integrated exposure-BMD analysis and translation to fracture risk provided an interdisciplinary model-informed drug development framework for clinical benefit-risk evaluation and enabled approval of longer treatment duration to benefit the patient.

Impact of endometriosis on women's life decisions and goal attainment: a cross-sectional survey of members of an online patient community.

OBJECTIVES: To examine women's perceptions of endometriosis-associated disease burden and its impact on life decisions and goal attainment. DESIGN: An anonymous online survey was distributed in October 2018 through the social media network MyEndometriosisTeam.com. PARTICIPANTS: Women aged 19 years and older living in several English-speaking countries who self-identified as having endometriosis. OUTCOME MEASURES: Patients' perspectives on how endometriosis has affected their work, education, relationships, overall life decisions and attainment of goals. Subanalyses were performed for women who identified as 'less positive about the future' (LPAF) or had 'not reached their full potential' (NRFP) due to endometriosis. RESULTS: 743 women completed the survey. Women reported high levels of pain when pain was at its worst (mean score, 8.9 on severity scale of 0 (no pain) to 10 (worst imaginable pain)) and most (56%, n=415) experienced pain daily. Women reported other negative experiences attributed to endometriosis, including emergency department visits (66%, n=485), multiple surgeries (55%, n=406) and prescription treatments for symptoms of endometriosis (72%, n=529). Women indicated that they believed endometriosis had a negative impact on their educational and professional achievements, social lives/relationships and overall physical health. Most women 'somewhat agreed'/'strongly agreed' that endometriosis caused them to lose time in life (81%, n=601), feel LPAF (80%, n=589) and feel they had NRFP (75%, n=556). Women who identified as LPAF or NRFP generally reported more negative experiences than those who were non-LPAF or non-NRFP. CONCLUSIONS: Women who completed this survey reported pain and negative experiences related to endometriosis that were perceived to negatively impact major life-course decisions and attainment of goals. Greater practitioner awareness of the impact that endometriosis has on a woman's life course and the importance of meaningful dialogue with patients may be important for improving long-term management of the disease and help identify women who are most vulnerable.

Uterine fibroids and incidence of depression, anxiety and self-directed violence: a cohort study.

BACKGROUND: Depression and anxiety are prevalent among women with uterine fibroids (UF). The rate of mental health diagnoses in women with UF has not been studied. METHODS: Women aged 18-50 years with diagnosed UF were identified in the Optum Clinformatics commercial insurance claims database (OptumInsight, Eden Prairie, Minnesota) from 1 May 2000 to 31 March 2020 (n=313 754) and were matched 1:2 on age and calendar time to women without (n=627 539). Cox proportional hazards models estimated HRs and 95% CIs between UF and diagnosed depression, anxiety and self-directed violence, adjusting for demographics and comorbidities. Among women with diagnosed UF, the association between hysterectomy and mental health outcomes was estimated. RESULTS: After adjusting for confounders, women with diagnosed UF had a higher rate of depression (HR: 1.12; 95% CI 1.10 to 1.13), anxiety (HR: 1.12; 95% CI 1.10 to 1.13) and self-directed violence (HR: 1.46; 95% CI 1.29 to 1.64) than women without. Among women with pain symptoms and heavy menstrual bleeding, the HR comparing women with diagnosed UF to women without was 1.21 (95% CI 1.18 to 1.25) for depression, 1.18 (95% CI 1.15 to 1.21) for anxiety and 1.68 (95% CI 1.35 to 2.09) for self-directed violence. Among women with diagnosed UF, the HR comparing women who underwent a hysterectomy to women who did not was 1.22 (95% CI 1.17 to 1.27) for depression, 1.13 (95% CI 1.09 to 1.17) for anxiety and 1.86 (95% CI 1.39 to 2.49) for self-directed violence. CONCLUSIONS: Rates of depression, anxiety and self-directed violence were higher among women with diagnosed UF, particularly among those who experienced pain symptoms or who underwent hysterectomy.

Method used to identify adenomyosis and potentially undiagnosed adenomyosis in a large, U.S. electronic health record database.

