A Statistical Framework for Assessing the Relationship between Biomarkers and Clinical Endpoints in Alzheimer's Disease.

Changes in biomarker levels of Alzheimer's disease (AD) reflect underlying pathophysiological changes in the brain and can provide evidence of direct and downstream treatment effects linked to disease modification. Recent results from clinical trials of anti-amyloid β (Aβ) treatments have raised the question of how to best characterize the relationship between AD biomarkers and clinical endpoints. Consensus methodology for assessing such relationships is lacking, leading to inconsistent evaluation and reporting.

Prenatal cannabinoid exposure: why expecting individuals should take a pregnancy pause from using cannabinoid products.

Cannabinoid use in all populations is increasing as legalization across the United States continues. Concerningly, there is a lack of caution provided by medical providers to pregnant individuals as to the impact the use of cannabinoids could have on the developing fetus. Research continues in both the preclinical and clinical areas, and is severely needed, as the potency of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, has increased dramatically since the initial studies were completed.

Multivariate Modeling of Student Performance on NBME Subject Exams.

Aim This study sought to determine whether it was possible to develop statistical models which could be used to accurately correlate student performance on clinical subject exams based on their National Board of Medical Examiner (NBME) self-assessment performance and other variables, described below, as such tools are not currently available.  Methods Students at a large public medical school were provided fee vouchers for NBME self-assessments before clinical subject exams. Multivariate regression models were then developed based on how self-assessment performance correlated to student success on the subsequent subject exam (Medicine, Surgery, Family Medicine, Obstetrics-Gynecology, Pediatrics, and Psychiatry) while controlling for the proximity of the self-assessment to the exam, USMLE Step 1 score, and the academic quarter.

Investigating Partially Discordant Results in Phase 3 Studies of Aducanumab.

Objectives: Efficacy and safety results from the EMERGE (NCT02484547) and ENGAGE (NCT02477800) phase 3 studies of aducanumab in early Alzheimer's disease (AD) have been published. In EMERGE, but not in ENGAGE, high-dose aducanumab demonstrated significant treatment effects across primary and secondary endpoints. Low-dose aducanumab results were consistent across studies with non-significant differences versus placebo that were intermediate to the high-dose arm in EMERGE.

Antisense oligonucleotide targeting DMPK in patients with myotonic dystrophy type 1: a multicentre, randomised, dose-escalation, placebo-controlled, phase 1/2a trial.

Background: Myotonic dystrophy type 1 results from an RNA gain-of-function mutation, in which DM1 protein kinase (DMPK) transcripts carrying expanded trinucleotide repeats exert deleterious effects. Antisense oligonucleotides (ASOs) provide a promising approach to treatment of myotonic dystrophy type 1 because they reduce toxic RNA levels. We aimed to investigate the safety of baliforsen (ISIS 598769), an ASO targeting DMPK mRNA.

CSF biomarker concordance with amyloid PET in Phase 3 studies of aducanumab.

Introduction: We assessed the use of cerebrospinal fluid (CSF) biomarkers as an alternative to positron emission tomography (PET) for brain amyloid beta (Aβ) pathology confirmation in the EMERGE and ENGAGE clinical trials.

Methods: EMERGE and ENGAGE were randomized, placebo-controlled, Phase 3 trials of aducanumab in participants with early Alzheimer's disease. Concordance between CSF biomarkers (Aβ42, Aβ40, phosphorylated tau 181, and total tau) and amyloid PET status (visual read) at screening was examined.

Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer's Disease.

Background: Alzheimer's disease is a progressive, irreversible, and fatal disease for which accumulation of amyloid beta is thought to play a key role in pathogenesis. Aducanumab is a human monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta.

Objectives: We evaluated the efficacy and safety of aducanumab in early Alzheimer's disease.

Burnout in US hematologists and oncologists: impact of compensation models and advanced practice provider support.

Burnout is prevalent throughout medicine. Few large-scale studies have examined the impact of physician compensation or clinical support staff on burnout among hematologists and oncologists. In 2019, the American Society of Hematology conducted a practice survey of hematologists and oncologists in the AMA (American Medical Association) Masterfile; burnout was measured using a validated, single-item burnout instrument from the Physician Work-Life Study, while satisfaction was assessed in several domains using a 5-point Likert scale.

Brief assessment of cognitive function in myotonic dystrophy: Multicenter longitudinal study using computer-assisted evaluation.

Introduction/aims: Myotonic dystrophy type 1 (DM1) is known to affect cognitive function, but the best methods to assess central nervous system involvement in multicenter studies have not been determined. In this study our primary aim was to evaluate the potential of computerized cognitive tests to assess cognition in DM1.

Methods: We conducted a prospective, longitudinal, observational study of 113 adults with DM1 at six sites.

Tau positron emission tomography, cerebrospinal fluid and plasma biomarkers of neurodegeneration, and neurocognitive testing: an exploratory study of participants with myotonic dystrophy type 1.

