The Clinical Impact of Recent Methamphetamine Exposure in Aneurysmal Subarachnoid Patients.

Background: Methamphetamines (MA) are a frequently used drug class with potent sympathomimetic properties that can affect cerebral vasculature. Conflicting reports in literature exist about the effect of exposure to MA on vasospasm risk and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to characterize the impact of recent MA use on the timing, severity and features of vasospasm in aneurysmal subarachnoid as well as neurological outcomes. Methods: We retrospectively screened 441 consecutive patients admitted to a tertiary care hospital with a diagnosis of SAH who underwent at least one cerebral digital subtraction angiogram (DSA). Patients were excluded if no urinary toxicology screen was performed within 24 hours of admission, if there was a diagnosis of non-aneurysmal SAH, or if ictus was greater than 72 hours from hospital admission. Vasospasm characteristics were collected from DSA and transcranial doppler (TCD) studies and demographic as well as clinical outcome data was abstracted from the chart. Results: 129 patients were included and 24 tested positive for MA. Among the 312 excluded patients, 281 did not have a urinary toxicology screen and 31 had a non-aneurysmal pattern of SAH or ictus occurring greater than 72 hours from hospital admission. No significant differences were found in respect to patient age, sex, or admission Hunt and Hess Score or Modified Fisher Scale based on MA use. There was no difference in the severity of vasospasm or time to peak severity using either TCD or DSA criteria on multivariate analysis. Aneurysms were more likely to be in the anterior circulation for both groups, however the MA cohort experienced less vasospasm involving the anterior circulation and more isolated posterior circulation vasospasm. There was no difference in delayed cerebral ischemia (DCI) incidence, length of ICU stay, need for ventriculoperitoneal shunt placement, functional outcome at discharge or hospital mortality. Interpretation: Recent MA use was not associated with worse vasospasm severity, time to vasospasm, or DCI in aSAH patients. Further investigations about localized MA effects in the posterior circulation and impact on long-term functional outcomes are warranted.

Turning Back the Clock: Artificial Intelligence Recognition of Age Reduction after Face-Lift Surgery Correlates with Patient Satisfaction.

BACKGROUND: Patients desire face-lifting procedures primarily to appear younger, more refreshed, and attractive. Because there are few objective studies assessing the success of face-lift surgery, the authors used artificial intelligence, in the form of convolutional neural network algorithms alongside FACE-Q patient-reported outcomes, to evaluate perceived age reduction and patient satisfaction following face-lift surgery. METHODS: Standardized preoperative and postoperative (1 year) images of 50 consecutive patients who underwent face-lift procedures (platysmaplasty, superficial musculoaponeurotic system-ectomy, cheek minimal access cranial suspension malar lift, or fat grafting) were used by four neural networks (trained to identify age based on facial features) to estimate age reduction after surgery. In addition, FACE-Q surveys were used to measure patient-reported facial aesthetic outcome. Patient satisfaction was compared to age reduction. RESULTS: The neural network preoperative age accuracy score demonstrated that all four neural networks were accurate in identifying ages (mean score, 100.8). Patient self-appraisal age reduction reported a greater age reduction than neural network age reduction after a face lift (-6.7 years versus -4.3 years). FACE-Q scores demonstrated a high level of patient satisfaction for facial appearance (75.1 ± 8.1), quality of life (82.4 ± 8.3), and satisfaction with outcome (79.0 ± 6.3). Finally, there was a positive correlation between neural network age reduction and patient satisfaction. CONCLUSION: Artificial intelligence algorithms can reliably estimate the reduction in apparent age after face-lift surgery; this estimated age reduction correlates with patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

Interdisciplinary influences in headache literature: A network citation analysis of PubMed Central articles.

