Academic Appointments

Administrative Appointments

  • Associate Director, Stanford Center for Population Health Sciences, Stanford University School of Medicine (2014 - Present)
  • Chief, Division of Epidemiology (2001 - 2010)
  • Adjunct Investigator, Kaiser Division of Research (1995 - Present)
  • Co-Director, Graduate Program in Epidemiology, Dept. of Health Research & Policy (1994 - 2003)

Boards, Advisory Committees, Professional Organizations

  • Committee Member, Research Programs Action Committee (RPAC), National Multiple Sclerosis Society (2011 - Present)
  • Councilor, Executive Committee of the Neuroepidemiology Section, American Academy of Neurology (2012 - Present)
  • Associate Editor, Neuroepidemiology (1999 - Present)
  • Associate Editor, American Journal of Epidemiology (2000 - 2010)

Professional Education

  • PhD, University of Washington, Epidemiology (1991)
  • MS, Univ. of Colorado Sch. of Medicine, Biostatistics (1981)

Current Research and Scholarly Interests

Dr. Nelson's traditional research program is focused on the epidemiology and complex etiology of neurodegenerative disorders, including Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. A recent additional focus of her work is on the development of mobile health tools to carry out prospective research studies on neurologic disorders such as migraine headache.

As the Faculty Associate Director of Research for the Stanford Center for Population Health Sciences, Dr. Nelson is leading strategic initiatives that involve a growing number of population health scientists at Stanford. Our goal is to develop innovative and transdisciplinary approaches to address the critical determinants of population health, including but not limited to strategies that can be addressed using electronic health care records from health information exchanges in defined geographic regions.

2018-19 Courses

Stanford Advisees

Graduate and Fellowship Programs

All Publications

  • A new way to estimate neurologic disease prevalence in the United States: Illustrated with MS. Neurology Nelson, L. M., Wallin, M. T., Marrie, R. A., Culpepper, W. J., Langer-Gould, A., Campbell, J., Buka, S., Tremlett, H., Cutter, G., Kaye, W., Wagner, L., Larocca, N. G., United States Multiple Sclerosis Prevalence Workgroup 2019


    OBJECTIVE: Considerable gaps exist in knowledge regarding the prevalence of neurologic diseases, such as multiple sclerosis (MS), in the United States. Therefore, the MS Prevalence Working Group sought to review and evaluate alternative methods for obtaining a scientifically valid estimate of national MS prevalence in the current health care era.METHODS: We carried out a strengths, weaknesses, opportunities, and threats (SWOT) analysis for 3 approaches to estimate MS prevalence: population-based MS registries, national probability health surveys, and analysis of administrative health claims databases. We reviewed MS prevalence studies conducted in the United States and critically examined possible methods for estimating national MS prevalence.RESULTS: We developed a new 4-step approach for estimating MS prevalence in the United States. First, identify administrative health claim databases covering publicly and privately insured populations in the United States. Second, develop and validate a highly accurate MS case-finding algorithm that can be standardly applied in all databases. Third, apply a case definition algorithm to estimate MS prevalence in each population. Fourth, combine MS prevalence estimates into a single estimate of US prevalence, weighted according to the number of insured persons in each health insurance segment.CONCLUSIONS: By addressing methodologic challenges and proposing a new approach for measuring the prevalence of MS in the United States, we hope that our work will benefit scientists who study neurologic and other chronic conditions for which national prevalence estimates do not exist.

    View details for PubMedID 30770422

  • Validation of an algorithm for identifying MS cases in administrative health claims datasets. Neurology Culpepper, W. J., Marrie, R. A., Langer-Gould, A., Wallin, M. T., Campbell, J. D., Nelson, L. M., Kaye, W. E., Wagner, L., Tremlett, H., Chen, L. H., Leung, S., Evans, C., Yao, S., LaRocca, N. G., United States Multiple Sclerosis Prevalence Workgroup (MSPWG) 2019


    OBJECTIVE: To develop a valid algorithm for identifying multiple sclerosis (MS) cases in administrative health claims (AHC) datasets.METHODS: We used 4 AHC datasets from the Veterans Administration (VA), Kaiser Permanente Southern California (KPSC), Manitoba (Canada), and Saskatchewan (Canada). In the VA, KPSC, and Manitoba, we tested the performance of candidate algorithms based on inpatient, outpatient, and disease-modifying therapy (DMT) claims compared to medical records review using sensitivity, specificity, positive and negative predictive values, and interrater reliability (Youden J statistic) both overall and stratified by sex and age. In Saskatchewan, we tested the algorithms in a cohort randomly selected from the general population.RESULTS: The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT claims within a 1-year time period; a 2-year time period provided little gain in performance. Algorithms including DMT claims performed better than those that did not. Sensitivity (86.6%-96.0%), specificity (66.7%-99.0%), positive predictive value (95.4%-99.0%), and interrater reliability (Youden J = 0.60-0.92) were generally stable across datasets and across strata. Some variation in performance in the stratified analyses was observed but largely reflected changes in the composition of the strata. In Saskatchewan, the preferred algorithm had a sensitivity of 96%, specificity of 99%, positive predictive value of 99%, and negative predictive value of 96%.CONCLUSIONS: The performance of each algorithm was remarkably consistent across datasets. The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT use within 1 year. We recommend this algorithm as the standard AHC case definition for MS.

    View details for PubMedID 30770432

  • The prevalence of MS in the United States: A population-based estimate using health claims data. Neurology Wallin, M. T., Culpepper, W. J., Campbell, J. D., Nelson, L. M., Langer-Gould, A., Marrie, R. A., Cutter, G. R., Kaye, W. E., Wagner, L., Tremlett, H., Buka, S. L., Dilokthornsakul, P., Topol, B., Chen, L. H., LaRocca, N. G., US Multiple Sclerosis Prevalence Workgroup 2019


    OBJECTIVE: To generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets.METHODS: A validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017.RESULTS: The estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1-310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1-451.6) for women and 159.7 (95% CI 158.7-160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017.CONCLUSION: The estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions.

    View details for PubMedID 30770430

  • Evaluation of a Mobile Device Survey System for Behavioral Risk Factors (SHAPE): App Development and Usability Study. JMIR formative research Oakley-Girvan, I., Lavista, J. M., Miller, Y., Davis, S., Acle, C., Hancock, J., Nelson, L. M. 2019; 3 (1): e10246


    BACKGROUND: Risk factors, including limited exercise, poor sleep, smoking, and alcohol and drug use, if mitigated early, can improve long-term health. Risk prevalence has traditionally been measured using methods that now have diminished participation rates. With >75% of American citizens owning smartphones, new data collection methods using mobile apps can be evaluated.OBJECTIVE: The objective of our study was to describe the development, implementation, and evaluation of a mobile device-based survey system for behavioral risk assessment. Specifically, we evaluated its feasibility, usability, acceptability, and validity.METHODS: We enrolled 536 students from 3 Vermont State Colleges. Iterative mobile app development incorporated focus groups, extensive testing, and the following 4 app versions: iOS standard, iOS gamified, Android standard, and Android gamified. We aimed to capture survey data, paradata, and ambient data such as geolocation. Using 3 separate surveys, we asked a total of 27 questions that included demographic characteristics, behavioral health, and questions regarding the app's usability and survey process.RESULTS: Planned enrollment was exceeded in just a few days. There were 1392 "hits" to the landing page where the app could be downloaded. Excluding known project testers and others not part of the study population, 670 participants downloadeded the SHAPE app. Of those, 94.9% of participants (636/670) agreed to participate by providing in-app consent. Of the 636 who provided consent, 84.3% (536/636) were deemed eligible for the study. The majority of eligible respondents completed the initial survey (459/536, 85.6%), whereas 29.9% (160/536) completed the second survey and 28.5% (153/536) completed the third survey. The SHAPE survey obtained 414 participants on the behavioral risk items in survey 1, which is nearly double the 209 participants who completed the traditional Vermont College Health Survey in 2014. SHAPE survey responses were consistent with the traditionally collected Vermont College Health Survey data.CONCLUSIONS: This study provides data highlighting the potential for mobile apps to improve population-based health, including an assessment of recruitment methods, burden and response rapidity, and future adaptations. Although gamification and monetary rewards were relatively unimportant to this study population, item response theory may be technologically feasible to reduce individual survey burden. Additional data collected by smartphones, such as geolocation, could be important in additional analysis, such as neighborhood characteristics and their impact on behavioral risk factors. Mobile tools that offer rapid adaptation for specific populations may improve research data collection for primary prevention and could be used to improve engagement and health outcomes.

    View details for PubMedID 30684441

  • A High-Density Genome-Wide Association Screen of Sporadic ALS in US Veterans PLOS ONE Kwee, L. C., Liu, Y., Haynes, C., Gibson, J. R., Stone, A., Schichman, S. A., Kamel, F., Nelson, L. M., Topol, B., Van Den Eeden, S. K., Tanner, C. M., Cudkowicz, M. E., Grasso, D. L., Lawson, R., Muralidhar, S., Oddone, E. Z., Schmidt, S., Hauser, M. A. 2012; 7 (3)


    Following reports of an increased incidence of amyotrophic lateral sclerosis (ALS) in U.S. veterans, we have conducted a high-density genome-wide association study (GWAS) of ALS outcome and survival time in a sample of U.S. veterans. We tested ∼1.3 million single nucleotide polymorphisms (SNPs) for association with ALS outcome in 442 incident Caucasian veteran cases diagnosed with definite or probable ALS and 348 Caucasian veteran controls. To increase power, we also included genotypes from 5909 publicly-available non-veteran controls in the analysis. In the survival analysis, we tested for association between SNPs and post-diagnosis survival time in 639 Caucasian veteran cases with definite or probable ALS. After this discovery phase, we performed follow-up genotyping of 299 SNPs in an independent replication sample of Caucasian veterans and non-veterans (ALS outcome: 183 cases and 961 controls; survival: 118 cases). Although no SNPs reached genome-wide significance in the discovery phase for either phenotype, three SNPs were statistically significant in the replication analysis of ALS outcome: rs6080539 (177 kb from PCSK2), rs7000234 (4 kb from ZNF704), and rs3113494 (13 kb from LOC100506746). Two SNPs located in genes that were implicated by previous GWA studies of ALS were marginally significant in the pooled analysis of discovery and replication samples: rs17174381 in DPP6 (p = 4.4×10(-4)) and rs6985069 near ELP3 (p = 4.8×10(-4)). Our results underscore the difficulty of identifying and convincingly replicating genetic associations with a rare and genetically heterogeneous disorder such as ALS, and suggest that common SNPs are unlikely to account for a substantial proportion of patients affected by this devastating disorder.

    View details for DOI 10.1371/journal.pone.0032768

    View details for Web of Science ID 000304489000008

    View details for PubMedID 22470424

  • Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium JOURNAL OF THE NEUROLOGICAL SCIENCES McGuire, V., Van Den Eeden, S. K., Tanner, C. M., Kamel, F., Umbach, D. M., Marder, K., Mayeux, R., Ritz, B., Ross, G. W., Petrovitch, H., Topol, B., Popat, R. A., Costello, S., Manthripragada, A. D., Southwick, A., Myers, R. M., Nelson, L. M. 2011; 307 (1-2): 22-29


    To examine genetic associations of polymorphisms in the dopamine receptor D2 (DRD2) and D3 (DRD3) genes with risk of Parkinson's disease (PD).The study included 1325 newly diagnosed patients with PD and 1735 controls from a consortium of five North American case-control studies. We collected risk factor information by in-person or telephone interview. Six DRD2 and two DRD3 polymorphisms were genotyped using a common laboratory. Odds ratios were estimated using logistic regression.Among non-Hispanic whites, homozygous carriers of Taq1A DRD2 (rs1800497) polymorphism had an increased risk of PD compared to homozygous wildtype carriers (OR=1.5, 95% CI 1.0-2.3). In contrast, the direction of association for Taq1A polymorphism was opposite for African-Americans, showing an inverse association with PD risk (OR=0.10, 95% CI 0.2-0.7). Among white Hispanics who carried two alleles, the Ser9Gly DRD3 (rs6280) polymorphism was associated with a decreased risk of PD (OR=0.4, 95% CI 0.2-0.8). The inverse association of smoking with PD risk was not modified by any of the DRD2 or DRD3 polymorphisms.DRD2 polymorphisms are unlikely to be true disease-causing variants; however, three DRD2 polymorphisms (including Taq1A) may be in linkage disequilibrium with possible disease associated variants in the DRD2-ANKK1-NCAM1-TTC12 gene cluster.

    View details for DOI 10.1016/j.jns.2011.05.031

    View details for PubMedID 21663922

  • Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease EUROPEAN JOURNAL OF NEUROLOGY Popat, R. A., Van Den Eeden, S. K., Tanner, C. M., Kamel, F., Umbach, D. M., Marder, K., Mayeux, R., Ritz, B., Ross, G. W., Petrovitch, H., Topol, B., McGuire, V., Costello, S., Manthripragada, A. D., Southwick, A., Myers, R. M., Nelson, L. M. 2011; 18 (5): 756-765


    In 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine animal models of Parkinson's disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A (ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association.Parkinson's Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression.Two ADORA2A polymorphisms were inversely associated with PD risk - rs71651683, a 5' variant (adjusted allelic OR = 0.51, 95% CI 0.33-0.80, permutation-adjusted P = 0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wild-type genotype were 0.76 (95% CI 0.57-1.02) and 0.37 (95% CI 0.13-1.01), respectively (permutation-adjusted P for trend = 0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 0.04).In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms.

    View details for DOI 10.1111/j.1468-1331.2011.03353.x

    View details for PubMedID 21281405

  • Vitamin D, Pregnancy, Breastfeeding, and Postpartum Multiple Sclerosis Relapses ARCHIVES OF NEUROLOGY Langer-Gould, A., Huang, S., Van Den Eeden, S. K., Gupta, R., Leimpeter, A. D., Albers, K. B., Horst, R., Hollis, B., Steinman, L., Nelson, L. M. 2011; 68 (3): 310-313


    To determine whether low levels of 25-hydroxyvitamin D (25[OH]D) contribute to the increased risk of postpartum multiple sclerosis (MS) relapses.Prospective cohort study.Outpatients identified through membership records of Kaiser Permanente Northern California or Stanford University outpatient neurology clinics.Twenty-eight pregnant women with MS.We prospectively followed up patients through the postpartum year and assessed exposures and symptoms through structured interviews. Total serum 25(OH)D levels were measured using the DiaSorin Liaison Assay during the third trimester and 2, 4, and 6 months after giving birth. The data were analyzed using longitudinal multivariable methods.Levels of 25(OH)D and relapse rate.Fourteen (50%) women breastfed exclusively, and 12 women (43%) relapsed within 6 months after giving birth. During pregnancy, the average 25(OH)D levels were 25.4 ng/mL (range, 13.7-42.6) and were affected only by season (P=.009). In contrast, in the postpartum period, 25(OH)D levels were significantly affected by breastfeeding and relapse status. Levels of 25(OH)D remained low in the exclusive breastfeeding group, yet rose significantly in the nonexclusive breastfeeding group regardless of season (P=.007, unadjusted; P=.02, adjusted for season). By 4 and 6 months after childbirth, 25(OH)D levels were, on average, 5 ng/mL lower in the women who breastfed exclusively compared with the nonbreastfeeding group (P=.001).Pregnancy and exclusive breastfeeding are strongly associated with low 25(OH)D levels in women with MS. However, these lower vitamin D levels were not associated with an increased risk of postpartum MS relapses. These data suggest that low vitamin D in isolation is not an important risk factor for postpartum MS relapses.

    View details for DOI 10.1001/archneurol.2010.291

    View details for Web of Science ID 000288409400006

    View details for PubMedID 21059988

  • Familial Aggregation of Parkinson's Disease in a Multiethnic Community-Based Case-Control Study MOVEMENT DISORDERS Shino, M. Y., McGuire, V., Van Den Eeden, S. K., Tanner, C. M., Popat, R., Leimpeter, A., Bernstein, A. L., Nelson, L. M. 2010; 25 (15): 2587-2594


    To assess the familial aggregation of Parkinson's disease (PD), we compared the cumulative incidence of PD among first-degree relatives of PD cases and controls. We identified newly diagnosed patients with PD (n = 573) during 1994 to 1995 within Kaiser Permanente Medical Care Program of Northern California and recruited 496 cases (87%) for the case-control study. Of 720 eligible controls matched by birth year and sex to cases, 541 (75%) agreed to participate. Information on family history of PD and other neurodegenerative diseases was obtained by in-person structured interview. We used the reconstructed cohort approach that provides a better estimate of the risk. The cumulative incidence of PD was significantly higher among relatives of PD patients compared with relatives of controls (2.0 vs. 0.7%; relative risk (RR) = 3.4, 95% confidence interval (CI) 1.9-5.9; P = 0.0001). The degree of familial aggregation was higher among first-degree relatives of Hispanic PD cases compared with Hispanic controls (3.7% vs. 0.4%; RR = 8.5, 95% CI 1.0-68.9) than it was among non-Hispanic Caucasian cases and controls (2.0% vs. 0.8%; RR = 2.7, 95% CI 1.5-5.1; P = 0.02). The familial aggregation of PD was stronger among the siblings of PD cases (RR = 5.4, 95% CI 1.8-16.0) than among parents (RR = 2.7, 95% CI 1.3-5.2). The incidence and familial aggregation of PD is highest among Hispanics, warranting further studies of genetic and environmental risk factors in the Hispanic population.