BACKGROUND: The prevalence of adenomyosis is underestimated due to lack of a specific diagnostic code and diagnostic delays given most diagnoses occur at hysterectomy. OBJECTIVES: To identify women with adenomyosis using indicators derived from natural language processing (NLP) of clinical notes in the Optum Electronic Health Record database (2014-2018), and to estimate the prevalence of potentially undiagnosed adenomyosis. METHODS: An NLP algorithm identified mentions of adenomyosis in clinical notes that were highly likely to represent a diagnosis. The anchor date was date of first affirmed adenomyosis mention; baseline characteristics were assessed in the 12 months prior to this date. Characteristics common to adenomyosis cases were used to select a suitable pool of women from the underlying population, among whom undiagnosed adenomyosis might exist. A random sample of this pool was selected to form the comparator cohort. Logistic regression was used to compare adenomyosis cases to comparators; the predictive probability (PP) of being an adenomyosis case was assessed. Comparators having a PP ≥ 0.1 were considered potentially undiagnosed adenomyosis and were used to calculate the prevalence of potentially undiagnosed adenomyosis in the underlying population. RESULTS: Among 11 456 347 women aged 18-55 years in the underlying population, 19 503 were adenomyosis cases. Among 332 583 comparators, 22 696 women were potentially undiagnosed adenomyosis cases. The prevalence of adenomyosis and potentially undiagnosed adenomyosis was 1.70 and 19.1 per 1000 women aged 18-55 years, respectively. CONCLUSIONS: Considering potentially undiagnosed adenomyosis, the prevalence of adenomyosis may be 10x higher than prior estimates based on histologically confirmed adenomyosis cases only.

Integrating real-world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women.

Decline of bone mineral density (BMD) during menopause is related to increased risk of fractures in postmenopausal women, however, this relationship in premenopausal women has not been established. To quantify this relationship, real-world data (RWD) from the National Health and Nutrition Examination Survey (NHANES), and longitudinal data from the elagolix phase III clinical trials were modeled across a wide age range, and covariates were evaluated. The natural changes in femoral neck BMD (FN-BMD) were well-described by a bi-exponential relationship with first-order BMD formation (k1 ) and resorption (k2 ) rate constants. Body mass index (BMI) and race (i.e., Black) were significant predictors indicating that patients with high BMI or Black race experience a relatively lower BMD loss. Simulations suggest that untreated premenopausal women with uterine fibroids (UFs) from elagolix phase III clinical trials (median age 43 years [minimum 25-maximum 53]) lose 0.6% FN-BMD each year up to menopausal age. For clinical relevance, the epidemiological FRAX model was informed by the simulation results to predict the 10-year risk of major osteoporotic fracture (MOF). Premenopausal women with UFs, who received placebo only in the elagolix phase III trials, have a projected FN-BMD of 0.975 g/cm2 at menopause, associated with a 10-year risk of MOF of 2.3%. Integration of modeling, RWD, and clinical trials data provides a quantitative framework for projecting long-term postmenopausal risk of fractures, based on natural history of BMD changes in premenopausal women. This framework enables quantitative evaluation of the future risk of MOF for women receiving medical therapies (i.e., GnRH modulators) that adversely affect BMD.

Chronic opioid use and complication risks in women with endometriosis: A cohort study in US administrative claims.

BACKGROUND: Women with endometriosis are prescribed opioids for pain relief but may be vulnerable to chronic opioid use given their comorbidity profile. METHODS: A cohort study was conducted in the Clinformatics™ DataMart database between 2006 and 2017 comparing women aged 18-50 years with endometriosis (N = 36 373) to those without (N = 2 172 936) in terms of risk of chronic opioid use, opioid dependence diagnosis, and opioid overdose. Chronic opioid use was defined as ≥120 days' supply dispensed or ≥10 fills of an opioid during any 365-day interval. Among women with endometriosis, we evaluated factors associated with higher risk of chronic opioid use and quantified the risk of complications associated with the use of opioids. RESULTS: Women with endometriosis were at greater risk for chronic opioid use (OR: 3.76; 95%CI: 3.57-3.96), dependence (OR: 2.73, 95%CI: 2.38-3.13) and overdose (OR: 4.34, 95%CI: 3.06-6.15) compared to women without. Chronic users displayed dose escalation and increase in days supplied over time, as well as co-prescribing with benzodiazepines and sedatives. Approximately 34% of chronic users developed constipation, 20% experienced falls, and 8% reported dizziness. Among endometriosis patients, women in younger age groups, those with other comorbidities associated with pain symptoms, as well as those with depression or anxiety were at a higher risk of developing chronic opioid use. CONCLUSIONS: Women with endometriosis had a four times greater risk of chronic opioid use compared to women without. Multimorbidity among these patients was associated with the elevated risk of chronic opioid use and should be taken into account during treatment selection.

Impact of Endometriosis on Life-Course Potential: A Narrative Review.

