Revitalizing the drug pipeline: AntibioticDB, an open access database to aid antibacterial research and development.

The current state of antibiotic discovery, research and development is insufficient to respond to the need for new treatments for drug-resistant bacterial infections. The process has changed over the last decade, with most new agents that are in Phases 1-3, or recently approved, having been discovered in small- and medium-sized enterprises or academia. These agents have then been licensed or sold to large companies for further development with the goal of taking them to market. However, early drug discovery and development, including the possibility of developing previously discontinued agents, would benefit from a database of antibacterial compounds for scrutiny by the developers. This article describes the first free, open-access searchable database of antibacterial compounds, including discontinued agents, drugs under pre-clinical development and those in clinical trials: AntibioticDB (AntibioticDB.com). Data were obtained from publicly available sources. This article summarizes the compounds and drugs in AntibioticDB, including their drug class, mode of action, development status and propensity to select drug-resistant bacteria. AntibioticDB includes compounds currently in pre-clinical development and 834 that have been discontinued and that reached varying stages of development. These may serve as starting points for future research and development.

Determinants of Exposure Therapy Implementation in Clinical Practice for the Treatment of Anxiety, OCD, and PTSD: A Systematic Review.

Exposure therapy (ET) forms a vital part of effective psychotherapy for anxiety-related presentations including anxiety disorders, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD), and is often underutilised in clinical practice. Using the Theoretical Domains Framework (TDF), this systematic review synthesised existing literature on the determinants of ET implementation for anxiety-related presentations and examined differences across presentations and developmental subgroups. Fifty-two eligible studies were assessed using the Mixed Methods Appraisal Tool, with 389 results (99%) mapped onto the TDF. Results suggested that clinicians' negative beliefs about the consequences of ET were commonly associated with reduced implementation. It also appeared that whilst broad unspecified ET training may be related to improved implementation for anxiety disorders; greater implementation for complex presentations (i.e., PTSD) likely requires more specialised training involving practical components. A subset of domains (e.g., social/professional role and identity) accounted for most results, whilst some remain unexplored (i.e., optimism; reinforcement; memory, attention, and decision processes) or underexplored (i.e., behavioural regulation). Likewise, specific presentations and developmental subgroups (i.e., PTSD and adults) represented a greater proportion of results in the literature than others (i.e., OCD and youth). Future research exploring ET implementation, across specific presentations and developmental subgroups, would benefit from integrating implementation science frameworks to guide the development of targeted, comprehensive strategies to close the research-practice gap of ET for the treatment of anxiety-related presentations.

A multiple-site laboratory evaluation of three on-site urinalysis drug-testing devices.

Presented are findings from a multisite laboratory evaluation comparing on-site urinalysis drug-test results to results from Syva EMIT immunoassay and gas chromatography-mass spectrometry (GC-MS). Three laboratories participated in the NHTSA-funded project. Specimens were tested for amphetamines, benzodiazepines, cocaine, cannabinoids, and opiates. Each laboratory selected 20 urines that tested positive for a single drug/drug class and 20 that tested negative to challenge the on-site drug-testing devices. Qualitative and quantitative GC-MS confirmations were performed to ensure that all positive samples contained the target drug(s)/metabolite(s) and that all negative samples did not contain the target analytes. EZ-SCREEN, ONTRAK, and TRIAGE on-site test kits were selected for evaluation. On-site false-positive results, in which GC-MS-verified negative urine samples gave positive on-site results, were rare. Two such errors were recorded with both EZ-SCREEN and TRIAGE. Cross-reactivity from samples containing GC-MS-verified high concentrations of alternate drugs was also rare. One cross-reactive error was recorded while testing for cocaine with EZ-SCREEN, a second while testing for benzodiazepines with ONTRAK, and a third while testing for cocaine with ONTRAK. The EZ-SCREEN kit did not appear to adhere to a cutoff concentration as demonstrated by the number of samples that contained low concentrations of the target drugs that tested positive with this device. A significant finding of this study was that comparing on-site test device results with those of EMIT for samples with drug concentrations near the reporting cutoff was very complex. It required a thorough knowledge of the performance of each device, EMIT, and GC-MS. It also required an investigation of each discrepant result-a consideration not taken in many previous evaluations of on-site testing devices. Compared with current federal guidelines for workplace urinalysis testing, more donor samples would screen positive for cannabinoids and cocaine by the on-site devices than by EMIT immunoassay. However, fewer would be reported as positive because most contained GC-MS-determined drug concentrations lower than the federal confirmation and reporting limits.

Opioids - Effects on Human Performance and Behavior.

The purpose of the monograph is to provide readers with a summary of the literature relating selected opioids to performance issues, specifically driving. This monograph provides a summary of information to aid expert witnesses in preparing for court testimony. Information for codeine, hydrocodone, hydromorphone, methadone, morphine, and oxycodone is provided. In addition to a review of performance studies, a summary of acute and chronic pharmacology, pharmacokinetics, and metabolism is included. Opioids appear to impair psychomotor functioning likely to be important to the performance of complex, divided attention tasks such as driving. This impairment is notably more prevalent in individuals with no history of opioid use; individuals with long-term opioid use do not demonstrate as extensive of an impairment. Other factors such as personality, environment, and pain control also sharply modulate opioid impairment.