    View details for DOI 10.1002/mds.23361

    View details for Web of Science ID 000284060600016

    View details for PubMedID 20842689

    View details for PubMedCentralID PMC2978761

  • Comorbid Cancer in Parkinson's Disease MOVEMENT DISORDERS Lo, R. Y., Tanner, C. M., Van Den Eeden, S. K., Albers, K. B., Leimpeter, A. D., Nelson, L. M. 2010; 25 (12): 1809-1817


    The aim of this article was to evaluate cancer occurrence before and after diagnosis of Parkinson's disease (PD). We investigated 692 patients newly diagnosed with PD and 761 age- and sex-matched control subjects identified during two periods (1994-1995 and 2000-2003) within Kaiser Permanente Medical Care Program of Northern California. Primary cancers were searched and dated, and all participants were followed up until the end of membership, death, or December 31, 2008. We used unconditional logistic regression to evaluate the PD-cancer association before the date of PD diagnosis or the index date and Cox proportional hazards regression to evaluate the PD-cancer association after the index date. Nearly 20% (140 of 692) of the PD patients and 25% (188 of 761) of the non-PD controls had ever had a cancer diagnosis. Before the index date, the prevalence of cancer was not significantly lower in patients with PD (8.1% PD vs. 9.2% controls; OR = 0.83; 95% CI 0.54-1.3). After the index date, the risk of developing a cancer did not differ between PD cases and controls (relative risk [RR] = 0.94; 95% CI 0.70-1.3). Among specific cancers, melanoma was more common among PD cases (before PD, OR = 1.5; 95% CI 0.40-5.2; after PD, RR = 1.6; 95% CI 0.71-3.6), but independent of dopaminergic therapy. Cancer occurrence is not significantly lower among patients with PD. The positive association between PD and subsequent melanoma merits further investigation, as it does not seem to be attributable to dopaminergic therapy, pigmentation, or confounding by smoking.

    View details for DOI 10.1002/mds.23246

    View details for Web of Science ID 000282283100006

    View details for PubMedID 20669266

  • Autoimmune diseases prior to the diagnosis of multiple sclerosis: a population-based case-control study MULTIPLE SCLEROSIS JOURNAL Langer-Gould, A., Albers, K. B., Van Den Eeden, S. K., Nelson, L. M. 2010; 16 (7): 855-861


    The objective of this study was to determine whether patients with multiple sclerosis (MS) are more likely to have other autoimmune disorders particularly prior to the diagnosis of MS. We conducted a population-based case-control study of patients enrolled in the Northern California Kaiser Permanente Medical Care Program. Electronic clinical records through 2005 were used to ascertain incident and prevalent MS cases and identify the presence and timing of 44 other diagnoses. Controls were matched 5:1 for gender, age, and Kaiser membership characteristics. We identified 5296 MS cases (including 924 diagnosed between 2001 and 2004) and 26,478 matched controls. Prior to MS diagnosis, cases were more likely than controls to have uveitis (OR = 3.2, 95%; CI 1.7-5.7), inflammatory bowel disease (IBD, OR = 1.7; 95%CI 1.2-2.5), and Bell's palsy (OR = 3.2; 95%CI 1.2-8.3). Cases were also more likely to develop Guillain- Barré syndrome (GBS, OR = 5.0; 95%CI 1.6-15.4) and bullous pemphigoid (OR = 6.7; 95%CI 1.5-29.9). Cases were not more likely than controls to have or to develop rheumatoid arthritis, lupus or thyroiditis. MS may share environmental triggers, genetic susceptibilities and/or alterations in immune homeostasis with IBD and uveitis, but not with other autoimmune disorders.

    View details for DOI 10.1177/1352458510369146

    View details for Web of Science ID 000279725800012

    View details for PubMedID 20463037

  • Reliability and validity of two self-administered questionnaires for screening restless legs syndrome in population-based studies SLEEP MEDICINE Popat, R. A., Van Den Eeden, S. K., Tanner, C. M., Kushida, C. A., Rama, A. N., Black, J. E., Bernstein, A., Kasten, M., Chade, A., Leimpeter, A., Cassidy, J., McGuire, V., Nelson, L. M. 2010; 11 (2): 154-160


    A reliable and valid questionnaire for screening restless legs syndrome (RLS) is essential for determining accurate estimates of disease frequency. In a 2002 NIH-sponsored workshop, experts suggested three mandatory questions for identifying RLS in epidemiologic studies. We evaluated the reliability and validity of this RLS-NIH questionnaire in a community-based sample and concurrently developed and evaluated the utility of an expanded screening questionnaire, the RLS-EXP.The study was conducted at Kaiser Permanente of Northern California and the Stanford University Sleep Clinic. We evaluated test-retest reliability in a random sample of subjects with prior physician-assigned RLS (n=87), subjects with conditions frequently misclassified as RLS (n=31), and healthy subjects (n=9). Validity of both instruments was evaluated in a random sample of 32 subjects, and in-person examination by two RLS specialists was used as the gold standard.For the first three RLS-NIH questions, the kappa statistic for test-retest reliability ranged from 0.5 to 1.0, and sensitivity and specificity was 86% and 45%, respectively. For the subset of five questions on RLS-EXP that encompassed cardinal features for diagnosing RLS, kappas were 0.4-0.8, and sensitivity and specificity were 81% and 73%, respectively.Sensitivity of RLS-NIH is good; however, the specificity of the instrument is poor when examined in a sample that over-represents subjects with conditions that are commonly misclassified as RLS. Specificity can be improved by including separate questions on cardinal features, as used in the RLS-EXP, and by including a few questions that identify RLS mimics, thereby reducing false positives.

    View details for DOI 10.1016/j.sleep.2009.01.012

    View details for Web of Science ID 000275584500009

    View details for PubMedID 20089446

  • Interferon-gamma-Producing T Cells, Pregnancy, and Postpartum Relapses of Multiple Sclerosis ARCHIVES OF NEUROLOGY Langer-Gould, A., Gupta, R., Huang, S., Hagan, A., Atkuri, K., Leimpeter, A. D., Albers, K. B., Greenwood, E., Van Den Eeden, S. K., Steinman, L., Nelson, L. M. 2010; 67 (1): 51-57


    To determine whether fluctuations in functional T-cell subsets can explain why multiple sclerosis (MS) relapses decline during pregnancy and increase in the postpartum period.Case-control study.Kaiser Permanente Northern California and Stanford University.Twenty-six pregnant women with MS and 24 age-matched, pregnant controls. Intervention We prospectively followed up the pregnant women with MS and the age-matched, pregnant controls; conducted structured interviews; and collected peripheral blood mononuclear cells during each trimester and 2, 4, 6, 9, and 12 months post partum.Sixteen functional cell types, including interferon-gamma (IFN-gamma)- and tumor necrosis factor-producing T-cell subsets, were measured using multicolor flow cytometry. Since these cell types may also fluctuate with pregnancy, lactational amenorrhea, or MS treatment, the data were analyzed taking into account these factors.Fifteen women with MS (58%) had relapses during the postpartum year. CD4(+)IFN-gamma-producing cells fluctuated with MS relapses, declining during pregnancy in women with MS (P < .001) and continuing to decline after parturition in women with relapses (P = .001), yet rising or remaining stable in women with nonrelapsing MS or healthy pregnant women. Lactational amenorrhea was associated with a rise in CD4(+)IFN-gamma-producing cells in women with MS (P = .009). In contrast, CD4(+) tumor necrosis factor-producing cells decreased during lactational amenorrhea in all groups of women and, once this was taken into account, obscured any relationship to MS relapses. CD8(+)IFN-gamma-producing cells were elevated in women with MS throughout the study (P < .001) but did not fluctuate with relapses.Our findings suggest that a decline in circulating CD4(+)IFN-gamma-producing cells leads to postpartum MS relapses. Our findings also suggest that the decline in these cells may begin during late pregnancy and that lactational amenorrhea induced by exclusive breastfeeding may be able to interrupt this process.

    View details for Web of Science ID 000273535700007

    View details for PubMedID 20065129

  • Obstetric outcomes in women with multiple sclerosis and epilepsy NEUROLOGY Kelly, V. M., Nelson, L. M., Chakravarty, E. F. 2009; 73 (22): 1831-1836


    To estimate the national occurrence of pregnancies in women with multiple sclerosis (MS) and epilepsy and to compare these pregnancy outcomes cross-sectionally with those in women with pregestational diabetes mellitus (DM) and the general obstetric population.We studied the 2003-2006 Nationwide Inpatient Sample, of the Healthcare Cost and Utilization Project, to estimate the number of deliveries in women with MS, epilepsy, DM, and the general obstetric population. Pregnancy outcomes included length of hospital stay, hypertensive disorders including preeclampsia (HTN), premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), and cesarean delivery. Multivariable regression analyses used maternal age and race/ethnicity as covariates.Of an estimated 18.8 million deliveries, 10,055 occurred in women with MS, 4,730 with epilepsy, and 187,239 with DM. MS was associated with mildly increased odds of antenatal hospitalization (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.2-1.5), IUGR (OR 1.7, 95% CI 1.2-2.4), and cesarean delivery (OR 1.3, 95% CI 1.1-1.4). Similarly, epilepsy was associated with increased rates of antenatal hospitalization (OR 3.0, 95% CI 2.6-3.5), IUGR (OR 1.9, 95% CI 1.2-3.3), and cesarean delivery (OR 1.5, 95% CI 1.3-1.9). HTN and PROM were not increased in either group. DM was associated with an increased risk of all adverse outcomes. Length of stay was modestly increased in all groups compared with controls.In this large national database study of pregnancy outcomes in women with multiple sclerosis and epilepsy, rates of intrauterine growth restriction and cesarean delivery were only marginally higher than the general obstetric population without increases in other adverse outcomes.

    View details for DOI 10.1212/WNL.0b013e3181c3f27d

    View details for PubMedID 19923552

  • Clinical Features in Early Parkinson Disease and Survival ARCHIVES OF NEUROLOGY Lo, R. Y., Tanner, C. M., Albers, K. B., Leimpeter, A. D., Fross, R. D., Bernstein, A. L., McGuire, V., Quesenberry, C. P., Nelson, L. M., Van Den Eeden, S. K. 2009; 66 (11): 1353-1358


    To examine the association between demographic and clinical features in early Parkinson disease (PD) and length of survival in a multiethnic population.Clinical features within 2 years of diagnosis were determined for an inception cohort established during 1994-1995. Vital status was determined through December 31, 2005. Predictor variables included age at diagnosis, sex, race/ethnicity, as well as clinical subtype (modified tremor dominant, postural instability gait difficulty), symmetry, cognitive impairment, depression, dysphagia, and hallucinations. Cox proportional hazards regression analysis was used to identify factors associated with shorter survival.Kaiser Permanente Medical Care Program, northern California.Five hundred seventy-three men and women with newly diagnosed PD.Three hundred fifty-two participants in the PD cohort (61.4%) had died in the follow-up period. Older age at diagnosis (hazard ratio [HR], 1.1; 95% confidence interval [CI], 1.09-1.12), modified postural instability gait difficulty subtype (HR, 1.8; 95% CI, 1.3-2.7), symmetry of motor signs (HR, 2.0; 95% CI, 1.1-3.7), mild (HR, 1.7; 95% CI, 1.3-2.2) and severe (HR, 2.7; 95% CI, 1.9-3.9) cognitive impairment, dysphagia (HR, 1.4; 95% CI, 1.1-1.9), and hallucinations (HR, 2.1; 95% CI, 1.3-3.2) were associated with increased all-cause mortality, after adjusting for age, sex, and race/ethnicity. None of the other factors altered mortality risk. In an empirical predictive analysis, most previous significant predictors remained associated with shorter survival.Both motor and nonmotor features in early PD predict increased mortality risk, particularly postural instability gait difficulty, cognitive impairment, and hallucinations. These predictors may be useful in clinical practice and when designing clinical trials.

    View details for Web of Science ID 000271584400007

    View details for PubMedID 19901166

  • Exclusive Breastfeeding and the Risk of Postpartum Relapses in Women With Multiple Sclerosis ARCHIVES OF NEUROLOGY Langer-Gould, A., Huang, S. M., Gupta, R., Leimpeter, A. D., Greenwood, E., Albers, K. B., Van Den Eeden, S. K., Nelson, L. M. 2009; 66 (8): 958-963


    To determine if exclusive breastfeeding protects against postpartum relapses of multiple sclerosis (MS) and, if so, whether this protection is related to prolonged lactational amenorrhea.We conducted structured interviews to assess clinical, menstrual, and breastfeeding history during each trimester and 2, 4, 6, 9, and 12 months postpartum and collected neurological examination findings from the treating physicians of women with MS. Hazards ratios (HRs) were adjusted for measures of disease severity and age.Kaiser Permanente Northern California and Stanford University.We prospectively enrolled 32 pregnant women with MS and 29 age-matched, pregnant controls. Main Outcome Measure Postpartum relapse.Of the 52% of women with MS who did not breastfeed or began regular supplemental feedings within 2 months postpartum, 87% had a postpartum relapse, compared with 36% of the women with MS who breastfed exclusively for at least 2 months postpartum (unadjusted HR, 5.0; 95% confidence interval, 1.7-14.2; P = .003; adjusted HR, 7.1; 95% confidence interval, 2.1-24.3; P = .002). Sixty percent reported that the primary reason for foregoing exclusive breastfeeding was to resume MS therapies. Women who breastfed exclusively had a later return of menses (P = .001) than women who did not, and lactational amenorrhea was associated with a reduced risk of postpartum relapses (P = .01).Our findings suggest that exclusive breastfeeding and concomitant suppression of menses significantly reduce the risk of postpartum relapses in MS. Our findings call into question the benefit of foregoing breastfeeding to start MS therapies and should be confirmed in a larger study.

    View details for Web of Science ID 000268848100005

    View details for PubMedID 19506118

  • Genes and environmental exposures in veterans with amyotrophic lateral sclerosis: The GENEVA study NEUROEPIDEMIOLOGY Schmidt, S., Allen, K. D., Loiacono, V. T., Norman, B., Stanwyck, C. L., Nord, K. M., Williams, C. D., Kasarskis, E. J., Kamel, F., McGuire, V., Nelson, L. M., Oddone, E. Z. 2008; 30 (3): 191-204


    Recent reports of a potentially increased risk of amyotrophic lateral sclerosis (ALS) for veterans deployed to the 1990-1991 Persian Gulf War prompted the Department of Veterans Affairs to establish a National Registry of Veterans with ALS, charged with the goal of enrolling all US veterans with a neurologist-confirmed diagnosis of ALS. The Genes and Environmental Exposures in Veterans with ALS study (GENEVA) is a case-control study presently enrolling cases from the Department of Veterans Affairs registry and a representative sample of veteran controls to evaluate the joint contributions of genetic susceptibility and environmental exposures to the risk of sporadic ALS. The GENEVA study design, recruitment strategies, methods of collecting DNA samples and environmental risk factor information are described here, along with a summary of demographic characteristics of the participants (537 cases, 292 controls) enrolled to date.

    View details for DOI 10.1159/000126911

    View details for Web of Science ID 000255087100010

    View details for PubMedID 18421219

    View details for PubMedCentralID PMC2645711

  • Minimum incidence of primary cervical dystonia in a multiethnic health care population NEUROLOGY Marras, C., Van Den Eeden, S. K., Fross, R. D., Benedict-Albers, K. S., Klingman, J., Leimpeter, A. D., Nelson, L. M., Risch, N., Karter, A. J., Bernstein, A. L., Tanner, C. M. 2007; 69 (7): 676-680


    The two existing estimates of the incidence of primary cervical dystonia were based on observations in relatively ethnically homogeneous populations of European descent.To estimate the minimum incidence of primary cervical dystonia in the multiethnic membership of a health maintenance organization in Northern California.Using a combination of electronic medical records followed by medical chart reviews, we identified incident cases of cervical dystonia first diagnosed between 1997 and 1999.We identified 66 incident cases of cervical dystonia from 8.2 million person-years of observation. The minimum estimate of the incidence of cervical dystonia in this population is 0.80 per 100,000 person-years. Ethnicity-specific incidence rates were calculated for individuals over age 30. Incidence was higher in white individuals (1.23 per 100,000 person-years) than in persons of other races (0.15 per 100,000 person-years, p < 0.0001). The minimum estimated incidence was 2.5 times higher in women than in men (1.14 vs 0.45 per 100,000 person-years, p = 0.0005). The average age at diagnosis was higher in women (56 years) than in men (45 years, p = 0.0004). There was no significant difference in reported symptom duration prior to diagnosis between women and men (3.9 vs 5.3 years).The estimated incidence of diagnosed cervical dystonia among white individuals in this Northern Californian population is similar to previous estimates in more ethnically homogeneous populations of largely European descent. The incidence in other races, including Hispanic, Asian, and black appears to be significantly lower. The incidence is also higher in women than in men.

