Lessons for cannabinoid regulation from electronic nicotine delivery system product regulation.

Cannabis legalization continues to spread, with 38 states permitting the use of medical marijuana, 22 states permitting recreational use, and growing political momentum for federal legalization. The last time the Food and Drug Administration (FDA) was tasked with regulating a new product occurred with 2009's Family Smoking Prevention and Tobacco Control Act, which created the Center for Tobacco Products (CTP). Thus, the time is ripe to review the history of CTP with particular attention to difficulties the nascent center faced in regulating novel products such as e-cigarettes or electronic nicotine delivery systems (ENDS).

The 510(k) Third Party Review Program: Promise and Potential.

Every year, the Food and Drug Administration (FDA) clears approximately 3,000 medical devices for marketing via the 510(k) pathway. These constitute 99% of all devices approved for human use and includes the premarket review of many devices incorporating newer technology such as artificial intelligence (AI), machine learning (ML), and other software. As the complexity of these novel technologies and the number of applications is expected to increase in the coming years, statutory changes such as the 2016 21 Century Cures Act, regulations, and guidance documents have increased both the volume and complexity of device review.

Association of Health Insurance Literacy with Health Care Utilization: a Systematic Review.

Background: Given increasing numbers of people experiencing transitions in health insurance due to declines in employer-sponsored insurance and changes in health policy, the understanding and application of health insurance terms and concepts (health insurance literacy) may be important for navigating use of health care. The study objective was to systematically review evidence on the relationship between health insurance literacy and health care utilization.

Methods: Medline, SCOPUS, Web of Science, CINAHL, PsychInfo, Cochrane Library, and reference lists of published literature were searched in August 2019.

Comparative analysis of FoxP3(+) regulatory T cells in the target tissues and blood in chronic graft versus host disease.

Activation and migration of regulatory T cells (Treg) into tissue is critical in control of inflammation, but has not been examined extensively in chronic graft versus host disease (cGVHD). In parallel studies of tissues and blood, we determined that FoxP3(+) T cells increased in proportion to T effectors (Teff) in tissue infiltrates in oral and cutaneous lichenoid cGVHD. These FoxP3(+) cells expressed distinguishing phenotypic and functional markers of Treg (CD3(+), CD4(+), CD27(+), ICOS(+) and CD39(+)), not found on FoxP3(-) Teff.

Distinct roles of ppGpp and DksA in Legionella pneumophila differentiation.

To transit between hosts, intracellular Legionella pneumophila transform into a motile, infectious, transmissive state. Here we exploit the pathogen's life cycle to examine how guanosine tetraphosphate (ppGpp) and DksA cooperate to govern bacterial differentiation. Transcriptional profiling revealed that during transmission alarmone accumulation increases the mRNA for flagellar and Type IV-secretion components, secreted host effectors and regulators, and decreases transcripts for translation, membrane modification and ATP synthesis machinery.

An in vitro time-kill assessment of linezolid and anaerobic bacteria.

Linezolid is a novel oxazolidinone antibacterial agent active against staphylococci (including methicillin-resistant strains), enterococci (including vancomycin-resistant strains), streptococci (including penicillin-intermediate and -resistant Streptococcus pneumoniae), and other aerobic and facultative bacteria. The agent has also demonstrated activity against a broad spectrum of Gram-positive and Gram-negative anaerobic bacteria. Previous time-kill assessments have shown linezolid to be generally bacteriostatic against staphylococci and enterococci, and bactericidal against streptococci.

In vitro activity of linezolid and eperezolid, two novel oxazolidinone antimicrobial agents, against anaerobic bacteria.

Linezolid (formerly U-100766) and eperezolid (formerly U-100592) are novel oxazolidinone antimicrobial agents that are active against multi-drug-resistant staphylococci, streptococci, enterococci, corynebacteria, and mycobacteria. Preliminary studies also demonstrated that the compounds inhibited some test strains of anaerobic bacteria. Therefore, we extended the in vitro evaluation of these agents to include a total of 54 different anaerobic species.

Synthesis and biological evaluation of benzazepine oxazolidinone antibacterials.

Novel benzazepine oxazolidinone antibacterials were synthesized and evaluated against clinically relevant susceptible and resistant organisms. The effect of ring nitrogen position and N-substitution on antibacterial activity is examined.

The synthesis and antibacterial activity of 1,3,4-thiadiazole phenyl oxazolidinone analogues.

Replacement of the morpholine C-ring of linezolid 1 with a 1,3,4-thiadiazolyl ring leads to oxazolidinone analogues 5 having potent antibacterial activity against both gram-positive and gram-negative organisms. Conversion of the C5 acetamide group to a thioacetamide further increases the potency of these compounds.

Identification of phenylisoxazolines as novel and viable antibacterial agents active against Gram-positive pathogens.

