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BACKGROUND: Maternal cigarette smoking during pregnancy (MSDP) is associated with numerous adverse health outcomes in infants and children with potential lifelong consequences. Negative effects of MSDP on placental DNAmethylation (DNAm), placental structure, and function are well established. OBJECTIVE: Our aim was to develop biomarkers of MSDP using DNAm measured in placentas (푁 =96), collected as part of the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function double-blind, placebo-controlled randomized clinical trial conducted between 2012 and 2016. We also aimed to develop a digital polymerase chain reaction (PCR) assay for the top ranking cytosine–guanine dinucleotide (CpG) so that large numbers of samples can be screened for exposure at low cost. METHODS: We compared the ability of four machine learning methods [logistic least absolute shrinkage and selection operator (LASSO) regression, logistic elastic net regression, random forest, and gradient boosting machine] to classify MSDP based on placental DNAm signatures. We developed separate models using the complete EPIC array dataset and on the subset of probes also found on the 450K array so that models exist for both platforms. For comparison, we developed a model using CpGs previously associated with MSDP in placenta. For each final model, we used model coefficients and normalized beta values to calculate placental smoking index (PSI) scores for each sample. Final models were validated in two external datasets: the Extremely Low Gestational Age Newborn observational study, 푁 = 426; and the Rhode Island Children's Health Study, 푁 = 237. RESULTS: Logistic LASSO regression demonstrated the highest performance in cross-validation testing with the lowest number of input CpGs. Accuracy was greatest in external datasets when using models developed for the same platform. PSI scores in smokers only (푛 = 72) were moderately correlated with maternal plasma cotinine levels. One CpG (cg27402634), with the largest coefficient in two models, was measured accurately by digital PCR compared with measurement by EPIC array (푅² =0.98). DISCUSSION: To our knowledge, we have developed the first placental DNAm-based biomarkers of MSDP with broad utility to studies of prenatal disease origins. [ABSTRACT FROM AUTHOR]

Background: We previously reported in the "Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function" randomized clinical trial (RCT) that vitamin C (500 mg/day) supplementation to pregnant smokers is associated with improved respiratory outcomes that persist through 5 years of age. The objective of this study was to assess whether buccal cell DNA methylation (DNAm), as a surrogate for airway epithelium, is associated with vitamin C supplementation, improved lung function, and decreased occurrence of wheeze. Methods: We conducted epigenome-wide association studies (EWAS) using Infinium MethylationEPIC arrays and buccal DNAm from 158 subjects (80 placebo; 78 vitamin C) with pulmonary function testing (PFT) performed at the 5-year visit. EWAS were performed on (1) vitamin C treatment, (2) forced expiratory flow between 25 and 75% of expired volume (FEF25–75), and (3) offspring wheeze. Models were adjusted for sex, race, study site, gestational age at randomization (≤ OR > 18 weeks), proportion of epithelial cells, and latent covariates in addition to child length at PFT in EWAS for FEF25–75. We considered FDR p < 0.05 as genome-wide significant and nominal p < 0.001 as candidates for downstream analyses. Buccal DNAm measured in a subset of subjects at birth and near 1 year of age was used to determine whether DNAm signatures originated in utero, or emerged with age. Results: Vitamin C treatment was associated with 457 FDR significant (q < 0.05) differentially methylated CpGs (DMCs; 236 hypermethylated; 221 hypomethylated) and 53 differentially methylated regions (DMRs; 26 hyper; 27 hypo) at 5 years of age. FEF25–75 was associated with one FDR significant DMC (cg05814800), 1,468 candidate DMCs (p < 0.001), and 44 DMRs. Current wheeze was associated with 0 FDR-DMCs, 782 candidate DMCs, and 19 DMRs (p < 0.001). In 365/457 vitamin C FDR significant DMCs at 5 years of age, there was no significant interaction between time and treatment. Conclusions: Vitamin C supplementation to pregnant smokers is associated with buccal DNA methylation in offspring at 5 years of age, and most methylation signatures appear to be persistent from the prenatal period. Buccal methylation at 5 years was also associated with current lung function and occurrence of wheeze, and these functionally associated loci are enriched for vitamin C associated loci. Clinical trial registration ClinicalTrials.gov, NCT01723696 and NCT03203603. [ABSTRACT FROM AUTHOR]

Purpose: Environmental factors such as bathing may play a role in atopic dermatitis (AD) development. This analysis utilized data from the Community Assessment of Skin Care, Allergies, and Eczema (CASCADE) Trial (NCT03409367), a randomized controlled trial of emollient therapy for AD prevention in the general population, to estimate bathing frequency and associated factors within the first 9 weeks of life. Methods: Data were collected from 909 parent/newborn dyads recruited from 25 pediatric and family medicine clinics from the Meta‐network Learning and Research Center (Meta‐LARC) practice‐based research network (PBRN) consortium in Oregon, North Carolina, Colorado, and Wisconsin for the CASCADE trial. Ordinal logistic regression was used to conduct a cross‐sectional analysis of the association between bathing frequency (measured in baths per week) and demographic, medical, and lifestyle information about the infant, their family, and their household. Variables were selected using a backwards‐stepwise method and estimates from the reduced model are reported in the text. Results: Moisturizer use (OR = 2.03, 95% CI: 1.54–2.68), Hispanic or Latino ethnicity (OR = 1.97, 95% CI: 1.42–2.72), a parental education level lower than a 4‐year college degree (OR = 2.48, 95% CI: 1.70–3.62), living in North Carolina or Wisconsin (compared to Oregon; OR = 2.12 and 1.47, 95% CI: 1.53–2.93 and 1.04–2.08, respectively), and increasing child age (in days; OR = 1.02, 95% CI: 1.01–1.02) were significantly associated with more frequent bathing, while pet ownership (OR = 0.67, 95% CI: 0.52–0.87) was significantly associated with less frequent bathing. Conclusions: We found significant ethnic, geographic, and socioeconomic variation in bathing frequency before 9 weeks of age that may be of relevance to AD prevention studies. [ABSTRACT FROM AUTHOR]