    View details for Web of Science ID 000248723600009

    View details for PubMedID 17698789

  • Pooled analysis of tobacco use and risk of Parkinson disease ARCHIVES OF NEUROLOGY Ritz, B., Ascherio, A., Checkoway, H., Marder, K. S., Nelson, L. M., Rocca, W. A., Ross, G. W., Strickland, D., Van Den Eeden, S. K., Gorell, J. 2007; 64 (7): 990-997


    Epidemiologic studies have reported that cigarette smoking is inversely associated with Parkinson disease (PD). However, questions remain regarding the effect of age at smoking onset, time since quitting, and race/ethnicity that have not been addressed due to sample size constraints. This comprehensive assessment of the apparent reduced risk of PD associated with smoking may provide important leads for treatment and prevention.To determine whether race/ethnicity, sex, education, age at diagnosis, and type of tobacco modify the observed effects of smoking on PD.We conducted the first ever pooled analysis of PD combining individual-level data from 8 US case-control and 3 cohort studies (Nurses' Health Study, Health Professionals Follow-Up Study, and Honolulu-Asia Aging Study) conducted between 1960 and 2004. Case-control studies provided data for 2328 PD cases and 4113 controls matched by age, sex, and ethnicity; cohort studies contributed 488 cases and 4880 controls selected from age- and sex-matched risk sets.Incident PD.We confirmed inverse associations between PD and smoking and found these to be generally stronger in current compared with former smokers; the associations were stronger in cohort than in case-control studies. We observed inverse trends with pack-years smoked at every age at onset except the very elderly (>75 years of age), and the reduction of risk lessened with years since quitting smoking. The risk reductions we observed for white and Asian patients were not seen in Hispanic and African American patients. We also found an inverse association both for smoking cigars and/or pipes and for chewing tobacco in male subjects.Our data support a dose-dependent reduction of PD risk associated with cigarette smoking and potentially with other types of tobacco use. Importantly, effects seemed not to be influenced by sex or education. Differences observed by race and age at diagnosis warrant further study.

    View details for Web of Science ID 000247892100010

    View details for PubMedID 17620489

  • Effect of non-steroidal anti-inflammatory medications on the risk of amyotrophic lateral sclerosis AMYOTROPHIC LATERAL SCLEROSIS Popat, R. A., Tanner, C. M., Van Den Eeden, S. K., Bernstein, A. L., Bloch, D. A., Leimpeter, A., McGuire, V., Nelson, L. M. 2007; 8 (3): 157-163


    Inflammatory processes may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). We examined the association of non-steroidal anti-inflammatory drugs (NSAIDs) with the risk of ALS in case-control study of incident cases (n = 111) conducted within the Kaiser Permanente Medical Care Program of Northern California during the years 1996-2000. Controls (n = 258) randomly selected from the same population were frequency matched by age and gender to the ALS cases. Information regarding use of NSAIDs (non-aspirin and aspirin) and three classes of 'control' medications was collected by in-person structured interview. Subjects who used medication at least twice a week for at least a month were classified as 'ever users'. Multivariable logistic regression models were adjusted for age, gender, history of osteoarthritis/rheumatoid arthritis and pain, and other medication use. Overall, there was no association between NSAID use and ALS; however, some sex differences were noted for non-aspirin NSAID use. Among men, non-aspirin NSAID use was associated with a two-fold increased risk of ALS (adjusted odds ratio (OR) 2.0, 95% confidence interval (CI) 1.0-3.9), whereas among women, non-aspirin NSAID use was not associated with increased ALS risk (adjusted OR 0.5, 95% CI 0.2-1.2). ALS risk was not associated with aspirin use or with 'control' medications. This study did not find any evidence to suggest that NSAID use reduces the risk of ALS. The observed sex differences with non-aspirin NSAID use could be due to chance or an unmeasured confounder.

    View details for DOI 10.1080/17482960601179456

    View details for Web of Science ID 000246949600004

    View details for PubMedID 17538777

  • Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis - A systematic review ARCHIVES OF NEUROLOGY Langer-Gould, A., Popat, R. A., Huang, S. M., Cobb, K., Fontoura, P., Gould, M. K., Nelson, L. M. 2006; 63 (12): 1686-1691


    To identify clinical and demographic factors associated with long-term disability in patients with relapsing-remitting multiple sclerosis.We searched the MEDLINE (1966-May 2005), EMBASE, CINAHL, Cochrane, and PsycINFO computerized databases, and reviewed reference lists of retrieved articles.We included studies that examined predictors of long-term disability in patients with relapsing-remitting multiple sclerosis. We excluded studies that did not distinguish relapsing-remitting multiple sclerosis from primary progressive multiple sclerosis, enrolled fewer than 40 subjects, observed subjects for less than 5 years, or collected follow-up information in less than 80% of the inception cohort.Two reviewers assessed study quality in 4 domains: cohort assembly, definitions and assessments of prognostic factors and outcomes, and statistical methods. One reviewer extracted data on the direction, magnitude, precision, and statistical significance of the effect of each predictor on prognosis.Heterogeneity of study designs precluded us from pooling the results of 27 eligible studies. Study quality was limited by cross-sectional design, enrollment of prevalent cases from referral centers, and lack of multivariate adjustment. Sphincter symptoms at onset (hazard ratio, 1.1-3.1), incomplete recovery from the first attack (hazard ratio, 1.3-3.3), and a short interval between the first and second attack (hazard ratio, 1.6-1.9) were most strongly and consistently associated with poor prognosis. Other factors widely believed to be of prognostic importance, including sex and age at onset, demonstrated inconsistent or weak effects on prognosis.The most robust predictors of long-term physical disability in relapsing-remitting multiple sclerosis are sphincter symptoms at onset and early disease course outcomes. These factors can be used to guide treatment decisions for drugs with significant toxicities.

    View details for Web of Science ID 000242733000003

    View details for PubMedID 17172607

  • Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study LANCET NEUROLOGY Elbaz, A., Nelson, L. M., Payami, H., Ioannidis, J. P., Fiske, B. K., Annesi, G., Belin, A. C., Factor, S. A., Ferrarese, C., Hadjigeorgiou, G. M., Higgins, D. S., Kawakami, H., Krueger, R., Marder, K. S., Mayeux, R. P., Mellick, G. D., Nutt, J. G., Ritz, B., Samii, A., Tanner, C. M., Van Broeckhoven, C., Van Den Eeden, S. K., Wirdefeldt, K., Zabetian, C. P., Dehem, M., Montimurro, J. S., Southwick, A., Myers, R. M., Trikalinos, T. A. 2006; 5 (11): 917-923


    A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson's disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain.Investigators from three Michael J Fox Foundation for Parkinson's Research-funded genetics consortia-comprising 14 teams-contributed DNA samples from 5526 patients with Parkinson's disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies.In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0.89 to 1.09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0.95 to 1.08); there was little heterogeneity except for SNP rs7520966.Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson's disease.

    View details for DOI 10.1016/S1474-4422(06)70579-8

    View details for Web of Science ID 000241591600014

    View details for PubMedID 17052658

    View details for PubMedCentralID PMC3636768

  • Obstetric hospitalizations in the United States for women with systemic lupus erythematosus and rheumatoid arthritis ARTHRITIS AND RHEUMATISM Chakravarty, E. F., Nelson, L., Krishnan, E. 2006; 54 (3): 899-907


    To estimate the national occurrence of pregnancies in women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and to compare pregnancy outcomes in these patients with those in women with pregestational diabetes mellitus (DM) and with the general obstetric population.We studied the 2002 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project to estimate the number of obstetric hospitalizations, deliveries, and cesarean deliveries in women with SLE, RA, pregestational DM, and the general obstetric population. Pregnancy outcomes included length of hospital stay, hypertensive disorders including preeclampsia, premature rupture of membranes, and intrauterine growth restriction.Of an estimated 4.04 million deliveries, 3,264 occurred in women with SLE, 1,425 in women with RA, and 13,574 in women with pregestational DM. Women with SLE, RA, and pregestational DM had significantly increased rates of hypertensive disorders compared with the general obstetric population (23.2%, 11.1%, 27.4%, and 7.8%, respectively), longer hospital stays, and significantly higher risk of cesarean delivery. Although women with SLE, RA, and pregestational DM were significantly older than women in the general obstetric population, disparities in the risk of adverse outcomes of pregnancy remained statistically significant after adjustment for maternal age.To our knowledge, this is the first study to examine national data on pregnancy outcomes in women with common rheumatic diseases. As with underlying pregestational DM, women with SLE and RA appear to have a higher age-adjusted risk of adverse outcomes of pregnancy and longer hospital stays than do pregnant women in the general population, and careful antenatal monitoring should be performed.

    View details for DOI 10.1002/art.21663

    View details for Web of Science ID 000236019700023

    View details for PubMedID 16508972

  • Effect of reproductive factors and postmenopausal hormone use on the risk of amyotrophic lateral sclerosis NEUROEPIDEMIOLOGY Popat, R. A., Van Den Eeden, S. K., Tanner, C. M., Bernstein, A. L., Bloch, D. A., Leimpeter, A., McGuire, V., Nelson, L. M. 2006; 27 (3): 117-121


    To examine the associations of reproductive factors and postmenopausal hormone use with the risk of amyotrophic lateral sclerosis (ALS) among women.This case-control study was conducted within the Kaiser Permanente Medical Care Program (KPMCP) of Northern California during the years 1996-2000. Among the 193 postmenopausal women, 62 were incident ALS cases and 131 were controls randomly selected from KPMCP members and frequency matched by age and respondent type (self versus proxy) to the cases. Statistical analyses were carried out using logistic regression.Reproductive factors such as age at menarche, age at final menstrual period, parity, oral contraceptive use, and type of menopause (natural vs. hysterectomy with or without oophorectomy) were not associated with risk of ALS. Postmenopausal hormone use was positively, but not significantly, associated with the risk of ALS (adjusted OR 1.9, 95% CI 0.9-3.8).Reproductive factors were not associated with ALS risk. There is no evidence that suggests a protective effect of postmenopausal hormone use against the development of ALS. However, due to insufficient power, we cannot rule out a possible increase in ALS risk associated with postmenopausal hormone use.

    View details for DOI 10.1159/000095550

    View details for Web of Science ID 000241773900001

    View details for PubMedID 16946622

  • Effect of reproductive factors and postmenopausal hormone use on the risk of Parkinson disease NEUROLOGY Popat, R. A., Van Den Eeden, S. K., Tanner, C. M., McGuire, V., Bernstein, A. L., Bloch, D. A., Leimpeter, A., Nelson, L. M. 2005; 65 (3): 383-390


    Parkinson disease (PD) is less common in women possibly because of hormonal or reproductive influences. The objective of this study was to evaluate the associations of reproductive factors and postmenopausal hormone use with the risk of PD among postmenopausal women.Incident cases (n = 178) and randomly selected age-matched controls (n = 189) who were members of the Kaiser Permanente Medical Care Program (KPMCP) of Northern California participated in the study conducted during the years 1994 to 1995. Statistical analyses were carried out using logistic regression.The association of postmenopausal hormone use with PD risk depended on the type of menopause. Among women with history of a hysterectomy with or without an oophorectomy, estrogen use alone was associated with a 2.6-fold increased risk (adjusted odds ratio (OR) 2.6, 95% CI: 1.1 to 6.1) and significant trends in the risk of PD were observed with increasing duration of estrogen use, but disease risk was not influenced by recency of use. In contrast, among women with natural menopause, no increased risk of PD was observed with hormone use (estrogen alone or a combined estrogen-progestin regimen). Early age at final menstrual period (44 years or younger) was associated with reduction in risk (adjusted OR 0.5, 95% CI: 0.3 to 1.0). Age at menarche and parity were not associated with the risk of PD.Postmenopausal use of estrogen alone may increase the risk of Parkinson disease (PD) among women with a hysterectomy. Among women with natural menopause for whom the usual treatment is combined estrogen-progestin therapy, no increased risk of PD was observed.

    View details for Web of Science ID 000231067200010

    View details for PubMedID 16087902

  • The risk for malignant primary adult-onset glioma in a large, multiethnic, managed-care cohort: cigarette smoking and other lifestyle behaviors JOURNAL OF NEURO-ONCOLOGY Efird, J. T., Friedman, G. D., Sidney, S., Klatsky, A., Habel, L. A., Udaltsova, N. V., Van den Eeden, S., Nelson, L. M. 2004; 68 (1): 57-69


    To determine the risk for malignant primary adult-onset glioma (MPAG) associated with cigarette smoking and other lifestyle behaviors in a large, multiethnic, managed-care cohort.The study population included a cohort of 133,811 subscribers to the Kaiser Permanente Medical Care Program of Northern California who had received a multiphasic health checkup and questionnaire between 1977 and 1985, were at least 25 years old at their start of follow-up, and had no prior history of benign or malignant brain tumors. In this cohort, patients were followed for up to 21 years for the development of MPAG.Risk for MPAG among women increased with increasing packs of cigarettes smoked per day (p-for-trend = 0.04), adjusting for cigar and pipe smoking, patient age, sex, race, education, alcohol use and coffee consumption. A similar pattern was not observed for men. Individuals who smoked marijuana at least once a month, adjusting for cigarette smoking (packs smoked per day) and for the factors noted above, had a 2.8-fold (CI = 1.3-6.2) increased risk for MPAG. Relative risk for MPAG increased with increasing consumption of coffee (p-for-trend = 0.05).Cigarette smoking was associated with an increased risk for MPAG among women but not among men. Individuals who smoked marijuana at least once a month had an increased risk for MPAG, although no dose-response relation was observed. Drinkers of >7 cups of coffee per day had a 70% increased risk for MPAG and smaller risk elevation for lower consumption. Alcohol usage was not associated with an increased risk for MPAG.

    View details for Web of Science ID 000220928400009

    View details for PubMedID 15174522

  • Incidence of Parkinson's disease: Variation by age, gender, and Race/Ethnicity AMERICAN JOURNAL OF EPIDEMIOLOGY Van den Eeden, S. K., Tanner, C. M., Bernstein, A. L., Fross, R. D., Leimpeter, A., Bloch, D. A., Nelson, L. M. 2003; 157 (11): 1015-1022


    The goal of this study was to estimate the incidence of Parkinson's disease by age, gender, and ethnicity. Newly diagnosed Parkinson's disease cases in 1994-1995 were identified among members of the Kaiser Permanente Medical Care Program of Northern California, a large health maintenance organization. Each case met modified standardized criteria/Hughes diagnostic criteria as applied by a movement disorder specialist. Incidence rates per 100,000 person-years were calculated using the Kaiser Permanente membership information as the denominator and adjusted for age and/or gender using the direct method of standardization. A total of 588 newly diagnosed (incident) cases of Parkinson's disease were identified, which gave an overall annualized age- and gender-adjusted incidence rate of 13.4 per 100,000 (95% confidence interval (CI): 11.4, 15.5). The incidence rapidly increased over the age of 60 years, with only 4% of the cases being under the age of 50 years. The rate for men (19.0 per 100,000, 95% CI: 16.1, 21.8) was 91% higher than that for women (9.9 per 100,000, 95% CI: 7.6, 12.2). The age- and gender-adjusted rate per 100,000 was highest among Hispanics (16.6, 95% CI: 12.0, 21.3), followed by non-Hispanic Whites (13.6, 95% CI: 11.5, 15.7), Asians (11.3, 95% CI: 7.2, 15.3), and Blacks (10.2, 95% CI: 6.4, 14.0). These data suggest that the incidence of Parkinson's disease varies by race/ethnicity.

