Trends in Medical Encounters Involving Cannabis-Related Disorders Among US Medicare Beneficiaries, 2017-2022.

To characterize cannabis-related disorder medical encounter trends in the US Medicare population during 2017 to 2022. We conducted a descriptive study, which included 56 624 432 beneficiaries aged 65 years or older and 10 247 953 aged 18 to 64 years with disability. All were continuously enrolled in Medicare (Fee-for-Service or Advantage) for 183 or more days before the first day of the calendar year.

Persistence of quantal synaptic vesicle recycling in virtual absence of dynamins.

Dynamins are GTPases required for pinching vesicles off the plasma membrane once a critical curvature is reached during endocytosis. Here, we probed dynamin function in central synapses by depleting all three dynamin isoforms in postnatal hippocampal neurons down to negligible levels. We found a decrease in the propensity of evoked neurotransmission as well as a reduction in synaptic vesicle numbers.

Personalized genome assembly for accurate cancer somatic mutation discovery using tumor-normal paired reference samples.

Background: The use of a personalized haplotype-specific genome assembly, rather than an unrelated, mosaic genome like GRCh38, as a reference for detecting the full spectrum of somatic events from cancers has long been advocated but has never been explored in tumor-normal paired samples. Here, we provide the first demonstrated use of de novo assembled personalized genome as a reference for cancer mutation detection and quantifying the effects of the reference genomes on the accuracy of somatic mutation detection.

Results: We generate de novo assemblies of the first tumor-normal paired genomes, both nuclear and mitochondrial, derived from the same individual with triple negative breast cancer.

Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing.

Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers.

Concomitant drugs associated with increased mortality for MDMA users reported in a drug safety surveillance database.

3,4-Methylenedioxymethamphetamine (MDMA) is currently being evaluated by the Food and Drug Administration (FDA) for the treatment of post-traumatic stress disorder (PTSD). If MDMA is FDA-approved it will be important to understand what medications may pose a risk of drug-drug interactions. The goal of this study was to evaluate the risks due to MDMA ingestion alone or in combination with other common medications and drugs of abuse using the FDA drug safety surveillance data.

FDA Initiative for Drug Facts Label for Over-the-Counter Naloxone.

Background: The opioid crisis highlights the need to increase access to naloxone, possibly through regulatory approval for over-the-counter sales. To address industry-perceived barriers to such access, the Food and Drug Administration (FDA) developed a model drug facts label for such sales to assess whether consumers understood the key statements for safe and effective use.

Methods: In this label-comprehension study, we conducted individual structured interviews with 710 adults and adolescents, including 430 adults who use opioids and their family and friends.

Collaboration of the NIH and PHS Commissioned Corps in the International Ebola Clinical Research Response.

The U.S. response to the Ebola epidemic resulted in many federal agencies assessing their ability to respond to global threats and improve the efficiency of humanitarian efforts.

Maintenance on naltrexone+amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys.

Background: Cocaine use disorder remains a significant public health issue for which there are no FDA-approved pharmacotherapies. Amphetamine maintenance reduces cocaine use in preclinical and clinical studies, but the mechanism of this effect is unknown. Previous studies indicate a role for endogenous opioid release and subsequent opioid receptor activation in some amphetamine effects; therefore, the current study examined the role of mu-opioid receptor activation in d-amphetamine treatment effects in an assay of cocaine-vs-food choice.

Alternative Models of Developmental and Reproductive Toxicity in Pharmaceutical Risk Assessment and the 3Rs.

In the pharmaceutical industry, preclinical developmental and reproductive toxicity studies are conducted in laboratory animals in order to predict and prevent adverse effects of drugs on human reproductive health and development. However, these studies require a relatively large number of animals and are usually conducted late in the drug development process. Early, simple, and inexpensive screening assays could facilitate smarter decisions, reductions in animal use, and development of safe drugs.

Trends in the Prevalence of Coronary Heart Disease in the U.S.: National Health and Nutrition Examination Survey, 2001-2012.

Introduction: This study evaluated recent trends in the prevalence of coronary heart disease in the U.S. population aged ≥40 years.

Anesthetic neurotoxicity--clinical implications of animal models.

Some anesthetics and sedatives have been shown to cause neurotoxic effects in laboratory animals. The FDA collaboration SmartTots recommends undertaking large-scale clinical studies and avoiding nonurgent surgical procedures requiring anesthesia in children younger than 3 years of age.