Background: Pulmonary embolism (PE) is a frequent diagnostic consideration in emergency department (ED) patients, yet diagnosis is challenging because symptoms of PE are nonspecific. Guidelines recommend the use of clinical decision tools to increase efficiency and avoid harms from overtesting, including D‐dimer screening in patients not at high risk for PE. Women undergo testing for PE more often than men yet have a lower yield from testing. Our study objective was to determine whether patient sex influenced the odds of received guideline‐consistent care. Methods: We performed a retrospective cohort study at two large U.S. academic EDs from January 1, 2016, to December 31, 2018. Nonpregnant patients aged 18–49 years were included if they presented with chest pain, shortness of breath, hemoptysis, or syncope and underwent testing for PE with D‐dimer or imaging. Demographic and clinical data were exported from the electronic medical record (EMR). Pretest risk scores were calculated using manually abstracted EMR data. Diagnostic testing was then compared with recommended testing based on pretest risk. The primary outcome was receipt of guideline‐consistent care, which required an elevated screening D‐dimer prior to imaging in all non–high‐risk patients. Results: We studied 1991 discrete patient encounters; 37% (735) of patients were male and 63% (1256) were female. Baseline characteristics, including revised Geneva scores, were similar between sexes. Female patients were more likely to receive guideline‐consistent care (70% [874/1256] female vs. 63% [463/735] male, p < 0.01) and less likely to be diagnosed with PE (3.1% [39/1256] female vs. 5.3% [39/735] male, p < 0.05). The most common guideline deviation in both sexes was obtaining imaging without a screening D‐dimer in a non–high‐risk patient (75% [287/382] female vs. 75% [205/272] male). Conclusions: In this cohort, females were more likely than males to receive care consistent with current guidelines and less likely to be diagnosed with PE. [ABSTRACT FROM AUTHOR]

Background: Long‐term follow‐up for clinician–scientist training programs is sparse. We describe the outcomes of clinician–scientist scholars in the National Heart Lung and Blood Institute (NHLBI) K12 program in emergency care research up to 8.7 years after matriculation in the program. Methods: This was a cohort study of faculty clinician–scientist scholars enrolled in a NHLBI K12 research training program at 6 sites across the US, with median follow‐up 7.7 years (range 5.7–8.7 years) from the date of matriculation. Scholars completed electronic surveys in 2017 and 2019, with the 2019 survey collecting information for their current work setting, percent time for research, and grant funding from all sources. We used NIH RePorter and online resources to verify federal grants through March 2021. The primary outcome was a funded career development award (CDA) or research project grant (RPG) where the scholar was principal investigator. We included funding from all federal sources and national foundations. Results: There were 43 scholars, including 16 (37%) women. Over the follow‐up period, 32 (74%) received an individual CDA or RPG, with a median of 36 months (range 9–83 months) after entering the program. Of the 43 scholars, 23 (54%) received a CDA and 22 (51%) received an RPG, 7 (16%) of which were R01s. Of the 23 scholars who received a CDA, 13 (56%) subsequently had an RPG funded. Time to CDA or RPG did not differ by sex (women vs. men log‐rank test p = 0.27) or specialty training (emergency medicine versus other specialties, p = 0.59). Conclusions: After 7 years of follow‐up for this NHLBI K12 emergency care research training program, three quarters of clinician–scientist scholars had obtained CDA or RPG funding, with no notable differences by sex or clinical training. [ABSTRACT FROM AUTHOR]

The document titled "97 BUILD EXITO: a successful collaborative training program for STEM undergraduates to improve workforce diversity" discusses the BUILD EXITO program, which aims to improve health equity and accessibility by developing a diverse and inclusive workforce. The program provides research training for underrepresented and disadvantaged students, including opportunities for learning, research experience, and mentorship. The program has been successful in increasing diversity in the research workforce and has developed a sustainable model for training a diverse research workforce. [Extracted from the article]

The text discusses various research studies and initiatives in different medical fields. It mentions a study on follicle growth and survival, predictors of autologous fat grafting in breast reconstruction, a mentoring program for Hispanic junior investigators, participant recruitment challenges in clinical research, the creation of a database to study bronchiolitis in pediatric intensive care units, and a centralized support service for investigator-initiated multi-site clinical trials. These studies and initiatives aim to improve understanding, treatment, and support in their respective fields. [Extracted from the article]

