Smoking as a risk factor for multiple sclerosis

Background: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure. Objective: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples. Methods: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression. Results: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0–2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3–3.8). Conclusions: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.

Download Full-text

Obstructive Sleep Apnea as a Risk Factor for Intracerebral Hemorrhage

Stroke ◽

10.1161/strokeaha.120.033342 ◽

2021 ◽

Author(s):

Jacqueline H. Geer ◽

Guido J. Falcone ◽

Kevin N. Vanent ◽

Audrey C. Leasure ◽

Daniel Woo ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Logistic Regression ◽

Risk Factor ◽

Sleep Apnea ◽

Intracerebral Hemorrhage ◽

Odds Ratio ◽

Berlin Questionnaire ◽

Multivariable Logistic Regression Model ◽

Obstructive Sleep ◽

Increased Risk

Background and Purpose: To determine whether obstructive sleep apnea (OSA) is associated with intracerebral hemorrhage (ICH) risk, we assessed premorbid OSA exposure of patients with nontraumatic ICH and matched controls. Methods: Ethnic/Racial Variations of Intracerebral Hemorrhage is a multicenter, case-control study evaluating risk factors for ICH that recruited 3000 cases with ICH and 3000 controls. OSA status was ascertained using the Berlin Questionnaire as a surrogate for premorbid OSA. We performed logistic regression analyses to evaluate the association between OSA and ICH. Results: Two thousand and sixty-four (71%) cases and 1516 (52%) controls were classified as having OSA by the Berlin Questionnaire. Cases with OSA were significantly more likely to be male and have hypertension, heart disease, hyperlipidemia, and higher body mass index compared with those without OSA. OSA was more common among cases compared with controls (71% versus 52%, odds ratio, 2.28 [95% CI, 2.05–2.55]). In a multivariable logistic regression model, OSA was associated with increased risk for ICH (odds ratio, 1.47 [95% CI, 1.29–1.67]). Conclusions: OSA is a risk factor for ICH.

Download Full-text

Risk of Surgery and Anesthesia for Ischemic Stroke

Anesthesiology ◽

10.1097/00000542-200002000-00024 ◽

2000 ◽

Vol 92 (2) ◽

pp. 425-425 ◽

Cited By ~ 46

Author(s):

Gilbert Y. Wong ◽

David O. Warner ◽

Darrell R. Schroeder ◽

Kenneth P. Offord ◽

Mark A. Warner ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Ischemic Stroke ◽

High Risk ◽

Confidence Interval ◽

Odds Ratio ◽

Independent Risk Factor ◽

Index Date ◽

Stroke Index ◽

Increased Risk

Background The goal of this study was to determine if the combination of surgery and anesthesia is an independent risk factor for the development of incident (first-time) ischemic stroke. Methods All residents of Rochester, MN, with incident ischemic stroke from 1960 through 1984 (1,455 cases and 1,455 age- and gender-matched controls) were used to identify risk factors associated with ischemic stroke. Cases and controls undergoing surgery involving general anesthesia or central neuroaxis blockade before their stroke/index date of diagnosis were identified. A conditional logistic regression model was used to estimate the odds ratio of surgery and anesthesia for ischemic stroke while adjusting for other known risk factors. Results There were 59 cases and 17 controls having surgery within 30 days before their stroke/index date. After adjusting for previously identified risk factors, surgery within 30 days before the stroke/index date (perioperative period) was found to be an independent risk factor for stroke (P<0.001; odds ratio, 3.9; 95% confidence interval, 2.1-7.4). In an analysis that excluded matched pairs where the case and/or control underwent surgery considered "high risk" for stroke (cardiac, neurologic, or vascular procedures), "non-high-risk surgery" was also found to be an independent risk factor for perioperative stroke (P = 0.002; odds ratio, 2.9; 95% confidence interval, 1.5-5.7). Conclusion Our results suggest that there is an increased risk of ischemic stroke in the 30 days after surgery and anesthesia. This risk remains elevated even after excluding surgeries (cardiac, neurologic, and vascular surgeries) considered to be high risk for ischemic stroke.