BACKGROUND: Non-headache literature inevitably influences headache research, but the way this interdisciplinary interaction occurs has seldom been evaluated. OBJECTIVE: Utilizing network analysis techniques within the PubMed Central (PMC) database, we illustrate a novel method by which to identify and characterize the important non-headache literature with significant impact within the headache world. METHODS: Using the National Center for Biotechnology Information E-utilities application programing interface and custom backend software, all PMC articles containing the words "headache(s)" and/or "migraine(s)" in the title were identified. This generated a list of "seed articles" to represent the body of primary headache literature. Articles referenced by the seeds were then found, generating the list of articles with one degree of separation from the seeds (first-degree neighbors). This was iterated twice more to find the second- and third-degree neighbors. A directed network graph was generated for each level of separation using these articles and their referential connections. The hyperlink-induced topic search (HITS) and PageRank algorithms were used on these graphs to find the top 50 articles in the network (hub and authority rank via HITS, general rank via PageRank). Removing seed articles from the ranked lists left the influential non-headache articles at each level of separation. RESULTS: We extracted 6890 seed articles. The first-, second-, and third-degree models contained 16,451, 105,496, and 431,748 articles, respectively. As expected, most first-degree neighbors were part of the seed group (headache literature). Using HITS, at the second degree, only two seed articles were found in the top 50 hubs (none in the authorities); the majority of non-seed articles were basic neuroscience, involving ion channel function or cell signaling. At the third degree, there were no seeds and all articles involved imaging/structure of brain connectivity networks. PageRank gave more varied results, with 35/50 second-degree articles being seeds, and the remainder a mixture of articles describing rating scales (3), epidemiology/disease burden (3), basic statistical/trial methods (3), and mixed basic science (6). At the third degree, five were seeds; non-seed articles were represented heavily by genomic mapping studies, brain connectivity networks, and ion channel/neurotransmitter studies. CONCLUSION: This work demonstrates the value of network citation analysis in the identification of interdisciplinary influences on headache medicine. Articles found with this technique via HITS identified and grouped basic science applicable to headache medicine at the molecular scale (ion channels/transmitters), and whole-brain scale (connectivity networks). Both groups have direct clinical correlates, with the former implicating pharmacological targets, and the latter implicating functional neuroanatomy and pathophysiology of various headache disorders. Likely, in-depth analysis of the whole network (rather than the top 50) would reveal further clusters where the relationship to headache may not be as immediately obvious. This may not only help to guide ongoing work, but also identify new targets where seemingly unrelated work may have future applications in headache management.

Neurovascular physiology and neurocritical care.

The neurological intensive care unit plays an integral role in the management of cerebrovascular disease in the acute and perioperative period. Understanding the use of intracranial pressure (ICP) monitoring and how to apply the appropriate intervention for ICP elevation to ensure adequate cerebral perfusion is the foundation of neurocritical care. Careful management of the interplay between cerebral and systemic physiology, particularly in disorders of cerebral autoregulation, is critical in preventing secondary brain injury. Finally, understanding the cerebral pathophysiology of the underlying injured brain in acute stroke, subarachnoid hemorrhage, and arterial stenosis can help to guide the optimal use of interventional endovascular procedures in these disease states.

Facelift Surgery Turns Back the Clock: Artificial Intelligence and Patient Satisfaction Quantitate Value of Procedure Type and Specific Techniques.

