Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.

BACKGROUND: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. METHODS: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. FINDINGS: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). INTERPRETATION: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. FUNDING: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

Magnetic Resonance Imaging Assists With Determining Etiology After Transient Ischemic Attack or Minor Stroke.

BACKGROUND: Magnetic resonance imaging infarct topography may assist with determining stroke etiology. The influence of diffusion-weighted imaging (DWI)-positive lesions on etiology determination in patients with transient ischemic attack or minor stroke is not well studied. METHODS AND RESULTS: We prospectively enrolled patients between 2010 and 2017 in 2 studies; participants with a final diagnosis of probable or definite transient ischemic attack or stroke were pooled for analysis. The primary outcome was the adjudicated ischemic etiology. We compared proportion of each etiology (cardioembolic, large-vessel, small-vessel disease, other) in patients who had DWI positivity compared with DWI negativity. We used logistic regression to determine the adjusted odds ratio (OR) for each etiology compared with undetermined by DWI positivity. The final analysis included 1498 patients: 832 (55.5%) were DWI-positive. DWI-positive patients were more likely to be diagnosed with small-vessel disease (19.1% versus 5.3%) and less likely with undetermined etiology (36.9% versus 53.0%; P<0.001). After adjustment, the presence of any DWI lesion was associated with increased odds of assigning any etiology (OR, 1.8 [95% CI, 1.3-2.5]). A single DWI lesion was associated with increased odds of small-vessel disease diagnosis (OR, 9.5 [95% CI, 6.4-14.0]), and multiple DWI lesions with reduced odds of small-vessel disease (OR, 0.2 [95% CI, 0.1-0.4]) but increased odds of all other etiologies compared with undetermined etiology. CONCLUSIONS: Any DWI-positive lesion after suspected transient ischemic attack or minor stroke was associated with increased odds of assigning a etiology. Presence and topography of DWI lesions on magnetic resonance imaging may assist with etiology determination and may impact stroke prevention therapies.

Presenting Symptoms and Diffusion-Weighted MRI Positivity by Time After Transient Neurologic Events: A Pooled Analysis of 3 Cohort Studies

BACKGROUND AND OBJECTIVE: The association between focal vs nonfocal presenting symptom and diffusion-weighted imaging (DWI) positivity in relation to onset-to-imaging time in patients with transient neurologic events remains unclear. We hypothesize that episodes consisting of focal symptoms would have proportionally higher DWI-positive imaging at later onset-to-imaging times. METHODS: Patients with transient neurologic symptoms and a normal neurologic examination who had DWI in the combined data set of 3 cohort studies were included. We used logistic regression models to evaluate the association between each type of presenting symptom (motor weakness, speech impairment, sensory symptoms, vision loss, diplopia, gait instability, dizziness, headache, presyncope, and amnesia) and DWI positivity after adjusting for clinical variables (age, sex, history of stroke, dyslipidemia, coronary artery disease, atrial fibrillation, symptoms duration [<10, 10-59, ≥60 minutes, or unclear], and study source). We stratified the results by onset-to-imaging time categories (<6 hours, 6-23 hours, and ≥24 hours). RESULTS: Of the total 2,411 patients (1,345 male, median age 68 years), DWI-positive lesions were detected in 598 patients (24.8%). The prevalence of DWI positivity was highest in those with motor weakness (34.7%), followed by speech impairment (33.5%). In a multivariable analysis, the presence of motor weakness, speech impairment, and sensory symptoms was associated with DWI positivity, while vision loss and headache were associated with lower odds of DWI positivity, but nevertheless had 13.6% and 15.3% frequency of DWI positive. The odds of being DWI positive varied by onset-to-imaging time categories for motor weakness, with greater odds of being DWI positive at later imaging time (<6 hours: odds ratio [OR] 1.25, 95% confidence interval [CI] 0.84-1.87; 6-23 hours: OR 2.24, 95% CI 1.47-3.42; and ≥24 hours: OR 2.42, 95% CI 1.74-3.36; interaction p = 0.033). Associations of other symptoms with DWI positivity did not vary significantly by time categories. DISCUSSION: We found that onset-to-imaging time influences the relationship between motor weakness and DWI positivity in patients with transient neurologic events. Compared with motor, speech, and sensory symptoms, visual or nonfocal symptoms carry a lower but still a substantive association with DWI positivity.