    View details for DOI 10.1093/aie/kwg068

    View details for Web of Science ID 000183420800010

    View details for PubMedID 12777365

  • Principles, organization, and operation of a DNA bank for clinical trials: a Department of Veterans Affairs cooperative study CONTROLLED CLINICAL TRIALS Lavori, P. W., Krause-Steinrauf, H., Brophy, M., Buxbaum, J., Cockroft, J., Cox, D. R., Fiore, L., Greely, H. T., Greenberg, H., Holmes, E. W., Nelson, L. M., Sugarman, J. 2002; 23 (3): 222-239


    The mapping and sequencing of the human genome promises rapid growth in understanding the genetically influenced mechanisms that underlie human disease. To realize this promise fully, it is necessary to relate genetic information to clinical phenotypes. Genetic tissue banking in clinical studies provides opportunities to analyze the genetic contribution to variation in response to treatments. The challenges to progress are likely to come from the complex organizational, social, political, and ethical issues that must be resolved in order to put clinical and DNA bank information together. Concerns about subjects' rights, informed consent, privacy, and ownership of genetic material require attention in the development of DNA banks. In this paper we describe one approach to the solution of these problems that was adopted by one clinical trials group, the Department of Veterans Affairs Cooperative Studies Program.

    View details for Web of Science ID 000175963200001

    View details for PubMedID 12057876

  • Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. I. Cigarette smoking and alcohol consumption AMERICAN JOURNAL OF EPIDEMIOLOGY Nelson, L. M., McGuire, V., Longstreth, W. T., Matkin, C. 2000; 151 (2): 156-163


    The associations of cigarette smoking and alcohol consumption with the risk of amyotrophic lateral sclerosis (ALS) were investigated in a population-based case-control study conducted in three counties of western Washington State from 1990 to 1994. Incident ALS cases (n = 161) were identified and were matched to population controls (n = 321) identified through random digit dialing and Medicare enrollment files. Conditional logistic regression analysis was used to compute odds ratios adjusted for age, gender, respondent type, and education. The authors found that alcohol consumption was not associated with the risk of ALS. Ever having smoked cigarettes was associated with a twofold increase in risk (alcohol-adjusted odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.3, 3.2). A greater than threefold increased risk was observed for current smokers (alcohol-adjusted OR = 3.5, 95% CI: 1.9, 6.4), with only a modestly increased risk for former smokers (alcohol-adjusted OR = 1.5, 95% CI: 0.9, 2.4). Significant trends in the risk of ALS were observed with duration of smoking (p for trend = 0.001) and number of cigarette pack-years (p for trend = 0.001). The finding that cigarette smoking is a risk factor for ALS is consistent with current etiologic theories that implicate environmental chemicals and oxidative stress in the pathogenesis of ALS.

    View details for Web of Science ID 000084821000009

    View details for PubMedID 10645818

  • Population-based case-control study of amyotrophic lateral sclerosis in western Washington Sate. II. Diet AMERICAN JOURNAL OF EPIDEMIOLOGY Nelson, L. M., Matkin, C., Longstreth, W. T., McGuire, V. 2000; 151 (2): 164-173


    The association of nutrient intake with the risk of amyotrophic lateral sclerosis (ALS) was investigated in a population-based case-control study conducted in three counties of western Washington State from 1990 to 1994. Incident ALS cases (n = 161) were identified and individually matched on age and gender to population controls (n = 321). A self-administered food frequency questionnaire was used to assess nutrient intake. Conditional logistic regression analysis was used to compute odds ratios adjusted for education, smoking, and total energy intake. The authors found that dietary fat intake was associated with an increased risk of ALS (highest vs. lowest quartile, fiber-adjusted odds ratio (OR) = 2.7, 95% confidence interval (CI): 0.9, 8.0; p for trend = 0.06), while dietary fiber intake was associated with a decreased risk of ALS (highest vs. lowest quartile, fat-adjusted OR = 0.3, 95% CI: 0.1, 0.7; p for trend = 0.02). Glutamate intake was associated with an increased risk of ALS (adjusted OR for highest vs. lowest quartile = 3.2, 95% CI: 1.2, 8.0; p for trend < 0.02). Consumption of antioxidant vitamins from diet or supplement sources did not alter the risk. The positive association with glutamate intake is consistent with the etiologic theory that implicates glutamate excitotoxicity in the pathogenesis of ALS, whereas the associations with fat and fiber intake warrant further study and biologic explanation.

    View details for Web of Science ID 000084821000010

    View details for PubMedID 10645819

  • Epidemiologic approaches to the study of Parkinson's disease etiology EPIDEMIOLOGY Checkoway, H., Nelson, L. M. 1999; 10 (3): 327-336


    The etiology of Parkinson's disease has been enigmatic to clinicians, epidemiologists, and basic scientists since the clinical syndrome was first described in 1817. Mendelian inheritance probably accounts for a small proportion of Parkinson's disease. Apart from an increasing risk with age, the most consistent epidemiologic observation has been an inverse relation with cigarette smoking. Neither selective survival of nonsmokers nor behavioral characteristics of smokers can explain this seemingly protective association. Interest in environmental exposures, particularly pesticides, metals, and industrial solvents, heightened substantially following the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a street drug contaminant, as a cause of human parkinsonism. Epidemiologic and toxicologic research has since been guided to a great extent, although not exclusively, by mechanisms of MPTP toxicity. Efforts to characterize gene/environment interactions have also intensified in recent years. In this review, we evaluate recent evidence concerning the etiology of Parkinson's disease, with emphasis on environmental and lifestyle exposures and their potential interactions with genetic susceptibility traits. The most challenging aspects of epidemiologic research into Parkinson's disease causation include methodologic difficulties surrounding case definition, completeness of case ascertainment, selection of appropriate controls in case-control studies, and assessment of environmental exposures. We conclude with recommendations for future research directions.

    View details for Web of Science ID 000079891400023

    View details for PubMedID 10230846

  • Physical trauma and family history of neurodegenerative diseases in amyotrophic lateral sclerosis: A population-based case-control study NEUROEPIDEMIOLOGY Cruz, D. C., Nelson, L. M., McGuire, V., Longstreth, W. T. 1999; 18 (2): 101-110


    This population-based case-control study was conducted in three counties in western Washington state (USA) between 1990 and 1994 to assess the association between amyotrophic lateral sclerosis (ALS) and several hypothesized risk factors, including a family history of neurodegenerative diseases, physical trauma (fractures, electrical shocks, and surgeries), rural residence, travel, and medical history. One hundred seventy-four cases with ALS, newly diagnosed by neurologists, were identified through several case-finding methods. Two controls (n = 348), who were matched to each case by gender and age (+/-5 years), were identified through random digit telephone dialing or Medicare lists. Exposure data were collected through structured in-person interviews. A greater proportion of cases (2. 3%) than controls (0.9%) reported a first-degree relative with ALS, resulting in an odds ratio of 3.1 (95% CI, 0.6-15.7). For a positive family history of ALS among second-degree relatives, the odds ratio was 4.0 (95% CI, 1.0-16.6). Overall, reports of first- or second-degree relatives with ALS yielded a significantly elevated odds ratio of 3.3 (95% CI, 1.1-9.9). No association was found with a family history of Alzheimer's disease or Parkinson's disease, or with a family history of the neurodegenerative diseases as a group. No significant associations were demonstrated for any of the other factors analyzed, including a history of fractures, electrical shocks, or surgeries, a history of residence in rural areas, a history of travel to areas in the western Pacific where ALS is endemic, and a medical history of polio, polio immunization, or tetanus immunization.

    View details for Web of Science ID 000078917000006

    View details for PubMedID 10023133

  • Study design in genetic epidemiology: theoretical and practical considerations. Journal of the National Cancer Institute. Monographs Whittemore, A. S., Nelson, L. M. 1999: 61-69


    Recent advances in molecular genetics have created new opportunities and challenges for genetic epidemiologists. Here we review some of the issues that arise when designing a study involving the genetic epidemiology of chronic diseases of late onset, such as cancer. We discuss two considerations that influence the choice of design. The first consideration is the study's goals. We describe the goals of identifying new susceptibility genes for a disease, of estimating important characteristics of known genes, and of learning how to prevent the disease in the genetically susceptible. We indicate how these goals affect the choice of design and present some guidelines for choosing designs that effectively address them. The second consideration is the set of practical constraints to successfully conducting the research. These contraints include problems of potential selection bias, reduced response rates, problems particular to family registries, problems particular to the cultures of various ethnic groups, and ethical issues. We indicate how these constraints affect the choice of design and discuss ways to deal with them.

    View details for PubMedID 10854488

  • Recursive partitioning for the identification of disease risk subgroups: A case-control study of subarachnoid hemorrhage JOURNAL OF CLINICAL EPIDEMIOLOGY Nelson, L. M., Bloch, D. A., Longstreth, W. T., Shi, H. 1998; 51 (3): 199-209


    Recursive partitioning is a nonparametric technique that produces a classification tree in which subjects are assigned to mutually exclusive subsets according to a set of predictor variables. We examined the utility of recursive partitioning as a supplement to logistic regression for the multivariable analysis of data from case-control studies, demonstrating the technique using data from women enrolled in a population-based study of subarachnoid hemorrhage. The classification tree produced by recursive partitioning consisted of three main risk subgroups: (1) elderly women who had long-standing hypertension and who were not smokers, (2) middle-aged women who were cigarette smokers and frequent binge drinkers, and (3) women in whom risk variables indicate relative estrogen deficiency (i.e., postmenopausal status, no recent exposure to hormone replacement therapy, cigarette smoking). As a supplemental method, recursive partitioning not only identifies subgroups with varying risks, but also may uncover interactions between variables that may be overlooked in the traditional application of logistic regression to case-control data.

    View details for Web of Science ID 000072147700004

    View details for PubMedID 9495685

  • Assessment of occupational exposures in community-based case-control studies ANNUAL REVIEW OF PUBLIC HEALTH McGuire, V., Nelson, L. M., Koepsell, T. D., Checkoway, H., Longstreth, W. T. 1998; 19: 35-53


    Assessing occupational exposures in community-based studies is a challenge for investigators because there are no standardized or validated approaches for collecting information regarding occupational history. The strengths and limitations of the methods available for assessing occupational exposures are reviewed. In community-based case-control studies, the prevalence of most chemical agents is low. The common sources of misclassification in these studies are addressed, as are strategies for dealing with misclassification bias. Methods to assess the presence and magnitude of differential reporting by cases and controls are outlined, together with analytic strategies to improve the classification of occupational exposures.

    View details for Web of Science ID 000073657500003

    View details for PubMedID 9611611

  • Occupational exposures and amyotrophic lateral sclerosis - A population-based case-control study AMERICAN JOURNAL OF EPIDEMIOLOGY McGuire, V., Longstreth, W. T., Nelson, L. M., Koepsell, T. D., Checkoway, H., Morgan, M. S., VANBELLE, G. 1997; 145 (12): 1076-1088


    This population-based case-control study was conducted in three countries in western Washington State to evaluate associations between workplace exposures and the risk of amyotrophic lateral sclerosis (ALS). Cases (n = 174) were all newly diagnosed with ALS by neurologists during 1990-1994, and controls (n = 348), who were matched according to age (+/-5 years) and sex, were identified via random-digit dialing or Medicare enrollment files. Four industrial hygienists blindly assessed detailed lifetime job histories for exposures to metals, solvents, and agricultural chemicals. Case-control comparisons were made for jobs held between 15 years of age and 10 years prior to the cases' dates of diagnosis. After adjustment for age and education, ever exposure to agricultural chemicals was associated with ALS (odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.1-3.5); this association was observed separately in men (OR = 2.4, 95% CI 1.2-4.8) but not in women (OR = 0.9, 95% CI 0.2-3.8). Among men, the odds ratio for low exposure to agricultural chemicals (below the median level for exposed controls) relative to no exposure was 1.5 (95% CI 0.4-5.3), and for high exposure, it was 2.8 (95% CI 1.3-6.1) (p for trend = 0.03). Similar analyses based on the panel's assessment of exposures to metals and solvents showed no associations. These findings suggest an association between ALS and agricultural chemicals in men.

    View details for Web of Science ID A1997XG00800002

    View details for PubMedID 9199537

  • Case finding for epidemiological surveys of multiple sclerosis in United States communities. Multiple sclerosis Nelson, L. M., ANDERSON, D. W. 1995; 1 (1): 48-55


    In regard to prevalence surveys of MS in US communities, this article considers the relative merits of case finding through hospitals, physicians, MS service organisations, neurology practices, death certificates, chronic care facilities and media announcements and lay referrals. The current value of hospitals and non-neurological practitioners for case finding is questionable, given the changes in clinical practice with respect to MS and the data collection problems inherent with surveys of physicians. We suggest giving priority to the following case-finding methods: manually reviewing patient records of neurology practices, screening patient rolls of local MS service organisations and surveying chronic care facilities. In some US communities, these methods may need to be augmented by also surveying internists, general practitioners and family practitioners. Capture-recapture methodology offers a way to evaluate the completeness of case ascertainment.

    View details for PubMedID 9345469

  • Epidemiology of ALS. Clinical neuroscience Nelson, L. M. 1995; 3 (6): 327-331


    Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder of unknown etiology. ALS onset is rare before age 40 and increases with age thereafter. Men are at higher risk than women (ratio 1.3:1). Other than age and gender, the only indisputable risk factor for ALS is genetic susceptibility, with familial cases occurring in about 10% of most case series. Genetic linkage studies have provided evidence that a mutant form of the gene that codes for Cu/Zn superoxide dismutase, an endogenous free radical scavenger, is important in 15-20% of familial cases. Epidemiologic studies have identified associations of sporadic ALS with work in occupations that involve toxicant exposure. Environmental toxicants may act against a background of increased genetic susceptibility; however, genetically acquired biochemical defects have not been identified in sporadic ALS patients. Other epidemiologic theories of disease etiology have emphasized the potential role of physical trauma, electrical shock, and vigorous physical exertion, but evidence regarding these factors is inconsistent.

    View details for PubMedID 9021253



    To determine the degree to which endogenous and exogenous hormonal factors influence the risk for subarachnoid hemorrhage in women.A population-based case-control study.King County, Washington.103 women with an incident, spontaneous subarachnoid hemorrhage and 2 age- and sex-matched controls per case-patient who were identified through random-digit dialing.Information on exposures was collected during in-person interviews of case-patients, controls, and their surrogates.Premenopausal women, especially those without a history of smoking or hypertension, were at a reduced risk for subarachnoid hemorrhage compared with age-matched postmenopausal women (odds ratio, 0.24; 95% CI, 0.09 to 0.68). The use of hormone replacement therapy was associated with a reduced risk (odds ratio, 0.47; CI, 0.26 to 0.86); the reduction was significantly greater in women who had smoked than in those that had never smoked. Of the 23 premenopausal case-patients, 74% were either menstruating when hemorrhaging occurred or had had their last menstrual period 21 or more days before hemorrhaging compared with the expected 43% (difference, 31%; CI, 4% to 58%).Premenopausal women are at reduced risk for subarachnoid hemorrhage, especially those without a history of smoking or hypertension. Hormone replacement therapy reduced the risk only in postmenopausal women who had ever smoked. Among women still menstruating, the risk for hemorrhage was greatest in the perimenstrual period.

    View details for Web of Science ID A1994NY33800002

    View details for PubMedID 8017743



    To evaluate the quality of exposure data provided by proxy respondents, we used a dual interview protocol in a case-control study of subarachnoid hemorrhage. All control subjects and their proxy respondents were interviewed (N = 283 control-proxy pairs), as were the cases who were able to provide their own information and their proxy respondents (N = 68 case-proxy pairs). The reliability of proxy-derived data was excellent for demographic and body habitus measures (kappa or intraclass correlation range = 0.86-0.99), and all aspects of cigarette smoking history (range = 0.79-0.93). Proxy reliability was somewhat lower for questions regarding medications and hormone preparations (range = 0.55-0.88), alcohol consumption (range = 0.52-0.82), and recreational physical activity (range = 0.55-0.67). Proxy reliability varied according to the relationship of the proxy to the index subject. Relative to the index subjects, proxy respondents tended to underreport the presence or level of exposure. For most exposures, odds ratios computed with proxy-derived data were similar in magnitude to odds ratios obtained with index subject data; important bias due to differential nonresponse or differential misclassification was suggested only for questions regarding hormone replacement therapy. Epidemiologic studies that rely on proxy respondents may require more subjects to offset the effect of nondifferential nonresponse and misclassification on the precision of effect estimates.

    View details for Web of Science ID A1994MZ61300011

    View details for PubMedID 8172996


    View details for Web of Science ID A1990EM70000006

    View details for PubMedID 2286227



    Studies in the past have reported an increased risk of exacerbations in multiple sclerosis during the postpartum period; it is not known whether breast-feeding alters this risk. We interviewed 435 women regarding pregnancy and breast-feeding history, providing for analysis 191 pregnancies that had occurred during a nonprogressive phase of the disease. The exacerbation rates during the nine-month postpartum period (34%) were more than three times the exacerbation rate during the nine months of pregnancy (10%). The exacerbation risk was highest in the three-month period following childbirth and appeared to stabilize after the sixth postpartum month. The exacerbation rates in breast-feeding and non-breast-feeding pregnancies were 38% and 31%, respectively. The average time to exacerbation was similar in breast-feeding (3.0 months) and non-breast-feeding (3.1 months) pregnancies. Although differential exacerbation rates during pregnancy and the postpartum period may be related to hormonal effects on the immune system, the hormonal effects of breast-feeding do not appear to similarly affect the risk of exacerbation.

