Search

Objective: To assess the effect of World Trade Center (WTC) exposure on cardiovascular disease (CVD) in career firefighters. Methods: Firefighters from four US cities completed health questionnaires that provide information about demographics, CVD diagnoses, and CVD risk factors. Firefighters were also compared with respondents of the 2019 National Health Interview Survey. Results: Greater WTC exposure was positively associated with combined coronary artery disease, myocardial infarction, and angina (termed "CAD") when comparing WTC-exposed with non-WTC-exposed firefighters. Compared with the National Health Interview Survey population, firefighters had lower odds of CAD and stroke. Conclusions: An occupationally appropriate comparison is important to mitigate potential bias from the healthy worker effect. While the risk of CVD in WTC-exposed and non-WTC-exposed firefighters was significantly lower than a general US population, we observed an exposure gradient where greater WTC exposure was associated with greater odds of CVD., Competing Interests: Conflict of interest: H.C. received funding from the American Journal of Hypertension for work as a guest editor. All other authors have no conflicts of interest to declare., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

Background and Objective: We investigated the associations between the APOE genotype, intracerebral hemorrhage (ICH), and neuroimaging markers of cerebral amyloid angiopathy (CAA)., Methods: We included patients from a prospective, multicenter UK observational cohort study of patients with ICH and representative UK population controls. First, we assessed the association of the APOE genotype with ICH (compared with controls without ICH). Second, among patients with ICH, we assessed the association of APOE status with the hematoma location (lobar or deep) and brain CT markers of CAA (finger-like projections [FLP] and subarachnoid extension [SAE])., Results: We included 907 patients with ICH and 2,636 controls. The mean age was 73.2 (12.4 SD) years for ICH cases vs 69.6 (0.2 SD) for population controls; 50.3% of cases and 42.1% of controls were female. Compared with controls, any APOE ε2 allele was associated with all ICH (lobar and nonlobar) and lobar ICH on its own in the dominant model (OR 1.38, 95% CI 1.13-1.7, p = 0.002 and OR 1.50, 95% CI 1.1-2.04, p = 0.01, respectively) but not deep ICH in an age-adjusted analyses (OR 1.26, 95% CI 0.97-1.63, p = 0.08). In the cases-only analysis, the APOE ε4 allele was associated with lobar compared with deep ICH in an age-adjusted analyses (OR 1.56, 95% CI 1.1-2.2, p = 0.01). When assessing CAA markers, APOE alleles were independently associated with FLP (ε4: OR 1.74, 95% CI 1.04-2.93, p = 0.04 and ε2/ε4: 2.56, 95% CI 0.99-6.61, p = 0.05). We did not find an association between APOE alleles and SAE., Discussion: We confirmed associations between APOE alleles and ICH including lobar ICH. Our analysis shows selective associations between APOE ε2 and ε4 alleles with FLP, a CT marker of CAA. Our findings suggest that different APOE alleles might have diverging influences on individual neuroimaging biomarkers of CAA-associated ICH., (© 2022 American Academy of Neurology.)

Objective: To determine whether CT-based cerebral small vessel disease (SVD) biomarkers are associated with 6-month functional outcome after intracerebral hemorrhage (ICH) and whether these biomarkers improve the performance of the preexisting ICH prediction score., Methods: We included 864 patients with acute ICH from a multicenter, hospital-based prospective cohort study. We evaluated CT-based SVD biomarkers (white matter hypodensities [WMH], lacunes, brain atrophy, and a composite SVD burden score) and their associations with poor 6-month functional outcome (modified Rankin Scale score >2). The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test were used to assess discrimination and calibration of the ICH score with and without SVD biomarkers., Results: In multivariable models (adjusted for ICH score components), WMH presence (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.12-2.06), cortical atrophy presence (OR 1.80, 95% CI 1.19-2.73), deep atrophy presence (OR 1.66, 95% CI 1.17-2.34), and severe atrophy (either deep or cortical) (OR 1.94, 95% CI 1.36-2.74) were independently associated with poor functional outcome. For the revised ICH score, the AUROC was 0.71 (95% CI 0.68-0.74). Adding SVD markers did not significantly improve ICH score discrimination; for the best model (adding severe atrophy), the AUROC was 0.73 (95% CI 0.69-0.76). These results were confirmed when lobar and nonlobar ICH were considered separately., Conclusions: The ICH score has acceptable discrimination for predicting 6-month functional outcome after ICH. CT biomarkers of SVD are associated with functional outcome, but adding them does not significantly improve ICH score discrimination., Trial Registration Information: ClinicalTrials.gov Identifier: NCT02513316., (© 2021 American Academy of Neurology.)