Background: Maternal smoking during pregnancy (MSDP) affects development of multiple organ systems including the placenta, lung, brain, and vasculature. In particular, children exposed to MSDP show lifelong deficits in pulmonary function and increased risk of asthma and wheeze. Our laboratory has previously shown that vitamin C supplementation during pregnancy prevents some of the adverse effects of MSDP on offspring respiratory outcomes. Epigenetic modifications, including DNA methylation (DNAm), are a likely link between in utero exposures and adverse health outcomes, and MSDP has previously been associated with DNAm changes in blood, placenta, and buccal epithelium. Analysis of placental DNAm may reveal critical targets of MSDP and vitamin C relevant to respiratory health outcomes. Results: DNAm was measured in placentas obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (37 supplemented with vitamin C, 35 with placebo) and 24 never-smokers for reference. Methylation at one CpG, cg20790161, reached Bonferroni significance and was hypomethylated in vitamin C supplemented smokers versus placebo. Analysis of spatially related CpGs identified 93 candidate differentially methylated regions (DMRs) between treatment groups, including loci known to be associated with lung function, oxidative stress, fetal development and growth, and angiogenesis. Overlap of nominally significant differentially methylated CpGs (DMCs) in never-smokers versus placebo with nominally significant DMCs in vitamin C versus placebo identified 9059 candidate "restored CpGs" for association with placental transcript expression and respiratory outcomes. Methylation at 274 restored candidate CpG sites was associated with expression of 259 genes (FDR < 0.05). We further identified candidate CpGs associated with infant lung function (34 CpGs) and composite wheeze (1 CpG) at 12 months of age (FDR < 0.05). Increased methylation in the DIP2C, APOH/PRKCA, and additional candidate gene regions was associated with improved lung function and decreased wheeze in offspring of vitamin C-treated smokers. Conclusions: Vitamin C supplementation to pregnant smokers ameliorates changes associated with maternal smoking in placental DNA methylation and gene expression in pathways potentially linked to improved placental function and offspring respiratory health. Further work is necessary to validate candidate loci and elucidate the causal pathway between placental methylation changes and outcomes of offspring exposed to MSDP. Clinical trial registration ClinicalTrials.gov, NCT01723696. Registered November 6, 2012. https://clinicaltrials.gov/ct2/show/record/NCT01723696. [ABSTRACT FROM AUTHOR]

Introduction: Addiction consult services (ACS) engage hospitalized patients with opioid use disorder (OUD) in care and help meet their goals for substance use treatment. Little is known about how ACS affect mortality for patients with OUD. The objective of this study was to design and validate a model that estimates the impact of ACS care on 12-month mortality among hospitalized patients with OUD. Methods: We developed a Markov model of referral to an ACS, post-discharge engagement in SUD care, and 12-month drug-related and non-drug related mortality among hospitalized patients with OUD. We populated our model using Oregon Medicaid data and validated it using international modeling standards. Results: There were 6,654 patients with OUD hospitalized from April 2015 through December 2017. There were 114 (1.7%) drug-related deaths and 408 (6.1%) non-drug related deaths at 12 months. Bayesian logistic regression models estimated four percent (4%, 95% CI = 2%, 6%) of patients were referred to an ACS. Of those, 47% (95% CI = 37%, 57%) engaged in post-discharge OUD care, versus 20% not referred to an ACS (95% CI = 16%, 24%). The risk of drug-related death at 12 months among patients in post-discharge OUD care was 3% (95% CI = 0%, 7%) versus 6% not in care (95% CI = 2%, 10%). The risk of non-drug related death was 7% (95% CI = 1%, 13%) among patients in post-discharge OUD treatment, versus 9% not in care (95% CI = 5%, 13%). We validated our model by evaluating its predictive, external, internal, face and cross validity. Discussion: Our novel Markov model reflects trajectories of care and survival for patients hospitalized with OUD. This model can be used to evaluate the impact of other clinical and policy changes to improve patient survival. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Improvements in lung function following vitamin C supplementation to pregnant smokers are associated with buccal DNA methylation at 5 years of age" published in the journal Clinical Epigenetics. The correction states that there was an error in listing the NCBI Gene Expression Omnibus (GEO) accession series in the "Availability of data and materials section" of the original article. The correct GEO series for this work is GSE252169. The correction notice also includes a statement from the publisher, Springer Nature, emphasizing their neutrality regarding jurisdictional claims and institutional affiliations. The authors of the original article are listed as Lyndsey E. Shorey-Kendrick, Cindy T. McEvoy, Kristin Milner, Julia Harris, Julie Brownsberger, Robert S. Tepper, Byung Park, Lina Gao, Annette Vu, Cynthia D. Morris, and Eliot R. Spindel. [Extracted from the article]

The document titled "524 Navigator: Providing a foundation for cross team collaboration and custom research service through the CTSA Hub" discusses the Oregon Clinical and Translational Research Institute's (OCTRI) Clinical Research Navigator program, which serves as a single point of entry for clinical and translational research services, support, advice, and guidance. The program receives requests through various methods and triages an average of 964 research requests annually, connecting researchers to the resources they need. The document emphasizes the importance of CTSA resources in supporting researchers and highlights the role of technology and experienced staff in efficiently providing research support. [Extracted from the article]

The document titled "162 Training in Responsible Conduct of Research: Evolution over 12 years" discusses the development and implementation of institution-wide training in responsible conduct of research (RCR) at Oregon Health & Science University. The training aims to include all required elements of RCR, support trainees in identifying ethical questions in research, and disseminate the results. The document presents the evolution of the curriculum over the past 12 years, the challenges identified by participants, and the impact of the training on participants' confidence in ethical decision making. The approach to RCR training is well-received and allows for choice in relevant topics. [Extracted from the article]

This document is an abstract from the Journal of Clinical & Translational Science. It includes three separate studies related to translational science training. The first study describes the use of a multi-session case study in a team science graduate course, which helps participants understand team science concepts and practice incorporating them into teams. The second study evaluates the expansion of a predoctoral TL1 training grant to all research-intensive universities in Oregon, tracking applicants, trainee feedback, and success in research. The third study focuses on an interdisciplinary course in Puerto Rico that teaches undergraduate students about clinical and translational research, with positive feedback from students and opportunities for professional development. [Extracted from the article]

Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write. Common strategies to maintain research productivity involved time management, virtual connections with colleagues, and shifting to research activities not requiring laboratory/clinic settings. Strategies for mitigating the impact of the COVID-19 pandemic on training and career development are described. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a common, chronic skin disorder often beginning in infancy. Skin barrier dysfunction early in life serves as a central event in the pathogenesis of AD. In infants at high risk of developing AD, preventative application of lipid-rich emollients may reduce the risk of developing AD. This study aims to measure the effectiveness of this intervention in a population not selected for risk via a pragmatic, randomized, physician-blinded trial in the primary care setting.Methods: Infant-parent dyads are recruited from a primary care practice participating through one of four practice-based research networks in Oregon, Colorado, Wisconsin, and North Carolina. Eligible dyads are randomized to the intervention (daily use of lipid-rich emollient) or the control (no emollient) group (n = 625 infants in each) and are followed for 24 months. The primary outcome is the cumulative incidence of physician-diagnosed AD and secondary outcomes include caregiver-reported measures of AD and development of other atopic diseases. Data collection occurs via chart review and surveys, with no study visits required. Data will be analyzed utilizing intention-to-treat principles.Discussion: AD is a common skin condition in infants that affects quality of life and is associated with the development of other atopic diseases. If a safe intervention, such as application of lipid-rich emollients, in the general population effectively decreases AD prevalence, this could alter the guidance given by providers regarding routine skin care of infants. Because of the pragmatic design, we anticipate that this trial will yield generalizable results.Trial Registration: ClinicalTrials.gov: NCT03409367. Registered on 11 February 2018. [ABSTRACT FROM AUTHOR]

Optimal escape theory has proven useful for understanding the dynamics of antipredator behaviour in animals; however, approaches are often limited to single-population studies. We studied how the escape behaviour of tree lizards (Urosaurus ornatus) varied across a disturbance gradient. We also considered how sex, body temperature, and perch temperature affected their escape decisions. Both sexes exhibited similar response patterns; however, lizards in the most-disturbed habitat, as well as cooler (body or perch temperature) lizards, initiated escape earlier (but did not flee further) than other animals. Increased wariness as indicated by earlier escape suggests that frequently-disturbed, more-open localities may be stressful habitats for species like U. ornatus. In addition, because cooler temperatures limit locomotor performance capacity, escape decisions should also depend on a species' thermal ecology. Overall, we stress the importance of multi-population approaches for capturing the variety of ways species adaptively respond to the threat of predation across habitat gradients. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Colon cancer screening is effective. To complete screening in 80% of individuals over age 50 years by 2018 will require adequate colonoscopy capacity throughout the country, including rural areas, where colonoscopy providers may have less specialized training. Our aim was to study the quality of colonoscopy in rural settings. Methods: The Clinical Outcomes Research Initiative (CORI) and the Oregon Rural Practice‐based Research Network (ORPRN) collaborated to recruit Oregon rural practices to submit colonoscopy reports to CORI's National Endoscopic Database (NED). Ten ORPRN sites were compared to non‐ORPRN rural (n = 11) and nonrural (n = 43) sites between January 2009 and October 2011. Established colonoscopy quality measures were calculated for all sites. Results: No ORPRN physicians were gastroenterologists compared with 82% of nonrural physicians. ORPRN practices reached the cecum in 87.4% of exams compared with 89.3% of rural sites (P = .0002) and 90.9% of nonrural sites (P < .0001). Resected polyps were less likely to be retrieved (84.7% vs 91.6%; P < .0001) and sent to pathology (77.1% vs 91.3%; P < .0001) at ORPRN practices compared to nonrural sites. The overall polyp detection (39.0% vs 40.3%) was similar (P = .217) between ORPRN and nonrural practices. Of exams with polyps, the rate for largest polyp on exam 6‐9 mm was 20.8% at ORPRN sites, compared to 26.8% at nonrural sites (P < .0001), and for polyps >9mm 16.6% vs 18.7% (P = .106). Conclusion: ORPRN sites performed well on most colonoscopy quality measures, suggesting that high‐quality colonoscopy can be performed in rural settings. [ABSTRACT FROM AUTHOR]

Background and purpose: As part of the NIH BUILD initiative to diversify the scientific workforce, the EXITO project is a large multi-institutional effort to provide comprehensive support and training for undergraduates from traditionally underrepresented student populations who aspire to health-related research careers. Portland State University, a major public urban university that prioritizes student access and opportunity, and Oregon Health & Science University, a research-intensive academic health center, lead the EXITO network comprised of eleven 2-year and 4-year institutions of higher education spanning Oregon, Washington, Alaska, Hawaii, Guam, American Samoa, and the Northern Mariana Islands. The EXITO project aims for impact in biomedical research by training diverse scholars from indigenous and underserved communities affected by adverse health disparities. Project approach: Guided by socio-ecological theory, the EXITO project is a multi-level intervention offering a threeyear research training pathway for scholars in the biomedical, behavioral, health, and social sciences. Fundamental components of the model include student outreach and engagement, integrated curricular enhancements, intensive research experiences, multi-faceted developmental mentoring, supportive community and services, and rigorous evaluation and quality improvement. EXITO also advances faculty and institutional development in these domains by holding curriculum development conferences, creating research learning communities, awarding pilot project research funding, providing mentor training and ongoing support, collaborating with other research equity programs, and developing campus infrastructure and services to support scholars with diverse backgrounds and needs. Highlights: The large and geographically broad network of EXITO institutions engages a range of diverse students, including indigenous populations and students beginning post-secondary education at community colleges. The EXITO model specifically accommodates many students transferring from 2-year partner institutions and facilitates seamless transfer to the 4-year institution. EXITO features several approaches to research training, including supported summer entry into research placements, the incorporation of responsible conduct of research content into general education curriculum, and the intentional matching of scholars with three types of mentors (e.g., peer, career, research). Implications: EXITO provides an example of a comprehensive research training initiative for traditionally underrepresented students that can be implemented across a diverse range of 2-year and 4-year institutions. [ABSTRACT FROM AUTHOR]