A Pragmatic, Person-Centered View of Cannabis in the United States: Pursuing Care That Transcends Beliefs.

BACKGROUND: Rates of cannabis use are increasing in the United States, likely as a result of changes in societal attitudes and expanding legalization. Although many patients report wanting to discuss the risks and benefits of cannabis use with their clinical providers, many providers hold conflicting beliefs regarding cannabis use and often do not engage patients in discussion about cannabis. This dilemma is underscored by the limitations imposed on cannabis related research, and lack of empirically based best-practice guidelines for clinicians when addressing cannabis use with patients. OBJECTIVES: We aimed to briefly summarize clinician and patient attitudes toward cannabis use and review current clinical guidelines and provide suggestions to assist health care providers and clinicians in increasing their comfort and skill in discussing cannabis use with patients. METHODS: A narrative review on attitudes toward cannabis use and clinical guidelines was performed to summarize the literature and provide evidence-based recommendations. RESULTS: Attitudes toward cannabis use have been shaped by personal and political factors and contribute to clinician hesitance in speaking with patients about the topic. Administrative barriers have hindered the development of clearer public health guidelines that might enable the dissemination of evidence-based information on the health effects of cannabis use and might ultimately lead to better health outcomes. CONCLUSION: Not discussing cannabis use with patients may be a crucial missed opportunity for harm reduction. In the absence of empirically supported best-practice guidelines, a person-centered approach can facilitate conversations on the harms and benefits of cannabis use.

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. Main Outcomes and Measures: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. Results: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Conclusions and Relevance: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03866174.

Association Between Duration of Transient Neurological Events and Diffusion-Weighted Brain Lesions.

Background The relationship between duration of transient neurological events and presence of diffusion-weighted lesions by symptom type is unclear. Methods and Results This was a substudy of SpecTRA (Spectrometry for Transient Ischemic Attack Rapid Assessment), a multicenter prospective cohort of patients with minor ischemic cerebrovascular events or stroke mimics at academic emergency departments in Canada. For this study we included patients with resolved symptoms and determined the presence of diffusion-weighted imaging (DWI) lesion on magnetic resonance imaging within 7 days. Using logistic regression, we evaluated the association between symptom duration and DWI lesion, assessing for interaction with symptom type (focal only versus nonfocal/mixed), and adjusting for age, sex, education, comorbidities, and systolic blood pressure. Of 658 patients included, a DWI lesion was present in 232 (35.1%). There was a significant interaction between symptom duration and symptom type. For those with focal-only symptoms, there was a continuous increase in DWI probability up to 24 hours in duration (ranging from ≈40% to 80% probability). In stratified analyses, the increase in probability of DWI lesion with increased duration of focal symptoms was seen in women but not men. For those with nonfocal or mixed symptoms, predicted probability of DWI lesion was ≈35% and was greater in men, but did not increase with longer duration. Conclusions Increased duration of neurological deficits is associated with greater probability of DWI lesion in those with focal symptoms only. For individuals with nonfocal or mixed symptoms, about one-third had DWI lesions, but the probability did not increase with duration. These results may be important to improve risk stratification of transient neurological events.

Synaptic Dysfunction by Mutations in GRIN2B: Influence of Triheteromeric NMDA Receptors on Gain-of-Function and Loss-of-Function Mutant Classification.

