Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Unlabelled: The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice.

Potential Impact of Slowing Disease Progression in Early Symptomatic Alzheimer's Disease on Patient Quality of Life, Caregiver Time, and Total Societal Costs: Estimates Based on Findings from GERAS-US Study.

Background: Impact of Alzheimer's disease (AD) progression on patient health-related quality of life (HRQoL), caregiver time, and societal costs is not well characterized in early AD.

Objective: To assess the association of change in cognition with HRQoL, caregiver time, and societal costs over 36 months, and estimate the impact of slowing disease progression on these outcomes.

Methods: This post-hoc analysis included patients with amyloid-positive mild cognitive impairment (MCI) and mild AD dementia (MILD AD) from the 36-month GERAS-US study.

Assessing the Cost-effectiveness of a Hypothetical Disease-modifying Therapy With Limited Duration for the Treatment of Early Symptomatic Alzheimer Disease.

Purpose: Clinical trials have produced promising results for disease-modifying therapies (DMTs) for Alzheimer's disease (AD); however, the evidence on their potential cost-effectiveness is limited. This study assesses the cost-effectiveness of a hypothetical DMT with a limited treatment duration in AD.

Methods: We developed a Markov state-transition model to estimate the cost-effectiveness of a hypothetical DMT plus best supportive care (BSC) versus BSC alone among Americans living with mild cognitive impairment (MCI) due to AD or mild AD.

The Association Between the Occurrence of Common Treatment-Emergent Adverse Events and Efficacy Outcomes After Lasmiditan Treatment of a Single Migraine Attack: Secondary Analyses from Four Pooled Randomized Clinical Trials.

Background: In controlled clinical trials, compared with placebo, a significantly greater proportion of participants using lasmiditan to treat a migraine attack achieved 2-h pain freedom (PF) and experienced ≥ 1 treatment-emergent adverse event (TEAE).

Objective: To better inform clinicians about treatment expectations by evaluating the association between TEAEs and efficacy outcomes after lasmiditan treatment.

Methods: Pooled data from SAMURAI, SPARTAN, MONONOFU, and CENTURION were analyzed.

Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine.

Background: Lasmiditan (LTN) is a selective 5-HT receptor agonist for the acute treatment of migraine in adults. We present detailed safety findings from the placebo-controlled, double-blind Phase 3 study, of LTN treatment across 4 attacks (CENTURION).

Methods: Patients were randomized 1:1:1 to LTN 200 mg (LTN200), LTN100, or a control group that received placebo for 3 attacks and LTN50 for either the 3rd or 4th attack (1:1).

What are the clinical effects of the different emergency department imaging options for suspected renal colic? A scoping review.

Objectives: Clinicians have minimal guidance regarding the clinical consequences of each radiologic imaging option for suspected renal colic in the emergency department (ED), particularly in relation to patient-centered outcomes. In this scoping review, we sought to identify studies addressing the impact of imaging options on patient-centered aspects of ED renal colic care to help clinicians engage in informed shared decision making. Specifically, we sought to answer questions regarding the effect of obtaining computed tomography (CT; compared with an ultrasound or delayed imaging) on safety outcomes, accuracy, prognosis, and cost (financial and length of stay [LOS]).

Highly Strained Pn(CH) (Pn = N, P, As, Sb, Bi) Tetrahedranes: Theoretical Characterization.

Recent experimental research by Cummins and co-workers has established the existence of a tetrahedrane molecule with one CH moiety replaced by phosphorus. We present here the first theoretical studies of the entire Pn(CH) (Pn = N, P, As, Sb, Bi) class of molecules. Geometries are obtained at the highly reliable CCSD(T)/aug-cc-pwCVTZ(-PP) level of theory.

Randomized, controlled trial of lasmiditan over four migraine attacks: Findings from the CENTURION study.

Background: We present findings from the multicenter, double-blind Phase 3 study, CENTURION. This study was designed to assess the efficacy of and consistency of response to lasmiditan in the acute treatment of migraine across four attacks.