Rationale: Infants whose mothers smoked during pregnancy demonstrate lifelong decreases in pulmonary function. DNA methylation changes associated with maternal smoking during pregnancy have been described in placenta and cord blood at delivery, in fetal lung, and in buccal epithelium and blood during childhood. We demonstrated in a randomized clinical trial ( ClinicalTrials.gov identifier, NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the impact of maternal smoking on offspring pulmonary function and decrease the incidence of wheeze at 1 year of age.Objectives: To determine whether vitamin C supplementation reduces changes in offspring methylation in response to maternal smoking and whether methylation at specific CpGs is also associated with respiratory outcomes.Methods: Targeted bisulfite sequencing was performed with a subset of placentas, cord blood samples, and buccal samples collected during the NCT00632476 trial followed by independent validation of selected cord blood differentially methylated regions, using bisulfite amplicon sequencing.Measurements and Main Results: The majority (69.03%) of CpGs with at least 10% methylation difference between placebo and nonsmoker groups were restored (by at least 50%) toward nonsmoker levels with vitamin C treatment. A significant proportion of restored CpGs were associated with phenotypic outcome with greater enrichment among hypomethylated CpGs.Conclusions: We identified a pattern of normalization in DNA methylation by vitamin C supplementation across multiple loci. The consistency of this pattern across tissues and time suggests a systemic and persistent effect on offspring DNA methylation. Further work is necessary to determine how genome-wide changes in DNA methylation may mediate or reflect persistent effects of maternal smoking on lung function. [ABSTRACT FROM AUTHOR]

Objective. To assess reliability, validity, and responsiveness of a 29-item short-form version of the Patient Reported Outcomes Measurement Information System (PROMIS) and a novel "impact score" calculated from those measures. Design. Prospective cohort study. Setting. Rural primary care practices. Subjects. Adults aged≥55 years with chronic musculoskeletal pain, not currently receiving prescription opioids. Methods. Subjects completed the PROMIS short form at baseline and after 3 months. Patient subsets were compared to assess reliability and responsiveness. Construct validity was tested by comparing baseline scores among patients who were or were not applying for Worker's Compensation; those with higher or lower catastrophizing scores; and those with or without recent falls. Responsiveness was assessed with mean score changes, effect sizes, and standardized response means. Results. Internal consistency was good to excellent, with Cronbach's alpha between 0.81 and 0.95 for all scales. Among patients who rated their pain as stable, test-retest scores at 3 months were around 0.70 for most scales. PROMIS scores were worse among patients seeking or receiving worker's compensation, those with high catastrophizing scores, and those with recent falls. Among patients rating pain as "much less" at 3 months, absolute effect sizes for the various scales ranged from 0.24 (Depression) to 1.93 (Pain Intensity). Conclusions. Results indicate that the PROMIS short 29-item form may be useful for the study of patients with chronic musculoskeletal pain. Our findings also support use of the novel "impact score" recommended by the National Institutes of Health (NIH) Task Force on Research Standards for Chronic Low Back Pain. [ABSTRACT FROM AUTHOR]

Objectives To develop mortality risk prediction models for older adults with chronic kidney disease ( CKD) that include comorbidities and measures of health status and use not associated with particular comorbid conditions (nondisease-specific measures). Design Retrospective cohort study. Setting Kaiser Permanente Northwest ( KPNW) Health Maintenance Organization. Participants Individuals with severe CKD (estimated glomerular filtration rate <30 mL/min per 1.73 m2; N = 4,054; n = 1,915 aged 65-79, n = 2,139 aged ≥80) who received care at KPNW between 2000 and 2008. Measurements Cox proportional hazards analysis was used to examine the association between selected participant characteristics and all-cause mortality and to generate age group-specific risk prediction models. Predicted and observed risks were evaluated according to quintile. Predictors from the Cox models were translated into a points-based system. Internal validation was used to provide best estimates of how these models might perform in an external population. Results The risk prediction models used 16 characteristics to identify participants with the highest risk of mortality at 2 years for adults aged 65 to 79 and 80 and older. Predicted and observed risks agreed within 5% for each quintile; a 4 to 5 times difference in 2-year predicted mortality risk was observed between the highest and lowest quintiles. The c-statistics for each model (0.68-0.69) indicated effective discrimination without evidence of significant overfit (slope shrinkage 0.06-0.09). Models for each age group performed similarly for mortality prediction at 6 months and 2 years in terms of discrimination and calibration. Conclusion When validated, these risk prediction models may be helpful in supporting discussions about prognosis and treatment decisions sensitive to prognosis in older adults with CKD in real-world clinical settings. [ABSTRACT FROM AUTHOR]

Background: The education and training of early career biomedical translational researchers often involves formal mentoring by more experienced colleagues.Purposes: This study investigated the nature of these mentoring relationships from the perspective of mentees. The objective was to understand the challenges and issues encountered by mentees in forming and maintaining productive mentoring relationships.Methods: Three focus groups (n= 14) were conducted with early career researchers who had mentored career development awards. Thematic analysis identified, categorized, and illustrated the challenges and issues reported by mentees.Results: The range of mentee challenges was reflected in five major categories: (a) network—finding appropriate mentors to meet various needs; (b) access—structuring schedules and opportunities to receive mentoring; (c) expectations—negotiating the mechanics of the mentoring relationship and its purpose; (d) alignment—managing mentor–mentee mismatches regarding interests, priorities, and goals; and (e) skills and supports—developing the institutional supports to be successful.Conclusions: Mentoring relationships created for academic training and career development contend with tasks common to many other relationships, namely, recognizing compatibility, finding time, establishing patterns, agreeing to goals, and achieving aims. Identifying challenges faced by mentees can facilitate the development of appropriate trainings and supports to foster mentoring relationships in academic and career settings. [ABSTRACT FROM PUBLISHER]

