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Kurth, Tobias

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Kurth

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Tobias

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Kurth, Tobias
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    Genome-wide meta-analysis identifies new susceptibility loci for migraine
    (2014) Anttila, Verneri; Winsvold, Bendik S.; Gormley, Padhraig; Kurth, Tobias; Bettella, Francesco; McMahon, George; Kallela, Mikko; Malik, Rainer; de Vries, Boukje; Terwindt, Gisela; Medland, Sarah E.; Todt, Unda; McArdle, Wendy L.; Quaye, Lydia; Koiranen, Markku; Ikram, M. Arfan; Lehtimäki, Terho; Stam, Anine H.; Ligthart, Lannie; Wedenoja, Juho; Dunham, Ian; Neale, Benjamin; Palta, Priit; Hamalainen, Eija; Schürks, Markus; Rose, Lynda M; Buring, Julie; Ridker, Paul; Steinberg, Stacy; Stefansson, Hreinn; Jakobsson, Finnbogi; Lawlor, Debbie A.; Evans, David M.; Ring, Susan M.; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari A; Freilinger, Tobias; Schoenen, Jean; Frants, Rune R.; Pelzer, Nadine; Weller, Claudia M.; Zielman, Ronald; Heath, Andrew C.; Madden, Pamela A.F.; Montgomery, Grant W.; Martin, Nicholas G.; Borck, Guntram; Göbel, Hartmut; Heinze, Axel; Heinze-Kuhn, Katja; Williams, Frances M.K.; Hartikainen, Anna-Liisa; Pouta, Anneli; van den Ende, Joyce; Uitterlinden, Andre G.; Hofman, Albert; Amin, Najaf; Hottenga, Jouke-Jan; Vink, Jacqueline M.; Heikkilä, Kauko; Alexander, Michael; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Wichmann, Heinz Erich; Aromaa, Arpo; Eriksson, Johan G.; Traynor, Bryan; Trabzuni, Daniah; Rossin, Elizabeth; Lage, Kasper; Jacobs, Suzanne B.R.; Gibbs, J. Raphael; Birney, Ewan; Kaprio, Jaakko; Penninx, Brenda W.; Boomsma, Dorret I.; van Duijn, Cornelia; Raitakari, Olli; Jarvelin, Marjo-Riitta; Zwart, John-Anker; Cherkas, Lynn; Strachan, David P.; Kubisch, Christian; Ferrari, Michel D.; van den Maagdenberg, Arn M.J.M.; Dichgans, Martin; Wessman, Maija; Smith, George Davey; Stefansson, Kari; Daly, Mark; Nyholt, Dale R.; Chasman, Daniel; Palotie, Aarno
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    Selectivity in Genetic Association with Sub-classified Migraine in Women
    (Public Library of Science, 2014) Chasman, Daniel; Anttila, Verneri; Buring, Julie; Ridker, Paul; Schürks, Markus; Kurth, Tobias
    Migraine can be sub-classified not only according to presence of migraine aura (MA) or absence of migraine aura (MO), but also by additional features accompanying migraine attacks, e.g. photophobia, phonophobia, nausea, etc. all of which are formally recognized by the International Classification of Headache Disorders. It remains unclear how aura status and the other migraine features may be related to underlying migraine pathophysiology. Recent genome-wide association studies (GWAS) have identified 12 independent loci at which single nucleotide polymorphisms (SNPs) are associated with migraine. Using a likelihood framework, we explored the selective association of these SNPs with migraine, sub-classified according to aura status and the other features in a large population-based cohort of women including 3,003 active migraineurs and 18,108 free of migraine. Five loci met stringent significance for association with migraine, among which four were selective for sub-classified migraine, including rs11172113 (LRP1) for MO. The number of loci associated with migraine increased to 11 at suggestive significance thresholds, including five additional selective associations for MO but none for MA. No two SNPs showed similar patterns of selective association with migraine characteristics. At one extreme, SNPs rs6790925 (near TGFBR2) and rs2274316 (MEF2D) were not associated with migraine overall, MA, or MO but were selective for migraine sub-classified by the presence of one or more of the additional migraine features. In contrast, SNP rs7577262 (TRPM8) was associated with migraine overall and showed little or no selectivity for any of the migraine characteristics. The results emphasize the multivalent nature of migraine pathophysiology and suggest that a complete understanding of the genetic influence on migraine may benefit from analyses that stratify migraine according to both aura status and the additional diagnostic features used for clinical characterization of migraine.