Download Full-text

Neuraxial analgesia is not associated with an increased risk of post-partum relapses in MS

Multiple Sclerosis Journal ◽

10.1177/1352458518763080 ◽

2018 ◽

Vol 25 (4) ◽

pp. 591-600 ◽

Cited By ~ 4

Author(s):

Caroline Lavie ◽

Fabien Rollot ◽

Françoise Durand-Dubief ◽

Romain Marignier ◽

Iuliana Ionescu ◽

...

Keyword(s):

Multiple Sclerosis ◽

Logistic Regression ◽

Regression Analysis ◽

Odds Ratio ◽

Post Partum ◽

Neuraxial Analgesia ◽

Increased Risk ◽

Obstetrical Analgesia ◽

The Impact ◽

Risk Of Relapse

Background: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses. Objective: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy. Methods: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992–1995 and 2005–2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis. Results: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78). Conclusion: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.

Download Full-text

Exposure to passive smoking during adolescence is associated with an increased risk of developing multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458520912500 ◽

2020 ◽

pp. 135245852091250 ◽

Cited By ~ 1

Author(s):

Ditte Bang Oturai ◽

Helle Bach Søndergaard ◽

Nils Koch-Henriksen ◽

Christina Andersen ◽

Julie Hejgaard Laursen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Logistic Regression ◽

Environmental Factors ◽

Passive Smoking ◽

Odds Ratio ◽

Blood Donors ◽

Propensity Scores ◽

Increased Risk ◽

Female Case ◽

Never Smokers

Background: Environmental factors are associated with acquiring multiple sclerosis (MS) particularly in adolescence. Objective: To test for association between MS and exposure to passive smoking at the age of 10–19. Methods: A total of 919 patients from the Danish MS Registry and Biobank and 3419 healthy blood donors who had not smoked before the age of 19 were targeted. We analyzed separately for each sex and for those never-smokers (cohort 1) and active smokers above the age of 19 (cohort 2). All participants completed standardized questionnaires about smoking and lifestyle. We matched cases and controls in the ratio of 1:2 by propensity scores discarding unmatchable individuals and used logistic regression adjusted for all covariates and interactions. Results: After matching, we included 110/213 male cases/controls and 232/377 female case/controls in cohort 1. In cohort 2, the numbers were 160/320 and 417/760, respectively. Among women in cohort 1, the odds ratio (OR) for MS by passive smoking at the age of 10–19 was 1.432 ( p = 0.037) but in men it was 1.232 ( p = 0.39). Among men in cohort 2, OR was 1.593 ( p = 0.022) but among women it was only 1.102 ( p = 0.44). Conclusion: Among never smokers, female MS cases were more often than female controls reported with passive smoking between the age of 10 and 19, and among smokers above the age of 19, male MS patients were more often than male controls reported with passive smoking.

Download Full-text

Bisphosphonates after Denosumab withdrawal reduce the vertebral fractures incidence

Acta Endocrinologica ◽

10.1530/eje-21-0157 ◽

2021 ◽

Author(s):

Giorgia Grassi ◽

Iacopo Chiodini ◽

Serena Palmieri ◽

Elisa Cairoli ◽

Maura Arosio ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Vertebral Fracture ◽