Importance: Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function.Objective: To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo.Design, Setting, and Participants: Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year.Interventions: Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90).Main Outcomes and Measures: The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed.Results: Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction).Conclusions and Relevance: Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities.Trial Registration: clinicaltrials.gov Identifier: NCT00632476. [ABSTRACT FROM AUTHOR]

IMPORTANCE Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. OBJECTIVE To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. INTERVENTIONS Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). MAIN OUTCOMES AND MEASURES The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram[Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. RESULTS Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the a5 nicotinic receptor (rs16969968) (P < .001 for interaction). CONCLUSIONS AND RELEVANCE Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. [ABSTRACT FROM AUTHOR]

Background/context Systematic evidence reviews (SERs) identify knowledge gaps in the literature, a logical starting place for prioritizing future research. Varied methods have been used to elicit diverse stakeholders' input in such prioritization. Objective To pilot a simple, easily replicable process for simultaneously soliciting consumer, clinician and researcher input in the identification of research priorities, based on the results of the 2009 SER on screening adults for depression in primary care. Methods We recruited 20 clinicians, clinic staff, researchers and patient advocates to participate in a half-day event in October 2009. We presented SER research methods and the results of the 2009 SER. Participants took part in focus groups, organized by profession; broad themes from these groups were then prioritized in a formal exercise. The focus group content was also subsequently analysed for specific themes. Results Focus group themes generally reacted to the evidence presented; few were articulated as research questions. Themes included the need for resources to respond to positive depression screens, the impact of depression screening on delivery systems, concerns that screening tools do not address comorbid or situational causes of depression and a perceived 'disconnect' between screening and treatment. The two highest-priority themes were the system effects of screening for depression and whether depression screening effectively leads to improved treatment. Conclusion We successfully piloted a simple, half-day, easily replicable multi-stakeholder engagement process based on the results of a recent SER. We recommend a number of potential improvements in future endeavours to replicate this process. [ABSTRACT FROM AUTHOR]

BACKGROUND: The current study was performed to determine, in rural settings, the relation between the type and status of insurance coverage and being up-to-date for breast, cervical, and colorectal cancer screening. METHODS: Four primary care practices in 2 rural Oregon communities participated. Medical chart reviews that were conducted between October 2008 and August 2009 assessed insurance coverage and up-to-date status for breast, cervical, and colorectal cancer screening. Inclusion criteria involved having at least 1 health care visit within the past 5 years and being aged ≥ 55 years. RESULTS: The majority of patients were women aged 55 years to 70 years, employed or retired, and who had private health insurance and an average of 2.5 comorbid conditions. The overall percentage of eligible women who were up-to-date for cervical cancer screening was 30%; approximately 27% of women were up-to-date for clinical breast examination, 37% were up-to-date for mammography, and 19% were up-to-date for both mammography and clinical breast examination. Approximately 38% of men and 35% of women were up-to-date for colorectal cancer screening using any test at appropriate screening intervals. In general, having any insurance versus being uninsured was associated with undergoing cancer screening. For each type of screening, patients who had at least 1 health maintenance visit were significantly more likely to be up-to-date compared with those with no health maintenance visits. A significant interaction was found between having health maintenance visits, having any health insurance, and being up-to-date for cancer screening tests. CONCLUSIONS: Overall, the percentage of patients who were up-to-date for any cancer screening, especially cervical cancer screening, was found to be very low in rural Oregon. Patients with some form of health insurance were more likely to have had a health maintenance visit within the previous 2 years and to be up-to-date for breast, cervical, and/or colorectal cancer screening. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Hypothesis: Screening for esophageal adenocarcinoma has focused on identifying Barrett esophagus (BE) in patientswithsevere, long-standing symptoms of gastroesophageal reflux disease(GERD). Unfortunately, 95% of patients who develop esophageal adenocarcinoma are unaware of the presence of BE before their cancer diagnosis, which meansthey neverhadbeen selected for screening.Onepossible explanation is that no correlation exists between the severity ofGERDsymptoms and cancer risk. Wehypothesize that severe GERD symptoms are not associated with an increase in the prevalence of BE, dysplasia, or cancer in patients undergoing primary endoscopic screening. Design: Cross-sectional study. Setting: University hospital. Patients: A total of 769 patients with GERD. Interventions: Primary screening endoscopy performed from November 1, 2004, through June 7, 2007. Main Outcomes Measures: Symptom severity, proton pump inhibitor therapy, and esophageal adenocarcinogenesis (ie, BE, dysplasia, or cancer). Results: Endoscopy revealed adenocarcinogenesis in 122 patients. An increasing number of severe GERD symptoms correlated positively with endoscopic findings of esophagitis (odds ratio, 1.05; 95% confidence interval, 1.01-1.09). Conversely, an increasing number of severe GERD symptoms were associated with decreased odds of adenocarcinogenesis (odds ratio, 0.94; 95% confidence interval, 0.89-0.98). Patients taking proton pump inhibitors were 61.3% and 81.5% more likely to have adenocarcinogenesis if they reported no severe typical or atypical GERD symptoms, respectively, compared with patients taking proton pump inhibitors, who reported that all symptoms were severe. Conclusions: Medically treated patients with mild or absent GERD symptoms have significantly higher odds of adenocarcinogenesis compared with medically treated patients with severe GERD symptoms. This finding may explain the failure of the current screening paradigm in which the threshold for primary endoscopic examination is based on symptom severity. [ABSTRACT FROM AUTHOR]

