Safety and effectiveness of diazepam nasal spray in male and female patients: Post hoc analysis of data from a phase 3 safety study.

Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]).

Analyses of patients who self-administered diazepam nasal spray for acute treatment of seizure clusters.

For acute treatment of seizure clusters in patients with epilepsy, intranasal administration of acute seizure therapies has been shown to provide accessibility and ease of use to care partners as well as the potential for self-administration by patients. Diazepam nasal spray (Valtoco®) was approved by the US Food and Drug Administration for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Self-administration consistent with the prescribing information is feasible and was reported by a subgroup of patients (n = 27 of 163) in a long-term phase 3 safety study.

A phase 1 open-label pilot study of low-dose interleukine-2 immunotherapy in patients with Alzheimer's disease.

Trial Registration: ClinicalTrials.gov Identifier: NCT05821153, Registered April 20 2023, Retrospectively registered, https://classic.

Clinicaltrials: gov/ct2/show/NCT05821153.

Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification.

Introduction: Amyloid beta (Aβ) oligomers are one of the most toxic structural forms of the Aβ protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer's disease (AD) patients' brain tissue. We previously demonstrated that antagonists of the sigma-2 receptor complex effectively block Aβ oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma-2 receptor complex that appears safe and well tolerated in healthy elderly volunteers.

Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer's Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial.

Background: LMTM is being developed as a treatment for AD based on inhibition of tau aggregation.

Objectives: To examine the efficacy of LMTM as monotherapy in non-randomized cohort analyses as modified primary outcomes in an 18-month Phase III trial in mild AD.

Methods: Mild AD patients (n = 800) were randomly assigned to 100 mg twice a day or 4 mg twice a day.

Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial.

Background: Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease.

PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury.

Background: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI).

Methods: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily.

A Randomized, Double-Blind, Active- and Placebo-Controlled Efficacy and Safety Study of Arhalofenate for Reducing Flare in Patients With Gout.

Objective: Arhalofenate is a novel antiinflammatory uricosuric agent. The objective of this study was to evaluate its antiflare activity in patients with gout.

Methods: This was a 12-week, randomized, double-blind, controlled phase IIb study.

An open-label study to assess safety, tolerability, and effectiveness of dextromethorphan/quinidine for pseudobulbar affect in dementia: PRISM II results.

Background: Dextromethorphan (DM)/quinidine (Q) is an approved treatment for pseudobulbar affect (PBA) based on trials in amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness and tolerability for PBA secondary to dementia, stroke, or traumatic brain injury; dementia cohort results are reported.

Methods: This was an open-label, multicenter, 90 day trial; patients received DM/Q 20/10 mg twice daily.

Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial.

Importance: Agitation is common among patients with Alzheimer disease; safe, effective treatments are lacking.

Objective: To assess the efficacy, safety, and tolerability of dextromethorphan hydrobromide-quinidine sulfate for Alzheimer disease-related agitation.

Design, Setting, And Participants: Phase 2 randomized, multicenter, double-blind, placebo-controlled trial using a sequential parallel comparison design with 2 consecutive 5-week treatment stages conducted August 2012-August 2014.

Single-entity hydrocodone extended-release capsules in opioid-tolerant subjects with moderate-to-severe chronic low back pain: a randomized double-blind, placebo-controlled study.

Objective: A single-agent, extended-release formulation of hydrocodone (HC) has been developed for treatment of chronic moderate-to-severe pain. This study was designed to examine the safety and efficacy of HC extended release in opioid-experienced adults with moderate-to-severe chronic low back pain (CLBP).

Methods: This multicenter, enriched enrollment, randomized withdrawal study comprised an open-label conversion/titration phase (≤6 weeks) followed by placebo-controlled, double-blind treatment (12 weeks).

Robustness of ProsVue linear slope for prognostic identification of patients at reduced risk for prostate cancer recurrence: Simulation studies on effects of analytical imprecision and sampling time variation.

Objective: The ProsVue assay measures serum total prostate-specific antigen (PSA) over three time points post-radical prostatectomy and calculates rate of change expressed as linear slope. Slopes ≤ 2.0 pg/ml/month are associated with reduced risk for prostate cancer recurrence.

Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial.

Background: In an open-label phase 1 trial, gene delivery of the trophic factor neurturin via an adeno-associated type-2 vector (AAV2) was well tolerated and seemed to improve motor function in patients with advanced Parkinson's disease. We aimed to assess the safety and efficacy of AAV2-neurturin in a double-blind, phase 2 randomised trial.