Confidence Interval ◽

Odds Ratio ◽

Treated Group ◽

Single Infusion ◽

Risk Increase ◽

Increased Risk ◽

Frax Score

Objective: Several studies showed the occurrence of vertebral fracture (VFx) in patients discontinuing denosumab (Dmab), suggesting the need of bisphosphonate (BPs) therapy to mitigate this VFx risk increase. However, the morphometric VFx (morphoVFx) incidence after Dmab discontinuation and the BPs effect on VFx risk in this setting are still a matter of debate. Design: Retrospective, monocentric study. Methods: In 120 patients (111 females) discontinuing Dmab, 19 have not been treated (Not-treated Group, 16 females, age 63.5±15.0 years) and 101 patients have been treated (Treated Group, 95 females, age 70.0±10.6 years) with BPs (28 alendronate, ALN; 73 zoledronate, ZOL, single infusion), respectively. We evaluated the incidence of both clinical VFx and morphoVFx in Treated Group and Non-treated Group. Results: Patients in Treated Group showed a 5.5% VFx incidence (n=6, 3 clinical, 3 morpho VFx), which was anyway lower than Not-treated Group patients (n=4, 21.1%, 4 clinical, 3 multiple, p=0.029), despite a comparable FRAX score at the time of Dmab initiation. The logistic regression analysis showed that the VFx incidence was independently associated with the lack of BPs treatment (odds ratio 13.9, 95% confidence interval 1.7-111.1, p=0.014), but not with the number of Dmab injections, age, duration of BPs before Dmab initiation, the BMD at Dmab withdrawal and the prevalence of VFx at Dmab withdrawal. Conclusions: The Dmab withdrawal is associated with an increased risk of clinical but not morphometric VFx. Therapy with ALN or with a single ZOL treatment are partially effective in reducing the increased VFx risk after Dmab withdrawal.

Download Full-text

A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese

Multiple Sclerosis Journal ◽

10.1177/1352458513482512 ◽

2013 ◽

Vol 19 (13) ◽

pp. 1696-1703 ◽

Cited By ~ 5

Author(s):

Jian Huang ◽

Satoshi Yoshimura ◽

Noriko Isobe ◽

Takuya Matsushita ◽

Tomomi Yonekawa ◽

...

Keyword(s):

Multiple Sclerosis ◽

Logistic Regression ◽

Confidence Interval ◽

Missense Mutation ◽

Clinical Features ◽

Odds Ratio ◽

Demyelinating Disease ◽

Healthy Controls ◽

Dominant Model ◽

Regression Analyses

Background: The G allele of NOTCH4 rs422951 is protective against demyelinating disease in Japanese. Objectives: The purpose of this study was to assess the relation of the G allele to neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) and multiple sclerosis (MS) and the interaction between the G allele and HLA-DRB1 alleles, and to clarify any association of the G allele with clinical features. Methods: DNA sequencing was used to genotype 106 NMO/NMOSD patients, 118 MS patients and 152 healthy controls (HCs) for rs422951. Results: G allele frequency in MS patients, but not that in NMO/NMOSD patients, was lower than that in HCs (8.9% vs 21.7%, p<0.0001, odds ratio (OR)=0.35). HLA-DRB1*0405 was positively associated with MS (OR=2.22, pcorr=0.0380) while DRB1*0901 was negatively associated (OR=0.32, pcorr =0.0114). Logistic regression analyses revealed that, after adjusting for gender and either HLA-DRB1*0405 or DRB1*0901, rs422951 was associated with MS in the dominant model (OR=0.37, 95% confidence interval (CI)= 0.20–0.66, p=0.0012). Haplotype analyses identified two susceptible and three resistant haplotypes formed from rs422951 and either HLA-DRB1*0405 or DRB1*0901. There were no statistically significant differences in clinical features between G allele carriers and non-G allele carriers. Conclusion: This NOTCH4 missense mutation decreased the risk for developing MS in Japanese, but did not affect clinical features of those who had already developed the disease.

Download Full-text

Symptoms from repeated intentional and unintentional head impact in soccer players

Neurology ◽

10.1212/wnl.0000000000003657 ◽

2017 ◽

Vol 88 (9) ◽

pp. 901-908 ◽

Cited By ~ 37

Author(s):

Walter F. Stewart ◽

Namhee Kim ◽

Chloe S. Ifrah ◽

Richard B. Lipton ◽

Tamar A. Bachrach ◽

...

