Challenges and complexities in designing cluster headache prevention clinical trials: A narrative review.

Objective: To provide a review of challenges in clinical trials for the preventive treatment of cluster headache (CH) and highlight considerations for future studies.

Background: Current guidelines for preventive treatment of CH are largely based on off-label therapies supported by a limited number of small randomized controlled trials. Guidelines for clinical trial design for CH treatments from the International Headache Society were last issued in 1995.

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature.

Phase 3 randomized, placebo-controlled study of galcanezumab in patients with chronic cluster headache: Results from 3-month double-blind treatment.

Objective: To report efficacy and safety of galcanezumab in adults with chronic cluster headache.

Background: Galcanezumab is a humanized monoclonal antibody that binds to calcitonin gene-related peptide and inhibits its biological activity.

Methods: This study comprised a prospective baseline period, a 12-week double-blind, placebo-controlled treatment period, and a 52-week open-label period.

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature.

Trial of Galcanezumab in Prevention of Episodic Cluster Headache.

Background: Episodic cluster headache is a disabling neurologic disorder that is characterized by daily headache attacks that occur over periods of weeks or months. Galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, may be a preventive treatment for cluster headache.

Methods: We enrolled patients who had at least one attack every other day, at least four total attacks, and no more than eight attacks per day during a baseline assessment, as well as a history of cluster headache periods lasting at least 6 weeks, and randomly assigned them to receive galcanezumab (at a dose of 300 mg) or placebo, administered subcutaneously at baseline and at 1 month.

Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial.

Importance: Migraine is a disabling neurological disease characterized by severe headache attacks. Treatment options reduce migraine frequency for many patients, but adverse effects lead to discontinuation in many patients.

Objective: To demonstrate that galcanezumab is superior to placebo in the prevention of episodic migraine with or without aura.

Improvements in Tritrichomonas foetus molecular testing.

Bovine trichomoniasis is a sexually transmitted disease that results in infertility, abortion, and calf age variability. To date, management strategies include testing for Tritrichomonas foetus and culling of infected males. Challenges associated with testing include cost of culture medium, time and labor burden of sample incubation and processing, and adverse effects of bacterial growth on detection sensitivity.

Core Clinical Data Elements for Cancer Genomic Repositories: A Multi-stakeholder Consensus.

The Center for Medical Technology Policy and the Molecular Evidence Development Consortium gathered a diverse group of more than 50 stakeholders to develop consensus on a core set of data elements and values essential to understanding the clinical utility of molecularly targeted therapies in oncology.

Pharmacogenomic associations with weight gain in olanzapine treatment of patients without schizophrenia.

Objective: Pharmacogenomic analyses of weight gain during treatment with second-generation antipsychotics have resulted in a number of associations with variants in ankyrin repeat and kinase domain containing 1 (ANKK1)/dopamine D2 receptor (DRD2) and serotonin 2C receptor (HTR2C) genes. These studies primarily assessed subjects with schizophrenia who had prior antipsychotic exposure that may have influenced the amount of weight gained from subsequent therapies. We assessed the relationships between single-nucleotide polymorphisms (SNPs) in these genes with weight gain during treatment with olanzapine in a predominantly antipsychotic-naive population.

Antipsychotic monotherapy among outpatients with schizophrenia treated with olanzapine or risperidone in Japan: a health care database analysis.

Purpose: Antipsychotic monotherapy is often recommended over antipsychotic polypharmacy because of fewer adverse events, reduced treatment complexity, and lower medication cost. This study compared the rate and the duration of antipsychotic monotherapy following initiation of olanzapine or risperidone in the treatment of outpatients with schizophrenia in Japan.

Methods: Outpatients diagnosed with schizophrenia in the Japan Medical Data Center database were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, diagnosis codes.

Dopamine pathology in schizophrenia: analysis of total and phosphorylated tyrosine hydroxylase in the substantia nigra.