BACKGROUND: Patients desire facelifting procedures to look younger, refreshed, and attractive. Unfortunately, there are few objective studies assessing the success of types of facelift procedures and ancillary techniques. OBJECTIVES: The authors sought to utilize convolutional neural network algorithms alongside patient-reported FACE-Q outcomes to evaluate perceived age reduction and patient satisfaction following various facelift techniques. METHODS: Standardized preoperative and postoperative (1-year) images of patients who underwent facelift procedures were analyzed by 4 neural networks to estimate age reduction after surgery (n = 105). FACE-Q surveys were employed to measure patient-reported facial aesthetic outcome. We compared (1) facelift procedure type: skin-only vs superficial musculoaponeurotic system (SMAS)-plication, vs SMAS-ectomy; and (2) ancillary techniques: fat grafting (malar) vs no fat grafting. Outcomes were based on complications, estimated age-reduction, and patient satisfaction. RESULTS: The neural network preoperative age accuracy score demonstrated that all neural networks were accurate in identifying our patients' ages (mean score = 100.4). SMAS-ectomy and SMAS-plication had significantly greater age-reduction (5.85 and 5.35 years, respectively) compared with skin-only (2.95 years, P < 0.05). Fat grafting compared to no fat grafting demonstrated 2.1 more years of age reduction. Facelift procedure type did not affect FACE-Q scores; however, patients who underwent fat grafting had a higher satisfaction with outcome (78.1 ± 8 vs 69 ± 6, P < 0.05) and decision to have the procedure (83.0 ± 6 vs 72 ± 9, P < 0.05). CONCLUSIONS: Artificial intelligence algorithms can reliably estimate the reduction in apparent age after facelift surgery. Facelift technique, like SMAS-ectomy or SMAS-plication, and specific technique, like fat grafting, were found to enhance facelifting outcomes and patient satisfaction.

Accelerated transsulfuration metabolically defines a discrete subclass of amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis is a disease characterized by progressive paralysis and death. Most ALS-cases are sporadic (sALS) and patient heterogeneity poses challenges for effective therapies. Applying metabolite profiling on 77-sALS patient-derived-fibroblasts and 43-controls, we found ~25% of sALS cases (termed sALS-1) are characterized by transsulfuration pathway upregulation, where methionine-derived-homocysteine is channeled into cysteine for glutathione synthesis. sALS-1 fibroblasts selectively exhibited a growth defect under oxidative conditions, fully-rescued by N-acetylcysteine (NAC). [U13C]-glucose tracing showed transsulfuration pathway activation with accelerated glucose flux into the Krebs cycle. We established a four-metabolite support vector machine model predicting sALS-1 metabotype with 97.5% accuracy. Both sALS-1 metabotype and growth phenotype were validated in an independent cohort of sALS cases. Importantly, plasma metabolite profiling identified a system-wide cysteine metabolism perturbation as a hallmark of sALS-1. Findings reveal that sALS patients can be stratified into distinct metabotypes with differential sensitivity to metabolic stress, providing novel insights for personalized therapy.

Prescribed Drug Spending in Canada, 2019: A Focus on Public Drug Programs.

Public drug program spending accounts for 43.1% of prescribed drug spending in Canada. This report provides an in-depth look at public drug program spending in Canada, using the Canadian Institute for Health Information's (CIHI) National Prescription Drug Utilization Information System. Public drug program spending does not include spending on drugs dispensed in hospitals or on those funded through cancer agencies and other special programs.

Outcomes and Spectrum of Major Neurovascular Events Among COVID-19 Patients: A 3-Center Experience.

BACKGROUND: Preliminary data suggest that Coronavirus Disease-2019 (COVID-19) is associated with hypercoagulability and neurovascular events, but data on outcomes is limited. OBJECTIVE: To report the clinical course and outcomes of a case series of COVID-19 patients with a variety of cerebrovascular events. METHODS: We performed a multicentric, retrospective chart review at our three academic tertiary care hospitals, and identified all COVID-19 patients with cerebrovascular events requiring neuro-intensive care and/or neurosurgical consultation. RESULTS: We identified 26 patients between March 1 and May 24, 2020, of whom 12 (46%) died. The most common event was a large-vessel occlusion (LVO) in 15 patients (58%), among whom 8 died (8/15, 53%). A total of 9 LVO patients underwent mechanical thrombectomy, of whom 5 died (5/9, 56%). A total of 7 patients (27%) presented with intracranial hemorrhage. Of the remaining patients, 2 had small-vessel occlusions, 1 had cerebral venous sinus thrombosis, and another had a vertebral artery dissection. Acute Respiratory Distress Syndrome occurred in 8 patients, of whom 7 died. Mortalities had a higher D-dimer on admission (mean 20 963 ng/mL) than survivors (mean 3172 ng/mL). Admission Glasgow Coma Scale (GCS) score was poor among mortalities (median 7), whereas survivors had a favorable GCS at presentation (median 14) and at discharge (median 14). CONCLUSION: COVID-19 may be associated with hemorrhage as well as ischemia, and prognosis appears poorer than expected-particularly among LVO cases, where outcome remained poor despite mechanical thrombectomy. However, a favorable neurological condition on admission and lower D-dimer may indicate a better outcome.

