[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: in animal models such as SOD1 transgenic mice, cell based models, autopsy studies and molecular genetic 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 fi ndings 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 defi nition of familial versus sporadic ALS, syndromic aspects of ALS; specifi c 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 Pacifi c; 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.
[Show abstract][Hide abstract] ABSTRACT: Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.
Journal of Autoimmunity 06/2012; · 8.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
PLoS ONE 01/2012; 7(3):e32768. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Cancer 07/2011; 118(4):1119-29. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of the neurological sciences 06/2011; 307(1-2):22-9. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
European Journal of Neurology 01/2011; 18(5):756-65. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Movement Disorders 11/2010; 25(15):2587-94. · 5.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Archives of neurology 11/2010; 68(3):310-3. · 7.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Movement Disorders 09/2010; 25(12):1809-17. · 5.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Arthritis care & research. 07/2010; 62(7):993-1001.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
Sleep Medicine 02/2010; 11(2):154-60. · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
Archives of neurology 01/2010; 67(1):51-7. · 7.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Archives of neurology 11/2009; 66(11):1353-8. · 7.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.