    View details for Web of Science ID A1988N729500026

    View details for PubMedID 3373681

  • REFERRAL BIAS IN MULTIPLE-SCLEROSIS RESEARCH JOURNAL OF CLINICAL EPIDEMIOLOGY Nelson, L. M., Franklin, G. M., Hamman, R. F., BOTELER, D. L., BAUM, H. M., Burks, J. S. 1988; 41 (2): 187-192


    Referral bias is a significant problem affecting the generalizability of clinical studies conducted in a university setting. To examine referral bias in our university-based multiple sclerosis referral center, we analyzed the characteristics of referral center patients compared to the population-based group of multiple sclerosis patients from which the referral center patients originated. The referral center patient group differed from those that remained in the population-based group in the following important ways: (1) they were younger, (2) they had more mobility impairment for their age, (3) disabled females were overrepresented compared to disabled males, (4) they more often reported recent disease worsening, (5) they had a higher frequency of early diagnosis supported by laboratory tests, and (6) they more often relied on neurologists and therapists for routine care of their disease. The multiple sclerosis referral center setting would appear to be ideal for the conduct of intervention trials, but inadequate for collecting representative natural history data.

    View details for Web of Science ID A1988L652600010

    View details for PubMedID 3335884

  • Fetal antiepileptic drug exposure and learning and memory functioning at 6 years of age: The NEAD prospective observational study. Epilepsy & behavior : E&B Cohen, M. J., Meador, K. J., May, R., Loblein, H., Conrad, T., Baker, G. A., Bromley, R. L., Clayton-Smith, J., Kalayjian, L. A., Kanner, A., Liporace, J. D., Pennell, P. B., Privitera, M., Loring, D. W., NEAD Study Group 2019; 92: 154–64


    The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study was a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on learning and memory functions in 221 six-year-old children (including four sets of twins) whose mothers took one of these AEDs during pregnancy. Their performance was compared with that of a national sample of normally developing six year olds from the standardization sample of the Children's Memory Scale (CMS). The major results of this study indicate that the mean performance levels of children exposed to valproate were significantly below that of the children in the normal comparison group across all seven of the CMS Indexes. With one exception, this finding held up at the subtest level as well. These findings taken together with nonsignificant verbal and nonverbal forgetting scores appear to indicate that, as a group, children exposed to valproate experienced significant difficulty in their ability to process, encode, and learn both auditory/verbal as well as visual/nonverbal material. In addition, they exhibited significant difficulty holding and manipulating information in immediate auditory working memory. However, once the information was learned and stored, the valproate-exposed children appeared to be able to retrieve the information they did learn at normal levels. Finally, the processing, working memory, and learning deficits demonstrated by the valproate-exposed children are dose-related. In contrast to valproate, the findings pertaining to the children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy are less clear. Therefore, further research will be required to delineate the potential risks to learning and memory functions in children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy during pregnancy. Additional research employing larger prospective studies will be required to confirm the long-term cognitive and behavioral risks to children of mothers who are prescribed these four AEDs during pregnancy as well as to delineate any potential risks of newer AEDs and to understand the underlying mechanisms of adverse AED effects on the immature brain.

    View details for PubMedID 30660966

  • Estimation of the Prevalence of Amyotrophic Lateral Sclerosis in the United States Using National Administrative Healthcare Data from 2002 to 2004 and Capture-Recapture Methodology. Neuroepidemiology Nelson, L. M., Topol, B., Kaye, W., Williamson, D., Horton, D. K., Mehta, P., Wagner, T. 2018; 51 (3-4): 149–57


    BACKGROUND: National administrative healthcare data may be used as a case-finding method for prevalence studies of chronic disease in the United States, but the completeness of ascertainment likely varies depending on the disease under study.METHODS: We used 3 case-finding sources (Medicare, Medicaid, and Veterans Administration data) to estimate the prevalence of amyotrophic lateral sclerosis (ALS) in the United States for 2002-2004, and applied the capture-recapture methodology to estimate the degree of under-ascertainment when relying solely on these sources for case identification.RESULTS: Case-finding completeness was 76% overall and did not vary by race, but was lower for males (77%) than for females (88%), and lower for patients under age 65 (66%) than patients over age 65 (79%). The uncorrected ALS prevalence ratio was 2.8/100,000 in 2002, 3.3/100,000 in 2003, and 3.7/100,000 in 2004. After correcting for under-ascertainment, the annual prevalence increased by approximately 1 per 100,000 to 3.7/100,000 in 2002 (95% CI 3.66-3.80), 4.4/100,000 in 2003 (95% CI 4.34-4.50), and 4.8/100,000 in 2004 (95% CI 4.76-4.91).CONCLUSIONS: Federal healthcare claims databases ascertained are a very efficient method for identifying the majority of ALS-prevalent cases in the National ALS Registry, and may be enhanced by having patients self-register through the registry web portal.

    View details for DOI 10.1159/000488798

    View details for PubMedID 30092573

  • Resilience and Transition Readiness in Pediatric SLE Patients Lai, J., Nelson, L., Balboni, I., Lee, T., Hsu, J. WILEY. 2017
  • The prevalence of multiple sclerosis in the United States: a population-based healthcare database approach Wallin, M. T., Culpepper, W. J., Campbell, J., Nelson, L., Langer-Gould, A., Marrie, R. A., Cutter, G., Kaye, W., Wagner, L., Tremlett, H., Buka, S., Larocca, N., Leung, S., Dilokthornsakul, P., Topol, B., Chen, L. H., US Multiple Sclerosis Prevalence SAGE PUBLICATIONS LTD. 2017: 125
  • Risk Factors for Severe Postpartum Hemorrhage After Cesarean Delivery: Case-Control Studies. Anesthesia and analgesia Butwick, A. J., Ramachandran, B., Hegde, P., Riley, E. T., El-Sayed, Y. Y., Nelson, L. M. 2017


    Women who undergo intrapartum caesarean delivery (CD) are at increased risk of postpartum hemorrhage (PPH) compared with those undergoing prelabor CD. To determine whether the presence and strength of the associations between individual risk factors and severe PPH vary among women undergoing prelabor CD or intrapartum CD, stratified analyses are needed according to CD subtype.To identify risk factors for severe PPH within 2 distinct CD populations, prelabor CD and intrapartum CD, we performed 2 case-control studies. Women in each study cohort delivered at a tertiary obstetric center in the United States between 2002 and 2012. For each study, cases were women who had a blood loss ≥1500 mL or who received an intraoperative or postoperative transfusion up to 48 hours after delivery. Risk factors for severe PPH among women undergoing prelabor CD or intrapartum CD were examined in separate logistic regression models.For prelabor CD, we identified 269 cases and 550 controls. Clinical factors with the highest adjusted odds for severe PPH during prelabor CD were general anesthesia (adjusted odds ratio [aOR] = 22.3; 95% confidence interval [CI] = 4.9-99.9; reference group = spinal anesthesia), multiple pregnancies (aOR = 8.0; 95% CI = 4.2-15.0; reference group = singleton pregnancy), and placenta previa (aOR = 6.3; 95% CI = 3.4-11.8). For intrapartum CD, we identified 278 cases and 572 controls. Clinical factors with the highest adjusted odds for severe PPH during intrapartum CD were general anesthesia (aOR = 5.4; 95% CI = 1.7-17.1), multiple pregnancies (aOR = 3.2; 95% CI = 1.7-6.3), and a predelivery hemoglobin ≤ 9.9 g/dL (aOR = 3.0; 95% CI = 1.3-6.9; reference group = predelivery hemoglobin ≥ 11 g/dL).Women who undergo prelabor CD and intrapartum CD have several shared risk factors for severe PPH (general anesthesia and multiple pregnancies). However, the risk factor profiles for severe PPH differed between these CD cohorts. Recognizing these differences may be important when planning resources and interventions for high-risk patients undergoing either prelabor or intrapartum CD.

    View details for DOI 10.1213/ANE.0000000000001962

    View details for PubMedID 28277324

  • Racial and Ethnic Disparities in Mode of Anesthesia for Cesarean Delivery ANESTHESIA AND ANALGESIA Butwick, A. J., Blumenfeld, Y. J., Brookfield, K. F., Nelson, L. M., Weiniger, C. F. 2016; 122 (2): 472-479


    Racial and ethnic disparities have been identified in the provision of neuraxial labor analgesia. These disparities may exist in other key aspects of obstetric anesthesia care. We sought to determine whether racial/ethnic disparities exist in mode of anesthesia for cesarean delivery (CD).Women who underwent CD between 1999 and 2002 at 19 different obstetric centers in the United States were identified from the Maternal-Fetal Medicine Units Network Cesarean Registry. Race/ethnicity was categorized as: Caucasian, African American, Hispanic, and Non-Hispanic Others (NHOs). Mode of anesthesia was classified as neuraxial anesthesia (spinal, epidural, or combined spinal-epidural anesthesia) or general anesthesia. To account for obstetric and non-obstetric covariates that may have influenced mode of anesthesia, multiple logistic regression analyses were performed by using sequential sets of covariates.The study cohort comprised 50,974 women who underwent CD. Rates of general anesthesia among racial/ethnic groups were as follows: 5.2% for Caucasians, 11.3% for African Americans, 5.8% for Hispanics, and 6.6% for NHOs. After adjustment for obstetric and non-obstetric covariates, African Americans had the highest odds of receiving general anesthesia compared with Caucasians (adjusted odds ratio [aOR] = 1.7; 95% confidence interval [CI], 1.5-1.8; P < 0.001). The odds of receiving general anesthesia were also higher among Hispanics (aOR = 1.1; 95% CI, 1.0-1.3; P = 0.02) and NHOs (aOR = 1.2; 95% CI, 1.0-1.4; P = 0.03) compared with Caucasians, respectively. In our sensitivity analysis, we reconstructed the models after excluding women who underwent neuraxial anesthesia before general anesthesia. The adjusted odds of receiving general anesthesia were similar to those in the main analysis: African Americans (aOR = 1.7; 95% CI, 1.5-1.9; P < 0.001); Hispanics (aOR = 1.2; 95% CI, 1.1-1.4; P = 0.006); and NHOs (aOR = 1.2; 95% CI, 1.0-1.5; P = 0.05).Based on data from the Cesarean Registry, African American women had the highest odds of undergoing general anesthesia for CD compared with Caucasian women. It is uncertain whether this disparity exists in current obstetric practice.

    View details for DOI 10.1213/ANE.0000000000000679

    View details for Web of Science ID 000368646500001

    View details for PubMedCentralID PMC4724639

  • Risk Factors for Prolonged Postpartum Length of Stay Following Cesarean Delivery AMERICAN JOURNAL OF PERINATOLOGY Blumenfeld, Y. J., El-Sayed, Y. Y., Lyell, D. J., Nelson, L. M., Butwick, A. J. 2015; 32 (9): 825-832


    Objective This study aims to identify risk factors for prolonged postpartum length of stays (LOS) after cesarean delivery (CD). Study Design Patients undergoing CD were sourced from a multicenter registry of 19 academic centers between 1999 and 2002 (n = 57,067). Prolonged postpartum LOS was defined as a hospitalization duration ≥ 90th centile. Maternal, antepartum, perioperative, and neonatal variables were compared between women with and without prolonged postpartum LOS. Results The 90th centile for postpartum LOS was 4 days, with 14,954 women experiencing prolonged postpartum LOS. Women with perioperative complications had the highest independent risk for a prolonged postpartum LOS: ileus (adjusted odds ratio [aOR] = 12.28; 95% confidence interval CI = 8.98-16.8); endometritis (aOR = 10.45; 95% CI = 9.51-11.5), and wound complications (aOR = 5.49; 95% CI = 4.54-6.63). Several antepartum, perioperative, and neonatal variables were associated with a prolonged postpartum LOS. Conclusion Perioperative complications had the highest risk for prolonged LOS after CD. Strategies to reduce perioperative complications are needed to decrease the health care burden of prolonged post-CD LOS.

    View details for DOI 10.1055/s-0034-1543953

    View details for Web of Science ID 000358571000004

  • Second-line uterotonics and the risk of hemorrhage-related morbidity. American journal of obstetrics and gynecology Butwick, A. J., Carvalho, B., Blumenfeld, Y. J., El-Sayed, Y. Y., Nelson, L. M., Bateman, B. T. 2015; 212 (5): 642 e1-7


    Uterine atony is a leading cause of postpartum hemorrhage (PPH). Although most cases of PPH respond to first line therapy with uterine massage and oxytocin administration, second line uterotonics including methylergonovine and carboprost are integral for the management of refractory uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of hemorrhage-related morbidity differs in women exposed to methylergonovine or carboprost at Cesarean delivery (CD).We performed a secondary analysis using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified women who underwent CD and received either methylergonovine or carboprost for refractory uterine atony. The primary outcome was hemorrhage-related morbidity defined as intraoperative or postoperative red blood cells (RBC) transfusion or the need for additional surgical interventions including uterine artery ligation, hypogastric artery ligation, or peripartum hysterectomy for atony. We compared the risk of hemorrhage-related morbidity in those exposed to methylergonovine vs. carboprost. Propensity-score matching was used to account for potential confounders.The study cohort comprised 1,335 women; 870 (65.2%) women received methylergonovine and 465 (34.8%) women received carboprost. After accounting for potential confounders, the risk of hemorrhage-related morbidity was higher in the carboprost group than the methylergonovine group (RR = 1.7; 95% CI = 1.2 - 2.6).In this propensity-score matched analysis, methylergonovine was associated with reduced risk of hemorrhage-related morbidity during CD compared to carboprost. Based on these results, methylergonovine may be a more effective second line uterotonic.

    View details for DOI 10.1016/j.ajog.2015.01.008

    View details for PubMedID 25582104

  • Second-line uterotonics and the risk of hemorrhage-related morbidity AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Butwick, A. J., Carvalho, B., Blumenfeld, Y. J., El-Sayed, Y. Y., Nelson, L. M., Bateman, B. T. 2015; 212 (5)


    Uterine atony is a leading cause of postpartum hemorrhage (PPH). Although most cases of PPH respond to first line therapy with uterine massage and oxytocin administration, second line uterotonics including methylergonovine and carboprost are integral for the management of refractory uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of hemorrhage-related morbidity differs in women exposed to methylergonovine or carboprost at Cesarean delivery (CD).We performed a secondary analysis using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified women who underwent CD and received either methylergonovine or carboprost for refractory uterine atony. The primary outcome was hemorrhage-related morbidity defined as intraoperative or postoperative red blood cells (RBC) transfusion or the need for additional surgical interventions including uterine artery ligation, hypogastric artery ligation, or peripartum hysterectomy for atony. We compared the risk of hemorrhage-related morbidity in those exposed to methylergonovine vs. carboprost. Propensity-score matching was used to account for potential confounders.The study cohort comprised 1,335 women; 870 (65.2%) women received methylergonovine and 465 (34.8%) women received carboprost. After accounting for potential confounders, the risk of hemorrhage-related morbidity was higher in the carboprost group than the methylergonovine group (RR = 1.7; 95% CI = 1.2 - 2.6).In this propensity-score matched analysis, methylergonovine was associated with reduced risk of hemorrhage-related morbidity during CD compared to carboprost. Based on these results, methylergonovine may be a more effective second line uterotonic.

