CAR T-cell therapy: A collaboration between authorized treatment centers and community oncologists.

With the approval of the first CAR T-cell products for hematological malignancies in 2017, these autologous cell therapies have changed the treatment paradigm for patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL), who have a poor prognosis and few effective treatment options. Despite the demonstrated clinical benefit in patients with r/r diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, many patients who are eligible for CAR T-cell therapies do not receive them or are treated with CAR T cells as a later line of therapy at advanced stages of disease. Several barriers exist for referring patients to an authorized treatment center (ATC) for CAR T-cell therapy.

A randomized, multicenter trial assessing the effects of rapastinel compared to ketamine, alprazolam, and placebo on simulated driving performance.

N-methyl-D-aspartate ionotropic glutamatergic receptor (NMDAR) modulators, including rapastinel and ketamine, elicit rapid and sustained antidepressant responses in patients with treatment-resistant major depressive disorder. This phase I, randomized, multicenter, placebo-controlled, five-period, crossover, single-dose study evaluated simulated driving performance of healthy participants (N = 107) after single doses of rapastinel slow intravenous (i.v.

Simulated driving performance in healthy adults after night-time administration of 20 mg tasimelteon.

An impairment in next day driving performance has been reported for almost every drug currently United States Food and Drug Administration (FDA) approved for improvement of sleep in chronic and transient insomnia. Tasimelteon, a melatonin receptor agonist, demonstrated significant improvements in night-time sleep, daytime naps, and sleep timing in non-24-hr sleep-wake disorder (Non-24) by entraining these patients to a 24-hr day as measured by melatonin and cortisol rhythms. Given this new mechanism of action of entraining the biological clock, we conducted a study to evaluate the potential effect tasimelteon may have on the ability to operate a motor vehicle.

Safety and Tolerability of GRF6019 Infusions in Severe Alzheimer's Disease: A Phase II Double-Blind Placebo-Controlled Trial.

Background: The plasma fraction GRF6019 shows multiple benefits on brain aging in mice, including enhanced cognition, neurogenesis, and synaptic density, as well as reduced neuroinflammation.

Objective: To evaluate the safety, tolerability, and preliminary efficacy of GRF6019 in patients with severe Alzheimer's disease (AD).

Methods: A phase II, double-blind, placebo-controlled study in patients with severe AD (Mini-Mental State Examination score 0-10).

Safety and tolerability of GRF6019 in mild-to-moderate Alzheimer's disease dementia.

Introduction: This phase 2 trial evaluated the safety, tolerability, and feasibility of repeated infusions of the plasma fraction GRF6019 in mild-to-moderate Alzheimer's disease.

Methods: In this randomized, double-blind, dose-comparison trial, 47 patients were randomized 1:1 to receive daily infusions of 100 mL (n = 24) or 250 mL (n = 23) of GRF6019 for 5 consecutive days over two dosing periods separated by a treatment-free interval of 3 months.

Results: The mean (standard deviation [SD]) age of the enrolled patients was 74.

NSI-189 phosphate, a novel neurogenic compound, selectively benefits moderately depressed patients: A post-hoc analysis of a phase 2 study of major depressive disorder.

Background: NSI-189 phosphate (NSI-189) is a novel neurogenic molecule with pleiotropic properties, including antidepressant, procognitive, synaptoplastic, and neurotrophic activities demonstrated in preclinical studies. Its antidepressant activity is monoamine-independent. NSI-189 was previously tested in patients with recurrent major depressive disorder in an inpatient setting.

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.

An assessment of the centrally acting muscle relaxant tolperisone on driving ability and cognitive effects compared to placebo and cyclobenzaprine.

What Is Known And Objective: Tolperisone is a centrally acting muscle relaxant under development in the United States as a treatment for acute and painful symptoms of muscle spasms. The objective of this three-way, randomized, blinded, three-period crossover study was to assess the safety and cognitive effects of tolperisone compared to placebo and the widely used muscle relaxant cyclobenzaprine in healthy volunteers.

