Increased topical generic prices by manufacturers.

BACKGROUND: There is limited data regarding generic medication prices. Recent studies have shown price changes at the retail level, but much is not known about the pharmaceutical supply chain or price changes at the manufacturer level. OBJECTIVE: We sought to examine the extent of price changes for topical generic medications. METHODS: A comprehensive review of average wholesale prices (AWPs) and manufacturers of topical generics and available corresponding branded medications was conducted for 2005 and 2016. RESULTS: A total of 51 topical chemical entities were examined. Between 2005 and 2016, the AWP of topical generic medications increased by 273% and the AWP of topical branded medications increased by 379%. The topical generic with the greatest price change increased by 2529%. Eight of the top 20 topical generic medications with the greatest increases in AWP also had an increase in the number of manufacturers. LIMITATIONS: These findings are not generalizable to medications used in other areas of medicine. CONCLUSION: Topical generic prices are rapidly increasing at the manufacturer level.

Advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers: a systematic review.

BACKGROUND: Nonhealing ulcers affect patient quality of life and impose a substantial financial burden on the health care system. PURPOSE: To systematically evaluate benefits and harms of advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers. DATA SOURCES: MEDLINE (1995 to June 2013), the Cochrane Library, and reference lists. STUDY SELECTION: English-language randomized trials reporting ulcer healing or time to complete healing in adults with nonhealing ulcers treated with advanced therapies. DATA EXTRACTION: Study characteristics, outcomes, adverse events, study quality, and strength of evidence were extracted by trained researchers and confirmed by the principal investigator. DATA SYNTHESIS: For diabetic ulcers, 35 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with a biological skin equivalent (relative risk [RR], 1.58 [95% CI, 1.20 to 2.08]) and negative pressure wound therapy (RR, 1.49 [CI, 1.11 to 2.01]) compared with standard care and low-strength evidence for platelet-derived growth factors and silver cream compared with standard care. For venous ulcers, 20 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with keratinocyte therapy (RR, 1.57 [CI, 1.16 to 2.11]) compared with standard care and low-strength evidence for biological dressing and a biological skin equivalent compared with standard care. One small trial of arterial ulcers reported improved healing with a biological skin equivalent compared with standard care. Overall, strength of evidence was low for ulcer healing and low or insufficient for time to complete healing. LIMITATIONS: Only studies of products approved by the U.S. Food and Drug Administration were reviewed. Studies were predominantly of fair or poor quality. Few trials compared 2 advanced therapies. CONCLUSION: Compared with standard care, some advanced wound care therapies may improve the proportion of ulcers healed and reduce time to healing, although evidence is limited. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.

Induction of a stress response in Lactococcus lactis is associated with a resistance to ribosomally active antibiotics.

The acquisition of multidrug resistance in bacteria underlies the failure of antimicrobial therapy, and the emergence of pathogens that are resistant to almost the entire armoury of antibiotics. Among the proteins that can mediate or contribute to the drug-resistance profile in Gram-positive bacteria is a subset of ATP-binding cassette proteins that are comprised of a tandem-repeated nucleotide-binding domain. In this study, we expressed one of these NBD(2) proteins, LmrC, in an antibiotic-sensitive Gram-positive host strain (Lactococcus lactis) and demonstrated the acquisition of resistance to ribosomally active antibiotics. Mutation of key catalytic residues suggested that the resistance profile was the result of a cellular response, rather than being a function of the NBD(2) protein itself. This observation was confirmed by 2D SDS/PAGE, which demonstrated that the expression of the NBD(2) protein induced a stress response in L. lactis. A model combining this stress response induction and the acquisition of antibiotic resistance is proposed.

Heterologous expression of a membrane-spanning auxin importer: implications for functional analyses of auxin transporters.

Biochemical studies of plant auxin transporters in vivo are made difficult by the presence of multiple auxin transporters and auxin-interacting proteins. Furthermore, the expression level of most such transporters in plants is likely to be too low for purification and downstream functional analysis. Heterologous expression systems should address both of these issues. We have examined a number of such systems for their efficiency in expressing AUX1 from Arabidopsis thaliana. We find that a eukaryotic system based upon infection of insect cells with recombinant baculovirus provides a high level, easily scalable expression system capable of delivering a functional assay for AUX1. Furthermore, a transient transfection system in mammalian cells enables localization of AUX1 and AUX1-mediated transport of auxin to be investigated. In contrast, we were unable to utilise P. pastoris or L. lactis expression systems to reliably express AUX1.