Keyword(s):

Logistic Regression ◽

Confidence Interval ◽

Repeated Measures ◽

Odds Ratio ◽

Soccer Players ◽

Single Exposure ◽

Head Impacts ◽

Increased Risk ◽

On Line ◽

Differential Contribution

Objective:To determine the rate and differential contribution of heading vs unintentional head impacts (e.g., head to head, goal post) to CNS symptoms in adult amateur soccer players.Methods:Amateur soccer players completed baseline and serial on-line 2-week recall questionnaires (HeadCount) and reported (1) soccer practice and games, (2) heading and unintentional soccer head trauma, and (3) frequency and severity (mild to very severe) of CNS symptoms. For analysis, CNS symptoms were affirmed if one or more moderate, severe, or very severe episodes were reported in a 2-week period. Repeated measures logistic regression was used to assess if 2-week heading exposure (i.e., 4 quartiles) or unintentional head impacts (i.e., 0, 1, 2+) were associated with CNS symptoms.Results:A total of 222 soccer players (79% male) completed 470 HeadCount questionnaires. Mean (median) heading/2 weeks was 44 (18) for men and 27 (9.5) for women. One or more unintentional head impacts were reported by 37% of men and 43% of women. Heading-related symptoms were reported in 20% (93 out of 470) of the HeadCounts. Heading in the highest quartile was significantly associated with CNS symptoms (odds ratio [OR] 3.17, 95% confidence interval [CI] 1.57–6.37) when controlling for unintentional exposure. Those with 2+ unintentional exposures were at increased risk for CNS symptoms (OR 6.09, 95% CI 3.33–11.17) as were those with a single exposure (OR 2.98, 95% CI 1.69–5.26) when controlling for heading.Conclusions:Intentional (i.e., heading) and unintentional head impacts are each independently associated with moderate to very severe CNS symptoms.

Download Full-text

KNG1 Ile581Thr and susceptibility to venous thrombosis

Blood ◽

10.1182/blood-2010-11-319053 ◽

2011 ◽

Vol 117 (13) ◽

pp. 3692-3694 ◽

Cited By ~ 36

Author(s):

Pierre-Emmanuel Morange ◽

Tiphaine Oudot-Mellakh ◽

William Cohen ◽

Marine Germain ◽

Noémie Saut ◽

...

Keyword(s):

Risk Factor ◽

Confidence Interval ◽

Venous Thrombosis ◽

Partial Thromboplastin Time ◽

Genetic Risk ◽

Odds Ratio ◽

Activated Partial Thromboplastin Time ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Increased Risk

Abstract Three single nucleotide polymorphisms (SNPs) were recently found to be associated with activated partial thromboplastin time (aPTT). Because shortened aPTT levels have been observed in patients experiencing venous thrombosis (VT), we investigated the effects of these 3 aPTT-associated SNPs, rs2731672, rs9898, and rs710446, on the risk of VT in a sample of 1110 healthy patients and 1542 patients with VT. Among the 3 tested SNPs, only rs710446 was associated with VT risk; the rs710446-C allele was associated with an increased risk of VT (odds ratio 1.196, 95% confidence interval 1.071-1.336, P = .0012). This association also was observed in an independent sample of 590 controls and 596 patients (odds ratio 1.171, 95% confidence interval 0.889-1.541, P = .059). We also confirmed that the rs710446-C allele was associated with decreased aPTT levels, making this nonsynonymous Ile581Thr variant a new genetic risk factor for VT.

Download Full-text

Do Children Who Experience Laryngospasm Have an Increased Risk of Upper Respiratory Tract Infection?

Anesthesiology ◽

10.1097/00000542-199609000-00005 ◽

1996 ◽

Vol 85 (3) ◽

pp. 475-480. ◽

Cited By ~ 107

Author(s):

Mark S. Schreiner ◽

Irene O'Hara ◽

Dorothea A. Markakis ◽

George D. Politis

Keyword(s):