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    Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study
    (BMJ Publishing Group Ltd., 2015) Ladha, Karim; Vidal Melo, Marcos; McLean, Duncan J; Wanderer, Jonathan P; Grabitz, Stephanie D; Kurth, Tobias; Eikermann, Matthias
    Objective: To evaluate the effects of intraoperative protective ventilation on major postoperative respiratory complications and to define safe intraoperative mechanical ventilator settings that do not translate into an increased risk of postoperative respiratory complications. Design: Hospital based registry study. Setting: Academic tertiary care hospital and two affiliated community hospitals in Massachusetts, United States. Participants: 69 265 consecutively enrolled patients over the age of 18 who underwent a non-cardiac surgical procedure between January 2007 and August 2014 and required general anesthesia with endotracheal intubation. Interventions Protective ventilation, defined as a median positive end expiratory pressure (PEEP) of 5 cmH2O or more, a median tidal volume of less than 10 mL/kg of predicted body weight, and a median plateau pressure of less than 30 cmH2O. Main outcome measure Composite outcome of major respiratory complications, including pulmonary edema, respiratory failure, pneumonia, and re-intubation. Results: Of the 69 265 enrolled patients 34 800 (50.2%) received protective ventilation and 34 465 (49.8%) received non-protective ventilation intraoperatively. Protective ventilation was associated with a decreased risk of postoperative respiratory complications in multivariable regression (adjusted odds ratio 0.90, 95% confidence interval 0.82 to 0.98, P=0.013). The results were similar in the propensity score matched cohort (odds ratio 0.89, 95% confidence interval 0.83 to 0.97, P=0.004). A PEEP of 5 cmH2O and median plateau pressures of 16 cmH2O or less were associated with the lowest risk of postoperative respiratory complications. Conclusions: Intraoperative protective ventilation was associated with a decreased risk of postoperative respiratory complications. A PEEP of 5 cmH2O and a plateau pressure of 16 cmH2O or less were identified as protective mechanical ventilator settings. These findings suggest that protective thresholds differ for intraoperative ventilation in patients with normal lungs compared with those used for patients with acute lung injury.
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    Structural brain lesions and restless legs syndrome: a cross-sectional population-based study
    (BMJ Publishing Group, 2014) Rist, Pamela; Tzourio, Christophe; Elbaz, Alexis; Soumaré, Aïcha; Dufouil, Carole; Mazoyer, Bernard; Kurth, Tobias
    Objective: To evaluate the association between white matter lesion (WML) volume, silent infarcts and restless legs syndrome (RLS) in a population-based study of elderly individuals. Design: Cross-sectional study. Setting: Population-based Three-City study. Participants: 1035 individuals from the Dijon, France, centre of the Three-City study who had available information on volume of WMLs from MRIs and who answered questions about the prevalence of RLS. Primary outcome measure Prevalence of RLS. Results: WML volume was measured using an automated tissue segmentation method. Logistic regression was used to evaluate adjusted associations between tertiles of WML volume and RLS and between silent infarcts and RLS. 218 individuals (21.1%) were determined to have RLS. Compared with those in the first tertile of WML volume, individuals in the second tertile (OR=1.09; 95% CI 0.75 to 1.60) or third tertile (OR=1.17; 95% CI 0.79 to 1.74) did not have an increased prevalence of RLS. We also did not observe associations between the volume of deep or periventricular WML and RLS; nor did we observe an association between silent brain infarcts and RLS (OR=0.74; 95% CI 0.40 to 1.39). These findings were not modified by age or gender. Conclusions: Higher volume of WML and the presence of silent infarcts were not associated with an increased prevalence of RLS in this population-based cohort of elderly individuals.