Background and Purpose: The causes of recurrent ischemic stroke despite anticoagulation for atrial fibrillation are uncertain but might include small vessel occlusion. We investigated whether magnetic resonance imaging markers of cerebral small vessel disease (SVD) are associated with ischemic stroke risk during follow-up in patients anticoagulated for atrial fibrillation after recent ischemic stroke or transient ischemic attack., Methods: We analyzed data from a prospective multicenter inception cohort study of ischemic stroke or transient ischemic attack anticoagulated for atrial fibrillation (CROMIS-2 [Clinical Relevance of Microbleeds in Stroke Study]). We rated markers of SVD on baseline brain magnetic resonance imaging: basal ganglia perivascular spaces (number ≥11); cerebral microbleeds (number ≥1); lacunes (number ≥1); and white matter hyperintensities (periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2). We investigated the associations of SVD presence (defined as presence of ≥1 SVD marker) and severity (composite SVD score) with the risk of ischemic stroke during follow-up using a Cox proportional hazards model adjusted for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74, female score., Results: We included 1419 patients (mean age: 75.8 years [SD, 10.4]; 42.1% female). The ischemic stroke rate during follow-up in patients with any SVD was 2.20 per 100-patient years (95% CI, 1.60-3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59-1.62) in those without SVD ( P =0.008). After adjusting for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74, female score, SVD presence remained significantly associated with ischemic stroke during follow-up (hazard ratio, 1.89 [95% CI, 1.01-3.53]; P =0.046); the risk of recurrent ischemic stroke increased with SVD score (hazard ratio per point increase, 1.33 [95% CI, 1.04-1.70]; P =0.023)., Conclusions: In patients anticoagulated for atrial fibrillation after ischemic stroke or transient ischemic attack, magnetic resonance imaging markers of SVD are associated with an increased risk of ischemic stroke during follow-up; improved stroke prevention treatments are required in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02513316.

