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.

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.

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.

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.

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.

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.

Useful Interplay Between Spontaneous ADR Reports and Electronic Healthcare Records in Signal Detection.

Background And Objective: Spontaneous reporting systems (SRSs) remain the cornerstone of post-marketing drug safety surveillance despite their well-known limitations. Judicious use of other available data sources is essential to enable better detection, strengthening and validation of signals. In this study, we investigated the potential of electronic healthcare records (EHRs) to be used alongside an SRS as an independent system, with the aim of improving signal detection.

Evaluating Social Media Networks in Medicines Safety Surveillance: Two Case Studies.

Introduction: There is growing interest in whether social media can capture patient-generated information relevant for medicines safety surveillance that cannot be found in traditional sources.

Objective: The aim of this study was to evaluate the potential contribution of mining social media networks for medicines safety surveillance using the following associations as case studies: (1) rosiglitazone and cardiovascular events (i.e.

Increased risk of microscopic colitis with use of proton pump inhibitors and non-steroidal anti-inflammatory drugs.

Objectives: Microscopic colitis (MC) is characterized by chronic watery diarrhea. Recently, several drugs were reported to increase the risk of MC. However, studies lacked a clear exposure definition, did not address duration relationships, and did not take important biases into account.

The role of electronic healthcare record databases in paediatric drug safety surveillance: a retrospective cohort study.

Aim: Electronic healthcare record (EHR)-based surveillance systems are increasingly being developed to support early detection of safety signals. It is unknown what the power of such a system is for surveillance among children and adolescents. In this paper we provide estimates of the number and classes of drugs, and incidence rates (IRs) of events, that can be monitored in children and adolescents (0-18 years).

NSAIDs, statins, low-dose aspirin and PPIs, and the risk of oesophageal adenocarcinoma among patients with Barrett's oesophagus: a population-based case-control study.

Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), low-dose aspirin and statins may decrease the risk of oesophageal adenocarcinoma (OAC) among patients with Barrett's oesophagus (BO). However, previous studies did not adequately address bias and confounding. Our objective was to estimate the risk of OAC among patients with BO exposed to NSAIDs, statins and PPIs.

Evaluating performance of electronic healthcare records and spontaneous reporting data in drug safety signal detection.

Background: Electronic reporting and processing of suspected adverse drug reactions (ADRs) is increasing and has facilitated automated screening procedures. It is crucial for healthcare professionals to understand the nature and proper use of data available in pharmacovigilance practice.

Objectives: To (a) compare performance of EU-ADR [electronic healthcare record (EHR) exemplar] and FAERS [spontaneous reporting system (SRS) exemplar] databases in detecting signals using "positive" and "negative" drug-event reference sets; and (b) evaluate the impact of timing bias on sensitivity thresholds by comparing all data to data restricted to the time before a warning/regulatory action.

Using real-world healthcare data for pharmacovigilance signal detection - the experience of the EU-ADR project.

A prospective pharmacovigilance signal detection study, comparing the real-world healthcare data (EU-ADR) and two spontaneous reporting system (SRS) databases, US FDA's Adverse Event Reporting System and WHO's Vigibase is reported. The study compared drug safety signals found in the EU-ADR and SRS databases. The potential for signal detection in the EU-ADR system was found to be dependent on frequency of the event and utilization of drugs in the general population.

A description of signals during the first 18 months of the EMA pharmacovigilance risk assessment committee.

Background And Objective: New pharmacovigilance legislation in the European Union has underlined the importance of signal management, giving the European Medicines Agency's newly established Pharmacovigilance Risk Assessment Committee (PRAC) the mandate to oversee all aspects of the use of medicinal products including detection, assessment, minimization, and communication relating to the risk of adverse reactions. In this study, we describe the signals as brought to the PRAC during the first 18 months of its operation and the ensuing regulatory actions.

Methods: Data were collected from publicly available sources, for the period July 2012-December 2013, classified according to predefined rules, and described using the appropriate descriptive statistics.