GRIN2B mutations are rare but often associated with patients having severe neurodevelopmental disorders with varying range of symptoms such as intellectual disability, developmental delay and epilepsy. Patient symptoms likely arise from mutations disturbing the role that the encoded NMDA receptor subunit, GluN2B, plays at neuronal connections in the developing nervous system. In this study, we investigated the cell-autonomous effects of putative gain- (GoF) and loss-of-function (LoF) missense GRIN2B mutations on excitatory synapses onto CA1 pyramidal neurons in organotypic hippocampal slices. In the absence of both native GluN2A and GluN2B subunits, functional incorporation into synaptic NMDA receptors was attenuated for GoF mutants, or almost eliminated for LoF GluN2B mutants. NMDA-receptor-mediated excitatory postsynaptic currents (NMDA-EPSCs) from synaptic GoF GluN1/2B receptors had prolonged decays consistent with their functional classification. Nonetheless, in the presence of native GluN2A, molecular replacement of native GluN2B with GoF and LoF GluN2B mutants all led to similar functional incorporation into synaptic receptors, more rapidly decaying NMDA-EPSCs and greater inhibition by TCN-201, a selective antagonist for GluN2A-containing NMDA receptors. Mechanistic insight was gained from experiments in HEK293T cells, which revealed that GluN2B GoF mutants slowed deactivation in diheteromeric GluN1/2B, but not triheteromeric GluN1/2A/2B receptors. We also show that a disease-associated missense mutation, which severely affects surface expression, causes opposing effects on NMDA-EPSC decay and charge transfer when introduced into GluN2A or GluN2B. Finally, we show that having a single null Grin2b allele has only a modest effect on NMDA-EPSC decay kinetics. Our results demonstrate that functional incorporation of GoF and LoF GluN2B mutants into synaptic receptors and the effects on EPSC decay times are highly dependent on the presence of triheteromeric GluN1/2A/2B NMDA receptors, thereby influencing the functional classification of NMDA receptor variants as GoF or LoF mutations. These findings highlight the complexity of interpreting effects of disease-causing NMDA receptor missense mutations in the context of neuronal function.

The Pharmacology and Clinical Applications of Psychedelic Medicines Within Midwifery Practice.

The research and use of psychedelic medicines to treat common mental health disorders has increased substantially in the past 2 decades. At the same time, knowledge is relatively uncommon among midwives regarding (1) the relative benefits of psychedelic-assisted therapy, (2) best practices associated with the delivery of psychedelic-assisted therapy, and (3) responsible integration of this potentially useful intervention into mental health treatment plans. The purpose of this review is to describe current applications of psychedelic medicines to treat common mental health disorders, to describe the current legal status of these medicines used in this context, and to explore the potential for midwifery practice in this area with further training. This article also addresses the disparities regarding LGBTQIA+ and BIPOC populations in relation to this topic and their historical exclusion from research and treatment access in this field.

A multi-hit hypothesis for an APOE4-dependent pathophysiological state.

The APOE gene encoding the Apolipoprotein E protein is the single most significant genetic risk factor for late-onset Alzheimer's disease. The APOE4 genotype confers a significantly increased risk relative to the other two common genotypes APOE3 and APOE2. Intriguingly, APOE4 has been associated with neuropathological and cognitive deficits in the absence of Alzheimer's disease-related amyloid or tau pathology. Here, we review the extensive literature surrounding the impact of APOE genotype on central nervous system dysfunction, focussing on preclinical model systems and comparison of APOE3 and APOE4, given the low global prevalence of APOE2. A multi-hit hypothesis is proposed to explain how APOE4 shifts cerebral physiology towards pathophysiology through interconnected hits. These hits include the following: neurodegeneration, neurovascular dysfunction, neuroinflammation, oxidative stress, endosomal trafficking impairments, lipid and cellular metabolism disruption, impaired calcium homeostasis and altered transcriptional regulation. The hits, individually and in combination, leave the APOE4 brain in a vulnerable state where further cumulative insults will exacerbate degeneration and lead to cognitive deficits in the absence of Alzheimer's disease pathology and also a state in which such pathology may more easily take hold. We conclude that current evidence supports an APOE4 multi-hit hypothesis, which contributes to an APOE4 pathophysiological state. We highlight key areas where further study is required to elucidate the complex interplay between these individual mechanisms and downstream consequences, helping to frame the current landscape of existing APOE-centric literature.