Introduction: Despite the importance of dopamine neurotransmission in schizophrenia, very few studies have addressed anomalies in the mesencephalic dopaminergic neurons of the substantia nigra/ventral tegmental area (SN/VTA). Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the production of dopamine, and a possible contributor to the anomalies in the dopaminergic neurotransmission observed in schizophrenia.

Objectives: In this study, we had three objectives: (1) Compare TH expression (mRNA and protein) in the SN/VTA of schizophrenia and control postmortem samples.

Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States.

Objective: Although the use of innovative drug delivery systems, like orally disintegrating antipsychotic tablets (ODT), may facilitate medication adherence and help reduce the risk of relapse and hospitalization, no information is available about the comparative cost-effectiveness of standard oral tablets (SOT) vs ODT formulations in the treatment of schizophrenia. This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of outpatients with schizophrenia from a US healthcare perspective. The study also compared olanzapine ODT with risperidone and aripiprazole, two other atypical antipsychotics available in both ODT and SOT formulations.

Rimonabant for neurocognition in schizophrenia: a 16-week double blind randomized placebo controlled trial.

Objective: To examine the effect of rimonabant on neurocognitive impairments in people with schizophrenia.

Methods: Participants entered a 16-week double-blind, placebo-controlled, randomized clinical trial. A neurocognitive battery was administered at baseline and end of study.

Responses to antipsychotic therapy among patients with schizophrenia or schizoaffective disorder and either predominant or prominent negative symptoms.

Patients with schizophrenia who have predominant negative symptoms are often considered less responsive to treatment. This analysis of patients with schizophrenia or schizoaffective disorder compares changes in symptom severity between those with predominant versus merely prominent negative symptoms. Prominent negative symptoms were defined by a baseline score of ≥4 on at least 3, or ≥5 on at least 2, of the 7 Positive and Negative Syndrome Scale (PANSS) negative subscale items.

Decline in hospitalization risk and health care cost after initiation of depot antipsychotics in the treatment of schizophrenia.

Purpose: To assess change in hospitalization and cost of care from 6 months pre- to 6 months post-initiation on any depot antipsychotic among schizophrenia patients.

Patients And Methods: Using a large United States commercial claims and encounters database, patients younger than 65 years diagnosed with schizophrenia were identified. Patients initiated on a depot antipsychotic were studied in a mirror-image design to assess change in hospitalization rates, mean duration hospitalized, and hospitalization cost.

Striatal mitochondria in subjects with chronic undifferentiated vs. chronic paranoid schizophrenia.

Schizophrenia (SZ) is a heterogeneous disease with a spectrum of symptoms, risk factors, and etiology. Abnormalities in mitochondria, the energy-producing organelles of the cell, have been observed in mixed cohorts of subjects with SZ. The purpose of the present study was to determine if striatal mitochondria were differentially affected in two different DSM-IV subgroups of SZ.

Analysis of gene variants previously associated with iloperidone response in patients with schizophrenia who are treated with risperidone.

Objective: We examined 6 single nucleotide polymorphisms (SNPs) previously reported to be associated with response to iloperidone therapy for association with response to risperidone therapy.

Method: Patients with schizophrenia (DSM-IV) were assessed during 2006 and 2007 for response/nonresponse (defined as ≥ 20%/<20% improvement in Positive and Negative Syndrome Scale [PANSS] total score) after 2 weeks of risperidone treatment (2 to 6 mg/d). Responders continued risperidone treatment; nonresponders were randomly assigned to either risperidone or olanzapine treatment (10 to 20 mg/d) for an additional 10 weeks.

Identification of early changes in specific symptoms that predict longer-term response to atypical antipsychotics in the treatment of patients with schizophrenia.

Background: To identify a simple decision tree using early symptom change to predict response to atypical antipsychotic therapy in patients with (Diagnostic and Statistical Manual, Fourth Edition, Text Revised) chronic schizophrenia.

Methods: Data were pooled from moderately to severely ill patients (n = 1494) from 6 randomized, double-blind trials (N = 2543). Response was defined as a ≥ 30% reduction in Positive and Negative Syndrome Scale (PANSS) Total score by Week 8 of treatment.