Confidence Interval ◽

Respiratory Infection ◽

Odds Ratio ◽

Signs And Symptoms ◽

Control Group ◽

Upper Respiratory Tract ◽

Upper Respiratory Infection ◽

Airway Surgery ◽

Increased Risk ◽

Upper Respiratory

Background Laryngospasm is the most frequently reported respiratory complication associated with upper respiratory infection and general anesthesia in retrospective studies, but prospective studies have failed to demonstrate any increase in risk. Methods A case-control study was performed to examine whether children with laryngospasm were more likely to have an upper respiratory infection on the day of surgery. The parents of all patients (N = 15,183) who were admitted through the day surgery unit were asked if their child had an active or recent (within 2 weeks of surgery) upper respiratory infection and were questioned about specific signs and symptoms to determine if the child met Tait and Knight's definition of an upper respiratory infection. Control subjects were randomly selected from patients whose surgery had occurred within 1 day of the laryngospasm event. Results Patients who developed laryngospasm (N = 123) were 2.05 times (95% confidence interval 1.21-3.45) more likely to have an active upper respiratory infection as defined by their parents than the 492 patients in the control group (P < or = 0.01). The development of laryngospasm was not related to Tait and Knight's definition for an upper respiratory infection or to recent upper respiratory infection. Children with laryngospasm were more likely to be younger (odds ratio = 0.92, 95% confidence interval 0.87-0.99), to be scheduled for airway surgery (odds ratio = 2.08, 95% confidence interval 1.21-3.59), and to have their anesthesia supervised by a less experienced anesthesiologist (odds ratio = 1.69, 95% confidence interval 1.04-2.7) than children in the control group. Conclusion Laryngospasm was more likely to occur in children with an active upper respiratory infection, children who were younger, children who were undergoing airway surgery, and children whose anesthesia were supervised by less experienced anesthesiologists. Understanding the risk factors and the magnitude of the likely risk should help clinicians make the decision as to whether to anesthetize children with upper respiratory infection.

Download Full-text

Systemic sclerosis portends increased risk of conduction and rhythm abnormalities at diagnosis and during disease course: A US population-based cohort

Journal of Scleroderma and Related Disorders ◽

10.1177/23971983211034074 ◽

2021 ◽

pp. 239719832110340

Author(s):

Yasser A Radwan ◽

Reto D Kurmann ◽

Avneek S Sandhu ◽

Edward A El-Am ◽

Cynthia S Crowson ◽

...

Keyword(s):

Risk Factors ◽

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Confidence Interval ◽

Cumulative Incidence ◽

Disease Onset ◽

Population Based ◽

Hazard Ratio ◽

Conduction Disorders ◽

Increased Risk

Objectives: To study the incidence, risk factors, and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis versus nonsystemic sclerosis comparators. Methods: An incident cohort of patients with systemic sclerosis (1980–2016) from Olmsted County, MN, was compared to age- and sex-matched nonsystemic sclerosis subjects (1:2). Electrocardiograms, Holter electrocardiograms, and a need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: Seventy-eight incident systemic sclerosis cases and 156 comparators were identified (mean age 56 years, 91% female). The prevalence of any conduction disorder before systemic sclerosis diagnosis compared to nonsystemic sclerosis subjects was 15% versus 7% ( p = 0.06), and any rhythm disorder was 18% versus 13% ( p = 0.33). During a median follow-up of 10.5 years in patients with systemic sclerosis and 13.0 years in nonsystemic sclerosis comparators, conduction disorders developed in 25 patients with systemic sclerosis with cumulative incidence of 20.5% (95% confidence interval: 12.4%–34.1%) versus 28 nonsystemic sclerosis patients with cumulative incidence of 10.4% (95% confidence interval: 6.2%–17.4%) (hazard ratio: 2.57; 95% confidence interval: 1.48–4.45), while rhythm disorders developed in 27 patients with systemic sclerosis with cumulative incidence of 27.3% (95% confidence interval: 17.9%–41.6%) versus 43 nonsystemic sclerosis patients with cumulative incidence of 18.0% (95% confidence interval: 12.3%–26.4%) (hazard ratio: 1.62; 95% confidence interval: 1.00–2.64). Age, pulmonary hypertension, and smoking were identified as risk factors. Conclusion: Patients with systemic sclerosis have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to nonsystemic sclerosis patients. These findings warrant increased vigilance and screening for electrocardiogram abnormalities in systemic sclerosis patients with pulmonary hypertension.

Download Full-text