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    Neostigmine reversal doesn’t improve postoperative respiratory safety
    (BMJ Publishing Group Ltd., 2013) Meyer, Matthew; Bateman, Brian; Kurth, Tobias; Eikermann, Matthias
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    Effects of obstructive sleep apnoea risk on postoperative respiratory complications: protocol for a hospital-based registry study
    (BMJ Publishing Group, 2016) Shin, Christina; Zaremba, Sebastian; Devine, Scott; Nikolov, Milcho; Kurth, Tobias; Eikermann, Matthias
    Introduction: Obstructive sleep apnoea (OSA), the most common type of sleep-disordered breathing, is associated with significant immediate and long-term morbidity, including fragmented sleep and impaired daytime functioning, as well as more severe consequences, such as hypertension, impaired cognitive function and reduced quality of life. Perioperatively, OSA occurs frequently as a consequence of pre-existing vulnerability, surgery and drug effects. The impact of OSA on postoperative respiratory complications (PRCs) needs to be better characterised. As OSA is associated with significant comorbidities, such as obesity, pulmonary hypertension, myocardial infarction and stroke, it is unclear whether OSA or its comorbidities are the mechanism of PRCs. This project aims to (1) develop a novel prediction score identifying surgical patients at high risk of OSA, (2) evaluate the association of OSA risk on PRCs and (3) evaluate if pharmacological agents used during surgery modify this association. Methods: Retrospective cohort study using hospital-based electronic patient data and perioperative data on medications administered and vital signs. We will use data from Partners Healthcare clinical databases, Boston, Massachusetts. First, a prediction model for OSA will be developed using OSA diagnostic codes and polysomnography procedural codes as the reference standard, and will be validated by medical record review. Results of the prediction model will be used to classify patients in the database as high, medium or low risk of OSA, and we will investigate the effect of OSA on risk of PRCs. Finally, we will test whether the effect of OSA on PRCs is modified by the use of intraoperative pharmacological agents known to increase upper airway instability, including neuromuscular blockade, neostigmine, opioids, anaesthetics and sedatives. Ethics and dissemination The Partners Human Research Committee approved this study (protocol number: 2014P000218). Study results will be made available in the form of manuscripts for publication and presentations at national and international meetings.
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    Headache, migraine and risk of brain tumors in women: prospective cohort study
    (Springer Milan, 2015) Kurth, Tobias; Buring, Julie; Rist, Pamela
    Background: While headache is a common symptom among brain tumors patients, often patients with common headache have concerns of being at risk for developing brain tumors. We aimed to disprove that migraine or headache in general is associated with increased risk of developing brain tumors. Methods: Prospective study among 39,534 middle-aged women, free of any cancer, and who provided information on headache history at baseline. We followed participants for occurrence of medical record-confirmed brain tumors. We ran multivariable-adjusted Cox proportional hazards models to evaluate associations between any headache, migraine, and non-migraine headache with incident brain tumors. We further evaluated whether migraine frequency and updated headache information during follow-up could be linked with brain tumors. Results: A total of 13,022 (32.9%) women reported headache, of which 5,731 were classified as non-migraine headache and 7,291 as migraine. During a mean follow-up of 15.8 years, 52 brain tumors were confirmed. The multivariable-adjusted hazard ratios (95% confidence interval) for brain tumors were 1.33 (0.76-2.34) for any headache, 1.18 (0.58-2.41) for migraine and 1.53 (0.75-3.12) for non-migraine headache. The association for any headache was further attenuated in time-varying analyses (1.15; 0.58-2.24). Those who experience migraine six times/year were also not at increased risk of brain tumor (0.67; 0.13-3.32). Conclusions: Results of this large, prospective cohort study in women do not provide evidence that headache in general or migraine in particular are associated with the occurrence of brain tumors. Our data should reassure patients with headache that brain tumor is not a long-term consequence of headache. Electronic supplementary material The online version of this article (doi:10.1186/s10194-015-0501-0) contains supplementary material, which is available to authorized users.
