Safety and tolerability of cariprazine for the adjunctive treatment of major depressive disorder: a pooled analysis of phase 2b/phase 3 clinical trials.

To characterize the safety and tolerability of adjunctive cariprazine in patients with major depressive disorder (MDD) and inadequate response to monotherapy antidepressant treatment (ADT). Post hoc analyses evaluated pooled data from 2 fixed-dose phase 3 cariprazine studies (1.5 and 3 mg/d [approved doses for MDD]).

Novel predictors of permanent pacemaker implantation following transcatheter aortic valve replacement.

Background: Conduction and rhythm abnormalities requiring permanent pacemakers (PPM) are short-term complications following transcatheter aortic valve replacement (TAVR), and their clinical outcomes remain conflicting. Potential novel predictors of post-TAVR PPM, like QRS duration, QTc prolongation, and supraventricular arrhythmias, have been poorly studied.

Aim: To evaluate the effects of baseline nonspecific interventricular conduction delay and supraventricular arrhythmia on post-TAVR PPM requirement and determine the impact of PPM implantation on clinical outcomes.

Cariprazine for the Adjunctive Treatment of Major Depressive Disorder in Patients With Inadequate Response to Antidepressant Therapy: Results of a Randomized, Double-Blind, Placebo-Controlled Study.

To assess the efficacy of cariprazine, a dopamine D-preferring D/D and serotonin 5-HT receptor partial agonist, as adjunctive treatment for patients with major depressive disorder (MDD) and inadequate response to ongoing antidepressant therapy (ADT). This randomized, double-blind, placebo-controlled study was conducted from November 2018 to September 2021. Adults with MDD per criteria were randomized (1:1:1) to cariprazine 1.

Cariprazine in Pediatric Patients with Autism Spectrum Disorder: Results of a Pharmacokinetic, Safety and Tolerability Study.

Cariprazine is a dopamine D-preferring D/D and serotonin 5-HT receptor partial agonist approved to treat adults with schizophrenia and manic/mixed or depressive episodes associated with bipolar I disorder. This study, which is the first to evaluate cariprazine in pediatric patients with autism spectrum disorder (ASD) (including children 5-9 years of age) using an oral solution formulation, evaluated the safety, tolerability, pharmacokinetics (PK), and exploratory efficacy of cariprazine and its two major active metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR). This clinical pharmacology, open-label, multiple-dose study enrolled 25 pediatric patients from 5 to 17 years of age, who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for ASD.

Adjunctive Cariprazine for the Treatment of Patients With Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

Objective: The purpose of this study was to investigate the efficacy of cariprazine, a dopamine D-preferring D/D and serotonin 5-HT receptor partial agonist, as adjunctive therapy for patients with major depressive disorder and nonresponse to at least one antidepressant monotherapy.

Methods: In this double-blind placebo-controlled study, adults with major depressive disorder and inadequate response to antidepressants alone were randomized in a 1:1:1 ratio to placebo, cariprazine at 1.5 mg/day, or cariprazine at 3.

Pharmacokinetics, Safety, and Tolerability of Cariprazine in Pediatric Patients with Bipolar I Disorder or Schizophrenia.

Cariprazine is a dopamine D-preferring D/D and serotonin 5-HT receptor partial agonist approved to treat adults with schizophrenia and manic/mixed or depressive episodes associated with bipolar I disorder. This sequential-cohort, dose-escalation study was the first to evaluate the pharmacokinetic, safety, and tolerability profile of cariprazine and its two major active metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR), in pediatric patients with schizophrenia or bipolar I disorder. This phase I open-label study enrolled patients with schizophrenia (13-17 years of age) or bipolar I disorder (10-17 years of age).

Striatal dopamine synthesis capacity and its association with negative symptoms upon resolution of positive symptoms in first-episode schizophrenia and delusional disorder.

Rationale: How striatal dopamine synthesis capacity (DSC) contributes to the pathogenesis of negative symptoms in first-episode schizophrenia (SZ) and delusional disorder (DD) has seldom been explored. As negative symptoms during active psychotic episodes can be complicated by secondary influences, such as positive symptoms, longitudinal investigations may help to clarify the relationship between striatal DSC and negative symptoms and differentiate between primary and secondary negative symptoms.

Objective: A longitudinal study was conducted to examine whether baseline striatal DSC would be related to negative symptoms at 3 months in first-episode SZ and DD patients.