Facial Recognition Neural Networks Confirm Success of Facial Feminization Surgery.

BACKGROUND: Male-to-female transgender patients desire to be identified, and treated, as female, in public and social settings. Facial feminization surgery entails a combination of highly visible changes in facial features. To study the effectiveness of facial feminization surgery, we investigated preoperative/postoperative gender-typing using facial recognition neural networks. METHODS: In this study, standardized frontal and lateral view preoperative and postoperative images of 20 male-to-female patients who completed hard- and soft-tissue facial feminization surgery procedures were used, along with control images of unoperated cisgender men and women (n = 120 images). Four public neural networks trained to identify gender based on facial features analyzed the images. Correct gender-typing, improvement in gender-typing (preoperatively to postoperatively), and confidence in femininity were analyzed. RESULTS: Cisgender male and female control frontal images were correctly identified 100 percent and 98 percent of the time, respectively. Preoperative facial feminization surgery images were misgendered 47 percent of the time (recognized as male) and only correctly identified as female 53 percent of the time. Postoperative facial feminization surgery images were gendered correctly 98 percent of the time; this was an improvement of 45 percent. Confidence in femininity also improved from a mean score of 0.27 before facial feminization surgery to 0.87 after facial feminization surgery. CONCLUSIONS: In the first study of its kind, facial recognition neural networks showed improved gender-typing of transgender women from preoperative facial feminization surgery to postoperative facial feminization surgery. This demonstrated the effectiveness of facial feminization surgery by artificial intelligence methods. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Opioids in Canada.

The opioid crisis in Canada is a complex issue with devastating consequences for individuals, families and communities. Pan-Canadian data that provide a better understanding of the crisis are a high priority to help guide efforts for reducing opioid-related harms. The objective of this study is to summarize recent trends of opioid-related harms and opioid prescribing across Canada. Opioid-related harms examined in this study include opioid poisonings, opioid use disorders, adverse reactions to opioids and infants born with neonatal withdrawal symptoms. Data are reported at the pan-Canadian, provincial and community levels.

Comparison of Two Techniques to Measure Optic Nerve Sheath Diameter in Patients at Risk for Increased Intracranial Pressure.

OBJECTIVES: Intracranial pressure over 20 mm Hg is associated with poor neurologic prognosis, but measuring intracranial pressure directly requires an invasive procedure. Dilation of the optic nerve sheath on axial ultrasound of the eye has been correlated with elevated intracranial pressure, but optimal cutoffs have been inconsistent possibly related to the measurement technique. A coronal technique has been studied on healthy volunteers but not on patients with high intracranial pressure. We compared two measurement techniques (axial and coronal) in patients with suspected high intracranial pressure due to trauma, bleeding, tumor, or infection. DESIGN: Prospective blinded observational study. SETTING: Two tertiary referral center ICUs. PATIENTS: Twenty adults admitted to the ICU at risk for increased intracranial pressure expected to receive invasive intracranial monitoring. INTERVENTIONS: Ultrasound measurements of the optic nerve sheath in axial and coronal views either averaged between eyes or the highest in either eye. MEASUREMENTS AND MAIN RESULTS: Coronal measurements showed less variability between each eye than axial measurements (mean difference 0.5 mm vs 1 mm; p = 0.03) and were associated with high intracranial pressure at first measurement and over 24 hours (area under the receiver operating characteristic range 0.7-0.8). Mean and highest axial measurements showed improved association with first (area under the receiver operating characteristic 0.87-0.94) and highest intracranial pressure measurement (area under the receiver operating characteristic 0.89-0.96) within 24 hours. A cutoff of highest axial measurement in either eye greater than 6.2 mm or mean axial measurement between eyes of 5.6 mm had a sensitivity of 100% in predicting high intracranial pressure over the following 24 hours. CONCLUSIONS: The highest axial measurement of optic nerve sheath diameter in either eye is the most predictive of patients with high intracranial pressure in our population. This comparison of measurement techniques has not previously been described and should be further explored to set test cutoffs for ultrasound of the optic nerve sheath diameter.