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    Prospective comorbidity-matched study of Parkinson's disease and risk of mortality among women
    (BMJ Publishing Group, 2016) Winter, Anke C; Rist, Pamela; Buring, Julie; Kurth, Tobias
    Background: Individuals with Parkinson's disease (PD) may have an increased risk of overall mortality compared to the general population. Women may have lower mortality rates from PD than men; however, studies among women on the effect of PD on mortality have been limited and may not have adequately controlled for confounding by comorbidities. Methods: We conducted a matched cohort study among participants in the Women's Health Study. 396 incident PD cases were identified through self-report. Each PD case was matched by age to a comparator who was alive and had the same modified Charlson comorbidity score as the PD case. The PD cases and matched comparators were followed for all-cause mortality. Cox proportional hazards models adjusted for age at the index date, smoking, alcohol consumption, exercise and body mass index were used to determine the association between PD and mortality. Results: During a median of 6.2 years of follow-up, 72 women died (47 PD cases and 25 comparators). The multivariable-adjusted HR for mortality was 2.60 (95% CI 1.56 to 4.32). Conclusions: PD was associated with more than a twofold increased risk of all-cause mortality among women. Results are similar to those observed among men.
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    Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas
    (Springer Berlin Heidelberg, 2016) Eising, Else; Huisman, Sjoerd M. H.; Mahfouz, Ahmed; Vijfhuizen, Lisanne S.; Anttila, Verneri; Winsvold, Bendik S.; Kurth, Tobias; Ikram, M. Arfan; Freilinger, Tobias; Kaprio, Jaakko; Boomsma, Dorret I.; van Duijn, Cornelia M.; Järvelin, Marjo-Riitta R.; Zwart, John-Anker; Quaye, Lydia; Strachan, David P.; Kubisch, Christian; Dichgans, Martin; Davey Smith, George; Stefansson, Kari; Palotie, Aarno; Chasman, Daniel; Ferrari, Michel D.; Terwindt, Gisela M.; de Vries, Boukje; Nyholt, Dale R.; Lelieveldt, Boudewijn P. F.; van den Maagdenberg, Arn M. J. M.; Reinders, Marcel J. T.
    Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology. Electronic supplementary material The online version of this article (doi:10.1007/s00439-016-1638-x) contains supplementary material, which is available to authorized users.
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    Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study
    (BMJ Publishing Group Ltd., 2012) Grosse-Sundrup, Martina; Henneman, Justin P; Sandberg, Warren S; Bateman, Brian; Uribe, Jose Villa; Nguyen, Nicole Thuy; Ehrenfeld, Jesse M.; Martinez, Elizabeth; Kurth, Tobias; Eikermann, Matthias
    Objective: To determine whether use of intermediate acting neuromuscular blocking agents during general anesthesia increases the incidence of postoperative respiratory complications. Design: Prospective, propensity score matched cohort study. Setting: General teaching hospital in Boston, Massachusetts, United States, 2006-10. Participants: 18 579 surgical patients who received intermediate acting neuromuscular blocking agents during surgery were matched by propensity score to 18 579 reference patients who did not receive such agents. Main outcome measures: The main outcome measures were oxygen desaturation after extubation (hemoglobin oxygen saturation <90% with a decrease in oxygen saturation after extubation of >3%) and reintubations requiring unplanned admission to an intensive care unit within seven days of surgery. We also evaluated effects on these outcome variables of qualitative monitoring of neuromuscular transmission (train-of-four ratio) and reversal of neuromuscular blockade with neostigmine to prevent residual postoperative neuromuscular blockade. Results: The use of intermediate acting neuromuscular blocking agents was associated with an increased risk of postoperative desaturation less than 90% after extubation (odds ratio 1.36, 95% confidence interval 1.23 to 1.51) and reintubation requiring unplanned admission to an intensive care unit (1.40, 1.09 to 1.80). Qualitative monitoring of neuromuscular transmission did not decrease this risk and neostigmine reversal increased the risk of postoperative desaturation to values less than 90% (1.32, 1.20 to 1.46) and reintubation (1.76, 1.38 to 2.26). Conclusion: The use of intermediate acting neuromuscular blocking agents during anesthesia was associated with an increased risk of clinically meaningful respiratory complications. Our data suggest that the strategies used in our trial to prevent residual postoperative neuromuscular blockade should be revisited.