Effects of Naturalistic Psychedelic Use on Depression, Anxiety, and Well-Being: Associations With Patterns of Use, Reported Harms, and Transformative Mental States.

Survey-based studies suggest naturalistic psychedelic use provides mental health benefits similar to those observed in clinical trials. The current study sought to confirm these findings in a large group of psychedelic users and to conduct a novel examination of associations between amount of psychedelic use and behavioral outcomes, as well as frequency of harms ascribed to psychedelic use. A cross-sectional, online survey was completed by 2,510 adults reporting at least one lifetime psychedelic experience. Participants retrospectively completed a battery of instruments assessing depression, anxiety, and emotional well-being prior to and following psychedelic exposure. Participants also reported preferred psychedelic agent, number of uses, and harms attributed to psychedelic use. Psychedelic use was associated with significant improvements in depressive and anxious symptoms and with increased emotional well-being. These improvements increased in magnitude with increasing psychedelic exposure, with a ceiling effect. However, improvements were noted following a single lifetime use. Strong evidence for benefit of one preferred psychedelic agent over another was not observed, but enduring increases in factors related to mystical-experience and prosocial perspective taking associated with enhanced mental health. Thirteen percent of the survey sample (n = 330) endorsed at least one harm from psychedelic use, and these participants reported less mental health benefit. Results from the current study add to a growing database indicating that psychedelic use-even outside the context of clinical trials-may provide a wide range of mental health benefits, while also posing some risk for harm in a minority of individuals.

Common synaptic phenotypes arising from diverse mutations in the human NMDA receptor subunit GluN2A.

Dominant mutations in the human gene GRIN2A, encoding NMDA receptor (NMDAR) subunit GluN2A, make a significant and growing contribution to the catalogue of published single-gene epilepsies. Understanding the disease mechanism in these epilepsy patients is complicated by the surprising diversity of effects that the mutations have on NMDARs. Here we have examined the cell-autonomous effect of five GluN2A mutations, 3 loss-of-function and 2 gain-of-function, on evoked NMDAR-mediated synaptic currents (NMDA-EPSCs) in CA1 pyramidal neurons in cultured hippocampal slices. Despite the mutants differing in their functional incorporation at synapses, prolonged NMDA-EPSC current decays (with only marginal changes in charge transfer) were a common effect for both gain- and loss-of-function mutants. Modelling NMDA-EPSCs with mutant properties in a CA1 neuron revealed that the effect of GRIN2A mutations can lead to abnormal temporal integration and spine calcium dynamics during trains of concerted synaptic activity. Investigations beyond establishing the molecular defects of GluN2A mutants are much needed to understand their impact on synaptic transmission.

Psychedelic-Assisted Therapy: Emerging Treatments in Mental Health Disorders

Psychedelics are a class of psychoactive substances that were studied extensively between 1943 and 1970 as potential therapies for treating a host of mental health disorders, including addiction. Despite promising early results, U.S. psychedelic research was halted in the early 1970s with the enactment of the Controlled Substances Act. As the field of psychedelic-assisted therapy develops, nurses can decide the role they will play in the continuing clinical and scholarly research of these substances, which may soon be used in controlled settings to treat some of the most widespread mental health disorders. To prepare for this task, this article proposes that nurses * become familiar with the history, relevant language, and scientific findings related to the field of psychedelic research. * learn about existing psychedelic-assisted therapy and research resources. * examine their thoughts, judgments, and opinions about therapeutic psychedelic use. * consider the potential role of nursing in psychedelic-assisted therapies going forward.