Background: The relationship between diabetes, GERD symptoms and acid-related mucosal damage has not been well studied.Aims: To better quantify risk of acid-related mucosal damage among patients with and without diabetes.Methods: A prospective study using 10 sites from the Clinical Outcomes Research Initiative (CORI) National Endoscopy Database surveyed patients undergoing EGD by telephone within 30 days on medical history, symptoms and demographics. Varices and feeding tube indications were excluded. Acid-related damage was defined as any of these findings recorded in CORI: Barrett's esophagus; esophageal inflammation (unless non-acid-related etiology); healed ulcer, duodenal, gastric or esophageal ulcer; stricture; and mucosal abnormality with erosion or ulcer.Results: Of 1,569 patients, 16% had diabetes, 95% being type 2. Diabetic patients were significantly more likely to be male, older and have a higher body mass index, and less likely to report frequent heartburn and non-steroidal anti-inflammatory drug use. No significant differences were found in acid reflux and proton pump inhibitor (PPI) use between groups. In unadjusted analyses, diabetic patients had a similar risk for acid-related damage than non-diabetic patients (OR 1.09; 95% CI: 0.83, 1.42) which persisted after adjusting for gender, age, acid reflux, acid indication and PPI use (OR 1.04; 95% CI: 0.79, 1.39).Conclusions: No difference in risk of acid-related mucosal damage was found, even after adjustment for potential confounders. Our data do not support the need for a lower threshold to perform endoscopy in diabetic patients. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates association of chronic opioid therapy (COT) for chronic noncancer pain (CNCP) and receipt of preventive services. The study made use of the medical records of 704, 000 patients to compare the receipt of four preventive services in patients of COT for CNCP and non-COT patients. Results indicate that patients who use COT for CNCP have lower relative risk (RR) of receipt of screening for cervical cancer compared to patients not using COT.

Background: Distortion of esophagogastric junction anatomy in patients with gastroesophageal reflux disease produces permanent dilation of the gastric cardia proportional to disease severity, but it remains unclear whether this mechanism underlies reflux in patients with isolated laryngopharyngeal reflux symptoms.Method: In a prospective study, 113 patients were stratified into three populations based on symptom complex: laryngopharyngeal reflux symptoms, typical reflux symptoms, and both laryngopharyngeal and typical symptoms. Subjects underwent small-caliber upper endoscopy in the upright position. Outcome measures included gastric cardia circumference, presence and size of hiatal hernia, and prevalence of esophagitis and Barrett's esophagus within each group.Results: There were no differences in gastric cardia circumference between patient groups. The prevalence of Barrett's esophagus was 20.4% overall and 15.6% in pure laryngopharyngeal reflux patients. Barrett's esophagus patients had a greater cardia circumference compared to those without it. In the upright position, patients with isolated laryngopharyngeal reflux display the same degree of esophagogastric junction distortion as those with typical reflux symptoms, suggesting a similar pathophysiology.Conclusion: This indicates that, although these patients may sense reflux differently, they have similar risks as patients with typical symptoms. Further, the identification of Barrett's esophagus in the absence of typical reflux symptoms suggests the potential for occult disease progression and late discovery of cancer. [ABSTRACT FROM AUTHOR]

The article discusses colorectal cancer rates in black and white patients, examining the possible connections between the higher rates of incidence and mortality of colorectal cancer in black individuals and the possibility that colorectal cancer screening might be less effective in such individuals. From 1985 until 2008, colorectal cancer rates in white individuals have gone down while rates for black individuals have either increased or remained unchanged, depending on gender. Also discussed is the occurrence of polyps greater than 9 mm in diameter.

Background: Complementary and alternative medicine (CAM) use is high in people with multiple sclerosis (MS), yet there are limited reports on safety and effectiveness of CAM in MS. Naturopathic medicine encompasses a broad range of CAM modalities and may improve quality of life in patients with MS. Objective: To assess quality of life in MS subjects who received interventions designed to “model” the “whole practice” of naturopathy. Design: A pilot, randomized, controlled study with a 6-month intervention period. Participants: Participants who met criteria for clinically definite MS. Interventions: The 3 intervention arms were usual care, naturopathic medicine plus usual care, and MS education plus usual care. Outcome measures: The primary outcome measure was quality of life (36-item short form health survey [SF-36]). Secondary outcome measures included fatigue (Modified Fatigue Impact Scale); depression (Beck Depression Inventory); cognition battery (Stroop test and Paced Auditory Serial Addition Test 3), and neurologic impairment (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite). Adverse event reporting and laboratory measures were used to assess safety. Results: Forty-five (45) participants (15 per group) were randomized and all completed the 6-month intervention. There were no significant differences between groups on any outcome measure. There was a trend in favoring the naturopathic group in the General Health subscale of the SF-36 ( p = 0.11), Timed Walk ( p = 0.11), and neurologic impairment (EDSS) ( p = 0.07). There was a trend favoring the Education group in the Stroop attention test ( p = 0.07). There was no difference between groups in adverse events or laboratory changes. Conclusions: Naturopathic medicine combined with usual care for MS showed a trend in improvement in the General Health subscale of the SF-36, Timed Walk, and neurologic impairment. Evaluation of naturopathic medicine, as a multimodality regimen, warrants further investigation. [ABSTRACT FROM AUTHOR]