Effects of fremanezumab in patients with chronic migraine and comorbid depression: Subgroup analysis of the randomized HALO CM study.

Objective: To evaluate the efficacy of fremanezumab in patients with chronic migraine (CM) and moderate to severe depression.

Background: Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, has been approved for the preventive treatment of migraine in adults. CM and depression are highly comorbid.

Long-term safety, tolerability, and efficacy of fremanezumab in migraine: A randomized study.

Objective: To assess the long-term safety, tolerability, and efficacy of fremanezumab, a fully humanized monoclonal antibody approved for the preventive treatment of migraine.

Methods: A 52-week, multicenter, randomized, double-blind, parallel-group study evaluated fremanezumab monthly or quarterly in adults with chronic migraine (CM) or episodic migraine (EM). Safety and tolerability were assessed by adverse event (AE) monitoring (performed by the investigators), systematic local injection-site assessments (immediately and 1 hour after injection), laboratory/vitals assessments, and immunogenicity testing.

Effect of fremanezumab on quality of life and productivity in patients with chronic migraine.

Objective: To evaluate fremanezumab quarterly or monthly vs placebo on health-related quality of life, health status, patients' global impression of change, and productivity in patients with chronic migraine (CM).

Methods: HALO CM was a double-blind, placebo-controlled trial in patients with CM. Patients were randomized 1:1:1 to treatment with fremanezumab quarterly (675 mg at baseline, placebo at weeks 4 and 8), fremanezumab monthly (225 mg at baseline, weeks 4 and 8), or placebo.

Effects of a Health Education Course on Pre-Service Teachers' Perceived Knowledge, Skills, Preparedness, and Beliefs in Teaching Health Education.

Background: In this study, we explore how a health education course may play a role in pre-service teachers' perceptions in teaching and integrating health education activities to nurture K-8 students' health literacy.

Methods: We used mixed methods to examine the effect of a health education course in a teacher education program. Of 55 pre-service teachers, 41voluntarily participated in the study.

Effects of fremanezumab on the use of acute headache medication and associated symptoms of migraine in patients with episodic migraine.

Background: Fremanezumab, a fully humanized monoclonal antibody targeting calcitonin gene-related peptide, has demonstrated efficacy for the preventive treatment of migraine in adults.

Objective: To evaluate the effect of fremanezumab treatment on acute headache medication use and migraine-associated symptoms in patients with episodic migraine.

Methods: In the Phase 3 HALO trial, patients with episodic migraine were randomized to receive subcutaneous fremanezumab monthly (225 mg at baseline, weeks 4 and 8), fremanezumab quarterly (675 mg at baseline, placebo at weeks 4 and 8), or placebo over a 12-week period.

Early Onset of Efficacy With Fremanezumab for the Preventive Treatment of Chronic Migraine.

Objective: To assess the onset of efficacy for fremanezumab in chronic migraine by evaluating pain-related clinical measures at different time points.

Background: Faster onset of efficacy of preventive treatments could benefit patients with migraine. Fremanezumab is a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, a neuropeptide involved in the pathophysiology of migraine.

Fremanezumab for the preventive treatment of migraine.

: The recent approval of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway introduced the first preventive treatments for migraine that were specifically designed to target the underlying pathophysiology of the disease. Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) administered via subcutaneous injection, is the first approved monoclonal antibody that targets the CGRP ligand and offers both quarterly (once every 3 months) and monthly dosing. : An introduction to migraine, overview of the migraine preventive treatments that target CGRP or its receptor, background on CGRP, and details on the fremanezumab clinical development program in both chronic and episodic migraine.

Safety and Tolerability of Fremanezumab for the Prevention of Migraine: A Pooled Analysis of Phases 2b and 3 Clinical Trials.

Objective: Presentation of pooled analysis of safety data for fremanezumab in patients with chronic (CM) or episodic migraine (EM) from 4 placebo-controlled phase 2b and phase 3 studies.

Background: There is a need for an effective, safe, and well-tolerated preventive therapy that specifically targets the pathophysiology of migraine to reduce the frequency and severity of migraine attacks in patients with CM or EM who experience 4 or more migraine days per month. Fremanezumab is a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, a neuropeptide involved in the pathophysiology of migraine.

Hypertrophic pulmonary osteoarthropathy: an unusual presentation.

Objectives: Hypertrophic pulmonary osteoarthropathy (HPOA) is a syndrome characterized by the triad of periostitis, digital clubbing and painful arthropathy of the large joints, especially involving the lower limbs. HPOA without clubbing of the digits is considered an incomplete form of HPOA and has been rarely reported. We are presenting here a case of HPOA without clubbing in a patient with lung cancer.

Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial.

Importance: Fremanezumab, a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, may be effective for treating episodic migraine.

Objective: To assess the efficacy of fremanezumab compared with placebo for prevention of episodic migraine with a monthly dosing regimen or a single higher dose.

Design And Setting: Randomized, double-blind, placebo-controlled, parallel-group trial conducted at 123 sites in 9 countries from March 23, 2016 (first patient randomized), to April 10, 2017, consisting of a screening visit, 28-day pretreatment period, 12-week treatment period, and final evaluation at week 12.

A phase 1 study to assess the pharmacokinetics, safety, and tolerability of fremanezumab doses (225 mg, 675 mg and 900 mg) in Japanese and Caucasian healthy subjects.

Objectives: The primary and secondary objectives of this phase 1 study were to evaluate the pharmacokinetic profile, safety, and immunogenicity of fremanezumab subcutaneous (sc) doses tested in phase 2 and 3 trials (225 mg, 675 mg and 900 mg) following single administration in Japanese (n = 32) and Caucasian (n = 32) healthy subjects.

Methods: Japanese and matched Caucasian healthy subjects were enrolled into one of four cohorts and were randomly assigned to one of four treatments: 225, 675, or 900 mg fremanezumab, or placebo. Pharmacokinetic and immunogenicity sampling, and safety and tolerability assessments occurred at one inpatient visit and 12 ambulatory visits during the 36-week study.

Fremanezumab for the Preventive Treatment of Chronic Migraine.

Background: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine.

Methods: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo.

Response to inhaled loxapine in patients with schizophrenia or bipolar I disorder: PANSS-EC responder analyses.

Background: Efficacy of inhaled loxapine 5 or 10 mg in treating agitation was shown using the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC) in two Phase III randomised, double-blind, placebo-controlled trials in 344 agitated patients with schizophrenia and 314 patients with bipolar I disorder (Clinicaltrials.gov: NCT00628589, NCT00721955).

Aims: To examine the five individual items comprising the PANSS-EC and the percentage of patients achieving a clinical response (reduction of ≥40%) in PANSS-EC (Response-40) for these two studies.

Health care resource use and cost differences by opioid therapy type among chronic noncancer pain patients.

The study assessed 12-month chronic pain (CP)-related health care utilization and costs among chronic noncancer pain (CNCP) patients who initiated various long-term opioid treatments. Treatments included monotherapy with long-acting opioids (mono-LAOs), mono-therapy with short-acting opioids (mono-SAOs), both LAOs and SAOs (combination), and opioid therapy initiated with SAO or LAO and switched to the other class (switch). Using MarketScan claims databases (2006-2012), we identified CNCP patients with ≥90 days opioid supply after pain diagnosis and continuous enrollment 12 months before pain diagnosis (baseline period) and 12 months after opioid start (post-index period).

Burden of Alcohol Abuse or Dependence Among Long-Term Opioid Users with Chronic Noncancer Pain.

Background: Substance abuse disorders among chronic noncancer pain (CNCP) patients add to the clinical challenges and economic burden of caring for such patients. Despite potential risks, some CNCP patients with a history of alcohol abuse or dependence (AAD) and pain that is refractory to nonopioid treatment options may still need opioids for pain management. However, there is a lack of data on adverse outcomes in long-term opioid users with CNCP and a history of substance abuse or AAD disorders.

Developing an online health literacy curriculum for two German universities: a key stakeholder approach.

Health literacy is a significant resource for daily life in society. Global evidence reveals that there are less than ideal levels of health literacy in populations. One potential straproviding them with the skills and tools that will improve their knowledge and practice as our future workforce.

Spectral Analysis of Electrocardiograms in Patients with Inducible Atrial Fibrillation after Catheter Ablation Predicts Sinus Rhythm Maintenance.

Background: We aimed to develop a novel predictive marker for atrial fibrillation (AF) recurrence in patients with inducible AF after catheter ablation, based on power spectral analysis of baseline and postablation electrocardiograms.

Methods: Twenty-five patients who had undergone their first AF ablation procedure (pulmonary vein isolation and ganglionated plexi ablation) and had inducible AF after ablation were included. A 30-second interval of AF was chosen for each patient before and after ablation, and a periodogram of the atrial activity was computed.