Sex Differences in Diagnosis and Diagnostic Revision of Suspected Minor Cerebral Ischemic Events.

OBJECTIVE: To describe sex differences in the presentation, diagnosis, and revision of diagnosis after early brain MRI in patients who present with acute transient or minor neurologic events. METHODS: We performed a secondary analysis of a prospective multicenter cohort study of patients referred to neurology between 2010 and 2016 with a possible cerebrovascular event and evaluated with brain MRI within 8 days of symptom onset. Investigators documented the characteristics of the event, initial diagnosis, and final diagnosis. We used multivariable logistic regression analyses to evaluate the association between sex and outcomes. RESULTS: Among 1,028 patients (51% women, median age 63 years), more women than men reported headaches and fewer reported chest pain, but there were no sex differences in other accompanying symptoms. Women were more likely than men to be initially diagnosed with stroke mimic (54% of women vs 42% of men, adjusted odds ratio (OR) 1.60, 95% confidence interval [CI] 1.24-2.07), and women were overall less likely to have ischemia on MRI (10% vs 17%, OR 0.52, 95% CI 0.36-0.76). Among 496 patients initially diagnosed with mimic, women were less likely than men to have their diagnosis revised to minor stroke or TIA (13% vs 20%, OR 0.53, 95% CI 0.32-0.88) but were equally likely to have acute ischemia on MRI (5% vs 8%, OR 0.56, 95% CI 0.26-1.21). CONCLUSIONS: Stroke mimic was more frequently diagnosed in women than men, but diagnostic revisions were common in both. Early brain MRI is a useful addition to clinical evaluation in diagnosing transient or minor neurologic events.

Biobanking for Genomic and Personalized Health Research: Participant Perceptions and Preferences.

Introduction: Biospecimens and associated data are invaluable tools in Genomics and Personalized Health (GAPH) research and can aid in the discovery of disease etiology and the development of therapeutics. Objective: To examine the experiences of patients invited to a particular GAPH study, Spectrometry in TIA Rapid Assessment (SpecTRA), and to explore broader biospecimen and data sharing preferences among a larger group of patients who had opted into a Permission to Contact for research program. Methods: An electronic survey was e-mailed to 515 participants. The survey was completed by 38% of participants, an unspecified number of whom were also SpecTRA participants. Results: Of those respondents who recalled participating in SpecTRA, 96% strongly agreed, agreed, or were neutral when asked if they received enough information to make an informed decision. Seventy-two percent agreed and 20% were neutral when asked if their study questions were addressed. Ninety-six percent of all respondents felt that SpecTRA's aim to develop a proteomic test for stroke was a worthwhile investment for health care, 98% said they were willing to provide a sample and/or information to facilitate the project's goals, and 96% to health research in general. Fifty-three percent of all participants suggested they would be comfortable sharing health information collected during SpecTRA with for-profit organizations, 87% with nonprofit organizations, and 38% said it matters to them where in the world their sample/information would be sent. Conclusions: Our results suggest that while there is room for improvement in providing adequate information to enable participants' understanding of the purpose of GAPH studies such as SpecTRA, patients are supportive of GAPH in general. Results also suggest that willingness to participate would likely be impacted by factors such as the study's commercial and national affiliations. This study indicates that further work is required to guide improvements on how the GAPH research community describes studies to potential participants, and to enable participation options that incorporate variable participant preferences.

White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.