Medication Incidents Involving Antiepileptic Drugs in Canadian Hospitals: A Multi-Incident Analysis.

Medication errors involving antiepileptic drugs (AEDs) are not well studied but have the potential to cause significant harm. We investigated the occurrence of medication incidents in Canadian hospitals that involve AEDs, their severity and contributing factors by analyzing data from two national databases. Our multi-incident analysis revealed that while medication errors were rarely fatal, errors do occur of which some are serious. Medication incidents were most commonly caused by dose omissions, the dose or its frequency being incorrect and the wrong AED being given. Our analysis could augment quality-improvement initiatives by medication safety administrators to reduce AED medication incidents in hospitals.

Vertical head translation impairs dynamic visual acuity during near viewing.

Dynamic visual acuity is an important clinical tool for assessment of the rotational vestibulo-ocular reflex (rVOR). It is based on the fact that the normal rVOR stabilizes vision and maintains visual acuity during head rotation. The translational VOR (tVOR) generates eye movements during linear head motion. Studies in humans have shown that gaze stabilization during translation is incomplete and that there is a strong effect of the visual environment: eye velocity is much greater in the light than in the dark. In this study, we measured visual acuity during vertical translation in 11 subjects and asked whether a more complex visual background would enhance the response and improve acuity. During 2 Hz whole-body translation, tumbling-E optotypes (0.0-0.9 logMAR in steps of 0.1 logMAR, six trials of each size randomly ordered) were flashed on a screen that was 30 cm in front of the subject's eyes. The subject reported the optotype's orientation with a joystick. Based on a threshold of 75% trials correctly identified, the group dynamic acuity was 0.72 logMAR, compared to a static acuity of 0.0 logMAR. When the background was enhanced with a stationary dot pattern, dynamic acuity improved to 0.42 logMAR. Our findings show that vertical head translation degrades vision more than head rotation. This may limit the use of dynamic acuity as a clinical measure of otolith function.

Using breakthrough series collaborative methodology to improve safe delivery of chemotherapy in Ontario.

PURPOSE: Chemotherapy delivery is complex, involving multiple providers across settings to deliver safe, effective care. Cancer Care Ontario initiated a provincial breakthrough series collaborative, based on methodology from the Institute for Healthcare Improvement (IHI), to improve the safe delivery of chemotherapy, from ordering through preparation and administration. METHODS: Over the 1-year period of the collaborative, three in-person sessions educated participants on improvement methodology. Twenty teams tested and implemented elements of a predefined change package in their local systems. Monthly teleconferences supplemented the education while encouraging a culture of knowledge sharing. Teams completed monthly self-assessment surveys that evaluated their progress using a 6-point scale, where 1 indicated no evidence of improvement and 5 indicated achievement of all goals and improvement objectives. RESULTS: Monthly self-assessment surveys revealed that over time, scores improved from 1 to 4, indicating significant progress. Moreover, 100% of participants reported in an exit survey that the collaborative had improved the culture of safety in their organizations. The gains of the collaborative have been sustained through development of a practice community and provision of ongoing coaching through the IHI Open School. CONCLUSION: Participation in the collaborative enabled local interdisciplinary teams to develop processes and structures to support ongoing quality improvement, including formation of a sustainable structure for knowledge translation and exchange. However, lack of a shared provincial target limited overall evaluation. Other lessons learned included providing adequate time for planning and clearly defining roles and responsibilities of involved teams and project sponsors.