Endometriosis may exert a profound negative influence on the lives of individuals with the disorder, adversely affecting quality of life, participation in daily and social activities, physical and sexual functioning, relationships, educational and work productivity, mental health, and well-being. Over the course of a lifetime, these daily challenges may translate into limitations in achieving life goals such as pursuing or completing educational opportunities; making career choices or advancing in a chosen career; forming stable, fulfilling relationships; or starting a family, all of which ultimately alter one's life trajectory. The potential for endometriosis to impact the life course is considerable, as symptom onset generally occurs at a time of life (menarche through menopause, adolescence through middle age) when multiple life-changing and trajectory-defining decisions are made. Using a life-course approach, we examine how the known effects of endometriosis on life-domain satisfaction may impact health and well-being across the life course of affected individuals. We provide a quasi-systematic, narrative review of the literature as well as expert opinion on recommendations for clinical management and future research directions.

Depression, Anxiety, and Self-Directed Violence in Women With Endometriosis: A Retrospective Matched-Cohort Study.

The purpose of this study was to compare the incidence of mental health outcomes in women in the United States with and without documented endometriosis. In a retrospective matched-cohort study using administrative health claims data from Optum's Clinformatics DataMart from May 1, 2000, through March 31, 2019, women aged 18-50 years with endometriosis (n = 72,677), identified by International Classification of Disease diagnosis codes (revisions 9 or 10), were matched 1:2 on age and calendar time to women without endometriosis (n = 147,251), with a median follow-up of 529 days (interquartile range, 195, 1,164). The rate per 1,000 person-years of anxiety, depression, and self-directed violence among women with endometriosis was 57.1, 47.7, and 0.9, respectively. Comparing women with endometriosis to those without, the adjusted hazard ratios and 95% confidence intervals were 1.38 (1.34, 1.42) for anxiety, 1.48 (1.44, 1.53) for depression, and 2.03 (1.60, 2.58) for self-directed violence. The association with depression was stronger among women younger than 35 years (P for heterogeneity < 0.01). Risk factors for incident depression, anxiety, and self-directed violence among women with endometriosis included endometriosis-related pain symptoms and prevalence of other chronic conditions associated with pain. The identification of risk factors for mental health conditions among women with endometriosis may improve patient-centered disease management.

Estimating the Effect of Elagolix Treatment for Endometriosis on Postmenopausal Bone Outcomes: A Model Bridging Phase III Trials to an Older Real-World Population.

Elagolix, a gonadotrophin-releasing hormone antagonist, is used in premenopausal women with endometriosis. There is a risk of bone loss with elagolix, but the long-term effects of BMD loss later in life cannot be directly assessed and has not been quantified. To address this gap in knowledge, this study indirectly estimated the impact of elagolix on postmenopausal fracture risk. BMD change in premenopausal women with endometriosis treated with elagolix was modeled from the phase III program data (elagolix group) and used to simulate treatment effects on (fracture risk assessment tool estimated) 10-year risks of hip and major osteoporotic fracture in women ages 50 to 79 years from the 2005-2010 National Health and Nutrition Examination Survey (NHANES; N = 2303). Change in the proportion of women reaching risk-based antiosteoporotic treatment thresholds was also estimated. For elagolix versus NHANES, median 10-year risk of major osteoporotic fracture was 4.73% versus 4.70% in women ages 50 to 59 years, 7.03% versus 6.97% in women ages 60 to 69 years, and 10.83% versus 10.68% in women ages 70 to 79 years. Median 10-year risk of hip fracture in these same groups was 0.19% versus 0.18% for women ages 50 to 59 years, 0.51% versus 0.49% for women 60 to 69 years, and 2.22% versus 2.14% for women 70 to 79 years. The proportion of women reaching risk-based antiosteoporotic treatment thresholds caused by elagolix 150 mg daily for 12 months was 0.36% higher at age 50 to 59 years, 0.23% at age 60 to 69 years, and 1.79% at age 70 to 79 years. The number needed to harm was 643 for one additional hip fracture and 454 for one additional major osteoporotic fracture. Results were similar for elagolix 200 mg twice a day for 3 months. In the modeled scenarios, elagolix had minimal impact on long-term risk of fracture and reaching risk-based treatment thresholds. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Improving Heart Disease Risk Through Quality-Focused Diet Logging: Pre-Post Study of a Diet Quality Tracking App.

