Lack of Efficacy of JNJ-18038683 on Cognitive Impairment in Patients With Stable Bipolar Disorder.

Background: The serotonin type 7 (5-HT7) receptor is one of 14 5-HT receptors. It has received attention for its possible role in mood disorders and cognition. The 5-HT7 receptor antagonist, JNJ-18038683, has been reported to be effective in rodent models of depression and REM sleep.

Amyloid-PET imaging predicts functional decline in clinically normal individuals.

Background: There is good evidence that elevated amyloid-β (Aβ) positron emission tomography (PET) signal is associated with cognitive decline in clinically normal (CN) individuals. However, it is less well established whether there is an association between the Aβ burden and decline in daily living activities in this population. Moreover, Aβ-PET Centiloids (CL) thresholds that can optimally predict functional decline have not yet been established.

Recruitment of pre-dementia participants: main enrollment barriers in a longitudinal amyloid-PET study.

Background: The mismatch between the limited availability versus the high demand of participants who are in the pre-dementia phase of Alzheimer's disease (AD) is a bottleneck for clinical studies in AD. Nevertheless, potential enrollment barriers in the pre-dementia population are relatively under-reported. In a large European longitudinal biomarker study (the AMYPAD-PNHS), we investigated main enrollment barriers in individuals with no or mild symptoms recruited from research and clinical parent cohorts (PCs) of ongoing observational studies.

The amyloid imaging for the prevention of Alzheimer's disease consortium: A European collaboration with global impact.

Background: Amyloid-β (Aβ) accumulation is considered the earliest pathological change in Alzheimer's disease (AD). The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) consortium is a collaborative European framework across European Federation of Pharmaceutical Industries Associations (EFPIA), academic, and 'Small and Medium-sized enterprises' (SME) partners aiming to provide evidence on the clinical utility and cost-effectiveness of Positron Emission Tomography (PET) imaging in diagnostic work-up of AD and to support clinical trial design by developing optimal quantitative methodology in an early AD population.

The Amypad Studies: In the Diagnostic and Patient Management Study (DPMS), 844 participants from eight centres across three clinical subgroups (245 subjective cognitive decline, 342 mild cognitive impairment, and 258 dementia) were included.

Clinical metabolomics for inborn errors of metabolism.

Metabolism is a highly regulated process that provides nutrients to cells and essential building blocks for the synthesis of protein, DNA and other macromolecules. In healthy biological systems, metabolism maintains a steady state in which the concentrations of metabolites are relatively constant yet are subject to metabolic demands and environmental stimuli. Rare genetic disorders, such as inborn errors of metabolism (IEM), cause defects in regulatory enzymes or proteins leading to metabolic pathway disruption and metabolite accumulation or deficiency.

The effects of JNJ-39393406 a positive allosteric nicotine modulator on mood and cognition in patients with unipolar depression: A double-blind, add-on, placebo-controlled trial.

Nicotinic agonists have been shown to improve cognition and mood, but this improvement is inconsistent and short-lived, possibly due to receptor desensitization. Positive Allosteric Modulators (PAMs) of the nicotinic alpha-7 nicotinic-acetyl-choline receptor (a7nAChR) are hypothesized to change the configuration of the nicotinic receptor and delay desensitization, potentially increasing the duration of the activation of the receptor, and improving clinical efficacy. This was a randomized controlled trial (RCT) adding JNJ-39393406 9 (a PAM of the a7nAChR) (n=35) or placebo (n=36) to treatment as usual for two weeks in 71 patients with unipolar depression.

Dementia, Subtype of Seizures, and the Risk of New Onset Seizures: A Cohort Study.

Background: Seizure disorders have been identified in patients suffering from different types of dementia. However, the risks associated with the seizure subtypes have not been characterized.

Objective: To compare the occurrence and risk of various seizure subtypes (focal and generalized) between patients with and without a dementia diagnosis.

Global biochemical analysis of plasma, serum and whole blood collected using various anticoagulant additives.

Introduction: Analysis of blood for the evaluation of clinically relevant biomarkers requires precise collection and sample handling by phlebotomists and laboratory staff. An important consideration for the clinical application of metabolomics are the different anticoagulants utilized for sample collection. Most studies that have characterized differences in metabolite levels in various blood collection tubes have focused on single analytes.

Quantitative amyloid PET in Alzheimer's disease: the AMYPAD prognostic and natural history study.

Introduction: The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Prognostic and Natural History Study (PNHS) aims at understanding the role of amyloid imaging in the earliest stages of Alzheimer's disease (AD). AMYPAD PNHS adds (semi-)quantitative amyloid PET imaging to several European parent cohorts (PCs) to predict AD-related progression as well as address methodological challenges in amyloid PET.

Methods: AMYPAD PNHS is an open-label, prospective, multi-center, cohort study recruiting from multiple PCs.

To err is human: Clinical incident calls to a national travel health advice line.

The National Travel Health Network and Centre (NaTHNaC) offers a telephone advice line for travel health practitioners in the UK. In this study we review clinical incidents concerning vaccines or malaria prophylaxis reported between 2016 and 2018. Two-hundred-and-fifty-one clinical incident calls were recorded, and commonly concerned scheduling or dosing errors.