Objective: To investigate whether enlarged perivascular spaces (PVS) within the basal ganglia or deep cerebral white matter are risk factors for intracranial hemorrhage in patients taking oral anticoagulants (OACs), independent of established clinical and radiologic risk factors, we conducted a post hoc analysis of Clinical Relevance of Microbleeds in Stroke (CROMIS-2) (atrial fibrillation [AF]), a prospective inception cohort study., Methods: Patients with atrial fibrillation and recent TIA or ischemic stroke underwent standardized MRI prior to starting OAC. We rated basal ganglia PVS (BGPVS) and centrum semiovale PVS (CSOPVS), cerebral microbleeds (CMBs), white matter hyperintensities, and lacunes. We dichotomized the PVS rating using a threshold of >10 PVS in the relevant region of either cerebral hemisphere. The primary outcome was symptomatic intracranial hemorrhage (sICH). We identified risk factors for sICH using Cox regression., Results: A total of 1,386 participants with available clinical and imaging variables were followed up for a mean of 2.34 years; 14 sICH occurred (11 intracerebral). In univariable analysis, diabetes, CMB presence, lacune presence, and >10 BGPVS, but not CSOPVS, were associated with sICH. In a multivariable model incorporating all variables with significant associations in univariable analysis, >10 BGPVS (hazard ratio [HR] 8.96, 95% [CI] 2.41-33.4, p = 0.001) and diabetes (HR 3.91, 95% CI 1.34-11.4) remained significant risk factors for sICH., Conclusion: Enlarged BGPVS might be a novel risk factor for OAC-related ICH. The strength of this association and potential use in predicting ICH in clinical practice should be investigated in larger cohorts., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Outcomes in pediatric patients with ventricular assist devices (VADs) for advanced heart failure (HF) are improving, but the risk of associated morbidity and mortality remains substantial. Few data exist on the involvement of pediatric palliative care (PPC) in this high-risk patient population. We aimed to characterize the extent of palliative care involvement in the care of patients requiring VAD placement at our institution. Single-center retrospective chart review analyzing all VAD patients at a large pediatric center over a 4 year period. Timing and extent of palliative care subspecialty involvement were analyzed. Between January 2014 and December 2017, 55 HF patients underwent VAD implantation at our institution. Pediatric palliative care utilization steadily increased over consecutive years (2014: <10% of patients, 2015: 20% of patients, 2016: 50% of patients, and 2017: 65% of patients) and occurred in 42% (n = 23) of all patients. Of these, 57% (n = 13) occurred before VAD placement while 43% (n = 10) occurred after implantation. Patients who died during their VAD implant hospitalization (24%, n = 13) were nearly twice as likely to have PPC involvement (62%) as those who reached transplant (38%). Of those who died, patients who had PPC involved in their care were more likely to limit resuscitation efforts before their death. Four patients had advanced directives in place before VAD implant, of which three had PPC consultation before device placement. Three families (5%) refused PPC involvement when offered. Pediatric palliative care utilization is increasing in VAD patients at our institution. Early PPC involvement occurred in the majority of patients and appears to lead to more frequent discussion of goals-of-care and advanced directives.

Animal-assisted interventions are part of the therapeutic plan in pediatric oncology. This is the first systematic review to summarize the literature and provide insights for new clinical approaches, policy, best practices, and standards. The results underline the potentially beneficial role for pediatric patients, parents, caregivers, and medical staff.

Although the major burden of disease caused by smoking is observed in the adult population, two-third of smokers start before the age of 18 years. Reducing the number of young smokers could lead to marked improvements to the health of the UK population and save billions of pounds in National Health Service finances. However, very little is known about what makes children decide to not smoke or to quit early. We believe that increased awareness of the health risks associated with smoking will reduce smoking uptake among children. This study identifies a significant lack of knowledge among children aged 11-17 years at two London secondary schools and potentially identifies an area for improving our antismoking programmes. Although 80% of pupils cited lung cancer as being a smoking-related disease, very few other conditions could be recalled. We must do all we can to reduce smoking uptake in children. Understanding their baseline knowledge is the first step towards addressing the deficits in our current antismoking programmes.

Background and Purpose: Although the association between cerebral amyloid angiopathy (CAA) and cognitive impairment is increasingly recognized, it is not clear whether this is because of the impact of recurrent intracerebral hemorrhage (ICH) events, disruptions caused by cerebral small vessel damage, or both. We investigated this by considering whether cognitive impairment before ICH was associated with neuroimaging features of CAA on magnetic resonance imaging., Methods: We studied 166 patients with neuroimaging-confirmed ICH recruited to a prospective multicentre observational study. Preexisting cognitive impairment was determined using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Magnetic resonance imaging markers of cerebral small vessel disease, including CAA, were rated by trained observers according to consensus guidelines., Results: The prevalence of cognitive impairment before ICH was 24.7% (n=41) and, in adjusted analyses, was associated with fulfilling the modified Boston criteria for probable CAA at presentation (odds ratio, 4.01; 95% confidence interval, 1.53-10.51; P =0.005) and a higher composite CAA score (for each point increase, odds ratio, 1.42; 95% confidence interval, 1.03-1.97; P =0.033). We also found independent associations between pre-ICH cognitive decline and the presence of cortical superficial siderosis, strictly lobar microbleeds, and lobar ICH location, but not with other neuroimaging markers, or a composite small vessel disease score., Conclusions: CAA (defined using magnetic resonance imaging markers) is associated with cognitive decline before symptomatic ICH. This provides evidence that small vessel disruption in CAA makes an independent contribution to cognitive impairment, in addition to effects due to brain injury caused directly by ICH., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02513316., (© 2017 The Authors.)