Methods: Patients were randomized 1:1:1 to one of three treatment groups - lasmiditan 200 mg; lasmiditan 100 mg; or a control group that received placebo for three attacks and lasmiditan 50 mg for either the third or fourth attack.

Medication overuse in a subgroup analysis of phase 3 placebo-controlled studies of galcanezumab in the prevention of episodic and chronic migraine.

Introduction: Acute medication overuse is prevalent in patients with migraine.

Methods: In three phase 3, double-blind, randomized, placebo-controlled studies, patients with episodic migraine (EVOLVE-1 and EVOLVE-2) or chronic migraine (REGAIN) were randomized 2:1:1 to monthly subcutaneous injections of placebo or galcanezumab 120 or 240 mg for 3 or 6 months. This subgroup analysis evaluated mean changes in the number of monthly migraine headache days in each treatment among patients with versus without baseline acute medication overuse via mixing modelling with repeated measures.

Evaluation of 2-Hour Post-Dose Efficacy of Lasmiditan for the Acute Treatment of Difficult-to-Treat Migraine Attacks.

Objective: To identify factors predicting response (2-hour headache pain freedom or most bothersome symptom freedom) to lasmiditan based on individual patient characteristics, migraine disease characteristics, and migraine attack characteristics. Further, efficacy specifically in difficult-to-treat patient/migraine disease characteristics or attack characteristics (ie, historically considered less responsive to certain acute therapies) subgroups was analyzed.

Background: Knowledge of factors associated with a positive or negative response to acute treatment would be useful to practitioners prescribing acute treatments for migraine.

The current state of acute treatment for migraine in adults in the United States.

Migraine is a common and disabling disorder with substantial personal, social, and economic burden that affects 37 million people in the United States. Risk factors for migraine include age, sex, and genetics. The goal of acute treatment of migraine attacks is to stop the pain and associated symptoms of the migraine attack and return the patient to normal function.

Effects of lasmiditan on simulated driving performance: Results of two randomized, blinded, crossover studies with placebo and active controls.

Objective: To evaluate the impact of lasmiditan, an oral, centrally-penetrant, selective serotonin 1F (5-HT ) receptor agonist developed for the acute treatment of migraine, on simulated driving.

Methods: Healthy adult volunteers enrolled in two randomized, placebo and active comparator-controlled, crossover studies. Study 1 (N = 90) tested lasmiditan (50-, 100-, 200-mg), alprazolam (1-mg), and placebo at 1.

Improvement in Function after Lasmiditan Treatment: Post Hoc Analysis of Data from Phase 3 Studies.

Introduction: Migraine is associated with substantial functional impairment and affects many aspects of daily life.

Methods: Using data from SAMURAI and SPARTAN (double-blind, placebo-controlled, phase 3 studies) and GLADIATOR (an open-label, phase 3 study enrolling patients who had completed SAMURAI or SPARTAN), we assessed the effects of lasmiditan on migraine-related functional disability at multiple time points from 0.5 to 48 h post dose by asking patients to rate how much the migraine was interfering with normal activities.

The Influence of Migraine on Driving: Current Understanding, Future Directions, and Potential Implications of Findings.

Objective: To review the published findings relevant to migraine and driving performance, with an intent to encourage discussion on research which may broaden understanding in this area and help educate healthcare providers and their patients.

Background: Motor vehicle crashes result in more than 35,000 deaths and more than 2 million injuries annually in the United States. Migraine is one of the most prevalent diseases in the world, and many symptoms associated with migraine attacks have the potential to negatively influence driving ability.

Abuse Potential of Lasmiditan: A Phase 1 Randomized, Placebo- and Alprazolam-Controlled Crossover Study.

Lasmiditan is a centrally penetrant, highly selective 5-hydroxytryptamine (serotonin) receptor 1F (5HT ) agonist under development as a novel therapy for acute treatment of migraine. A phase 1 randomized, placebo- and positive-controlled crossover study assessed the abuse potential of lasmiditan in adult recreational polydrug users. Following a qualification phase, subjects were randomized into treatment sequences, each consisting of 5 study treatments: placebo, alprazolam 2 mg, lasmiditan 100, 200 (lasmiditan 100 and 200 mg are proposed therapeutic doses), and 400 mg (supratherapeutic).