Background and Purpose- Acute minor neurological deficits are a common complaint in the emergency department and differentiation of transient ischemic attack/minor stroke from a stroke mimic is difficult. We sought to assess the ability of white matter hyperintensity (WMH) volume to aid the diagnosis in such patients. Methods- This is a post hoc analysis of the previously published SpecTRA study (Spectrometry in TIA Rapid Assessment) of adult patients that presented to the emergency department with acute minor neurological deficits between December 2013 and March 2017. WMH volumes were measured if fluid-attenuated inversion recovery imaging was available. Outcomes of interest were final diagnosis, symptoms at presentation, and 90-day stroke recurrence. Results- WMH volume was available for 1485 patients. Median age was 70 years (interquartile range, 59-80), and 46.7% were female. Mean WMH volume was higher in transient ischemic attack/minor strokes compared with stroke mimics (1.71 ln mL [95% CI, 1.63-1.79 ln mL] versus 1.15 ln mL [95% CI, 1.02-1.27 ln mL], P<0.001). In multivariable-adjusted logistic regression analysis, WMH volume was not associated with final diagnosis. However, the combination of both diffusion-weighted imaging positivity and high WMH volume led to lower odds of focal symptoms at presentation (P=0.035). Conclusions- The combination of diffusion-weighted imaging positivity and high WMH volume was associated with lower odds of focal symptoms at presentation in patients seen with minor neurological deficits in the emergency department. This suggests that WMH volume might be an important consideration and the absence of focal symptoms at presentation should not discourage clinicians from further investigating patients with suspected cerebral ischemia.

Systolic blood pressure as a predictor of transient ischemic attack/minor stroke in emergency department patients under age 80: a prospective cohort study.

BACKGROUND: Elevated blood pressure (BP) at emergency department (ED) presentation and advancing age have been associated with risk of ischemic stroke; however, the relationship between BP, age, and transient ischemic attack/minor stroke (TIA/MS) is not clear. METHODS: A multi-site, prospective, observational study of 1084 ED patients screened for suspected TIA/MS (symptom onset < 24 h, NIHSS< 4) between December 2013 and April 2016. Systolic and diastolic BP measurements (SBP, DBP) were taken at ED presentation. Final diagnosis was consensus adjudication by stroke neurologists; patients were diagnosed as either TIA/MS or stroke-mimic (non-cerebrovascular conditions). Conditional inference trees were used to define age cut-points for predicting binary diagnosis (TIA/MS or stroke-mimic). Logistic regression models were used to estimate the effect of BP, age, sex, and the age-BP interaction on predicting TIA/MS diagnosis. RESULTS: Over a 28-month period, 768 (71%) patients were diagnosed with TIA/MS: these patients were older (mean 71.6 years) and more likely to be male (58%) than stroke-mimics (61.4 years, 41%; each p < 0.001). TIA/MS patients had higher SBP than stroke-mimics (p < 0.001). DBP did not differ between the two groups (p = 0.191). SBP was predictive of TIA/MS diagnosis in younger patients, after accounting for age and sex; an increase of 10 mmHg systolic increased the odds of TIA/MS 18% (odds ratio [OR] 1.18, 95% CI 1.00-1.39) in patients < 60 years, and 23% (OR 1.23, 95% CI 11.12-1.35) in those 60-79 years, while not affecting the odds of TIA/MS in patients ≥80 years (OR 0.99, 95% CI 0.89-1.07). CONCLUSIONS: Raised SBP in patients younger than 80 with suspected TIA/MS may be a useful clinical indicator upon initial presentation to help increase clinicians' suspicion of TIA/MS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03050099 (10-Feb-2017) and NCT03070067 (3-Mar-2017). Retrospectively registered.

Cannabinoids and Mental Health, Part 2: The Search for Clinical Applications.

Patients with psychiatric conditions are increasingly using cannabinoids, particularly cannabidiol (CBD), to treat their own symptoms. After reviewing the mechanism of action of CBD, the current article examines the existing evidence for CBD in the treatment of schizophrenia, anxiety, autism, posttraumatic stress disorder, and insomnia, and discusses the challenges in translating these studies, often using very high doses of CBD, into clinical practice. Until additional, well-designed studies that examine the more common practice of lower doses of CBD are performed, a harm-reduction, patient-centered, empiric approach is encouraged to optimize symptom reduction while at the same time avoiding the known risks of cannabis. [Journal of Psychosocial Nursing and Mental Health Services, 57(10), 7-11.].