Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.

Background: Variants of the gene triggering receptor expressed on myeloid cells-2 (TREM2) increase the risk of Alzheimer's disease (AD) and other neurodegenerative disorders. Signaling by TREM2, an innate immune receptor expressed by microglia, is thought to enhance phagocytosis of amyloid beta (Aβ) and other damaged proteins, promote microglial proliferation, migration, and survival, and regulate inflammatory signaling. Thus, TREM2 activation has potential to alter the progression of AD.

Using qualitative exit interviews to explore schizophrenia burden and treatment experience in clinical trial patients.

Introduction: Qualitative research methods can be used to obtain a deeper understanding of patient experience by collecting information in the patients' own words about their encounters, perspectives, and feelings. In this study, patients with schizophrenia were interviewed to capture their voice and to complement the quantitative data typically obtained in clinical trials.

Methods: Semi-structured exit interviews were conducted with 41 patients who completed or prematurely discontinued from a phase 3, open-label trial (NCT02873208).

Efficacy and Safety of Ravulizumab, a Complement C5 Inhibitor, in Adults With Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

Importance: Additional therapies for amyotrophic lateral sclerosis (ALS) are urgently needed. Immune-mediated complement activation may be involved in ALS pathogenesis as evidenced by the upregulation of terminal components; thus, complement inhibition could potentially slow progression.

Objective: To evaluate the safety and efficacy of the terminal complement C5 inhibitor ravulizumab in adults with ALS.

Weight Gain and Metabolic Changes in Patients With First-Episode Psychosis or Early-Phase Schizophrenia Treated With Olanzapine: A Meta-Analysis.

Background: Patients with first-episode psychosis or early-phase schizophrenia are susceptible to olanzapine-associated weight gain and cardiometabolic dysregulation. This meta-analysis characterized weight and metabolic effects observed during olanzapine treatment in randomized clinical trials in this vulnerable patient population.

Methods: PubMed, EMBASE, and Dialog were searched for randomized controlled trials (RCTs) reporting weight or cardiometabolic outcomes associated with olanzapine treatment in first-episode psychosis or early-phase schizophrenia.

Olanzapine/Samidorphan in Young Adults With Schizophrenia, Schizophreniform Disorder, or Bipolar I Disorder Who Are Early in Their Illness: Results of the Randomized, Controlled ENLIGHTEN-Early Study.

Patients with early-phase schizophrenia or bipolar I disorder (BD-I) are at greater risk for antipsychotic-associated weight gain. This 12-week, randomized, double-blind study conducted between June 2017 and December 2021 evaluated weight effects of combination olanzapine and samidorphan (OLZ/SAM) versus olanzapine in early-phase illness. Young adults (16-39 years) with schizophrenia, schizophreniform disorder, or BD-I, < 4 years since symptom onset, body mass index < 30 kg/m, and < 24 weeks' cumulative antipsychotic exposure were randomized to OLZ/SAM (5-20/10 mg/d) or olanzapine (5-20 mg/d).

Olanzapine/samidorphan combination consistently mitigates weight gain across various subgroups of patients.

Objective: A combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) has been approved in the United States for the treatment of adults with schizophrenia or adults with bipolar I disorder. In a phase 3 study in adults with schizophrenia (ENLIGHTEN-2), OLZ/SAM treatment was associated with significantly less weight gain compared with olanzapine. Prespecified subgroup analyses explored the consistency of the weight mitigation effect of OLZ/SAM vs olanzapine across demographic subgroups in ENLIGHTEN-2.

An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder.

Olanzapine effectively treats schizophrenia and bipolar I disorder (BD-I); however, its use is limited by the risk of significant weight gain and metabolic effects. OLZ/SAM, a combination of olanzapine and samidorphan, was recently approved in the United States for the treatment of adults with schizophrenia or BD-I. OLZ/SAM provides the efficacy of olanzapine while mitigating olanzapine-associated weight gain through opioid-receptor blockade.