Methods: Subjects were randomized to 1 of 3 treatment arms to receive tolperisone (150 mg), cyclobenzaprine (10 mg) or placebo 3 times per day (TID) in 3 separate study periods.

Next-day residual effects of flibanserin on simulated driving performance in premenopausal women.

Objective: The objective of this study was to determine the next-day residual effects of acute and steady-state nighttime dosing of flibanserin on simulated driving performance and cognitive function in healthy premenopausal women.

Methods: In this randomized, double-blind, placebo-controlled, four-way crossover study, 72 subjects were treated with either acute oral doses of placebo, zopiclone 7.5 mg (positive control) or flibanserin 100 mg at bedtime (indicated therapeutic dose), or after chronic nightly oral doses of flibanserin 100 mg for 1 week followed by a single bedtime dose of flibanserin 200 mg (supratherapeutic dose).

Next-day residual effects of gabapentin, diphenhydramine, and triazolam on simulated driving performance in healthy volunteers: a phase 3, randomized, double-blind, placebo-controlled, crossover trial.

Objective: Next-day residual effects of a nighttime dose of gabapentin 250 mg were evaluated on simulated driving performance in healthy participants in a randomized, placebo-controlled, double-blind, multicenter, four-period crossover study that included diphenhydramine citrate 76 mg and triazolam 0.5 mg.

Methods: At treatment visits, participants (n = 59) were dosed at ~23:30, went to bed immediately, and awakened 6.

A randomized, crossover, placebo-controlled clinical trial to assess the sensitivity of the CRCDS Mini-Sim to the next-day residual effects of zopiclone.

Objectives: We sought to validate Cognitive Research Corporation's Driving Simulator (CRCDS Mini-Sim) for studies of drug safety with respect to driving ability.

Methods: A total of 30 healthy subjects were randomized to receive placebo or 7.5 mg zopiclone, a hypnotic known to impair driving, in random order during the 2 treatment periods of a 2 period crossover design.

Relationship Between Obesity and Driving.

Obesity, which has become epidemic throughout many parts of the world, is known to be a risk factor for a range of diseases including hypertension, diabetes, and vascular disease. Based on this review, it also appears that obesity is associated with increased crash risk and increased risk of serious or fatal injury in a crash. The problem is particularly an issue for commercial truck drivers.

Early-stage comparative effectiveness: randomized controlled trial with histamine inverse agonist MK-7288 in excessive daytime sleepiness patients.

Histaminergic neurons are regulators of the sleep-wake cycle. We evaluated the alerting effects of MK-7288 (10, 20 mg), a novel histamine-3 receptor inverse agonist (H3RIA), along with modafinil (200 mg), a standard treatment, in a randomized, double-blind, placebo controlled, crossover study of 56 patients with excessive daytime sleepiness (EDS). Efficacy was assessed using maintenance of wakefulness tests (MWT) and car driving simulation tests.

Effects of armodafinil on simulated driving and self-report measures in obstructive sleep apnea patients prior to treatment with continuous positive airway pressure.

Study Objectives: Obstructive sleep apnea (OSA) has been associated with an increased risk of motor vehicle crashes. This driving risk can be reduced (≥ 50%) by treatment with continuous positive airway pressure (CPAP). However residual excessive daytime sleepiness (EDS) can persist for some patients who regularly use CPAP.

Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES).

Study Objective: To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA).

Design, Setting, And Participants: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S.

Cognitive effects of oxybutynin chloride topical gel in older healthy subjects: a 1-week, randomized, double-blind, placebo- and active-controlled study.

Background And Objective: Oxybutynin is a common antimuscarinic therapy for overactive bladder. Transdermally administered oxybutynin chloride topical gel 10% (OTG) has a low propensity for anticholinergic adverse effects and possibly also a low risk of cognitive impairment. A randomized, double-blind, placebo- and active-controlled study evaluated the effects of OTG on cognitive and psychomotor functions in older healthy adults.