Evaluation of Cardiovascular Outcomes in Adult Patients With Episodic or Chronic Migraine Treated With Galcanezumab: Data From Three Phase 3, Randomized, Double-Blind, Placebo-Controlled EVOLVE-1, EVOLVE-2, and REGAIN Studies.

Objective: Blood pressure (BP), pulse, electrocardiogram (ECG), and clinical cardiovascular (CV) outcomes in patients with episodic or chronic migraine treated for up to 6 months with galcanezumab compared to placebo were evaluated.

Background: Calcitonin gene-related peptide, a potent microvascular vasodilator, has a hypothesized protective role in CV health. Increased CV risks have been reported in patients with migraine.

Onset of Efficacy Following Oral Treatment With Lasmiditan for the Acute Treatment of Migraine: Integrated Results From 2 Randomized Double-Blind Placebo-Controlled Phase 3 Clinical Studies.

Objective: To expand on available information on the efficacy of oral lasmiditan for the acute treatment of migraine with particular focus on the timing of the effect and on its impact on migraine-associated symptoms.

Background: Lasmiditan is a novel selective 5-hydroxytryptamine 1F receptor agonist that lacks vasoconstrictive activity. In 2 phase 3 studies, SAMURAI and SPARTAN, lasmiditan met primary and key secondary efficacy endpoints at 2 hours following initial dose.

Lasmiditan for acute treatment of migraine in patients with cardiovascular risk factors: post-hoc analysis of pooled results from 2 randomized, double-blind, placebo-controlled, phase 3 trials.

Background: In addition to the increased risk for cardiovascular (CV) disease and CV events associated with migraine, patients with migraine can also present with a number of CV risk factors (CVRFs). Existing treatment options can be limited due to contraindications, increased burden associated with monitoring, or patient avoidance of side effects. Safe and effective migraine treatment options are needed for patients with migraine and a history of CV or cerebrovascular disease or with increased risk for CV events.

Sustained responses to lasmiditan: Results from post-hoc analyses of two Phase 3 randomized clinical trials for acute treatment of migraine.

Background: Sustained pain freedom is an important attribute of acute migraine therapies for patients and physicians. Here we report efficacy of the centrally penetrant, highly selective, 5-HT agonist lasmiditan on sustained pain freedom and other outcomes at 24 and 48 hours post-dose.

Study Design And Methods: Data from the similarly designed, Phase 3, double-blind studies SAMURAI (NCT02439320) and SPARTAN (NCT02605174) were pooled to more precisely estimate efficacy effects in these post-hoc analyses.

Safety findings from Phase 3 lasmiditan studies for acute treatment of migraine: Results from SAMURAI and SPARTAN.

Background: We assessed the safety profile of lasmiditan, a selective 5-HT receptor agonist without vasoconstrictive activity being developed as an acute therapy for migraine.

Methods: SAMURAI and SPARTAN were Phase 3 double-blind studies of patients with migraine, randomized to oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo to be taken within 4 hours of onset of migraine pain. Safety data from the studies were integrated.

Counterintuitive results from observational data: a case study and discussion.

Objective: To explore the issue of counterintuitive data via analysis of a representative case in which the data obtained was unexpected and inconsistent with current knowledge. We then discuss the issue of counterintuitive data while developing a framework for approaching such findings.

Design: The case study is a retrospective analysis of a cohort of coronary artery bypass graft (CABG) patients.

Analysis of Initial Nonresponders to Galcanezumab in Patients With Episodic or Chronic Migraine: Results From the EVOLVE-1, EVOLVE-2, and REGAIN Randomized, Double-Blind, Placebo-Controlled Studies.

Objective: To examine the likelihood of response with continued galcanezumab treatment in patients with episodic or chronic migraine without initial clinical improvement.

Background: A percentage of patients with migraine may require additional time on pharmacotherapy but discontinue treatment prematurely. Additionally, recognizing when continued treatment is unlikely to provide improvement limits unnecessary exposure.