The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

An Epidemiological Assessment of the Risk of Fatal Motor Vehicle Collisions with Benzodiazepine Use in South Korea

Background: Motor vehicle collisions (MVCs) represent a major public health problem that has been associated with the use of benzodiazepines (BZDs) in several studies from Europe, North America, and Australia. Further epidemiological assessment is necessary to establish a similar association in Asian countries, which have different healthcare systems and patterns of medication use. In particular, South Korea has one of the highest rates of fatal MVCs and BZD prescriptions. The present epidemiological study aims to assess the risk of fatal MVCs among drivers with BZD exposure using a population-specific approach in South Korea. Methods: The Korean Traffic Accident Analysis System database was linked to the National Health Insurance database to obtain medical information for all individuals who experienced fatal MVCs between 2010 and 2014 in South Korea. First, we evaluated the prevalence of BZDs by calculating the odds ratios of BZD exposure among the MVC cohort compared to a random 2% sample of the entire South Korean population. To control for age, we also calculated the standardized prevalence rate ratio for BZD exposure. Second, we analyzed the responsibility of the drivers in causing the fatal MVC by assigning responsibility scores for various characteristics relevant to the traffic accident. These responsibility scores were subsequently compared between drivers with BZD exposure and those without BZD exposure. Finally, we used a case-crossover design to observe the transient effects of BZD exposure on the risk of fatal MVCs by comparing BZD exposure immediately before the onset of the fatal MVC (“hazard period”) to BZD exposure at four earlier time periods (“control periods”). Results: Prevalence of BZD exposure within the past year was significantly higher among the MVC cohort compared to the general population (OR: 2.66, 95% CI: 2.54- 2.79). With age-adjusted rates, the standardized prevalence rate ratio for BZD exposure among the MVC cohort was 1.60 (95% CI: 1.54-1.66). In the responsibility analysis, significantly more drivers with BZD exposure were classified as culpable, compared to drivers without BZD exposure (p<0.0001). In the case-crossover study, BZD exposure in a hazard period of one day before the MVC significantly increased the risk of fatal MVCs, even after adjusting for concurrent medications in the conditional logistic regression model (Adj. OR: 2.20, 95% CI: 1.88-2.58). Sensitivity analyses on various combinations of hazard and washout periods strengthened the robustness of this result. Conclusions: The present study has established a relationship between high rates of fatal MVCs and BZD prescriptions in South Korea through three comprehensive statistical analyses. With fatal MVCs serving as one of the leading causes of death globally, the results accentuate the need for clinical and traffic policies that protect drivers’ safety and address inappropriate BZD prescriptions. This study also motivates further investigation into the risk of medication use across all types of MVCs, especially in countries that demonstrate growing trends on the use of motor vehicles and prescription drugs

Immersive Surgical Anatomy of the Frontotemporal-Orbitozygomatic Approach.

The frontotemporal-orbitozygomatic (FTOZ) approach is widely used for accessing anterolateral lesions in skull base surgery. Many studies have described the technique and quantified the surgical exposure and freedom provided by the FTOZ approach. However, few studies have provided a detailed analysis of the technique and surgical landmarks using three-dimensional (3D) models. In this study, we aimed to create a collection of volumetric models (VMs) and stereoscopic media on the step-by-step surgical technique of the FTOZ approach using cadaveric dissections. The FTOZ approach was divided into eight major steps: positioning, incision of the skin, dissection of scalp flap, mobilization of the temporalis muscle, dissection of periorbita, craniotomy, drilling of basal structures, and dural opening. The MacCarty keyhole and inferior orbital fissure are major surgical landmarks that were referenced for the six bony cuts. Photogrammetry and structured light scanning were used to construct high-resolution VMs. We illustrated the two-piece FTOZ craniotomy, followed by the one-piece and three-piece FTOZ craniotomies. Stereoscopic images, videos, and VMs were produced for each step of the surgical procedure. In addition, the mini-orbitozygomatic (MOz) and orbitopterional (OPt) approaches were considered and described as possible alternatives to the FTOZ approach. Recent advances in 3D technology can be implemented in neurosurgical practice to further enhance our spatial understanding of neurovascular structures. Surgical approaches should be carefully selected and tailored according to the patient's unique pathology and needs

Immersive Surgical Anatomy of the Pterional Approach.