A phase 3, multicenter study to assess the 1-year safety and tolerability of a combination of olanzapine and samidorphan in patients with schizophrenia: Results from the ENLIGHTEN-2 long-term extension.

Aim: A combination of olanzapine and samidorphan (OLZ/SAM) is in development for the treatment of patients with schizophrenia or bipolar I disorder and is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension (NCT02873208; ENLIGHTEN-2-EXT) assessed the long-term safety and tolerability of OLZ/SAM in patients with schizophrenia.

Methods: Patients completing the 24-week randomized, double-blind, phase 3 ENLIGHTEN-2 study (NCT02694328) comparing weight change from baseline to week 24 with OLZ/SAM versus olanzapine were eligible to enroll in the 52-week ENLIGHTEN-2-EXT study.

Layperson/Plain Language Summaries: Can Sponsors, CROs, and Sites Deliver in 2020?

The much-anticipated 2014 European Union (EU) Clinical Trial Regulation requiring Layperson/ Plain Language Summaries (PLS) is slated for implementation in 2020. At the 10th Annual CNS Summit Conference (Fall 2019), a panel discussion was convened with the objective of evaluating the likelihood of the PLS legislation being implemented successfully in the EU and voluntarily (e.g.

Prospective Home-use Study on Non-invasive Neuromodulation Therapy for Essential Tremor.

Highlights: This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients.

Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor.

Effects of Olanzapine Combined With Samidorphan on Weight Gain in Schizophrenia: A 24-Week Phase 3 Study.

Objective: A combination of olanzapine and the opioid receptor antagonist samidorphan is under development for the treatment of schizophrenia and bipolar I disorder. The single-tablet combination treatment is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. In this phase 3 double-blind trial, the authors evaluated the weight profile of combined olanzapine/samidorphan compared with olanzapine in patients with schizophrenia.

Long-term safety and durability of effect with a combination of olanzapine and samidorphan in patients with schizophrenia: results from a 1-year open-label extension study.

Background: Combination olanzapine and samidorphan (OLZ/SAM), in development for schizophrenia and bipolar I disorder, is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. OLZ/SAM safety, tolerability, and efficacy from a 52-week open-label extension study in patients with schizophrenia are reported.

Methods: Patients previously completing the 4-week, double-blind ENLIGHTEN-1 study switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM.

Olanzapine Plus Samidorphan (ALKS 3831) in Schizophrenia and Comorbid Alcohol Use Disorder: A Phase 2, Randomized Clinical Trial.

Objective: Alcohol use disorder (AUD) is a common comorbidity of schizophrenia. No effective pharmacologic treatment is available for both disorders to date.

Methods: In a phase 2, double-blind study, patients with schizophrenia and AUD experiencing ≥ 10 drinking and ≥ 2 heavy-drinking days in the previous month and recent (≤ 6 mo) disease symptom exacerbation were recruited between June 2014 and March 2017.

Efficacy and Safety of a Combination of Olanzapine and Samidorphan in Adult Patients With an Acute Exacerbation of Schizophrenia: Outcomes From the Randomized, Phase 3 ENLIGHTEN-1 Study.

Objective: To assess the antipsychotic efficacy and safety of a combination of olanzapine and samidorphan (OLZ/SAM).

Methods: This 4-week, phase 3, randomized, double-blind, placebo- and olanzapine-controlled study was conducted from December 2015 to June 2017 in adults with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria who were experiencing an acute exacerbation. Patients were randomized 1:1:1 to OLZ/SAM, olanzapine monotherapy, or placebo.

Second-order cues to figure motion enable object detection during prey capture by praying mantises.

Detecting motion is essential for animals to perform a wide variety of functions. In order to do so, animals could exploit motion cues, including both first-order cues-such as luminance correlation over time-and second-order cues, by correlating higher-order visual statistics. Since first-order motion cues are typically sufficient for motion detection, it is unclear why sensitivity to second-order motion has evolved in animals, including insects.