OBJECTIVES: A major limitation to screening and surveillance of Barrett's esophagus is the complexity, expense, and risk associated with sedation for upper endoscopy. This study examines the feasibility, accuracy, and patient acceptability of office-based unsedated endoscopy as an alternative. METHODS: Of 274 eligible adults scheduled for endoscopic screening for gastroesophageal reflux symptoms or surveillance of Barrett's esophagus at a tertiary care center, 121 underwent unsedated small-caliber endoscopy and conventional endoscopy in a randomized crossover study. The two procedures were compared with regard to histological detection of Barrett's esophagus and dysplasia and biopsy size. Patients answered questionnaires assessing the tolerability of the procedures. RESULTS: The prevalence of Barrett's esophagus was 26% using conventional endoscopy and 30% using unsedated endoscopy ( P= 0.503). The level of agreement between the two approaches was “moderate” (κ= 0.591). Each modality detected four cases of low-grade dysplasia with concordance on one case. The tissue samples collected with unsedated endoscopy were smaller than with conventional endoscopy ( P < 0.001). The majority of subjects rated their experience with both procedures as being well tolerated with minimal or no difficulty. When asked which procedure they would prefer in the future, 71% (81/114) chose unsedated small-caliber endoscopy. CONCLUSIONS: Office-based unsedated small-caliber endoscopy is technically feasible, well tolerated, and accurate in screening for Barrett's esophagus, despite yielding a smaller biopsy specimen. This approach bears the potential to eliminate the infrastructure and cost required for intravenous sedation in this application. [ABSTRACT FROM AUTHOR]

Context Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. Objective To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Design and Setting Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. Patients Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. Intervention Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). Main Outcome Measures Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. Results Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). Conclusion Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients. [ABSTRACT FROM AUTHOR]

Objective: This paper describes the treatments and treatment outcome measures used by licensed naturopathic physicians in the United States who treat people with multiple sclerosis (MS). Design: A cross-sectional mail survey was used. Subjects: The participants were licensed naturopaths who were members of the American Association of Naturopathic Physicians. Outcome Measures: Outcome measures included practitioner demographics; patient demographics by practitioner report; recommended therapies; perceived effectiveness of treatments for MS; methods for measuring treatment effectiveness. Results: Forty three percent (43%) of the respondents (166/385) had treated at least one patient with MS while 56.9% (291/385) had never treated MS. 63.3% had treated 1-10 patients with MS, 19.9% had treated 11-20 patients with MS, and 16.8% had treated ≥20 patients with MS. Among the naturopaths, 68.1% communicated with an M.D. about their patient(s)' care and the majority of patients with MS were diagnosed by an M.D. (mean % = 96.3). The mean number of therapies recommended for M.S. was 3.91 (standard deviation [SD] = 2.01, range 1-10). The most frequently recommended therapies included, diet (52.4%), essential fatty acid supplementation (44.6%), vitamin/mineral supplementation (33.7%), homeopathy (30.7%), botanicals (22.3%), and antioxidants (18.1%). Respondents perceived their treatments as "very effective" for the following stages of MS: early stage (57.2%); middle stage (25.3%); and late stage (3.0%). Respondents perceived their treatments as "very effective" for the following disease-related outcomes: improved quality of life (59.0%); decrease relapse rates (48.2%); decreased symptom severity (45.8%); prevention of disease progression (41.6%). The methods used "most often" for measuring treatment effectiveness included, patient report (88.0%); physical examination (27.1%); medical records/laboratory testing (13.3%). The mean estimated percentage of patients not taking conventional disease-modifying medication was 51.2% (SD = 42.7%). Conclusions: Naturopaths use both a broad range and multiple complementary and alternative medicine CAM therapies for treating MS and report treatment effectiveness on the following outcomes: quality of life; symptom severity; relapse rates; and disease progression. Further research on single CAM therapies and holistic CAM systems is warranted in MS. [ABSTRACT FROM AUTHOR]

Background: Antioxidant vitamins are thought to play a role in atherosclerosis. Supplementation of these nutrients has been explored as a means of reducing cardiovascular morbidity and mortality. Purpose: To assess the evidence of the effectiveness of vitamin supplementation, specifically vitamins A, C, and E; β-carotene; folic acid; antioxidant combinations; and multivitamin supplements, in preventing cardiovascular disease. Data Sources: Cochrane Controlled Trials Registry and MED-LINE (1966 to September 2001), reference lists, and experts. Study Selection: The researchers selected English-language reports of randomized trials and cohort studies that assessed vitamin supplementation in western populations and reported incidence of or death from cardiovascular events. They also included reports of good- or fair-quality clinical trials of primary and secondary prevention and good- or fair-quality prospective cohort studies. Studies that examined only dietary nutrients or did not provide separate estimates for supplements were not included. Data Extraction: Two reviewers abstracted descriptive information and data on cardiovascular outcomes and mortality from included studies. The researchers assessed study quality using predetermined criteria. Data Synthesis: Evidence tables were constructed to summarize data from included studies. The researchers summarized the strength, level, and quality of the overall evidence for the effectiveness of each of the vitamin supplements in preventing or treating cardiovascular disease. Conclusions: Some good-quality cohort studies have reported an association between the use of vitamin supplements and lower risk for cardiovascular disease. Randomized, controlled trials of specific supplements, however, have failed to demonstrate a consistent or significant effect of any single vitamin or combination of vitamins on incidence of or death from cardiovascular disease. Understanding the sources of these differences will permit... [ABSTRACT FROM AUTHOR]