    View details for DOI 10.1016/j.ajog.2015.01.008

    View details for Web of Science ID 000353598500025

    View details for PubMedID 25582104

  • Risk of Cardiovascular Disease Associated with a Restless Legs Syndrome Diagnosis in a Retrospective Cohort Study from Kaiser Permanente Northern California. Sleep Van Den Eeden, S. K., Albers, K. B., Davidson, J. E., Kushida, C. A., Leimpeter, A. D., Nelson, L. M., Popat, R., Tanner, C. M., Bibeau, K., Quesenberry, C. P. 2015; 38 (7): 1009-1015


    Recent cross-sectional studies suggest that restless legs syndrome (RLS) may be associated with an increased prevalence of cardiovascular disease (CVD) comorbidity or risk factors. We evaluated whether primary or secondary RLS was associated with an increased risk of incident cardiovascular disease in a retrospective cohort study within Kaiser Permanente Northern California (KPNC).We identified members of KPNC with primary RLS and secondary RLS between 1999 and 2008 by an algorithm that incorporated longitudinal clinical records related to the diagnosis and treatment of RLS and comorbidities. We then matched each RLS case with up to 50 individuals with no clinical records of RLS by age, sex, race/ethnicity, zip code, and membership duration. For the analyses we excluded any individual with coronary artery disease (CAD: angina, acute myocardial infarction, coronary revascularization procedure, CAD death), CVD (CAD plus stroke), and hypertension at baseline. New cardiovascular events were determined from clinical records. Follow-up ended at an outcome event, disenrollment from KPNC, or death, whichever occurred earliest. There were over 473,358 person-y of follow-up in this cohort analysis with a mean follow-up time of 3.91 y and range from 6 mo to 12 y. Survival analysis techniques, including survival curves and proportional hazard regression models, were used to assess the association between RLS status and CVD.There were 7,621 primary RLS and 4,507 secondary RLS cases identified and included in the study. In general, primary RLS cases were younger and had less comorbidity than secondary RLS cases. During the follow-up period, CVD was diagnosed in 478 primary RLS cohort members, CAD was diagnosed in 310, and hypertension events were identified in 1,466. Diagnosis in secondary RLS cohort members was made during the follow-up period with 451, 338, and 598 CVD, CAD, and hypertension events, respectively. Subjects with primary RLS had a similar risk of incident CVD (hazard ratio (HR) = 0.95; 95% confidence interval (CI) = 0.86-1.04) and CAD (HR = 0.99; 95% CI = 0.89-1.13) to the comparison cohort, with a slight elevation in the risk of hypertension events (HR = 1.19; 95% CI = 1.12-1.25), after multivariable adjustment. Individuals classified as secondary RLS had a significant increased risk of CVD (HR = 1.33; 95% CI = 1.21-1.46), CAD (HR = 1.40; 95% CI = 1.25-1.56), and hypertension (HR = 1.28; 95% CI = 1.18-1.40).Primary restless legs syndrome (RLS) was not associated with new-onset cardiovascular disease (CVD) or coronary artery disease (CAD) but was associated with a slight increased risk of hypertension. In contrast, secondary RLS was associated with an increased risk of CVD, CAD, and hypertension.

    View details for DOI 10.5665/sleep.4800

    View details for PubMedID 26083613

    View details for PubMedCentralID PMC4481004

  • Patterns of care in palliative radiotherapy: a population-based study. Journal of oncology practice / American Society of Clinical Oncology Murphy, J. D., Nelson, L. M., Chang, D. T., Mell, L. K., Le, Q. 2013; 9 (5): e220-7


    Approximately one half of the radiotherapy (RT) prescribed in the United States is delivered with palliative intent. The purpose of this study was to investigate the patterns of delivery of palliative RT across the United States.Using the Surveillance, Epidemiology, and End Results-Medicare linked database, 51,610 patients were identified with incident stage IV breast, prostate, lung, or colorectal cancer diagnosed between 2000 and 2007 and observed through 2009. Multivariate logistic regression determined predictors of palliative RT.Forty-one percent of the study population received palliative RT, including 53% of patients with lung cancer, followed by those with breast (42%), prostate (40%), and colorectal cancers (12%). Multivariate analysis revealed that older patients (P<.001) and those with higher Charlson comorbidity scores (P<.001) were less likely to receive palliative RT. Black patients with prostate cancer were 20% less likely (P<.001), and black patients with colorectal cancer were 28% less likely (P<.001), than white patients to receive palliative RT. Among those treated with RT, 23% of patients with lung cancer died within 2 weeks of completing treatment, followed by those with colorectal (12%), breast (11%), and prostate cancers (8%). In addition to tumor site, significant predictors (P<.05) of death within 2 weeks of receiving RT included increased age, increased comorbidity, and male sex.Inequality in the receipt of palliative RT exists among the elderly and patients with comorbid conditions and varies with race. In addition, a significant number of patients die shortly after receiving RT. Understanding these patterns of care, along with further research into the underlying causes, will improve access and quality of palliative RT.

    View details for DOI 10.1200/JOP.2012.000835

    View details for PubMedID 23943892

  • Is exposure to cyanobacteria an environmental risk factor for amyotrophic lateral sclerosis and other neurodegenerative diseases? AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION Bradley, W. G., Borenstein, A. R., Nelson, L. M., Codd, G. A., Rosen, B. H., Stommel, E. W., Cox, P. A. 2013; 14 (5-6): 325-333


    There is a broad scientific consensus that amyotrophic lateral sclerosis (ALS) is caused by gene-environment interactions. Mutations in genes underlying familial ALS (fALS) have been discovered in only 5-10% of the total population of ALS patients. Relatively little attention has been paid to environmental and lifestyle factors that may trigger the cascade of motor neuron death leading to the syndrome of ALS, although exposure to chemicals including lead and pesticides, and to agricultural environments, smoking, certain sports, and trauma have all been identified with an increased risk of ALS. There is a need for research to quantify the relative roles of each of the identified risk factors for ALS. Recent evidence has strengthened the theory that chronic environmental exposure to the neurotoxic amino acid β-N-methylamino-L-alanine (BMAA) produced by cyanobacteria may be an environmental risk factor for ALS. Here we describe methods that may be used to assess exposure to cyanobacteria, and hence potentially to BMAA, namely an epidemiologic questionnaire and direct and indirect methods for estimating the cyanobacterial load in ecosystems. Rigorous epidemiologic studies could determine the risks associated with exposure to cyanobacteria, and if combined with genetic analysis of ALS cases and controls could reveal etiologically important gene-environment interactions in genetically vulnerable individuals.

    View details for DOI 10.3109/21678421.2012.750364

    View details for Web of Science ID 000322782800001

    View details for PubMedID 23286757

  • Current pathways for epidemiological research in amyotrophic lateral sclerosis AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION Factor-Litvak, P., Al-Chalabi, A., Ascherio, A., Bradley, W., Chio, A., Garruto, R., Hardiman, O., Kamel, F., Kasarskis, E., McKee, A., Nakano, I., Nelson, L. M., Eisen, A. 2013; 14: 33-43


    Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. The current status of the epidemiology, challenges to its study, and novel study design options are discussed in this paper. We focus on recent results from large-scale population based prospective studies, case-control studies and population based registries, risk factors, and neuropathologic findings in chronic traumatic encephalomyelopathy. We identify areas of interest for future research, including time-trends in the incidence and prevalence of ALS; the meaning of lifetime risk; the phenotypic description of ALS; the definition of familial versus sporadic ALS, syndromic aspects of ALS; specific risk factors such as military service, life style factors such as smoking, the use of statins, and the presence of β-N-methylamino-L-alanine (BMAA), an excitotoxic amino acid derivative possibly produced by cyanobacteria found in almost every terrestrial and aquatic habitat; the emergence and disappearance of an endemic ALS in areas of the Pacific; and gene-environment interactions in the etiology of ALS. To move the epidemiology forward, we suggest using well-characterized cohorts of newly diagnosed ALS patients to identify risk and prognostic factors; storing biological material for future studies; building on the National ALS Registry as a resource of future studies; working in multidisciplinary consortia; and addressing the possible early life etiology of ALS.

    View details for DOI 10.3109/21678421.2013.778565

    View details for Web of Science ID 000319014100004

    View details for PubMedID 23678878

  • Utility of Capture-Recapture Methodology to Assess Completeness of Amyotrophic Lateral Sclerosis Case Ascertainment NEUROEPIDEMIOLOGY Wittie, M., Nelson, L. M., Usher, S., Ward, K., Benatar, M. 2013; 40 (2): 133-141


    With the establishment of a national amyotrophic lateral sclerosis (ALS) registry in the United States, methods are needed to ascertain the completeness of case ascertainment, especially in view of the proposal to rely largely on existing data sources.Data about ALS patients residing in the 5-county metropolitan Atlanta area (within the State of Georgia) from 2001 to 2005 were categorized according to their source--ALS Association, clinical (Emory Healthcare, community neurologist, Veterans Health Administration, Veterans Benefits Administration), Medicare and death certificates. ALS diagnoses were verified using chart review. Capture-recapture analyses were carried out using log-linear modeling, stratified by age and race.The final model (based on 798 cases), which included the 4 main sources and 3 two-way interaction terms, yielded an estimated total population of 880 (95% CI 816-965), indicating that the combination of case-finding methods identified about 90.7% of cases. The estimated 5-year period prevalence is 38.5/100,000 (95% CI 35.66-42.19).This study highlights gaps in data based on existing data sources and illustrates a method for combining data from multiple sources to help facilitate the successful establishment of a US national ALS registry.

    View details for DOI 10.1159/000342156

    View details for Web of Science ID 000314751700009

    View details for PubMedID 23095852

  • Associations of welding and manganese exposure with Parkinson disease Review and meta-analysis NEUROLOGY Mortimer, J. A., Borenstein, A. R., Nelson, L. M. 2012; 79 (11): 1174-1180


    To examine associations of welding and manganese exposure with Parkinson disease (PD) using meta-analyses of data from cohort, case-control, and mortality studies.Epidemiologic studies related to welding or manganese exposure and PD were identified in a PubMed search, article references, published reviews, and abstracts. Inclusion criteria were 1) cohort, case-control, or mortality study with relative risk (RR), odds ratio (OR), or mortality OR (MOR) and 95 confidence intervals (95% CI); 2) RR, OR, and MOR matched or adjusted for age and sex; 3) valid study design and analysis. When participants of a study were a subgroup of those in a larger study, only results of the larger study were included to assure independence of datasets. Pooled RR/OR estimates and 95% CIs were obtained using random effects models; heterogeneity of study effects were evaluated using the Q statistic and I(2) index in fixed effect models.Thirteen studies met inclusion criteria for the welding meta-analysis and 3 studies for the manganese exposure meta-analysis. The pooled RR for the association between welding and PD for all study designs was 0.86 (95% CI 0.80-0.92), with absence of between-study heterogeneity (I(2) = 0.0). Effect measures for cohort, case-control, and mortality studies were similar (0.91, 0.82, 0.87). For the association between manganese exposure and PD, the pooled OR was 0.76 (95% CI 0.41-1.42).Welding and manganese exposure are not associated with increased PD risk. Possible explanations for the inverse association between welding and PD include confounding by smoking, healthy worker effect, and hormesis.

    View details for DOI 10.1212/WNL.0b013e3182698ced

    View details for Web of Science ID 000308745900037

    View details for PubMedID 22965675

  • Cost-effectiveness of modern radiotherapy techniques in locally advanced pancreatic cancer CANCER Murphy, J. D., Chang, D. T., Abelson, J., Daly, M. E., Yeung, H. N., Nelson, L. M., Koong, A. C. 2012; 118 (4): 1119-1129


    Radiotherapy may improve the outcome of patients with pancreatic cancer but at an increased cost. In this study, the authors evaluated the cost-effectiveness of modern radiotherapy techniques in the treatment of locally advanced pancreatic cancer.A Markov decision-analytic model was constructed to compare the cost-effectiveness of 4 treatment regimens: gemcitabine alone, gemcitabine plus conventional radiotherapy, gemcitabine plus intensity-modulated radiotherapy (IMRT); and gemcitabine with stereotactic body radiotherapy (SBRT). Patients transitioned between the following 5 health states: stable disease, local progression, distant failure, local and distant failure, and death. Health utility tolls were assessed for radiotherapy and chemotherapy treatments and for radiation toxicity.SBRT increased life expectancy by 0.20 quality-adjusted life years (QALY) at an increased cost of $13,700 compared with gemcitabine alone (incremental cost-effectiveness ratio [ICER] = $69,500 per QALY). SBRT was more effective and less costly than conventional radiotherapy and IMRT. An analysis that excluded SBRT demonstrated that conventional radiotherapy had an ICER of $126,800 per QALY compared with gemcitabine alone, and IMRT had an ICER of $1,584,100 per QALY compared with conventional radiotherapy. A probabilistic sensitivity analysis demonstrated that the probability of cost-effectiveness at a willingness to pay of $50,000 per QALY was 78% for gemcitabine alone, 21% for SBRT, 1.4% for conventional radiotherapy, and 0.01% for IMRT. At a willingness to pay of $200,000 per QALY, the probability of cost-effectiveness was 73% for SBRT, 20% for conventional radiotherapy, 7% for gemcitabine alone, and 0.7% for IMRT.The current results indicated that IMRT in locally advanced pancreatic cancer exceeds what society considers cost-effective. In contrast, combining gemcitabine with SBRT increased clinical effectiveness beyond that of gemcitabine alone at a cost potentially acceptable by today's standards.

    View details for DOI 10.1002/cncr.26365

    View details for PubMedID 21773972

  • Osteoporosis Screening, Prevention, and Treatment in Systemic Lupus Erythematosus: Application of the Systemic Lupus Erythematosus Quality Indicators ARTHRITIS CARE & RESEARCH Schmajuk, G., Yelin, E., Chakravarty, E., Nelson, L. M., Panopolis, P., Yazdany, J. 2010; 62 (7): 993-1001


    Osteoporosis and fragility fractures are associated with significant morbidity for patients with systemic lupus erythematosus (SLE). New quality indicators (QIs) for SLE advise bone mineral density testing, calcium and vitamin D use, and antiresorptive or anabolic treatment for specific subgroups of patients receiving high-dose steroids.Subjects were participants in the University of California, San Francisco Lupus Outcomes Study, an ongoing longitudinal study of patients with physician-confirmed SLE, in 2007-2008. Patients responded to an annual telephone survey and were queried regarding demographic, clinical, and other health care-related variables. Multiple logistic regression was used to predict receipt of care per the QIs described above.One hundred twenty-seven patients met the criteria for the formal definitions of the denominators for QI I (screening) and QI II (calcium and vitamin D); 91 met the formal criteria for QI III (treatment). The proportions of patients receiving care consistent with the QIs were 74%, 58%, and 56% for QIs I, II, and III, respectively. In a sensitivity analysis of all steroid users (n = 427 for QI I and II and n = 224 for QI III), rates were slightly lower. Predictors of receiving care varied by QI and by denominator; however, female sex, older age, white race, and longer disease duration were associated with higher-quality care.Bone health-related care in this community-based cohort of SLE patients is suboptimal. Quality improvement efforts should address osteoporosis prevention and care among all SLE patients, especially those receiving high-dose, prolonged steroids.

    View details for DOI 10.1002/acr.20150

    View details for Web of Science ID 000280980000014

    View details for PubMedID 20589692

    View details for PubMedCentralID PMC2953549

  • Meeting Report: Consensus Statement-Parkinson's Disease and the Environment: Collaborative on Health and the Environment and Parkinson's Action Network (CHE PAN) Conference 26-28 June 2007 ENVIRONMENTAL HEALTH PERSPECTIVES Bronstein, J., Carvey, P., Chen, H., Cory-Slechta, D., DiMonte, D., Duda, J., English, P., Goldman, S., Grate, S., Hansen, J., Hoppin, J., Jewell, S., Kamel, F., Koroshetz, W., Langston, J. W., Logroscino, G., Nelson, L., Ravina, B., Rocca, W., Ross, G. W., Schettler, T., Schwarzschild, M., Scott, B., Seegal, R., Singleton, A., Steenland, K., Tanner, C. M., Van Den Eeden, S., Weisskopf, M. 2009; 117 (1): 117-121


    Parkinson's disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk.In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD.We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs.PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.

    View details for DOI 10.1289/ehp.11702

    View details for Web of Science ID 000262483900039

    View details for PubMedID 19165397

  • Simple counts of ADL dependencies do not adequately reflect older adults' preferences toward states of functional impairment JOURNAL OF CLINICAL EPIDEMIOLOGY Sims, T., Holmes, T. H., Bravata, D. M., Garber, A. M., Nelson, L. M., Goldstein, M. K. 2008; 61 (12): 1261-1270


    To use unweighted counts of dependencies in activities of daily living (ADLs) to assess the impact of functional impairment requires an assumption of equal preferences for each ADL dependency. To test this assumption, we analyzed standard gamble (SG) utilities of single and combination ADL dependencies among older adults.Four hundred older adults used multimedia software (FLAIR1) to report SG utilities for their current health and hypothetical health states of dependency in each of 7 ADLs and 8 of 30 combinations of ADL dependencies.Utilities for health states of multiple ADL dependencies were often greater than for states of single ADL dependencies. Dependence in eating, which is the ADL dependency with the lowest utility rating of the single ADL dependencies, ranked lower than 7 combination states. Similarly, some combination states with fewer ADL dependencies had lower utilities than those with more ADL dependencies. These findings were consistent across groups by gender, age, and education.Our results suggest that the count of ADL dependencies does not adequately represent the utility for a health state. Cost-effectiveness analyses and other evaluations of programs that prevent or treat functional dependency should apply utility weights rather than relying on simple ADL counts.

