Drug-drug interactions with cannabidiol (CBD) appear to have no effect on treatment response in an open-label Expanded Access Program.

Objective: We have previously shown that cannabidiol (CBD; Epidiolex®) significantly affects levels of clobazam/N-desmethylclobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine. In the present study, we tested whether the presence of concomitant clobazam affected seizure frequency and severity (treatment response) 12 weeks after initiation of therapy with CBD in patients with treatment-resistant epilepsy (TRE). The secondary questions were whether the presence of any of the other antiepileptic drugs (AEDs) had an effect on seizure frequency or severity at 12, 24, or 48 weeks after therapy initiation.

Outcomes of Endovascular Thrombectomy vs Medical Management Alone in Patients With Large Ischemic Cores: A Secondary Analysis of the Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) Study.

Importance: The efficacy and safety of endovascular thrombectomy (EVT) in patients with large ischemic cores remains unknown, to our knowledge.

Objective: To compare outcomes in patients with large ischemic cores treated with EVT and medical management vs medical management alone.

Design, Setting, And Participants: This prespecified analysis of the Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) trial, a prospective cohort study of imaging selection that was conducted in 9 US comprehensive stroke centers, enrolled patients between January 2016 and February 2018, and followed them up for 90 days.

Early complement genes are associated with visual system degeneration in multiple sclerosis.

Multiple sclerosis is a heterogeneous disease with an unpredictable course and a wide range of severity; some individuals rapidly progress to a disabled state whereas others experience only mild symptoms. Though genetic studies have identified variants that are associated with an increased risk of developing multiple sclerosis, no variants have been consistently associated with multiple sclerosis severity. In part, the lack of findings is related to inherent limitations of clinical rating scales; these scales are insensitive to early degenerative changes that underlie disease progression.

Examining the Impact of Refractory Myasthenia Gravis on Healthcare Resource Utilization in the United States: Analysis of a Myasthenia Gravis Foundation of America Patient Registry Sample.

Background And Purpose: Patients with refractory myasthenia gravis (MG) experience ongoing disease burden that might be reflected in their healthcare utilization. Here we examine the impact of refractory MG on healthcare utilization.

Methods: The 825 included participants were aged 18-64 years, enrolled in the Myasthenia Gravis Foundation of America Patient Registry between July 2013 and February 2018, and had been diagnosed with MG ≥2 years previously.

Cognitive functioning following long-term cannabidiol use in adults with treatment-resistant epilepsy.

Cognitive dysfunction is a common comorbidity in adults with treatment-resistant epilepsy (TRE). Recently, cannabidiol (CBD) has demonstrated efficacy in epilepsy treatment. However, our understanding of CBD's cognitive effects in epilepsy is limited.

Clinical trials in multiple sclerosis: potential future trial designs.

Clinical trials of new treatments in multiple sclerosis (MS) currently require large sample sizes and long durations in order to yield reliable results. The differential responses of an already heterogeneous population of MS patients to individual disease-modifying therapies (DMTs) will further complicate future trials. MS trials with smaller samples and faster outcomes are conceivable through the substitution of current clinical and MRI outcomes with objectively measureable genomic and proteomic biomarkers.

Developing a crosswalk between the RAND-12 and the health utilities index for multiple sclerosis.

Background: Researchers studying health-related quality of life (HRQOL) in multiple sclerosis (MS) can choose from many instruments, but findings from studies which use different instruments cannot be easily combined. We aimed to develop a crosswalk that associates scores from the RAND-12 to scores on the Health Utilities Index-Mark III (HUI3) in persons with MS.

Methods: In 2018, participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry completed the RAND-12 and the HUI3 to assess HRQOL.

Impact of Refractory Myasthenia Gravis on Health-Related Quality of Life.

Objectives: Myasthenia gravis (MG) may be refractory to traditional therapies. Quality of life (QOL) and disease burden in patients with refractory and nonrefractory MG were compared using Myasthenia Gravis Foundation of America MG Patient Registry data.

Methods: Adults aged 18 years or older with MG diagnosed ≥2 years before enrollment were included.

Higher satisfaction and adherence with glatiramer acetate 40 mg/mL TIW vs 20 mg/mL QD in RRMS.

Background: Patients who perceive their medication to be ineffective or inconvenient are less likely to be adherent to treatment, with potentially significant consequences on long-term clinical outcomes. Many patients with multiple sclerosis (MS) are nonadherent to treatment despite demonstrated efficacy of disease-modifying therapies (DMTs). While glatiramer acetate (GA; Copaxone, Teva Pharmaceuticals) both 20 mg/mL once daily (GA20) and 40 mg/mL three times weekly (GA40) have demonstrated efficacy in relapsing-remitting MS (RRMS), GA40 has a superior tolerability profile in addition to a more convenient dosing schedule.

CYP3A5 genotype affects time to therapeutic tacrolimus level in pediatric kidney transplant recipients.

Background: Optimal management of immunosuppression in kidney transplantation requires a delicate balance of efficacy and toxicity. Tacrolimus (TAC) dose requirements are significantly impacted by genetic variation in CYP3A5 polymorphisms, however the impact that genotype has on clinical outcomes in the pediatric kidney transplant population remains unclear.

Methods: We evaluated a retrospective cohort of 98 pediatric kidney transplant recipients.

Measures of general and abdominal obesity and disability severity in a large population of people with multiple sclerosis.

Background: Metabolic comorbidity is overrepresented in people with multiple sclerosis (MS) and is associated with adverse MS outcomes. Excess visceral adiposity, approximated using waist circumference (WC), is a risk factor for metabolic comorbidity and predicts poorer outcomes in other neurologic diseases.

Objective: To evaluate the association between WC and clinical and disease characteristics in people with MS.