Validation of a Metabolite Panel for a More Accurate Estimation of Glomerular Filtration Rate Using Quantitative LC-MS/MS.

Background: Clinical practice guidelines recommend estimation of glomerular filtration rate (eGFR) using validated equations based on serum creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys). However, when compared with the measured GFR (mGFR), only eGFRcr-cys meets recommended performance standards. Our goal was to develop a more accurate eGFR method using a panel of metabolites without creatinine, cystatin C, or demographic variables.

Metabolomic profiling to improve glomerular filtration rate estimation: a proof-of-concept study.

Background: Estimation of glomerular filtration rate (GFR) using estimated glomerular filtration rate creatinine (eGFRcr) is central to clinical practice but has limitations. We tested the hypothesis that serum metabolomic profiling can identify novel markers that in combination can provide more accurate GFR estimates.

Methods: We performed a cross-sectional study of 200 African American Study of Kidney Disease and Hypertension (AASK) and 265 Multi-Ethnic Study of Atherosclerosis (MESA) participants with measured GFR (mGFR).

Deep Vein Thrombosis After Complex Posterior Spine Surgery: Does Staged Surgery Make a Difference?

Study Design: Retrospective review of a prospectively collected database.

Objective: To assess the incidence of deep vein thrombosis (DVT) associated with single- versus multistage posterior-only complex spinal surgeries.

Summary Of Background Data: Dividing the physiologic burden of spinal deformity surgery into multiple stages has been suggested as a potential means of reducing perioperative complications.

Initial Cross-Over Test of A Positive Allosteric Modulator of Alpha-7 Nicotinic Receptors to Aid Cessation in Smokers With Or Without Schizophrenia.

Preclinical research shows that compounds acting at α7 nicotinic receptors (nAChRs) can reduce nicotine self-administration, suggesting that a positive allosteric modulator (PAM) of α7 receptors, JNJ-39393406, may aid smoking cessation. Moreover, individuals with schizophrenia, who have very high rates of smoking, have reduced expression of α7 nAChRs and may particularly benefit from this compound. In two parallel studies using a within-subject cross-over design, 36 healthy smokers (Study 1) and 62 smokers with schizophrenia (Study 2), both groups high in quit interest, attempted to initiate quitting temporarily during each of two 3-week phases.

Structure elucidation of metabolite x17299 by interpretation of mass spectrometric data.

Introduction: A major bottleneck in metabolomic studies is metabolite identification from accurate mass spectrometric data. Metabolite x17299 was identified in plasma as an unknown in a metabolomic study using a compound-centric approach where the associated ion features of the compound were used to determine the true molecular mass.

Objectives: The aim of this work is to elucidate the chemical structure of x17299, a new compound by de novo interpretation of mass spectrometric data.

Comprehensive review of visual defects reported with topiramate.

Objective: The objective of this study was to analyze clinical patterns of visual field defects (VFDs) reported with topiramate treatment and assess possible mechanism of action (MOA) for antiepileptic drug (AED) associated VFDs.

Methods: A comprehensive topiramate database review included preclinical data, sponsor's clinical trials database, postmarketing spontaneous reports, and medical literature. All treatment-emergent adverse events (TEAEs) suggestive of retinal dysfunction/damage were summarized.

LC-MS/MS method for quantitation of seven biomarkers in human plasma for the assessment of insulin resistance and impaired glucose tolerance.

Early detection of insulin resistance (IR) and/or impaired glucose tolerance (IGT) is crucial for delaying and preventing the progression toward type 2 diabetes. We recently developed and validated a straightforward metabolite-based test for the assessment of IR and IGT in a single LC-MS/MS method. Plasma samples were diluted with isotopically-labeled internal standards and extracted by simple protein precipitation.

Is uveitis associated with topiramate use? A cumulative review.

Occasional reports of uveitis following topiramate use necessitated an investigation of relevant cases from safety databases and published biomedical literature. Data mining of the Food and Drug Administration Adverse Event Reporting System and cumulative review of cases from the global safety database (sponsor database) and published literature were conducted to assess association between topiramate use and uveitis. The Food and Drug Administration Adverse Event Reporting System search identified disproportional reporting of uveitis (n=23) and related terms (choroidal detachment, n=25; iridocyclitis, n=17).

Age-Stratified Prevalence of Mild Cognitive Impairment and Dementia in European Populations: A Systematic Review.

The prevalence of mild cognitive impairment (MCI) and dementia according to age remain uncertain. We systematically extracted age-stratified estimates of MCI and dementia prevalence reported in European studies published since 1995, and performed meta-analyses for dementia. We identified 10 relevant studies on MCI and 26 studies on dementia.

Metabolomics and its Application to the Development of Clinical Laboratory Tests for Prostate Cancer.

Introduction: There is a critical need to develop clinical laboratory assays that provide risk assessment for men at elevated risk for prostate cancer, and once diagnosed, could further identify those men with clinically significant disease.

Methods: Recent advancements in analytical instrumentation have enabled mass spectrometry-based metabolomics methodologies. Further advancements in chromatographic techniques have facilitated high throughput, quantitative assays for a broad spectrum of biochemicals.