BACKGROUND: Diet-tracking mobile apps have gained increased interest from both academic and clinical fields. However, quantity-focused diet tracking (eg, calorie counting) can be time-consuming and tedious, leading to unsustained adoption. Diet quality-focusing on high-quality dietary patterns rather than quantifying diet into calories-has shown effectiveness in improving heart disease risk. The Healthy Heart Score (HHS) predicts 20-year cardiovascular risks based on the consumption of foods from quality-focused food categories, rather than detailed serving sizes. No studies have examined how mobile health (mHealth) apps focusing on diet quality can bring promising results in health outcomes and ease of adoption. OBJECTIVE: This study aims to design a mobile app to support the HHS-informed quality-focused dietary approach by enabling users to log simplified diet quality and view its real-time impact on future heart disease risks. Users were asked to log food categories that are the main predictors of the HHS. We measured the app's feasibility and efficacy in improving individuals' clinical and behavioral factors that affect future heart disease risks and app use. METHODS: We recruited 38 participants who were overweight or obese with high heart disease risk and who used the app for 5 weeks and measured weight, blood sugar, blood pressure, HHS, and diet score (DS)-the measurement for diet quality-at baseline and week 5 of the intervention. RESULTS: Most participants (30/38, 79%) used the app every week and showed significant improvements in DS (baseline: mean 1.31, SD 1.14; week 5: mean 2.36, SD 2.48; 2-tailed t test t29=-2.85; P=.008) and HHS (baseline: mean 22.94, SD 18.86; week 4: mean 22.15, SD 18.58; t29=2.41; P=.02) at week 5, although only 10 participants (10/38, 26%) checked their HHS risk scores more than once. Other outcomes, including weight, blood sugar, and blood pressure, did not show significant changes. CONCLUSIONS: Our study showed that our logging tool significantly improved dietary choices. Participants were not interested in seeing the HHS and perceived logging diet categories irrelevant to improving the HHS as important. We discuss the complexities of addressing health risks and quantity- versus quality-based health monitoring and incorporating secondary behavior change goals that matter to users when designing mHealth apps.

Red blood cell membrane trans fatty acid levels and risk of non-Hodgkin lymphoma: a prospective nested case-control study.

BACKGROUND: Trans fatty acid (TFA) intake persists in much of the world, posing ongoing threats to public health that warrant further elucidation. Published evidence suggests a positive association of self-reported TFA intake with non-Hodgkin lymphoma (NHL) risk. OBJECTIVES: To confirm those reports, we conducted a prospective study of prediagnosis RBC membrane TFA levels and risk of NHL and common NHL histologic subtypes. METHODS: We conducted a nested case-control study in Nurses' Health Study and Health Professionals Follow-Up Study participants with archived RBC specimens and no history of cancer at blood draw (1989-1090 and 1994-1995, respectively). We confirmed 583 incident NHL cases (332 women and 251 men) and individually matched 583 controls on cohort (sex), age, race, and blood draw date/time. We analyzed RBC membrane TFA using GLC (in 2013-2014) and expressed individual TFA levels as a percentage of total fatty acids. We used unconditional logistic regression adjusted for the matching factors to estimate ORs and 95% CIs for overall NHL risk per 1 SD increase in TFA level and assessed histologic subtype-specific associations with multivariable polytomous logistic regression. RESULTS: Total and individual TFA levels were not associated with risk of all NHL or most subtypes. We observed a positive association of total TFA levels with diffuse large B cell lymphoma (DLBCL) risk [n = 98 cases; OR (95% CI) per 1 SD increase: 1.30 (1.05, 1.61); P = 0.015], driven by trans 18:1n-9(ω-9)/elaidic acid [OR (95% CI): 1.34 (1.08, 1.66); P = 0.007], trans 18:1n-7/vaccenic acid [OR (95% CI): 1.28 (1.04, 1.58); P = 0.023], and trans 18:2n-6t,t [OR (95% CI): 1.26 (1.01, 1.57); P = 0.037]. CONCLUSIONS: Our findings extended evidence for TFA intake and DLBCL risk but not for other NHL subtypes. Reduced TFA consumption through dietary choices or health policy measures may support prevention of DLBCL, an aggressive NHL subtype.

Habitual Fish Consumption, n-3 Fatty Acids, and Nuclear Magnetic Resonance Lipoprotein Subfractions in Women.