A new and promising group of antibacterial agents, collectively known as the oxazolidinones and exemplified by linezolid (PNU-100766, marketed as Zyvox), have recently emerged as important new therapeutic agents for the treatment of infections caused by Gram-positive bacteria. Because of their significance, extensive synthetic investigations into the structure-activity relationships of the oxazolidinones have been conducted at Pharmacia. One facet of this research effort has focused on the identification of bioisosteric replacements for the usual oxazolidinone A-ring.

Carbon-carbon-linked (pyrazolylphenyl)oxazolidinones with antibacterial activity against multiple drug resistant gram-positive and fastidious gram-negative bacteria.

In an effort to expand the spectrum of activity of the oxazolidinone class of antibacterial agents to include Gram-negative bacteria, a series of new carbon-carbon linked pyrazolylphenyl analogues has been prepared. The alpha-N-substituted methyl pyrazole (10alpha) in the C3-linked series exhibited very good Gram-positive activity with MICs View Article and Find Full Text PDF

3-Arylpiperidines as potentiators of existing antibacterial agents.

Important resistance patterns in Gram-negative pathogens include active efflux of antibiotics out of the cell via a cellular pump and decreased membrane permeability. A 3-arylpiperidine derivative (1) has been identified by high-throughput assay as a potentiator with an IC(50) approximately 90 microM. This report details the evaluation of the tether length, aryl substitution and the importance of the fluorine on antibiotic accumulation.

Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis.

A series of new nitrogen-carbon-linked (azolylphenyl)oxazolidinone antibacterial agents has been prepared in an effort to expand the spectrum of activity of this class of antibiotics to include Gram-negative organisms. Pyrrole, pyrazole, imidazole, triazole, and tetrazole moieties have been used to replace the morpholine ring of linezolid (2). These changes resulted in the preparation of compounds with good activity against the fastidious Gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis.

In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents.

Oxazolidinones make up a relatively new class of antimicrobial agents which possess a unique mechanism of bacterial protein synthesis inhibition. U-100592 (S)-N-[[3-[3-fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl]-acetamide and U-100766 (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]- 2-oxo-5-oxazolidinyl]methyl]-acetamide are novel oxazolidinone analogs from a directed chemical modification program. MICs were determined for a variety of bacterial clinical isolates; the respective MICs of U-100592 and U-100766 at which 90% of isolates are inhibited were as follows: methicillin-susceptible Staphylococcus aureus, 4 and 4 micrograms/ml; methicillin-resistant S.

The bactericidal activity and postantibiotic effect of trospectomycin.

Trospectomycin sulfate (trospectomycin, TRS) is a novel, broad-spectrum, aminocyclitol antibiotic that is being developed clinically for the treatment of upper respiratory tract infections, bacterial vaginosis, pelvic inflammatory disease, and gonorrhea. This study investigated the bactericidal activity (by time-kill kinetics) and the postantibiotic effect (PAE) of TRS. Species-dependent bacteriostatic/bactericidal activity was observed for TRS; the antibiotic was bacteriostatic for Staphylococcus epidermidis, Enterococcus faecalis, and Escherichia coli, and bactericidal for Haemophilus influenzae, Neisseria gonorrhoeae, Moraxella catarrhalis, and Bacteroides fragilis (one of two test strains).

Estimating the postantibiotic effect: a two-phase mathematical model.

The postantibiotic effect (PAE) is a suppression of bacterial growth that persists after a short exposure to antimicrobials. The active antibiotic delays the resumption of normal growth. This suppression of bacterial growth following antibiotic removal is described by a two-phase model.

In vitro antibacterial activity and interactions with beta-lactamases and penicillin-binding proteins of the new monocarbam antibiotic U-78608.

U-78608, a new monocarbam antibiotic, was evaluated for in vitro activity against 312 clinical isolates of aerobic and anaerobic bacteria and subjected to several in vitro biochemical tests characterizing its interactions with beta-lactamases and penicillin-binding proteins (PBPs). The antibacterial activity of the compound was compared directly with those of SQ 83,360 (pirazmonam) and aztreonam. U-78608, SQ 83,360, and aztreonam had generally poor activity against gram-positive aerobic bacteria and anaerobic bacteria.

In vitro activity of cefpodoxime proxetil (U-76,252; CS-807) against Neisseria gonorrhoeae.

Cefpodoxime proxetil is an oral cephalosporin antibiotic. The in vitro activities of cefpodoxime (the active metabolite of cefpodoxime proxetil), ceftriaxone, and cefuroxime against both antibiotic-susceptible and antibiotic-resistant clinical isolates of Neisseria gonorrhoeae were determined. Cefpodoxime inhibited all penicillin-susceptible strains and penicillinase-producing strains at less than or equal to 0.

In vitro antibacterial activity of trospectomycin (U-63366F), a novel spectinomycin analog.

Trospectomycin (U-63366F) is a novel spectinomycin analog with broad-spectrum antibacterial activity. The in vitro activity of this analog was compared with that of spectinomycin and other reference antibiotics against 411 clinical isolates of aerobic and anaerobic bacteria. MICs were determined by agar or broth dilution methods.