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| 102. |
- Vegrim, HM, et al.
(författare)
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Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 8079:111, s. 1130-1138
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Tidskriftsartikel (refereegranskat)abstract
- Women with epilepsy are recommended high doses of folic acid before and during pregnancy owing to risk of congenital anomalies associated with antiseizure medications. Whether prenatal exposure to high-dose folic acid is associated with increases in the risk of childhood cancer is unknown.ObjectiveTo assess whether high-dose folic acid supplementation in mothers with epilepsy is associated with childhood cancer.Design, Setting, and ParticipantsObservational cohort study conducted with nationwide registers in Denmark, Norway, and Sweden from 1997 to 2017. Analyses were performed during January 10, 2022, to January 31, 2022. Mother-child pairs were identified in medical birth registers and linked with information from patient, prescription, and cancer registers, as well as with sociodemographic information from statistical agencies, and were categorized by maternal diagnosis of epilepsy. The study population consisted of 3 379 171 children after exclusion of 126 711 children because of stillbirth or missing or erroneous values on important covariates.ExposuresMaternal prescription fills for high-dose folic acid tablets (≥1 mg daily) between 90 days before pregnancy start and birth.Main Outcomes and MeasuresFirst onset of childhood cancer at younger than 20 years. Cox proportional hazards models were used to calculate adjusted hazard ratios with corresponding 95% CIs, adjusted for potential confounders. Cumulative incidence at aged 20 years was used as a measure of absolute risk.ResultsThe median age at the end of follow-up in the study population of 3 379 171 children was 7.3 years (IQR, 3.5-10.9 years). Among the 27 784 children (51.4% male) born to mothers with epilepsy, 5934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with 18 exposed cancer cases compared with 29 unexposed, producing an adjusted hazard ratio of 2.7 (95% CI, 1.2-6.3), absolute risk if exposed of 1.4% (95% CI, 0.5%-3.6%), and absolute risk if unexposed of 0.6% (95% CI, 0.3%-1.1%). In children of mothers without epilepsy, 46 646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg), with 69 exposed and 4927 unexposed cancer cases and an adjusted hazard ratio of 1.1 (95% CI, 0.9-1.4; absolute risk, 0.4% [95% CI, 0.3%-0.5%]). There was no association between children born to mothers with epilepsy who were prenatally exposed to antiseizure medications, but not high-dose folic acid, and an increased risk of cancer (absolute risk, 0.6%; 95% CI, 0.2%-1.3%).Conclusions and RelevancePrenatal exposure to high-dose folic acid was associated with increased risk of cancer in children of mothers with epilepsy.
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| 104. |
- Videnovic, Aleksandar, et al.
(författare)
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Circadian Melatonin Rhythm and Excessive Daytime Sleepiness in Parkinson Disease.
- 2014
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 71:4, s. 463-469
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD. OBJECTIVE To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University. INTERVENTIONS Twenty-four hour monitoring of serum melatonin secretion. MAIN OUTCOMES AND MEASURES Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm. RESULTS Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm. CONCLUSIONS AND RELEVANCE Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD.
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| 105. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 106. |
- Wang, Yongjun, et al.
(författare)
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Efficacy and Safety of Ticagrelor and Aspirin in Patients With Moderate Ischemic Stroke : An Exploratory Analysis of the THALES Randomized Clinical Trial.