Background Supplementation with omega-3 (n-3) fatty acid or dietary fish may protect against atherosclerosis, but the potential mechanisms are unclear. Prior studies found modest triglyceride-lowering effects and slight increases in LDL (low-density lipoprotein) cholesterol. Limited evidence has examined n-3 effects on more detailed lipoprotein biomarkers. Methods and Results We conducted a study of 26 034 healthy women who reported information on fish and n-3 intake from a 131-item food-frequency questionnaire. We measured plasma lipids, apolipoproteins, and nuclear magnetic resonance spectroscopy lipoproteins and examined their associations with dietary intake of fish, total n-3, and the n-3 subtypes (eicosapentaenoic, docosahexaenoic, and α-linolenic acids). Top- versus bottom-quintile intake of fish and n-3 were significantly associated with lower triglyceride and large VLDL (very-low-density lipoprotein) particles. Fish intake, but not total n-3, was positively associated with total cholesterol, LDL cholesterol, apolipoprotein B, and larger LDL size, but only α-linolenic acid was associated with lower LDL cholesterol. Total n-3, docosahexaenoic acid, and α-linolenic acid intake were also positively associated with larger HDL (high-density lipoprotein) size and large HDL particles. High eicosapentaenoic acid intake was significantly associated with only a decreased level of VLDL particle concentration and VLDL triglyceride content. The n-3 fatty acids had some similarities but also differed in their associations with prospective cardiovascular disease risk patterns. Conclusions Higher consumption of fish and n-3 fatty acids were associated with multiple measures of lipoproteins that were mostly consistent with cardiovascular prevention, with differences noted for high intake of eicosapentaenoic acid versus docosahexaenoic acid and α-linolenic acid that were apparent with more detailed lipoprotein phenotyping. These hypothesis-generating findings warrant further study in clinical trials. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

Pharmacoepidemiologic Evaluation of Birth Defects from Health-Related Postings in Social Media During Pregnancy.

INTRODUCTION: Adverse effects of medications taken during pregnancy are traditionally studied through post-marketing pregnancy registries, which have limitations. Social media data may be an alternative data source for pregnancy surveillance studies. OBJECTIVE: The objective of this study was to assess the feasibility of using social media data as an alternative source for pregnancy surveillance for regulatory decision making. METHODS: We created an automated method to identify Twitter accounts of pregnant women. We identified 196 pregnant women with a mention of a birth defect in relation to their baby and 196 without a mention of a birth defect in relation to their baby. We extracted information on pregnancy and maternal demographics, medication intake and timing, and birth defects. RESULTS: Although often incomplete, we extracted data for the majority of the pregnancies. Among women that reported birth defects, 35% reported taking one or more medications during pregnancy compared with 17% of controls. After accounting for age, race, and place of residence, a higher medication intake was observed in women who reported birth defects. The rate of birth defects in the pregnancy cohort was lower (0.44%) compared with the rate in the general population (3%). CONCLUSIONS: Twitter data capture information on medication intake and birth defects; however, the information obtained cannot replace pregnancy registries at this time. Development of improved methods to automatically extract and annotate social media data may increase their value to support regulatory decision making regarding pregnancy outcomes in women using medications during their pregnancies.

Association Between a 20-Year Cardiovascular Disease Risk Score Based on Modifiable Lifestyles and Total and Cause-Specific Mortality Among US Men and Women.

Background The previously validated Healthy Heart Score effectively predicted the 20-year risk of cardiovascular disease (CVD). We examine whether the Healthy Heart Score may extend to an association with total and cause-specific mortality. Methods and results The prospective cohort study investigated 58 319 women (mean age 50.2 years) in the Nurses' Health Study (1984-2010) and 29 854 in men (mean age 52.7 years) in the Health Professionals' Follow-up Study (1986-2010) free of cancer and CVD at baseline. The Healthy Heart Score included baseline current smoking; high body mass index; low physical activity; no or excessive alcohol intake; low intake of fruits and vegetables, cereal fiber, or nuts; and high intake of sugar-sweetened beverages or red/processed meats. There were 19 122 total deaths. Compared with participants in the first quintile of the Healthy Heart Score (lowest CVD risk), participants in the fifth quintile (highest CVD risk) had a pooled hazard ratio of 2.26 (95% confidence interval [CI], 1.53-3.33) for total mortality; 2.85 (95 % CI, 1.92-4.23) for CVD mortality, and 2.14 (95% CI, 1.56-2.95) for cancer mortality. Participants in the fifth versus the first quintile also had significantly greater risk of death due to coronary heart disease (3.37; 95% CI, 2.16-5.25), stroke (1.75; 95% CI, 1.02-2.99), lung cancer (6.04; 95% CI, 2.78-13.13), breast cancer (1.45; 95% CI, 1.14-1.86), and colon cancer (1.51; 95% CI, 1.18-1.93). Conclusions The Healthy Heart Score, composed of 9 self-reported, modifiable lifestyle predictors of CVD, is a potentially useful tool for the counseling of healthy lifestyles that was strongly associated with greater risk of all-cause, CVD, and cancer mortality.