    View details for DOI 10.1016/j.jclinepi.2008.05.001

    View details for Web of Science ID 000261219700010

    View details for PubMedID 18722749

    View details for PubMedCentralID PMC2596888

  • Minimum incidence of primary task-specific focal hand dystonia 22nd Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinsons Disease and Other Movement Disorders Lo, R. Y., Tanner, C. M., Albers, K. B., Leimpeter, A. D., Fross, R., Comyns, K., Bernstein, A., Klingman, J., Goldman, S., Ozelius, L., Marras, C., Bressman, S., Comella, C., Risch, N., Nelson, L. M., McGee, B. S., Van Den Eeden, S. K. WILEY-BLACKWELL. 2008: 1630–30
  • Having IADL dependency does not prevent people from overestimating impact of ADL dependency. Annual Meeting of the American-Geriatrics-Society Sims, T., Mather, M., Mahlow, P., Nelson, L., Garber, A., Goldstein, M. WILEY-BLACKWELL. 2005: S2–S2
  • Invariance and inconsistency in utility ratings 22nd Annual Meeting of the Society-for-Medical-Decision-Making Bravata, D. M., Nelson, L. M., Garber, A. M., Goldstein, M. K. SAGE PUBLICATIONS INC. 2005: 158–67


    To assess utilities of composite health states for dependence in activities of daily living (ADLs) for invariance (i.e., when subjects provide a utility of 1 for all health states) and order inconsistency (i.e., when subjects order their utilities such that their utility for a combination of ADL dependencies is greater than their utility for any subset of the combination).Each of the 400 subjects, age 65 y and older, enrolled in one of several regional medical centers of the Kaiser Permanente Medical Care Program of Northern California and provided standard-gamble utilities for single ADL dependencies (e.g., bathing, dressing, continence) and for dependence in 8 other combinations of ADL dependencies. For order-inconsistent responses, the authors calculated the maximum magnitude of inconsistency as the maximum difference between the utility for the combined ADL dependence health state and that of its inconsistent subset.A total of 76 subjects (19%) gave a utility of 1.0 for all health states presented to them; 19 (5%) gave the same utility other than 1.0 for all health states; 130 (33%) gave at least 1 utility < 1.0 and had no order inconsistencies; and 175 (44%) had at least 1 order inconsistency. Invariance was associated with a Mini-Mental Status Examination score < 28.6 (P = 0.01), with education < 12 y (P = 0.004), with race/ethnicity other than non-Hispanic White/Caucasian (P = 0.001), and with shorter time spent on the utility elicitation task (P < 0.0001). Among the inconsistent subjects, 69% had a maximal magnitude of inconsistency that was within 1 standard deviation of the mean utilities. The maximal magnitude of inconsistency was associated with longer time spent on the elicitation task (P < 0.0001) and race/ethnicity other than non-Hispanic White/Caucasian (P = 0.005). The mean (s) utility for dependence in continence among consistent subjects who were not invariant (0.88 [0.24]) was higher than among inconsistent subjects (0.80 [0.27]; P = 0.01).Invariance and order inconsistencies in utility ratings for complex health states occur frequently. Utilities of consistent subjects may differ from those of inconsistent subjects. Utility assessments should attempt to measure and report these patterns.

    View details for DOI 10.1177/0272989X05275399

    View details for Web of Science ID 000228014000004

    View details for PubMedID 15800300

  • Environmental risk factors in multiple sclerosis - Causes, triggers, and patient autonomy NEUROLOGY Franklin, G. M., Nelson, L. 2003; 61 (8): 1032-1034

    View details for Web of Science ID 000186184500002

    View details for PubMedID 14581658

  • Risk of subsequent cancer following invasive or in situ squamous cell skin cancer ANNALS OF EPIDEMIOLOGY Efird, J. T., Friedman, G. D., Habel, L., Tekawa, I. S., Nelson, L. M. 2002; 12 (7): 469-475


    Determine the risk of subsequent cancer following squamous cell skin cancer.Using computerized surgical pathology records and membership data from a health maintenance organization, we retrospectively identified 822 individuals with primary squamous cell skin cancer (SCSC) and 3662 comparison subjects matched for age, sex, race, residence area, and length of membership. Patients were included in the study if they had no prior history of cancer, and received at least one multiphasic health checkup and questionnaire (MHC). Patients were followed for subsequent invasive cancer up to 24 years, with a mean follow-up time of 7.8 years.SCSC patients had a significantly greater risk [adjusted for body mass index (BMI) and education] for subsequent cancer overall (excluding non-melanoma skin cancer) [risk ratio (RR) = 1.4, 95% confidence interval (CI) = 1.2-1.6], and for basal cell skin cancer (RR = 13.8, 95% CI = 8.8-21.9), digestive (RR = 1.6, 95% CI = 1.1-2.4), and genitourinary cancers (RR = 1.5, 95% CI = 1.0-2.0). An increased, but not statistically significant, adjusted risk (RR > or = 1.4) was also observed for lip, oral cavity, and pharynx cancer (RR = 3.9, 95% CI = 0.6-25.0); non-cutaneous squamous cell cancer (RR = 1.9, 95% CI = 0.9-4.4); and respiratory and intrathoracic cancer (RR = 1.4, 95% CI = 0.8-2.6). The addition of alcohol consumption, combined occupational exposure, marital status, and smoking history to the multivariate model did not materially change any significant positive associations with SCSC.Our results suggest that patients diagnosed with SCSC may be at an increased risk of subsequent cancer at many sites, although several estimated risk estimates were within the limits of chance given no true association.

    View details for Web of Science ID 000178041400005

    View details for PubMedID 12377424

  • Household appliance use and residential exposure to 60-Hz magnetic fields JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY Mezei, G., Kheifets, L. I., Nelson, L. M., Mills, K. M., Iriye, R., Kelsey, J. L. 2001; 11 (1): 41-49


    We characterized the distribution of exposure to magnetic fields (MFs) during daily activities and during household appliance use, and estimated the relative contribution of various activities and appliances to total daily exposure. One hundred sixty-two subjects provided information on their patterns of appliance use and wore personal monitors for 24 h to collect MF exposure data. Of total exposure, 27% accumulated while subjects were in bed; 41% while at home but not in bed; 9% at work; and 24% elsewhere. Less than 2% of the total MF exposure accumulated during the use of each of the eight individual appliances considered, except computers, during the use of which 9% of the total exposure accumulated. Of the time subjects spent at exposure levels higher than 2 microT, 8% accumulated while they were using microwave ovens, and 4% and 3% while using computers and electric stoves, respectively. Mean MF measurements tended to be lowest when subjects were in bed and highest at work and during the use of microwave ovens, coffee grinders, hair dryers, and electric shavers. Results from questionnaires on household appliance use in the past year were not useful in predicting the total mean exposure level and over-threshold exposures measured by 24-h personal monitors. Significant MF exposure accumulates at home, at work, and elsewhere; therefore, accurate exposure assessment needs to consider residential, occupational, and other sources together. Questionnaire-based information on appliance use has limited value in the assessment of average and over-threshold exposure to MFs.

    View details for Web of Science ID 000167199800005

    View details for PubMedID 11246800

  • Reliability of proxy-reported and self-reported household appliance use EPIDEMIOLOGY Mills, K. M., Kheifets, L. I., Nelson, L. M., Bloch, D. A., Takemoto-Hambleton, R., Kelsey, J. L. 2000; 11 (5): 581-588


    Exposure assessment presents a major challenge for studies evaluating the association between household exposure to electric and magnetic fields and adverse health outcomes, especially the reliance on proxy respondents when study subjects themselves have died. We evaluated the reliability of proxy- and self-reported household appliance exposure. We recruited 92 healthy couples through either random-digit dialing or newspaper advertisements. Trained interviewers administered questionnaires to each member of a couple independently to assess the reliability of proxy-reported household appliance use. Eighty-five couples completed a second interview 2 months later to assess the reliability of self-reported appliance use. Reliability of proxy-reported appliance exposure was good when we inquired about having any exposure to each of the eight indicator appliances during the past year (range of kappa coefficients = 0.63-0.85; median = 0.76) but was lower with increased time to recall or increased detail. Reliability of self respondents reporting 2 months apart was excellent (range of kappa coefficients = 0.75-0.94; median = 0.87) for having any exposure to the eight indicator appliances during the past year, but reliability was again lower with increased detail. When we used self reports at the first interview as the standard, little systematic over- or underreporting occurred for proxy respondents or for self respondents reporting 2 months later. Because this study did not include cases of specific disease, these findings of no systematic differences in reporting do not refer to case or control status. In summary, reliability of self respondents' reports of appliance use is very good for recent time periods and good for broad aspects of exposure in distant time periods. Proxy respondents can provide information regarding broad aspects of appliance exposure in the past year, but detailed aspects of exposure or exposure in more distant time periods is not reliable.

    View details for Web of Science ID 000088854500015

    View details for PubMedID 10955412

  • International variation in the incidence of hip fractures: Cross-national project on osteoporosis for the World Health Organization program for research on aging OSTEOPOROSIS INTERNATIONAL Schwartz, A. V., Kelsey, J. L., Maggi, S., Tuttleman, M., Ho, S. C., Jonsson, P. V., Poor, G., de Castro, J. A., Xu, L., Matkin, C. C., Nelson, L. M., Heyse, S. P. 1999; 9 (3): 242-253


    A cross-national study of hip fracture incidence was carried out in five geographic areas--Beijing, China; Budapest, Hungary; Hong Kong; Porto Alegre, Brazil; and Reykjavik, Iceland--during the years 1990-1992. Cases of hip fracture among women and men of age 20 years and older were identified using hospital discharge data in conjunction with medical records, operating room logs, and radiology logs. Estimated incidence rates varied widely, with Beijing reporting the lowest rates (age-adjusted rate per 100,000 population for men 20 years and older = 45.4; women = 39.6) and Reykjavik the highest rates (man = 141.3; women = 274.1). Rates were higher for women than for men in every area except Beijing. In every area except Budapest, review of the operating room or radiology logs identified additional cases that were not reported in the discharge list, increasing the estimated number of hip fractures by 11% to 62%, depending on the area. Review of medical records identified miscoding of hip fractures (ICD 9820) as 'shaft of femur and other femur fractures' (ICD 9821) in the discharge lists of every area except Budapest, increasing the estimated number of hip fractures by 1% to 30%. The final estimates of hip fracture incidence taking into account all investigated sources of undercount and overcount ranged from 15% lower to 89% higher than an estimate based on the discharge diagnoses alone. Although these results indicate substantial limitations in relying on hospital discharge data alone to estimate hip fracture incidence rates, the extent of errors found in the discharge lists is smaller than the large international variation found here and previously reported in incidence rates. The findings support the conclusion that the differences reported among countries mainly reflect genuine variation in the hip fracture incidence rates.

    View details for Web of Science ID 000080177200010

    View details for PubMedID 10450414

  • Analysis of prenatal and gestational care given to women with epilepsy NEUROLOGY Seale, C. G., Morrell, M. J., Nelson, L., Druzin, M. L. 1998; 51 (4): 1039-1045


    To assess past care practices of neurologists and obstetricians to identify areas in which practice patterns differ from currently accepted optimal care.Retrospective chart review of 155 women identified as having a diagnosis of epilepsy (or seizure disorder) who had been pregnant any time between January 1988 and December 1995 and were admitted to Stanford University Hospital for delivery. A total of 161 pregnancies (132 women) were selected for study.An obstetrician was seen at some point during the pregnancy in 99% of the pregnancies, whereas a neurologist was seen at least once in only 64% of the pregnancies. In the 3 months before conception, an obstetrician was seen in 5% of the pregnancies and a neurologist was seen in 15%. Seventy-five percent of the patients taking antiepileptic medication and 65% of the untreated patients had documentation of folate supplementation at any time during pregnancy. Vitamin K supplementation in the final month of pregnancy was documented for only 41% of those receiving antiepileptic drugs. In over one-third of the pregnancies the mother did not have a maternal serum alpha-fetoprotein measure documented and a similar percentage did not receive genetic counseling. Monitoring of the maternal serum concentration of the non-protein-bound fraction of the prescribed antiepileptic drugs was not documented.We identified specific omissions of appropriate vitamin supplementation, genetic counseling, and drug level monitoring. Educational efforts should be targeted to improve the management of pregnancy in women with epilepsy.

    View details for Web of Science ID 000076399100024

    View details for PubMedID 9781526

  • Clinical and magnetic resonance imaging changes correlate in a clinical trial monitoring cyclosporine therapy for multiple sclerosis JOURNAL OF NEUROIMAGING Zhao, G. J., Redekop, W. K., Riddehough, A., Li, D. K., Cover, K., Wolinsky, J. S., Paty, D. W., Koopmans, R. A., Mietlowski, W., Scheinberg, L. C., Traugott, U., Aisen, M., Robbins, K., Hurwitz, B. J., Greenberg, S. M., FREDANE, L. M., HERBSTREITH, R., Hurwitz, J. G., Burk, J., McFarland, H. F., Goodman, A., McFarlin, D. E., Krebs, H., Maloni, H., Debronso, J., Franklin, G. M., Burks, J. S., Nelson, L., WANGAARD, C., Sears, S., Nath, A., Smith, L., McGinnis, J., TOURTELLOTE, W. W., Baumhefner, R. W., Ellison, G., Meyers, L., Syndulko, K., Newton, L. 1997; 7 (1): 1-7
  • Randomized trial of leaving messages on telephone answering machines for control recruitment in an epidemiologic study AMERICAN JOURNAL OF EPIDEMIOLOGY Koepsell, T. D., McGuire, V., Longstreth, W. T., Nelson, L. M., VANBELLE, G. 1996; 144 (7): 704-706


    To determine whether leaving messages on answering machines would aid control recruitment via random-digit telephone dialing, a randomized trial was conducted during 1992-1994 involving 1,323 western Washington households with answering machines. For the experimental group, a message was left informing them about the study and promising a call-back; for the control group, no message was left. Leaving a message increased the response rate by about 20 percentage points (p = 0.002). More households were successfully screened for eligible controls, and individuals found eligible were more likely to participate. Leaving a message can help to improve response rates in telephone surveys.

    View details for Web of Science ID A1996VJ77000011

    View details for PubMedID 8823067

  • HELICOBACTER-PYLORI, PEPSINOGEN, AND RISK FOR GASTRIC ADENOCARCINOMA CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Parsonnet, J., Samloff, I. M., Nelson, L. M., Orentreich, N., Vogelman, J. H., Friedman, G. D. 1993; 2 (5): 461-466


    The objective of this project was to determine the association of Helicobacter pylori infection and serum pepsinogen levels on subsequent risk for gastric adenocarcinoma. This nested case-control study was set in a large health maintenance organization. One hundred thirty-six cases of gastric adenocarcinoma and 136 matched controls without adenocarcinoma from a large cohort that had contributed serum in the 1960's were studied. The presence of IgG against H. pylori had previously been determined by enzyme-linked immunosorbent assay. Serum levels of pepsinogens I and II were ascertained by radioimmunoassay. In a sample of subjects, the presence of antiparietal cell antibodies was determined by immunofluorescent antibody assay (Nichols Laboratory). There were 98 cases of adenocarcinoma of the antrum, body, or fundus (distal cancers) and 30 of the cardia or gastroesophageal junction (proximal cancers). By univariate analysis, H. pylori infection [odds ratio (OR), 3.6; P < 0.001] and serum pepsinogen I < 50 ng/ml (OR = 2.9; P = 0.003) were both associated with development of distal cancer. In multivariate analysis, there was interaction between the two variables; H. pylori in the absence of low pepsinogen I was independently associated with cancer (OR, 2.4; P = 0.04) but low pepsinogen I in the absence of H. pylori infection was not associated with cancer (OR, 0.8; P > 0.5). In combination, however, H. pylori infection and a low pepsinogen I were associated with a marked increase in the risk of developing distal malignancy (OR, 10.0; P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1993LX26100010

    View details for PubMedID 8220091


    View details for Web of Science ID A1993KZ40600026

    View details for PubMedID 8474199



    Over 2 years, we identified 171 patients in King County, Washington, experiencing an incident subarachnoid hemorrhage and characterized their clinical course and outcome. Most (65%) were women and most (68%) were under age sixty-five. Only five died without medical attention. The remaining 166 patients were hospitalized and had CTs of the head. Of these, 103 underwent aneurysm surgery, 40 developed acute hydrocephalus, 32 had symptomatic vasospasm, and 30 re-bled. Sixty-eight percent (68%) survived to 1 month after the bleed and 62% to 1 year. Independent predictors of good recovery by 1 month after the bleed included youth, a high score on the admission Glasgow Coma Scale, and absence of blood on the first CT. In this population-based series, at 1 month after the bleed, approximately one-third of patients were dead, one-third had neurologic deficits, and one-third were doing well.

