No abstract

Pseudomonas aeruginosa is a prime opportunistic pathogen, one of the most important causes of hospital-acquired infections and the major cause of morbidity and mortality in cystic fibrosis lung infections. One reason for the bacterium’s pathogenic success is the large array of virulence factors that it can employ. Another is its high degree of intrinsic and acquired resistance to antibiotics. In this review, we first summarise the current knowledge about the regulation of virulence factor expression and production. We then look at the impact of sub-MIC antibiotic exposure and find that the virulence–antibiotic interaction for P. aeruginosa is antibiotic-specific, multifaceted, and complex. Most studies undertaken to date have been in vitro assays in batch culture systems, involving short-term (<24 h) antibiotic exposure. Therefore, we discuss the importance of long-term, in vivo-mimicking models for future work, particularly highlighting the need to account for bacterial physiology, which by extension governs both virulence factor expression and antibiotic tolerance/resistance.

Facility-level utilization patterns of non-pharmacologic, non-opioid, and opioid treatments for chronic pain are associated with subsequent patient-level initiation of LTOT among veterans with incident chronic pain. Further studies should seek to understand facility-level variation in chronic pain care and to identify facility-level utilization patterns that are associated with improved patient outcomes.

Objective Chronic pain is more common among veterans than among the general population. Expert guidelines recommend multimodal chronic pain care. However, there is substantial variation in the availability and utilization of treatment modalities in the Veterans Health Administration. We explored health care providers’ and administrators’ perspectives on the barriers to and facilitators of multimodal chronic pain care in the Veterans Health Administration to understand variation in the use of multimodal pain treatment modalities. Methods  We conducted semi-structured qualitative interviews with health care providers and administrators at a national sample of Veterans Health Administration facilities that were classified as either early or late adopters of multimodal chronic pain care according to their utilization of nine pain-related treatments. Interviews were conducted by telephone, recorded, and transcribed verbatim. Transcripts were coded and analyzed through the use of team-based inductive and deductive content analysis. Results  We interviewed 49 participants from 25 facilities from April through September of 2017. We identified three themes. First, the Veterans Health Administration’s integrated health care system is both an asset and a challenge for multimodal chronic pain care. Second, participants discussed a temporal shift from managing chronic pain with opioids to multimodal treatment. Third, primary care teams face competing pressures from expert guidelines, facility leadership, and patients. Early- and late-adopting sites differed in perceived resource availability. Conclusions Health care providers often perceive inadequate support and resources to provide multimodal chronic pain management. Efforts to improve chronic pain management should address both organizational and patient-level challenges, including primary care provider panel sizes, accessibility of training for primary care teams, leadership support for multimodal pain care, and availability of multidisciplinary pain management resources.

BACKGROUND: There is inadequate evidence of long-term benefit from opioid medications for chronic pain and substantial evidence of potential harms. For patients, dose reduction may be beneficial when implemented voluntarily and supported by a multidisciplinary team but experts have advised against involuntary opioid reduction. OBJECTIVES: To assess the prevalence of self-reported involuntary opioid reduction and to examine whether involuntary opioid reduction is associated with changes in pain severity. DESIGN: Prospective observational cohort study. PARTICIPANTS: Primary care patients treated with longterm opioid therapy in the Veterans Health Administration (N = 290). MAIN MEASURES: The primary exposure was selfreported past year involuntary opioid reduction. The primary outcome was the three-item PEG scale, which measures past-week average pain intensity and interference with enjoyment of life and general activity. KEY RESULTS: Past year opioid reduction or discontinuation was reported by 63% (184/290). Similar numbers reported involuntary (88/290) and voluntary (96/290) opioid reduction. At baseline, there were no significant differences in pain severity between the groups (mean PEG, 7.08 vs. 6.73 vs. 7.07 for past year involuntary opioid reduction, past year voluntary opioid reduction, and no past year opioid reduction, respectively; P = 0.32). For the primary outcome of change in pain severity from baseline to 18 months, there were no significant differences between groups (mean PEG change, − 0.05 vs. − 0.44 vs. − 0.23 for past year involuntary opioid reduction, past year voluntary opioid reduction, and no past year opioid reduction, respectively; P = 0.28). CONCLUSIONS: Self-reported past year involuntary opioid reduction was common among a national sample of veterans treated with long-term opioid therapy. Opioid dose reduction, whether involuntary or voluntary, was