Methods: We did a multicentre, double-blind, sham-surgery controlled trial in patients with advanced Parkinson's disease.

Comparison of predictive values of two diagnostic tests from the same sample of subjects using weighted least squares.

Screening and diagnostic tests are important in disease prevention or control. The predictive values of positive and negative (PPV and NPV) test results are two of four operational characteristics of a screening test. We review an existing method based on the generalized estimating equation (GEE) methodology for comparing predictive values from the same sample of subjects and propose two Wald test statistics derived from the weighted least squares (WLS) method for the analysis of categorical data.

Workplace accommodations for people with disabilities: National Health Interview Survey Disability Supplement, 1994-1995.

As American workers age, workers with impairments and functional limitations make up a larger percentage of our workforce. This investigation presents data from the National Health Interview Survey Disability Supplement 1994-1995 (NHIS-D) describing the nature of workplace accommodations in the American workforce and factors associated with the provision of such accommodations. Of a nationally representative sample of workers aged 18 to 69 years with a wide range of impairments, 12% reported receiving workplace accommodations.

Inhibition of oral cancer cell growth by adenovirusMnSOD plus BCNU treatment.

We hypothesized that inhibitors of peroxide removal, such as BCNU, an indirect inhibitor of glutathione peroxidase (GPx), and 3-amino-1,2,4-triazole (AT), a direct inhibitor of catalase (CAT), should cause toxicity to cancer cells after manganese superoxide dismutase (MnSOD) overexpression due to elevated peroxide levels. In vitro, hamster cheek pouch carcinoma cells (HCPC-1) and human oral squamous carcinoma cells (SCC-25) were infected with various combinations of adenovirus containing MnSOD cDNA (AdMnSOD). Cells were then treated with or without BCNU and assayed for viability using Annexin/PI staining and flow cytometry.

Preoperative CA 125 levels: an independent prognostic factor for epithelial ovarian cancer.

Objective: To estimate the association of preoperative CA 125 levels with outcome in primary ovarian cancer patients.

Methods: One hundred forty-two patients with epithelial ovarian cancer, who had a serum CA 125 level drawn before surgery, were retrospectively evaluated. The relationship of preoperative CA 125 levels and various preoperative and postoperative variables was evaluated.

Ovarian cancer p53 mutation is associated with tumor microvessel density.

Objective: The objective of this study was to investigate the relationship between microvessel density, as measured by CD31 staining, and histopathologic factors as well as p53 tumor suppressor gene mutation in ovarian cancer.

Methods: Ovarian cancers (n = 77) were analyzed for p53 gene mutations and CD31 immunohistochemical expression. Histopathologic and mutational data were related to CD31 staining utilizing the Mantel correlation statistic.

Failure of BRCA1 dysfunction to alter ovarian cancer survival.

Purpose: Many factors modify ovarian cancer survival. There are conflicting reports regarding survival of individuals with hereditary BRCA1-related ovarian cancer. None have controlled for other mechanisms of BRCA1 silencing in the control cohort.

Workforce participation by persons with disabilities: the National Health Interview Survey Disability Supplement, 1994 to 1995.

Using the National Health Interview Survey Disability Supplement of 1994 to 1995, we examined the factors associated with employment among Americans with disabilities. Persons with disabilities who were more educated were more likely to be working. Married men were more likely to work than unmarried men (odds ratio [OR], 1.

Issues in planning a placebo-controlled trial of manual methods: results of a pilot study.

Objective: There are fundamental differences between the administration of medications and the application of manual procedures, such as those used by chiropractors. The objective of this study was to gather preliminary information on how to address these differences in the design of a multisite, randomized placebo-controlled trial of chiropractic care for women with chronic pelvic pain (CPP).

Design: Pilot study for a multisite, randomized, placebo-controlled clinical trial.

Radiation-induced kidney injury: a role for chronic oxidative stress?

Kidney irradiation clearly leads to a progressive reduction in function associated with concomitant glomerulosclerosis and/or tubulointerstitial fibrosis. However, the particular cell types, mediators and/or mechanisms involved in the development and progression of radiation nephropathy remain ill defined. Angiotensin II (Ang II) plays a major pathogenic role; administration of Ang II blockers markedly abrogates the severity of radiation nephropathy in experimental models.