- 2021
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 78:9, s. 1091-1098
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Prior trials of dual antiplatelet therapy excluded patients with moderate ischemic stroke. These patients were included in the Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial, but results have not been reported separately, raising concerns about safety and efficacy in this subgroup.Objective: To evaluate the efficacy and safety of ticagrelor plus aspirin in patients with moderate ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 4 to 5).Design, Setting, and Participants: The THALES trial was a randomized trial conducted at 414 hospitals in 28 countries in January 2018 and December 2019. This exploratory analysis compared patients with moderate stroke (baseline NIHSS score of 4 to 5) with patients with less severe stroke (NIHSS score of 0 to 3). A total of 9983 patients with stroke were included in the present analysis, after excluding 2 patients with NIHSS scores greater than 5 and 1031 patients with transient ischemic attack. Data were analyzed from March to April 2021.Interventions: Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily on days 2 to 30) or placebo within 24 hours after symptom onset. All patients received aspirin, 300 to 325 mg, on day 1 followed by aspirin, 75 to 100 mg, daily on days 2 to 30. Patients were observed for 30 additional days.Main Outcomes and Measures: The primary outcome was time to stroke or death within 30 days. The primary safety outcome was time to severe bleeding.Results: In total, 3312 patients presented with moderate stroke and 6671 presented with less severe stroke. Of those in the moderate stroke group, 1293 (39.0%) were female, and the mean (SD) age was 64.5 (10.8) years; of those in the less severe stroke group, 2518 (37.7%) were female, and the mean (SD) age was 64.8 (11.2) years. The observed primary outcome event rate in patients with moderate stroke was 7.6% (129 of 1671) for those in the ticagrelor group and 9.1% (150 of 1641) for those in the placebo group (hazard ratio, 0.84; 95% CI, 0.66-1.06); the primary outcome event rate in patients with less severe stroke was 4.7% (158 of 3359) for those in the ticagrelor group and 5.7% (190 of 3312) for those in the placebo group (hazard ratio, 0.82; 95% CI, 0.66-1.01) (P for interaction = .88). Severe bleeding occurred in 8 patients (0.5%) in the ticagrelor group and in 4 patients (0.2%) in the placebo group in those with moderate stroke compared with 16 patients (0.5%) and 3 patients (0.1%), respectively, with less severe stroke (P for interaction = .26).Conclusions and Relevance: In this study, patients with a moderate ischemic stroke had consistent benefit from ticagrelor plus aspirin vs aspirin alone compared with patients with less severe ischemic stroke, with no further increase in the risk of intracranial bleeding or other severe bleeding events.Trial Registration: ClinicalTrials.gov Identifier: NCT03354429.
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| 107. |
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| 108. |
- Xu, Hui, et al.
(författare)
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Association of Lifespan Cognitive Reserve Indicator With Dementia Risk in the Presence of Brain Pathologies
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:10, s. 1184-1191
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Tidskriftsartikel (refereegranskat)abstract
- Importance Evidence on the association of lifespan cognitive reserve (CR) with dementia is limited, and the strength of this association in the presence of brain pathologies is unknown.Objective To examine the association of lifespan CR with dementia risk, taking brain pathologies into account.Design, setting, and participants This study used data from 2022 participants in the Rush Memory and Aging Project, an ongoing community-based cohort study with annual follow-up from 1997 to 2018 (mean follow-up, 6 years; maximum follow-up, 20 years). After excluding 420 individuals who had prevalent dementia, missing data on CR, or dropped out, 1602 dementia-free adults were identified at baseline and evaluated to detect incident dementia. During follow-up, 611 died and underwent autopsies. Data were analyzed from May to September 2018.Exposures Information on CR factors (education; early-life, midlife, and late-life cognitive activities; and social activities in late life) was obtained at baseline. Based on these factors, lifespan CR scores were captured using a latent variable from a structural equation model and was divided into tertiles (lowest, middle, and highest).Main outcomes and measures Dementia was diagnosed following international criteria. Neuropathologic evaluations for Alzheimer disease and other brain pathologies were performed in autopsied participants. The association of lifespan CR with dementia or brain pathologies was estimated using Cox regression models or logistic regression.Results Of the 1602 included participants, 1216 (75.9%) were women, and the mean (SD) age was 79.6 (7.5) years. During follow-up, 386 participants developed dementia (24.1%), including 357 participants with Alzheimer disease-related dementia (22.3%). The multiadjusted hazards ratios (HRs) of dementia were 0.77 (95% CI, 0.59-0.99) for participants in the middle CR score tertile and 0.61 (95% CI, 0.47-0.81) for those in the highest CR score tertile compared with those in the lowest CR score tertile. In autopsied participants, CR was not associated with most brain pathologies, and the association of CR with dementia remained significant after additional adjustment for brain pathologies (HR, 0.60; 95% CI, 0.42-0.86). The highest CR score tertile was associated with a reduction in dementia risk, even among participants with high Alzheimer disease pathology (HR, 0.57; 95% CI, 0.37-0.87) and any gross infarcts (HR, 0.34; 95% CI, 0.18-0.62).Conclusions and relevance High lifespan CR is associated with a reduction in dementia risk, even in the presence of high brain pathologies. Our findings highlight the importance of lifespan CR accumulation in dementia prevention.
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| 109. |
- Yuh, Esther L, et al.
(författare)
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Pathological computed tomography features associated with adverse outcomes after mild traumatic brain injury : A TRACK-TBI study with external validation in CENTER-TBI.
- 2021
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 78:9, s. 1137-1148
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood.OBJECTIVE: To identify pathological CT features associated with adverse outcomes after mTBI.DESIGN, SETTING, AND PARTICIPANTS: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021.EXPOSURES: Acute nonpenetrating head trauma.MAIN OUTCOMES AND MEASURES: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months.RESULTS: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study.CONCLUSIONS AND RELEVANCE: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.
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