Intravenous chemotherapy preparation errors: patient safety risks identified in a pan-Canadian exploratory study.

BACKGROUND: This exploratory study was launched following a critical chemotherapy medication incident to thoroughly and proactively examine the current processes for ordering, preparing, labeling, verifying, administering, and documenting ambulatory intravenous chemotherapy in Canada, and to identify factors that may contribute to preventable adverse drug events. METHODS: Field observations in six Canadian cancer centers to identify end-to-end processes in clinic, pharmacy, and treatment areas; analysis of processes to identify risks. RESULTS: Three types of previously locally unrecognized potential chemotherapy preparation errors in Canadian oncology pharmacies were uncovered, all of which are undetectable if they occur. Although the frequency of these errors is unknown, their impact is potentially catastrophic. INTERPRETATION: Dispensing errors in high-risk intravenous preparation have been studied in the past, but it is unlikely that these studies have detected these errors because of the inherent limitations of the detection methods used. Research on preparation errors using more sensitive methods is therefore urgently needed to establish the extent to which pharmacy preparation practices may be error-prone, and to allow reliable evaluation of the impact of mitigation strategies. Widespread practice changes in Canadian oncology pharmacies are necessary, and are currently underway.

Abnormal leg muscle latencies and relationship to dyscoordination and walking disability after stroke.

The purpose was to determine timing characteristics of leg muscle latencies for patients following stroke (>12 months) who had persistent coordination and gait deficits, and to determine the relationships among abnormal latencies, dyscoordination, and gait deficits. We compared nine healthy controls and 27 stroke survivors. Surface electromyography measured activation and deactivation latencies of knee flexor and extensor muscles during a ballistic knee flexion task, consistency of latencies across repetitions, and close coupling between agonist and antagonist muscle latencies. We measured Fugl-Meyer (FM) coordination and the functional gait measure, six minute walk test (6MWT). For stroke subjects, there were significant delays of muscle activation and deactivation, abnormal inconsistency, and abnormal decoupled agonist and antagonist activations. There was good correlation between activation latencies and FM and 6MWT. Results suggest abnormal timing characteristics underlie coordination impairment and dysfunctional gait. These abnormal muscle activation and deactivation timing characteristics are important targets for rehabilitation.

Identification of medication safety indicators in acute care settings for public reporting in Ontario.

In healthcare settings, indicators are useful tools to assess the structure, process and outcomes of care. Moreover, when used to report to the public, indicators ensure greater transparency for our healthcare system. The purpose of this study was to identify in acute care settings three medication safety indicators that are suitable for public reporting in Ontario. A multi-phase process was developed that included a literature review, compilation and evaluation of possible indicators and a consensus-generation process involving a focus group (modified nominal group technique) with Ontario healthcare experts from various disciplines. More than 300 potential medication safety indicators were identified through the literature review. Two analysts, working independently and using a defined set of selection criteria, narrowed the focus to 49 and subsequently 12 candidate indicators. A focus group of leading experts across the healthcare fields in Ontario was convened and reached consensus on three indicators. These three indicators focused on the areas of venous thromboembolism prevention, acute myocardial infarction discharge medications and medication reconciliation. This report describes a multi-phase process undertaken by the Institute for Safe Medication Practices Canada to identify in acute care settings three medication safety indicators suitable for public reporting in Ontario. These indicators point to important areas in medication safety at which deficiencies can result in significant patient harm. There is a potential for these indicators to provide hospitals and healthcare providers with tangible and realistic mechanisms for measuring performance and, ultimately, improving the quality of care.