The pterional approach (PA) is a versatile anterolateral neurosurgical technique that enables access to reach different structures contained in the cranial fossae. It is essential for neurosurgical practice to dominate and be familiarized with its multilayer anatomy. Recent advances in three-dimensional (3D) technology can be combined with dissections to better understand the spatial relationships between anatomical landmarks and neurovascular structures that are encountered during the surgical procedure. The present study aims to create a stereoscopic collection of volumetric models (VM) obtained from cadaveric dissections that depict the relevant anatomy and surgical techniques of the PA. Five embalmed heads and two dry skulls were used to record and simulate the PA. Relevant steps and anatomy of the PA were recorded using 3D scanning technology (e.g. photogrammetry, structured light scanner) to construct high-resolution VM. Stereoscopic images, videos, and VM were generated to demonstrate major anatomical landmarks for PA. Modifications of the standard PA, including the mini-pterional and two-part pterional approaches, were also described. The PA was divided into seven major steps: positioning, incision of the skin, dissection of skin flap, dissection of temporal fascia, craniotomy, drilling of basal structures, and dural opening. Emphasis was placed on preserving the temporal branches of the facial nerve and carefully dissecting the temporalis muscle. The interactive models presented in this article allow for clear visualization of the surgical anatomy and windows in 360-degrees and VR. This new modality of recording neuroanatomical dissections renders a closer look at every nuance of the topography experienced by our team in the laboratory. By accurately depicting essential landmarks, stereoscopy and VM can be valuable resources for anatomical education and surgical planning

Vestibular Migraine Following Radiosurgery for Vestibular Schwannoma.

Vestibular schwannoma (VS) is associated with dizziness and vertigo during all stages of treatment. This report describes a patient who presented with a one-year history of intermittent motion sickness, dizziness, headache, imbalance, and nausea. MRI showed a right-side VS in the cerebellopontine angle and internal auditory canal. The patient elected to undergo Gamma Knife radiosurgery for treatment. Within two to three months, she continued to experience recurring dizziness, vertigo, neck stiffness, and head pressure. She was referred for neurotology evaluation, which led to a diagnosis of vestibular migraine (VM). Her vestibular reflexes were intact. Subsequently, she was treated with diet modification and low-dose venlafaxine. She reported dramatically improved dizziness and vertigo symptoms at six-month follow-up. VM is a very common cause of dizziness that should always be included in the differential diagnosis, even in VS patients

Clipping of a giant partially thrombosed ophthalmic segment aneurysm

Ophthalmic segment aneurysms (OSA) originate from the paraclinoid portion of the internal carotid artery (ICA) usually at the origin of the ophthalmic artery. OSAs represent 1.5–10% of intracranial aneurysms, and although often asymptomatic, may lead to optic nerve (ON) compression and/or subarachnoid hemorrhage. When the dome is partially or completely thrombosed, microsurgical clipping can provide vascular exclusion and ON decompression through thrombectomy. Nevertheless, high expertise and knowledge of the regional anatomy are required to manage this complex surgical field.In this operative video, we show the management of a giant thrombosed OSA. The 52-year-old male patient presented with a recent history of worsening headache and progressive right visual loss. Neuroimaging revealed a 3 cm partially thrombosed right OSA, with mass effect on the ON and surrounding edema. An incidental 5 mm right middle cerebral artery (MCA) bifurcation aneurysm was also identified. Endovascular occlusion was not feasible, and the patient agreed to microsurgical treatment. A right pterional craniotomy was performed and the sylvian fissure was split, exposing both lesions. Parent vessel control was achieved with temporary clipping of the cervical ICA, and distal to the origin of the aneurysm. After debulking of the thrombosed and calcified dome with ultrasonic aspiration, the aneurysm was secured with combined clipping inside and outside the dome. The MCA aneurysm was subsequently exposed and clipped. Indocyanine green video-angiography confirmed exclusion of both aneurysms and flow patency of the rest of the circulation. The patient was discharged without complications and post-operative angiography showed complete occlusion of both aneurysms. Keywords: Ophthalmic segment, Internal carotid artery, Thrombose

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk