Efficacy, safety, and tolerability of nivasorexant in adults with binge-eating disorder: A randomized, Phase II proof of concept trial.

Objective: This Phase II, placebo-controlled, double-blind study investigated the efficacy, safety, and tolerability of nivasorexant in the treatment of adults with moderate to severe binge-eating disorder (BED).

Methods: Adults meeting the DSM-5 BED criteria were randomized 1:1 to placebo or nivasorexant (100 mg b.i.

Use of experimental medicine approaches for the development of novel psychiatric treatments based on orexin receptor modulation.

Despite progress in understanding the pathological mechanisms underlying psychiatric disorders, translation from animal models into clinical use remains a significant bottleneck. Preclinical studies have implicated the orexin neuropeptide system as a potential target for psychiatric disorders through its role in regulating emotional, cognitive, and behavioral processes. Clinical studies are investigating orexin modulation in addiction and mood disorders.

What evidence is there for implicating the brain orexin system in neuropsychiatric symptoms in dementia?

Neuropsychiatric symptoms (NPS) affect people with dementia (PwD) almost universally across all stages of the disease, and regardless of its exact etiology. NPS lead to disability and reduced quality of life of PwD and their caregivers. NPS include hyperactivity (agitation and irritability), affective problems (anxiety and depression), psychosis (delusions and hallucinations), apathy, and sleep disturbances.

Long-Term Safety and Tolerability of Daridorexant in Patients with Insomnia Disorder.

Background And Objective: Daridorexant is a dual orexin receptor antagonist for the treatment of insomnia. In two phase III, 12-week studies in patients with insomnia disorder, daridorexant improved sleep and daytime functioning while maintaining a favorable safety profile. The objective of this 40-week extension study was to assess the long-term safety and tolerability of daridorexant.

A proteome-scale map of the SARS-CoV-2-human contactome.

Understanding the mechanisms of coronavirus disease 2019 (COVID-19) disease severity to efficiently design therapies for emerging virus variants remains an urgent challenge of the ongoing pandemic. Infection and immune reactions are mediated by direct contacts between viral molecules and the host proteome, and the vast majority of these virus-host contacts (the 'contactome') have not been identified. Here, we present a systematic contactome map of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with the human host encompassing more than 200 binary virus-host and intraviral protein-protein interactions.

Electron-beam energy reconstruction for neutrino oscillation measurements.

Neutrinos exist in one of three types or 'flavours'-electron, muon and tau neutrinos-and oscillate from one flavour to another when propagating through space. This phenomena is one of the few that cannot be described using the standard model of particle physics (reviewed in ref. ), and so its experimental study can provide new insight into the nature of our Universe (reviewed in ref.

Connecting Cohorts to Diminish Alzheimer's Disease (CONCORD-AD): A Report of an International Research Collaboration Network.

Longitudinal observational cohort studies are being conducted worldwide to understand cognition, biomarkers, and the health of the aging population better. Cross-cohort comparisons and networks of registries in Alzheimer's disease (AD) foster scientific exchange, generate insights, and contribute to the evolving clinical science in AD. A scientific working group was convened with invited investigators from established cohort studies in AD, in order to form a research collaboration network as a resource to address important research questions.

Huntington's Disease in Israel: A Population-Based Study Using 20 Years of Routinely-Collected Healthcare Data.

Background: Huntington's disease (HD) is a rare, genetic, neurodegenerative disease. Obtaining population-level data on epidemiology and disease management is challenging.

Objective: To investigate the epidemiology, clinical manifestations, treatment, and healthcare utilization of patients with HD in Israel.

Application of the NIA-AA Research Framework: Towards a Biological Definition of Alzheimer's Disease Using Cerebrospinal Fluid Biomarkers in the AIBL Study.

Background: The National Institute on Aging and Alzheimer's Association (NIA-AA) have proposed a new Research Framework: Towards a biological definition of Alzheimer's disease, which uses a three-biomarker construct: Aß-amyloid, tau and neurodegeneration AT(N), to generate a biomarker based definition of Alzheimer's disease.

Objectives: To stratify AIBL participants using the new NIA-AA Research Framework using cerebrospinal fluid (CSF) biomarkers. To evaluate the clinical and cognitive profiles of the different groups resultant from the AT(N) stratification.

Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia.

Objectives: To examine the cross-sectional association between functional performance and Alzheimer's disease (AD) neuroimaging biomarkers in individuals without dementia (cognitively unimpaired (CU), and those with mild cognitive impairment (MCI)).

Design: Cross-sectional.

Setting: Olmsted County, Minnesota.

The Association of Multimorbidity With Preclinical AD Stages and SNAP in Cognitively Unimpaired Persons.

Background: Multimorbidity (defined as ≥2 chronic conditions) has been associated with increased risk of mild cognitive impairment and cross-sectionally with imaging biomarkers of neurodegeneration in cognitively unimpaired persons aged ≥70 years. Its association with preclinical Alzheimer's disease stages has not been studied in detail yet. The objective of the study was to assess the cross-sectional association of multimorbidity with preclinical Alzheimer's disease stages and suspected non-amyloid pathophysiology in cognitively unimpaired participants of the Mayo Clinic Study of Aging (≥50 years of age).

Can Electronic Health Records Databases Complement Spontaneous Reporting System Databases? A Historical-Reconstruction of the Association of Rofecoxib and Acute Myocardial Infarction.

Several initiatives have assessed if mining electronic health records (EHRs) may accelerate the process of drug safety signal detection. In Europe, Exploring and Understanding Adverse Drug Reactions (EU-ADR) Project Focused on utilizing clinical data from EHRs of over 30 million patients from several European countries. Rofecoxib is a prescription COX-2 selective Non-Steroidal Anti-Inflammatory Drugs (NSAID) approved in 1999.

Prevalence and Outcomes of Amyloid Positivity Among Persons Without Dementia in a Longitudinal, Population-Based Setting.

Importance: Brain amyloid deposition is a marker of Alzheimer disease (AD) pathology. The population-based prevalence and outcomes of amyloid positivity in a population without dementia are important for understanding the trajectory of amyloid positivity to clinically significant outcomes and for designing AD prevention trials.

Objective: To determine prevalence and outcomes of amyloid positivity in a population without dementia.

Double-Cascade Events from New Physics in Icecube.

A variety of new physics models allows for neutrinos to up-scatter into heavier states. If the incident neutrino is energetic enough, the heavy neutrino may travel some distance before decaying. In this work, we consider the atmospheric neutrino flux as a source of such events.

[A continuous series of 27 adult patients treated for L5-S1 isthmic spondylolisthesis by combined approach: Clinical and radiological outcomes at 1 year follow-up].

Through this single-center consecutive prospective study, we evaluated the results of a combined approach for L5-S1 isthmic spondylolisthesis, using a polyetheretherketone (PEEK) interbody lordotic cage during anterior approach and pedicle screw-based posterior fixation. Between 2010 and 2014, 27 adult patients were treated for L5-S1 isthmic spondylolisthesis (high and low grades) by a combined approach with a minimum follow-up of one year. Clinical outcome was assessed before surgical treatment and at four months and one year after surgery by: VAS, Oswestry Index (ODI) and Rolland-Morris scores.

The frequency and influence of dementia risk factors in prodromal Alzheimer's disease.

We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline.

Dementia incidence trend over 1992-2014 in the Netherlands: Analysis of primary care data.

Background: Recent reports have suggested declining age-specific incidence rates of dementia in high-income countries over time. Improved education and cardiovascular health in early age have been suggested to be bringing about this effect. The aim of this study was to estimate the age-specific dementia incidence trend in primary care records from a large population in the Netherlands.

Bicortical facet screws as a new option for posterior C2 fixation: anatomical study and clinical experience.

Purpose: C2 fixation is a demanding procedure, particularly in patients with variants of C1-C2 anatomy. The inferior articular process (IAP) of the axis can be an alternative for screw placement. We report the results of a CT study of C2 IAP anatomy and we present the clinical experience of 28 patients operated with this technique.

[Surgical correction of post-vertebroplasty kyphosis by pedicle substraction osteotomy. Regarding three cases].

We report a case of three patients treated with pedicle subtraction osteotomy for post-vertebroplasty kyphosis. These patients were initially treated with a vertebroplasty for vertebral fracture (two cases) and spinal lymphoma (1 case). All of these patients worsened progressively on a clinical and radiographic level with progression of the spinal deformity in the form of kyphosis.

Evaluating the Safety Profile of Non-Active Implantable Medical Devices Compared with Medicines.

Recent safety issues involving non-active implantable medical devices (NAIMDs) have highlighted the need for better pre-market and post-market evaluation. Some stakeholders have argued that certain features of medicine safety evaluation should also be applied to medical devices. Our objectives were to compare the current processes and methodologies for the assessment of NAIMD safety profiles with those for medicines, identify potential gaps, and make recommendations for the adoption of new methodologies for the ongoing benefit-risk monitoring of these devices throughout their entire life cycle.

Decision making in drug safety-a literature review of criteria used to prioritize newly detected safety issues.

Purpose: In drug safety, there is a lack of guidance on how prioritization of safety issues should be performed. The aim of this literature review is to provide an overview of criteria used for signal prioritization and of the associated decision support frameworks.

Methods: A search strategy was constructed to identify relevant articles in Medline/Embase databases from the period from 1 January 1995 to 31 August 2015.

Neutrino Masses from a Pseudo-Dirac Bino.

We show that, in U(1)_{R}-symmetric supersymmetric models, the bino and its Dirac partner (the singlino) can play the role of right-handed neutrinos and generate the neutrino masses and mixing, without the need for traditional bilinear or trilinear R-parity violating operators. The two particles form a pseudo-Dirac pair, the "biνo." An inverse seesaw texture is generated for the neutrino-biνo sector, and the lightest neutrino is predicted to be massless.

Identifying Cases of Type 2 Diabetes in Heterogeneous Data Sources: Strategy from the EMIF Project.

Due to the heterogeneity of existing European sources of observational healthcare data, data source-tailored choices are needed to execute multi-data source, multi-national epidemiological studies. This makes transparent documentation paramount. In this proof-of-concept study, a novel standard data derivation procedure was tested in a set of heterogeneous data sources.

Data Extraction and Management in Networks of Observational Health Care Databases for Scientific Research: A Comparison of EU-ADR, OMOP, Mini-Sentinel and MATRICE Strategies.

Introduction: We see increased use of existing observational data in order to achieve fast and transparent production of empirical evidence in health care research. Multiple databases are often used to increase power, to assess rare exposures or outcomes, or to study diverse populations. For privacy and sociological reasons, original data on individual subjects can't be shared, requiring a distributed network approach where data processing is performed prior to data sharing.

Risk of cardiac valvulopathy with use of bisphosphonates: a population-based, multi-country case-control study.

Unlabelled: Analyses of healthcare data from 30 million individuals in three countries showed that current use of bisphosphonates may be associated with a small increased risk of cardiac valvulopathy (vs. those not exposed within the previous year), although confounding cannot be entirely ruled out. The observed tendency for decreased valvulopathy risk with cumulative duration of bisphosphonate use >6 months may even indicate a protective effect with prolonged use.