Changes in body weight and psychotropic drugs: a systematic synthesis of the literature.

Introduction: Psychotropic medication use is associated with weight gain. While there are studies and reviews comparing weight gain for psychotropics within some classes, clinicians frequently use drugs from different classes to treat psychiatric disorders.

Objective: To undertake a systematic review of all classes of psychotropics to provide an all encompassing evidence-based tool that would allow clinicians to determine the risks of weight gain in making both intra-class and interclass choices of psychotropics.

Evaluation of cognitive function in healthy older subjects treated with fesoterodine.

Objective: To evaluate the cognitive effects of fesoterodine 4 and 8 mg versus placebo in healthy older adults.

Methods: This was an active- and placebo-controlled, double-blind, double-dummy crossover study conducted using healthy volunteers (aged 65-85 years) with baseline Mini-Mental State Examination score ≥ 26. The study comprised 4 treatment periods: fesoterodine 4 mg for 6 days; fesoterodine 4 mg for 3 days followed by fesoterodine 8 mg for 3 days; placebo for 6 days; and placebo for 6 days with alprazolam 1 mg on day 6.

Blood-brain barrier permeation and efflux exclusion of anticholinergics used in the treatment of overactive bladder.

Overactive bladder (OAB) is a common condition, particularly in the elderly. Anticholinergic agents are the mainstay of pharmacological treatment of OAB; however, many anticholinergics can cross the blood-brain barrier (BBB) and may cause central nervous system (CNS) effects, including cognitive deficits, which can be especially detrimental in older patients. Many anticholinergics have the potential to cause adverse CNS effects due to muscarinic (M(1)) receptor binding in the brain.

A comprehensive non-clinical evaluation of the CNS penetration potential of antimuscarinic agents for the treatment of overactive bladder.

What Is Already Known About This Subject: This study provides antimuscarinic agents for overactive bladder (OAB) display variable association with side effects mediated by the central nervous system (CNS), which may be of particular concern in the elderly. Adverse effects on CNS functioning are related to muscarinic receptor subtype selectivity and the ability of the agent to cross the blood-brain barrier, where P-gp plays a role in limiting permeability.

What This Study Adds: This study provides a parallel investigation of CNS penetration of antimuscarinic OAB agents in vivo and assessment of physical properties and permeability in cell monolayers in vitro.

The association between obstructive sleep apnea and neurocognitive performance--the Apnea Positive Pressure Long-term Efficacy Study (APPLES).

Study Objectives: To determine associations between obstructive sleep apnea (OSA) and neurocognitive performance in a large cohort of adults.

Study Design: Cross-sectional analyses of polysomnographic and neurocognitive data from 1204 adult participants with a clinical diagnosis of obstructive sleep apnea (OSA) in the Apnea Positive Pressure Long-term Efficacy Study (APPLES), assessed at baseline before randomization to either continuous positive airway pressure (CPAP) or sham CPAP.

Measurements: Sleep and respiratory indices obtained by laboratory polysomnography and several measures of neurocognitive performance.

Simulated driving changes in young adults with ADHD receiving mixed amphetamine salts extended release and atomoxetine.

Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD).

Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts-extended release (MAS XR) 50 mg/day (Cohort 1) and atomoxetine 80 mg/day (Cohort 2) in young adults with ADHD.

Results: Adults aged 19 to 25 years with AD/HD (N = 19) who were administered MAS XR significantly improved overall simulated driving performance versus placebo up to 12 hours after dosing.

A double-blind, placebo-controlled trial of memantine in age-associated memory impairment (memantine in AAMI).

Objectives: To determine the safety and efficacy of memantine in treating Age-Associated Memory Impairment (AAMI).

Methods: Sixty adults between 50-79 years of age meeting diagnostic requirements for AAMI were randomly assigned to either memantine (titrated to 20 mg) or a matched placebo and treated for 90 days. An extensive battery of computerized cognitive tests was administered at screening, baseline and, thereafter, at monthly intervals.