    View details for Web of Science ID A1993KX81200015

    View details for PubMedID 8469328

  • CIGARETTE-SMOKING, ALCOHOL-USE, AND SUBARACHNOID HEMORRHAGE STROKE Longstreth, W. T., Nelson, L. M., Koepsell, T. D., VANBELLE, G. 1992; 23 (9): 1242-1249


    Subarachnoid hemorrhage remains a devastating disease. Identification of etiologic risk factors would allow the possibility of prevention.We conducted a population-based case-control study in King County, Washington. Patients whose bleeds originated from a source other than an aneurysm were excluded. Two age- and gender-matched control subjects were identified for each case through random digit telephone dialing. A standardized in-person interview was conducted with the patient whenever possible, a proxy respondent for the case in all instances, the two control subjects, and their proxies. Analyses involved conditional logistic regression taking into account matching on age, gender and respondent type.Over 2 years, 169 cases were identified, and 149 participated in the case-control study. Compared with those who never smoked, the odds ratio for current heavy smokers (greater than 20 cigarettes/day) was 11.1 (95% confidence interval [CI], 5.0-24.9); for current light smokers (less than or equal to 20 cigarettes/day), 4.1 (95% CI, 2.3-7.3); and for former smokers, 1.8 (95% CI, 1.0-3.2). The risk associated with smoking was greatest in the 3 hours after a cigarette (odds ratio [OR] = 7.0; 95% CI, 3.7-13.1) and then fell, not reaching the risk in those who had never smoked until more than 10 years had passed since the last cigarette. Heavy alcohol use (greater than 2 drinks/day) was also associated with bleeds (OR = 2.2; 95% CI, 0.9-5.1, after adjusting for smoking status). These associations were not substantially altered after adjusting for several possible confounding factors, including a history of hypertension.Cigarette smoking and heavy alcohol use are associated with the occurrence of subarachnoid hemorrhage.

    View details for Web of Science ID A1992JK92600006

    View details for PubMedID 1519278

  • Utility of the sickness impact profile in Parkinson's disease. Journal of geriatric psychiatry and neurology Longstreth, W. T., Nelson, L., Linde, M., Muñoz, D. 1992; 5 (3): 142-148


    The Sickness Impact Profile (SIP) is a questionnaire consisting of 136 items grouped into 12 categories and two dimensions (physical and psychosocial). To characterize its utility in Parkinson's disease (PD), we administered the SIP to 44 consecutive clinic patients with PD. Compared to 44 age- and sex-matched control subjects, PD patients had their greatest dysfunction in the categories of mobility, communication, and home management. The two items that PD patients most commonly endorsed were, "I am having trouble writing or typing" (75%) and, "My sexual activity is decreased" (61%). In general, these treated PD patients had greater dysfunction in the psychosocial than physical dimensions. Two simple PD-specific scales correlated well with the physical dimension score but less so with the psychosocial dimension, suggesting that the SIP assesses more functional domains than the PD-specific scales used. The SIP holds some promise as a broad measure of functional status in PD patients.

    View details for PubMedID 1497791



    Weakness has been reported by patients as one side effect of baclofen. We evaluated torque production as a measure of contractile strength in 30 subjects with clinically definite multiple sclerosis. Participants, with minimal to moderate spasticity, were titrated onto baclofen by 5mg increments every other day for seven days and maintained at 20mg for one week. Using a KinCom isokinetic unit set at 60 degrees per second, subjects performed maximal concentric quadriceps contractions; three consecutive trials were recorded. Results indicated no significant difference in maximum torque production between sessions. Although torque values remained unchanged, the angle at which peak torque production occurred moved closer to normal values. Subjective reports of weakness do not appear related to physiologic properties of contraction, but may be a subjective interpretation that less stiffness is weakness because of less resistance to muscle contraction.

    View details for Web of Science ID A1992HH12300005

    View details for PubMedID 1543426



    Our purpose was to evaluate the association between spontaneous abortion and subsequent adverse birth outcomes.Washington State birth certificate records for 1984 to 1987 were used to examine the association between spontaneous abortion and adverse outcomes in the subsequent live birth. Adverse birth outcomes were examined for women with one spontaneous abortion before the index pregnancy (n = 2146) and for women with three or more prior spontaneous abortions and no other prior pregnancies (n = 638); compared with women with no prior spontaneous abortions (n = 3099). Logistic regression was used to estimate the relative risk associated with prior spontaneous abortion of each adverse outcome.Women with three or more prior spontaneous abortions were at higher risk for delivery at less than 37 weeks' gestation (relative risk 1.5, 95% confidence interval 1.1 to 2.1), placenta previa (relative risk 6.0, 95% confidence interval 1.6 to 22.2), having membranes ruptured greater than 24 hours (relative risk 1.8, 95% confidence interval 1.2 to 2.9), breech presentation (relative risk 2.4, 95% confidence interval 1.6 to 3.6), and having an infant with a congenital malformation (relative risk 1.8, 95% confidence interval 1.1 to 3.0).These findings suggest that common causes may underlie recurrent spontaneous abortion and certain adverse birth outcomes. They may also help guide clinical management of pregnancies in women with a history of recurrent spontaneous abortions.

    View details for Web of Science ID A1992HA45100027

    View details for PubMedID 1733179

  • CAFFEINE AND STROKE STROKE Longstreth, W. T., Nelson, L. M. 1992; 23 (1): 117-117

    View details for Web of Science ID A1992HA87600023

    View details for PubMedID 1731412

  • Cigarette smoking, alcohol use and subarchnoid hemorrhage Stroke Nelson LM, Longstreth WT Jr, Koepsell TD, van Belle G. 1992


    Thirty men and women diagnosed with definite multiple sclerosis (MS) were treated for ten weeks in a blinded, cross-over study. Patients with minimal to moderate spasticity were randomized to one of three sequences to evaluate the effects on MS-related spasticity of baclofen alone, stretching regimen with placebo, placebo alone, and stretching regimen with baclofen. The Cybex II isokinetic unit, timed gait, Ashworth scale, and subject's assessment of function were objective and subjective measures used to evaluate changes in hypertonicity. There was significant correlation between the Cybex and Ashworth as methods of measuring spasticity. Overall, treatment with baclofen alone significantly improved moderate quadriceps spasticity as measured by Cybex flexion scores. A trend, indicative of enhancing the beneficial effects of baclofen, was noted when stretching exercises were added to the treatment.

    View details for Web of Science ID A1991FA66400002

    View details for PubMedID 1998451



    Many epidemiologic studies indicate a relation between vigorous physical activity and amyotrophic lateral sclerosis. Physical activity itself is unlikely to cause amyotrophic lateral sclerosis, but could it modify the effects of other etiologic factors such as neurotoxins? Vigorous physical activity could potentiate the effect of a toxin to motor neurons by any of several mechanisms, especially if the toxin's effects were mediated through excitation. Exercise could alter the extent of exposure or could influence the distribution, metabolism or potency of an excitotoxin. Future epidemiologic studies of amyotrophic lateral sclerosis should include sufficient detail about vigorous physical exercise to explore this relationship further.

    View details for Web of Science ID A1991FA06900011

    View details for PubMedID 2041488

  • MULTIPLE-SCLEROSIS SIBLING PAIRS - CLUSTERED ONSET AND FAMILIAL PREDISPOSITION NEUROLOGY DOOLITTLE, T. H., Myers, R. H., LEHRICH, J. R., Birnbaum, G., Sheremata, W., Franklin, G. M., Nelson, L. M., Hauser, S. L. 1990; 40 (10): 1546-1552


    We evaluated 48 relapsing-remitting multiple sclerosis (R/R MS) sibling pairs derived from 44 families for age and date of onset of MS symptoms, clinical course, and family history of MS. Age- and sex-matched R/R MS clinic patients provided a statistical comparison group. The age of onset tended to cluster within multiplex families. The initial symptom of MS occurred within 5 years of age in 30/48 sibling pairs compared with 16/48 controls. A positive family history of MS (other than siblings) was present in 43% of the multiplex families compared with 20% among simplex controls. In 1st-, 2nd-, and 3rd-degree relatives who had lived into the age at risk, 22/1,134 family members of multiplex sibling pairs had probable or definite MS compared with 10/1,215 control family members. Age of onset clustering in siblings concordant for R/R MS and an increased risk of MS in other family members suggest that factors influencing disease onset may be in part inherited in these kindreds.

    View details for Web of Science ID A1990ED52000015

    View details for PubMedID 2215946

  • Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group. Annals of neurology 1990; 27 (6): 591-605


    Patients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between 1 and 3 grades in the year prior to entry were randomized to receive either cyclosporine (n = 273) or placebo (n = 274) in a 2-year, double-blinded, multicenter trial. Treatment groups at entry proved balanced for age, gender, duration of illness, and neurological disability. Cyclosporine dosage was adjusted for toxicity and a median trough whole-blood level was maintained between 310 and 430 ng/ml. The mean increase in EDSS score was 0.39 +/- 1.07 grades for cyclosporine-treated patients and 0.65 +/- 1.08 grades for placebo-treated patients from entry until the time of early withdrawal or completion of the study (p = 0.002). Of three primary efficacy criteria, cyclosporine delayed the time to becoming wheelchair bound (p = 0.038; relative risk, 0.765), but statistically significant effects were not observed for "time to sustained progression" or on a composite score of "activities of daily living." Active treatment did have a favorable effect on several secondary measures of disease outcome. A large and differential withdrawal rate (44% for cyclosporine-treated patients, 32% for placebo-treated patients) complicated the analysis but did not appear to explain the observed effect of cyclosporine in delaying disease progression. Multivariate analysis did not show institutional effects but did demonstrate substantial effects of baseline neurological disability on outcome. Nephrotoxicity and hypertension were common troublesome toxicities and accounted for most of the excess loss of patients in the cyclosporine arm of the study. Thus, chronic cyclosporine therapy was associated with a statistically significant but clinically modest delay of progression of disability in a group of patients with multiple sclerosis selected for moderately severe and progressive disease. Close supervision by physicians familiar with cyclosporine is mandatory to minimize known adverse effects, particularly nephrotoxicity, when considering the use of this immunosuppressant.

    View details for PubMedID 2193613



    Neuropsychological and neuroradiologic evidence of cerebral lesions is described for 12 patients with multiple sclerosis in whom cognitive disability was far greater than any other neurologic disability. Cognitive dysfunction resulted in significant functional impairment at work or home in three fourths (9 of 12) of the patients described here, despite mild physical disability (mean Kurtzke Expanded Disability Status Scale score, 3.2). A unique feature of the neurologic examination in these patients was the presence of prominent frontal release signs (gait apraxia and placing response) in the lower extremities. Two new scales, a Cognitive Function Scale and a Frontal Release Scale, were adapted for the investigation of these patients. The extensive literature relating to cognitive dysfunction in multiple sclerosis is reviewed and discussed with regard to its clinical relevance.

    View details for Web of Science ID A1989T148600009

    View details for PubMedID 2644924

  • A COMPARISON OF DEMENTIA IN ALZHEIMERS-DISEASE AND MULTIPLE-SCLEROSIS ARCHIVES OF NEUROLOGY Filley, C. M., Heaton, R. K., Nelson, L. M., Burks, J. S., Franklin, G. M. 1989; 46 (2): 157-161


    We compared results of comprehensive neuropsychological testing in 42 patients with clinically diagnosed Alzheimer's disease (AD) and in an equal number of patients with clinically definite chronic-progressive multiple sclerosis. Age, sex, and education were controlled using demographically corrected T scores based on a large normal sample. Both groups showed significant impairment on the test battery, but the degree of dementia was more severe in the patients with AD. A deviation score analysis, controlling for overall level of cognitive impairment, revealed significant differences between the groups. Alzheimer's disease was associated with relatively greater impairment of learning, memory, and verbal skills, whereas the MS group showed greater relative impairment of attention, incidental memory, and psychomotor functions. These data suggest that both the degree and pattern of mental impairement differ in patients with AD and patients with multiple sclerosis. Our results support a distinction between "gray matter" and "white matter" dementia, and may help clarify the issue of "cortical" vs "subcortical" dementia by demonstrating neuropsychological differences based on secure neuropathologic distinctions.

    View details for Web of Science ID A1989T148600008

    View details for PubMedID 2916954



    Cyclosporin is an immunosuppressive drug used with increasing frequency in patients with diabetes mellitus both as experimental primary therapy for insulin-dependent diabetes mellitus and as therapy accompanying pancreatic transplantation. However, reports have appeared contending that cyclosporin causes glucose intolerance and inhibits pancreatic islet beta-cell function. Consequently, concern has been raised that the beneficial effects of immunosuppression may be offset by adverse metabolic effects of the drug. To address this issue, we examined intravenous glucose tolerance and pancreatic islet beta-cell function in a group of nondiabetic multiple sclerosis patients before and during a 2-yr course of cyclosporin or placebo therapy. Patients were randomly assigned to one of the two drug groups and followed in a double-blind manner. Basal levels of glucose, insulin, and C-peptide as well as glucose disappearance rates and pancreatic islet beta-cell function after stimulation with intravenous glucose and arginine were determined immediately before therapy and after 3 wk, 6 mo, 1 yr, and 2 yr of therapy. No abnormalities in these parameters were observed in the cyclosporin of the placebo-treated group. It appears that cyclosporin can be give in conventional doses for as long as 2 yr without encountering evidence for impaired glucose homeostasis. However, whether adverse effects will materialize over longer periods of drug use remains a question.

    View details for Web of Science ID A1989R675300010

    View details for PubMedID 2642435



    Sixty patients with chronic/progressive MS received a newly assembled neuropsychological screening battery (NSB) and a brain MRI. A neuroradiologist blinded to NSB findings quantified cerebral lesions on MRI. We developed weighted brain area lesion scores according to number and size of cerebral lesions. Patients who were impaired on NSB testing had a significantly higher mean bihemispheric lesion score (X = 26.1) than those who were unimpaired (X = 17.4); this MRI lesion rating score correlated significantly with the cognitive summary score of the NSB (r = 0.35, p less than 0.01). However, we did not find a significant correlation between the Kurtzke Expanded Disability Status Scale and any MRI or NSB summary measures. Compared with the Mini-Mental State Exam (MMSE), the NSB cognitive summary score yielded a prevalence estimate for cognitive impairment that is more consistent with previous findings in chronic/progressive MS. The NSB is a useful screening test for cognitive dysfunction in chronic/progressive MS because of its relationship to cerebral lesions on MRI and its greater sensitivity than the frequently used MMSE.

    View details for Web of Science ID A1988R311300002

    View details for PubMedID 3194059

  • NEUROLOGY PRACTICE PATTERNS IN COLORADO NEUROLOGY Franklin, G. M., Ringel, S. P., Nelson, L. M., DELAPP, C. 1987; 37 (2): 287-289


    Eighty-one percent (47/58) of private-sector neurologists in Colorado responded to a mail survey of practice patterns. We evaluated patient load, degree of principal versus consultative care, and use of neurodiagnostic tests. Broad areas of neurologic education that were perceived to have been lacking during residency training were also addressed. Eight-four percent (41/49) of responding neurologists agreed to participate in a more comprehensive prospective study of neurology practice patterns. The prospective data will provide information to determine how many neurologists are needed and the applications for neurologic education.

    View details for Web of Science ID A1987F933500017

    View details for PubMedID 3808310

  • THE EFFECTS OF PREGNANCY IN MULTIPLE-SCLEROSIS - A RETROSPECTIVE STUDY NEUROLOGY Thompson, D. S., Nelson, L. M., Burns, A., Burks, J. S., Franklin, G. M. 1986; 36 (8): 1097-1099


    We reviewed the medical records of 178 women with multiple sclerosis to evaluate the number of completed pregnancies, current disability status, and relationship of pregnancy to onset of MS symptoms. We found no differences in the long-term disability of women with no pregnancies, one pregnancy, or two or more pregnancies. Women who had initial symptom onset in pregnancy experienced less subsequent disability than women whose symptoms began before or after pregnancy. Therefore, pregnancy per se or number of pregnancies has no effect on subsequent disability.

    View details for Web of Science ID A1986D492700016

    View details for PubMedID 3736873

  • Higher than expected prevalence of multiple sclerosis in northern Colorado: dependence on methodologic issues. Neuroepidemiology Nelson, L. M., Hamman, R. F., Thompson, D. S., BAUM, H. M., BOTELER, D. L., Burks, J. S., Franklin, G. M. 1986; 5 (1): 17-28


    A population-based study of multiple sclerosis (MS) was conducted in 2 northern Colorado counties in 1982 to determine MS prevalence, to compare the rates with recent North American surveys and to compare the methods used in these studies. Provisional cases were identified from: the patient rolls of MS service organizations, chart reviews in 2 neurology practices, a survey of physicians and a review of hospital discharge diagnoses. Crude-point prevalence for the 2-county region was 84 per 100,000. The age-adjusted rate was higher than the rate for the region above the 37th parallel projected from data in a 1976 national survey, but was comparable to rates obtained in localized surveys conducted in the northern tier of the country. The methodological results revealed that the highest yield sources were the MS service organizations and the neurology practice chart reviews. MS prevalence surveys which neglect these methods may underestimate MS prevalence by as much as 20-40%.

    View details for PubMedID 3489193


    View details for Web of Science ID A1985ADG6700014

    View details for PubMedID 3980815