Diagnostic delay and characterization of the clinical prodrome in AL amyloidosis among 1523 US adults diagnosed between 2001 and 2019.

Light-chain (AL) amyloidosis is a multisystem disorder with a high early mortality and diagnostic delays of >1 year from symptom onset. This retrospective observational study sought to characterize the clinical prodrome and diagnostic delay to inform early detection. We identified 1523 adults with newly diagnosed AL amyloidosis in the Optum de-identified Clinformatics Datamart US healthcare claims database as those with ≥2 new diagnosis codes for AL or other amyloidosis in 90 days with ≥1 multiple myeloma treatment within 730 days, excluding patients with prior hereditary or secondary amyloidosis and Familial Mediterranean Fever.

A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours.

Purpose: This phase 1b study determined the safety, tolerability, and recommended phase 2 dose (RP2D) and schedule of trametinib in combination with gemcitabine. Secondary objectives included assessment of clinical activity and steady-state pharmacokinetics.

Methods: Adults with advanced solid tumours, adequate organ function and Eastern Co-operative Oncology Group performance status (ECOG PS) ⩽ 1 were eligible.

A new approach to rater training and certification in a multicenter clinical trial.

Recent evidence demonstrates that the quality of raters' applied clinical skills is directly related to study outcome. As such, the training and evaluation of raters' clinical skill in administering symptom-rating scales is essential before being certified to rate patients in clinical trials. This study examined a novel approach to rater training and certification that focused on both conceptual knowledge and applied skills.

Paroxetine Controlled Release for Premenstrual Dysphoric Disorder: Remission Analysis Following a Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: To compare the efficacy and safety of paroxetine controlled release (CR) (12.5 mg/day or 25 mg/day) versus placebo in premenstrual dysphoric disorder (PMDD).Method: A double-blind, randomized, placebo-controlled trial was conducted over 3 menstrual cycles in women aged 18-45 years with confirmed DSM-IV PMDD in 47 outpatient centers across the United States and Canada from November 1999 to January 2002.

Hypertension and the rate of cognitive decline in patients with dementia of the Alzheimer type.

Hypertension has been suspected of being associated with Alzheimer disease (AD). To study this problem, a case-control study investigating the association between hypertension and cognitive decline was conducted as a secondary analysis of data from more than 700 patients diagnosed with AD who had been randomly assigned to the placebo arm of a clinical trial. Additional analyses were undertaken to investigate the effects of baseline disease severity, age, gender, apolipoprotein genotype, and the use of antihypertensive medication in this population.

Paroxetine controlled release for premenstrual dysphoric disorder: a double-blind, placebo-controlled trial.

Background: Better characterization of safety and efficacy of multiple doses of selective serotonin reuptake inhibitors for the treatment of a wider range of symptoms of premenstrual dysphoric disorder (PMDD) will provide clinicians with flexibility to provide symptom relief along with acceptable tolerability. This study was designed to assess the efficacy and tolerability of multiple doses of paroxetine controlled release (CR) in PMDD.

Methods: In a multicenter (43 outpatient U.