The association of fatigue and social participation in multiple sclerosis as assessed using two different instruments.

Introduction: Fatigue is an important aspect of health-related quality of life and a commonly reported symptom by many persons with multiple sclerosis (MS). There are multiple validated instruments available to assess fatigue in MS with differing benefits for each instrument.

Objective: We aimed to assess the relationship between the PROMIS Fatigue instrument and the Fatigue Performance Scale (FPS) in the NARCOMS registry.

Hand stereotypies: Lessons from the Rett Syndrome Natural History Study.

Objective: To characterize hand stereotypies (HS) in a large cohort of participants with Rett syndrome (RTT).

Methods: Data from 1,123 girls and women enrolled in the RTT Natural History Study were gathered. Standard tests for continuous and categorical variables were used at baseline.

An Intervention for Changing Sedentary Behavior Among African Americans With Multiple Sclerosis: Protocol.

Background: Sedentary behavior is a major concern among patients with multiple sclerosis (MS), as it may accelerate disease progression and exacerbate physical disability. This is especially concerning among African Americans, a segment of the MS population who present with greater neurological disability and higher odds of physical comorbidities than their Caucasian counterparts.

Objective: To date, researchers have not proposed interventions that focus on changing sedentary behavior in African Americans with MS.

Rationale and design of the STEP for MS Trial: Comparative effectiveness of Supervised versus Telerehabilitation Exercise Programs for Multiple Sclerosis.

Background: We propose a Phase III trial that compares the effectiveness of an exercise training program delivered in a facility-based setting with direct, in-person supervision or a home-based setting with remote supervision via telerehabilitation for improving walking performance in persons with multiple sclerosis(MS) who have walking dysfunction and mobility disability.

Methods/design: The study was developed with stakeholder engagement and is a multi-site trial that follows a 2-stage, randomized choice design. The trial compares the effectiveness of a 16-week evidence-based, individualized exercise program delivered in a supervised, facility-based setting versus a remotely coached/guided, home-based setting using telerehabilitation in physically inactive and cognitively intact people with MS who have walking dysfunction and mobility disability(N = 500).

Evaluation of a web-based fall prevention program among people with multiple sclerosis.

Background: Falls are common and impactful in people with multiple sclerosis (MS) but currently there is no accepted standard of care for fall prevention in MS. Evidence supports that the in-person, group-based, Free from Falls (FFF) program is associated with both immediate and six-month sustained improvements in mobility and balance and a reduction in falls, but program attendance is limited by access to the class at a given time and location and by the cost and availability of trained facilitators. Therefore, we developed and evaluated an online, web-based version of FFF, Free from Falls Online (FFFO).

Multiple sclerosis: clinical trial design 2019.

Purpose Of Review: Recent years have seen the approval of more than 15 disease-modifying drugs for multiple sclerosis (MS), mainly for its relapsing-remitting form (RRMS). The focus of the MS clinical trials is moving toward clinical trials aimed at progressive patients or based on putatively neuroprotective compounds. Here we reviewed the challenges of this paradigm shift.

Patient-Centered Outcomes and Key Study Procedure Finalization in the Pilot Feasibility Gout Randomized Trial: Comparative Feasibility Study in GOUt, CHerry Extract Versus Diet Modification (Mini-GOUCH).

Objective: The aim of this study was to report patient-centered outcomes and finalization of key study procedures from a 9-month pilot internet randomized controlled trial of cherry extract versus diet modification.

Methods: We randomized 84 people with physician-confirmed gout in an internet study to cherry extract (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via internet and phone calls.

Cortical Activation Elicited by Subthalamic Deep Brain Stimulation Predicts Postoperative Motor Side Effects.

Objective: Although deep brain stimulation (DBS) is an effective treatment for movement disorders, improvement varies substantially in individuals, across clinical trials, and over time. Noninvasive biomarkers that predict the individual response to DBS could be used to optimize outcomes and drive technological innovation in neuromodulation. We sought to evaluate whether noninvasive event related potentials elicited by subthalamic DBS during surgical targeting predict the tolerability of a given stimulation site in patients with advanced Parkinson's disease.

Evolution of clinical trials in multiple sclerosis.

Clinical trials have advanced the treatment of multiple sclerosis (MS) by demonstrating the safety and efficacy of disease-modifying therapies (DMTs). This review discusses major changes to MS clinical trials in the era of DMTs. As treatment options for MS continue to increase, patients in modern MS trials present earlier and with milder disease compared with historic MS populations.

The prevalence of MS in the United States: A population-based estimate using health claims data.

Objective: To generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets.

Methods: A validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region.

A new way to estimate neurologic disease prevalence in the United States: Illustrated with MS.

Objective: Considerable gaps exist in knowledge regarding the prevalence of neurologic diseases, such as multiple sclerosis (MS), in the United States. Therefore, the MS Prevalence Working Group sought to review and evaluate alternative methods for obtaining a scientifically valid estimate of national MS prevalence in the current health care era.

Methods: We carried out a strengths, weaknesses, opportunities, and threats (SWOT) analysis for 3 approaches to estimate MS prevalence: population-based MS registries, national probability health surveys, and analysis of administrative health claims databases.

Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial.

Background: The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events.

Methods: We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate.

Validation of the SymptoMScreen with performance-based or clinician-assessed outcomes.

Background: People with multiple sclerosis (MS) experience symptoms in multiple domains. High-quality patient-reported outcomes (PROs) that assess multiple domains can aid healthcare providers in assessing these symptoms and may support remote disease monitoring. The "SymptoMScreen" PRO correlates with other PROs in MS; however, whether the SymptoMScreen or its component domains are associated with performance-based or clinician-assessed outcomes is unknown.