Objective: To provide ICU clinicians with evidence-based guidance on safe medication use practices for the critically ill., Data Sources: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and ISI Web of Science for relevant material to December 2015., Study Selection: Based on three key components: 1) environment and patients, 2) the medication use process, and 3) the patient safety surveillance system. The committee collectively developed Population, Intervention, Comparator, Outcome questions and quality of evidence statements pertaining to medication errors and adverse drug events addressing the key components. A total of 34 Population, Intervention, Comparator, Outcome questions, five quality of evidence statements, and one commentary on disclosure was developed., Data Extraction: Subcommittee members were assigned selected Population, Intervention, Comparator, Outcome questions or quality of evidence statements. Subcommittee members completed their Grading of Recommendations Assessment, Development, and Evaluation of the question with his/her quality of evidence assessment and proposed strength of recommendation, then the draft was reviewed by the relevant subcommittee. The subcommittee collectively reviewed the evidence profiles for each question they developed. After the draft was discussed and approved by the entire committee, then the document was circulated among all members for voting on the quality of evidence and strength of recommendation., Data Synthesis: The committee followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation system to determine quality of evidence and strength of recommendations., Conclusions: This guideline evaluates the ICU environment as a risk for medication-related events and the environmental changes that are possible to improve safe medication use. Prevention strategies for medication-related events are reviewed by medication use process node (prescribing, distribution, administration, monitoring). Detailed considerations to an active surveillance system that includes reporting, identification, and evaluation are discussed. Also, highlighted is the need for future research for safe medication practices that is specific to critically ill patients.

Introduction: This study examined the effect of endurance exercise on dendritic arborization in the dentate gyrus subregion in rodents exposed to a predator scent stress (PSS)., Methods: Sprague-Dawley rats were randomly assigned to one of four treatment groups. In two of the groups, rats were unexposed to PSS but either remained sedentary (SED + UNEXP) or were exercised (EX + UNEXP). In the other two groups, rats were exposed to the PSS but either remained sedentary (SED + PSS) or were exercised (EX + PSS). After 6 wk of either exercise or sedentary lifestyle, rats were exposed to either the PSS or a sham protocol. During exercise, the animals ran on a treadmill at 15 m·min, 5 min·d gradually increasing to 20 min·d, 5 d·wk for 6 wk. Eight days after exposure to either PSS or sham protocol, changes in the cytoarchitecture (dendritic number, dendritic length, and dendrite spine density) of the dentate gyrus subregion of the hippocampus were assessed., Results: No differences (P = 0.493) were noted in dendritic number between the groups. However, dendritic length and dendrite spine density for SED + PSS was significantly smaller (P < 0.001) than that observed in all other groups. In addition, neurons from animals in SED + PSS had significantly fewer (P < 0.001) dendritic intersections than all other groups., Conclusion: The results of this study indicate that 6 wk of endurance training can protect dendritic length and complexity, suggesting a degree of resiliency to stress. This provides further evidence for supporting the inclusion of an exercise regimen for reducing the risk of posttraumatic stress disorder.

Study Design: This cross-sectional study was carried out on 196 adults (98 men and 98 women), aged between 18 and 91 years., Objective: To examine whether vertebral hemangiomas (VHs) are associated with other spinal pathologies, metabolic diseases, cardiovascular diseases, cancer and past trauma, to shed light on their possible pathophysiology., Summary of Background Data: VHs are the most common form of benign tumors in the spine. Their association with spinal and systemic pathologies has not yet been systematically studied., Methods: Clinical data were gathered from full spine CT scans and medical records., Results: VHs were significantly associated with disc lesions (P = 0.004), past trauma (P = 0.037), diabetes (χ = 5.179, P = 0.023), cardio-vascular diseases (χ = 8.625, P = 0.003), and cancer (χ = 5.820, P = 0.016), but not with obesity. Only medium-large size VHs were significantly associated with osteoporosis (χ = 6.695, P = 0.010)., Conclusion: The pattern of diseases related to VHs suggests a common cause for VH, namely, a disruption of vascular flow in the microvessels (accompanied by endothelium damage) within the vertebral body, eventually resulting in hypervascularization., Level of Evidence: 4.

Objective: To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated ICH., Methods: In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors., Results: We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3-5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0-21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037)., Conclusions: In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH., (© 2015 American Academy of Neurology.)

Introduction: This study examined the effects of endurance exercise on the behavioral response to stress and patterns of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), and δ-opioid receptor (phospho-DOR) expression in the hippocampus., Methods: Animals ran on a treadmill at 15 m·min, 5 min·d gradually increasing to 20 min·d, 5 d·wk for 6 wk. After training, one group of animals was exposed to a predator scent stress (PSS) protocol for 10 min. Outcome measurements included behavior in an elevated plus-maze (EPM) and acoustic startle response (ASR) 7 d after exposure to stress. Immunohistochemical technique was used to detect the expression of the BDNF, NPY, and phospho-DOR in the hippocampus 8 d after exposure., Results: Sedentary animals exposed to PSS were observed to have a greater incidence of extreme behavior responses including higher anxiety, less total activity in the EPM, and greater amplitude in the ASR than unexposed and/or trained animals. Exercise-trained animals exposed to PSS developed a resiliency to the stress, reflected by significantly greater total activity in the EPM, reduced anxiety, and reduced ASR compared to the sedentary, exposed animals. Exercise in the absence of stress significantly elevated the expression of BDNF and phospho-DOR, whereas exposure to PSS resulted in a significant decline in the expression of NPY, BDNF, and phospho-DOR. Trained animals that were exposed maintained expression of BDNF, NPY, and phospho-DOR in most subregions of the hippocampus., Conclusion: Results indicated that endurance training provided a mechanism to promote resilience and/or recovery from stress. In addition, exercise increased expression of BDNF, NPY, and DOR signaling in the hippocampus that was associated with the greater resiliency seen in the trained animals.

Lacosamide (LCM) is an antiepileptic medication used as an adjunctive treatment for partial seizures. Psychosis associated with LCM use is a rarely documented phenomenon, which may be difficult to detect in the context of the often complicated clinical presentation of epilepsy. We report the development of psychosis in a young woman after the use of LCM, which subsequently resolved with its discontinuation. The possible differential diagnosis and pharmacokinetic nuances are discussed. This is the first case report of LCM-induced psychosis in the United States.

Objectives: The aim of this study was to determine the ability of the central sensitization inventory (CSI), a new screening instrument, to assist clinicians in identifying patients with central sensitivity syndromes (CSSs)., Methods: Patients from a psychiatric medical practice (N=161), which specialized in the assessment and treatment of complex pain and psychophysiological disorders, were assessed for the presence of a CSS. CSI scores, using a previously determined cutoff of "40" of "100," were compared between the CSS patient group (n=99) and the non-CSS patient group (n=62). Information on false positives, false negatives, true positives, and true negatives were analyzed, and sensitivity and specificity analyses were conducted. In addition, CSS-relevant variables such as depression, abuse, and substance abuse were examined., Results: A large percentage of CSS patients had comorbid major depressive disorder (80%) and abuse history (43%), which was higher than rates for the patients without a CSS (55% and 24%, respectively). The CSI correctly identified 82.8% (n=82) of CSS patients as having a CSS (ie, sensitivity) and 54.8% (n=28) of non-CSS patients as not having a CSS (ie, specificity). False-positive patients (not diagnosed with a CSS, but scoring >40 on the CSI) reported more severe pain, interference in daily functioning, and abuse history, compared with the non-CSS patients who scored below 40 (ie, true negatives)., Conclusions: The CSI is a useful and valid instrument for screening patients for the possibility of a CSS, although the chances of false positives are relatively high when evaluating patients with complex pain and psychophysiological disorders.