Olanzapine Plus Samidorphan in Subjects with Schizophrenia and Comorbid Alcohol Use Disorder: Rationale and Design for a Phase II, Double-blind, Randomized Study.

Alcohol use disorder (AUD) is a common comorbidity in patients with schizophrenia. Although pharmacological options for the management of each disease exist separately, there is no agent approved for both. Moreover, studies conducted in this patient population, who face practical and social challenges as a consequence of being diagnosed with schizophrenia and comorbid AUD, are limited.

Patient preferences concerning the efficacy and side-effect profile of schizophrenia medications: a survey of patients living with schizophrenia.

Background: Despite the availability of numerous antipsychotic medications, many patients with schizophrenia continue to experience side effects that contribute to the overall burden of the illness. The present survey of patients with schizophrenia and schizoaffective disorder aimed to assess patient attitudes toward antipsychotic treatment, and understand key factors about willingness to try a new medication.

Methods: A cross-sectional survey was administered to 250 patients with a primary clinical diagnosis of a schizophrenia spectrum disorder across five outpatient clinics in the United States.

A Novel Form of Stereo Vision in the Praying Mantis.

Stereopsis is the ability to estimate distance based on the different views seen in the two eyes [1-5]. It is an important model perceptual system in neuroscience and a major area of machine vision. Mammalian, avian, and almost all machine stereo algorithms look for similarities between the luminance-defined images in the two eyes, using a series of computations to produce a map showing how depth varies across the scene [3, 4, 6-14].

Maternal cytomegalovirus-specific immune responses and symptomatic postnatal cytomegalovirus transmission in very low-birth-weight preterm infants.

Introduction: Transmission of cytomegalovirus (CMV) via breast milk can lead to severe acute illness in very low-birth-weight (VLBW) preterm infants. Although the majority of CMV-seropositive women shed CMV in milk, symptomatic postnatal infection of VLBW infants occurs infrequently, suggesting that virologic or immunologic factors in milk may be associated with the risk and severity of postnatal CMV infection.

Methods: We investigated the magnitude of CMV-specific cellular and humoral immune responses in milk of 30 seropositive mothers of VLWB preterm infants and assessed their relationship to milk CMV load and symptomatic CMV transmission.

Adverse events of conscious sedation in ambulatory spine procedures.

Background Context: Interventional spine procedures are commonly performed in the ambulatory surgical setting, often using conscious sedation. The rate of adverse events with conscious sedation has not been previously assessed in the interventional spine procedure setting.

Purpose: The goal of this study was to determine the rate of adverse events when using conscious sedation in the ambulatory interventional spine setting.

Vaginal microbicide gel for delivery of IQP-0528, a pyrimidinedione analog with a dual mechanism of action against HIV-1.

Pyrimidinediones, a novel class of compounds, have previously been shown to possess antiviral activity at nanomolar concentrations. One member of this class of compounds, IQP-0528, was selected as the lead molecule for formulation development owing to its stability at physiologically relevant conditions, wide therapeutic window, and antiviral activity in the nanomolar range. Here, we report the development of two vaginal gels--3.

Temporal excitation properties of paresthesias evoked by thalamic microstimulation.

Objective: The neuronal elements mediating the effects of deep brain stimulation (DBS) are unknown. The objective was to determine the strength-duration properties of the neuronal elements that mediate paresthesias evoked by thalamic microstimulation.

Methods: The strength-duration properties of the neuronal elements causing paresthesias were measured using intraoperative microstimulation of the human thalamus.

Changes in dispersal during species' range expansions.

Explanations for rapid species' range expansions have typically been purely ecological, with little attention given to evolutionary processes. We tested predictions for the evolution of dispersal during range expansion using four species of wing-dimorphic bush cricket (Conocephalus discolor, Conocephalus dorsalis, Metrioptera roeselii, and Metrioptera brachyptera). We observed distinct changes in dispersal in the two species with expanding ranges.