Objective: To investigate Tau pathology using multimodal biomarkers of neurodegeneration and neurocognition in participants with myotonic dystrophy type 1 (DM1).

Methods: We recruited twelve participants with DM1 and, for comparison, two participants with Alzheimer's Disease (AD). Participants underwent cognitive screening and social cognition testing using the Dépistage Cognitif de Québec (DCQ), among other tests.

Kinetics of myelin breakdown products: A labeling study in patients with progressive multiple sclerosis.

The majority of disease modifying therapies for multiple sclerosis (MS) reduce inflammation, but do no't target remyelination. Development of remyelinating therapies will benefit from a method to quantify myelin kinetics in patients with MS. We labeled myelin in vivo with deuterium, and modeled kinetics of myelin breakdown products β-galactosylceramide (β-GalC) and N-Octadecanoyl-sulfatide (NO-Sulf).

Associations between hematology/oncology fellows' training and mentorship experiences and hematology-only career plans.

As the adult hematology and oncology fellowship training pathways have merged in the United States and concerns have arisen about the aging of practicing hematologists, the American Society of Hematology and hematology education leaders are looking to improve their understanding of the factors that contribute to fellows' plans to enter hematology-only careers. With the support of the American Society of Hematology, we collected and analyzed data from a survey of hematology/oncology fellows (n = 626) to examine the relationship between training and mentorship experiences and fellows' plans to enter hematology-only careers. Fellows who planned to enter hematology-only careers were significantly more likely to report having clinical training and mentorship experiences in hematology throughout their training relative to fellows with oncology-only or combined hematology/oncology career plans.

Retinal microcirculation imaging in sickle cell disease patients.

Objectives: To explore the feasibility of a new quantitative method for microvascular function: non-invasive retinal function imaging (RFI). in sickle cell disease (SCD) patients and healthy controls and have it benchmarked against Laser Speckle Contrast Imaging (LSCI) measurements.

Methods: The variability of Microvascular measurements was assessed in 8 SCD patients and 8 healthy matched controls.

Quantifying Beta-Galactosylceramide Kinetics in Cerebrospinal Fluid of Healthy Subjects Using Deuterium Labeling.

Therapeutics promoting myelin synthesis may enhance recovery in demyelinating diseases, such as multiple sclerosis. However, no suitable method exists to quantify myelination. The turnover of galactosylceramide (myelin component) is indicative of myelination in mice, but its turnover has not been determined in humans.

Evidence regarding the utility of multiple mini-interview (MMI) for selection to undergraduate health programs: A BEME systematic review: BEME Guide No. 37.

Background: In the 11 years since its development at McMaster University Medical School, the multiple mini-interview (MMI) has become a popular selection tool. We aimed to systematically explore, analyze and synthesize the evidence regarding MMIs for selection to undergraduate health programs.

Methods: The review protocol was peer-reviewed and prospectively registered with the Best Evidence Medical Education (BEME) collaboration.

Synergic production of neutrophil chemotactic activity by colonic epithelial cells and eosinophils.

The presence of eosinophils in the lumen and mucosa of the intestine is characteristic of both ulcerative colitis (UC) and Crohn's disease (CD). There is evidence of eosinophil activation in the intestine during acute inflammatory episodes of these diseases; these episodes are also characterized by an influx of neutrophils, which have the potential to cause extensive tissue damage. We undertook a study to determine whether eosinophils in contact with colonic epithelial cells produce factors that may attract neutrophils in response to immunological stimulation.

Eosinophil chemotaxis.

Chemotaxis assays have a number of applications in the study of leukocyte biology and immune/inflammatory pathology. Multiwell "blind chamber"-type assays allow a large number of parallel measurements within a single assay. The development of fluorescence assays using microplate-based chemotaxis chambers has permitted a degree of automation to be applied to these assays.

Glass Microparticulate Ingestion: An Unusual and Difficult-to-Diagnose Cause of Chronic Abdominal Pain.

In the absence of overt structural abnormalities, the diagnostic approach to chronic abdominal pain can be challenging. Occupational particulate inhalation causing injury to an organ other than the lung is rare. We report a case of inadvertent glass microparticulate ingestion causing chronic abdominal pain with altered local and systemic inflammatory responses.

The Concise Guide to PHARMACOLOGY 2013/14: overview.

The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database.

Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study.

Background: Diabetes in pregnancy carries an increased risk of adverse pregnancy outcomes for both the mother and foetus, but it also provides an excellent early opportunity for intervention in the life course for both mother and baby. In the context of the escalating epidemic of chronic diseases among Indigenous Australians, it is vital that this risk is reduced as early as possible in the life course of the individual. The aims of the PANDORA Study are to: (i) accurately assess rates of diabetes in pregnancy in the Northern Territory (NT) of Australia, where 38% of babies are born to Indigenous mothers; (ii) assess demographic, clinical, biochemical, anthropometric, socioeconomic and early life development factors that may contribute to key maternal and neonatal birth outcomes associated with diabetes in pregnancy; and (iii) monitor relevant post-partum clinical outcomes for both the mothers and their babies.