Physician Reluctance to Intervene in Addiction: A Systematic Review.

Importance: The overdose epidemic continues in the US, with 107 941 overdose deaths in 2022 and countless lives affected by the addiction crisis. Although widespread efforts to train and support physicians to implement medications and other evidence-based substance use disorder interventions have been ongoing, adoption of these evidence-based practices (EBPs) by physicians remains low. Objective: To describe physician-reported reasons for reluctance to address substance use and addiction in their clinical practices using screening, treatment, harm reduction, or recovery support interventions. Data Sources: A literature search of PubMed, Embase, Scopus, medRxiv, and SSRN Medical Research Network was conducted and returned articles published from January 1, 1960, through October 5, 2021. Study Selection: Publications that included physicians, discussed substance use interventions, and presented data on reasons for reluctance to intervene in addiction were included. Data Extraction and Synthesis: Two reviewers (L.N., M.C., L.F., J.P., C.S., and S.W.) independently reviewed each publication; a third reviewer resolved discordant votes (M.C. and W.C.). This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and the theoretical domains framework was used to systematically extract reluctance reasons. Main Outcomes and Measures: The primary outcome was reasons for physician reluctance to address substance use disorder. The association of reasons for reluctance with practice setting and drug type was also measured. Reasons and other variables were determined according to predefined criteria. Results: A total of 183 of 9308 returned studies reporting data collected from 66 732 physicians were included. Most studies reported survey data. Alcohol, nicotine, and opioids were the most often studied substances; screening and treatment were the most often studied interventions. The most common reluctance reasons were lack of institutional support (173 of 213 articles [81.2%]), knowledge (174 of 242 articles [71.9%]), skill (170 of 230 articles [73.9%]), and cognitive capacity (136 of 185 articles [73.5%]). Reimbursement concerns were also noted. Bivariate analysis revealed associations between these reasons and physician specialty, intervention type, and drug. Conclusions and Relevance: In this systematic review of reasons for physician reluctance to intervene in addiction, the most common reasons were lack of institutional support, knowledge, skill, and cognitive capacity. Targeting these reasons with education and training, policy development, and program implementation may improve adoption by physicians of EBPs for substance use and addiction care. Future studies of physician-reported reasons for reluctance to adopt EBPs may be improved through use of a theoretical framework and improved adherence to and reporting of survey development best practices; development of a validated survey instrument may further improve study results.

National Institute on Drug Abuse: Dissemination of Scientific Knowledge to Improve Adolescent Health.

The wide and effective dissemination of research findings is crucial to the mission of the National Institute on Drug Abuse (NIDA). This article describes NIDA dissemination efforts and resources that are available to inform clinicians, teens, families, and educators about youth and substance use. Resources that are available include content addressing facts about youth drug use, trends in use, and stigma, in addition to substance use disorder (SUD) prevention and treatment. Information is provided about resources such as infographics, research-based practice guides, training, educational events, and online videos. How input is solicited to inform dissemination efforts is described and future directions for NIDA's dissemination efforts are outlined.

Supervisor versus self-assessment of trainee competence: Differences across developmental stages and competency domains.

OBJECTIVES: This research aimed to systematically examine supervisor-trainee differences in assessments of trainee competencies across domains and developmental stages. METHODS: Trainees and supervisors (N = 141 dyads) independently rated trainee performance at the end of placements using the Clinical Psychology Competencies Rating Scale. Based on the number of placement hours completed at the time competence was assessed, the 141 trainees were assigned to three developmental levels (61, 42, and 31 in the groups, respectively). Trajectories of 10 different competencies and trainee-supervisor differences for these competencies were examined across three developmental levels. RESULTS: Compared to their supervisor ratings, trainees underestimated their competence during early stages of training, with this discrepancy reducing at Level 2 and reversing into an overestimation at Level 3. Compared to their own ratings for overall competence, trainees rated Relational and Communication, Reflective Practice, and Professionalism domains as relative strengths, and rated their competence on assessment and intervention domains as relative weaknesses. CONCLUSION: Growth trajectories derived from supervisor assessments were much flatter than trajectories derived from trainee assessments. As predicted by the impostor theory of practitioner development, trainees significantly underestimated their competence early in training. The trend for trainees to overestimate their competence toward the end of their training is a potential concern that warrants further research.

National Institute on Drug Abuse: Dissemination of Scientific Knowledge to Improve Adolescent Health.

The wide and effective dissemination of research findings is crucial to the mission of the National Institute on Drug Abuse (NIDA). This article describes NIDA dissemination efforts and resources that are available to inform clinicians, teens, families, and educators about youth and substance use. Resources that are available include content addressing facts about youth drug use, trends in use, and stigma, in addition to substance use disorder (SUD) prevention and treatment. Information is provided about resources such as infographics, research-based practice guides, training, educational events, and online videos. How input is solicited to inform dissemination efforts is described and future directions for NIDA's dissemination efforts are outlined.

Antimicrobial Weapons of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a robust and versatile organism capable of surviving and prospering in a diverse array of environments and is an opportunistic pathogen of humans. One reason for the success of this pathogen is the large arsenal of antimicrobial weapons that it possesses. Here we focus our attention on these antimicrobial weapons and how they give P. aeruginosa a survival edge in polymicrobial environments. We define antimicrobial weapons as components produced by P. aeruginosa that are used to kill, inhibit growth and/or subvert key cellular functions in other microbes. P. aeruginosa has a large and complex genome and encodes an armament of antimicrobial weapons that fall into two subclasses; those that are delivered directly to competing microbes using a contact-dependent method, and those that are secreted in a contact-independent manner into the environment to then be available to target neighbouring cells. This chapter provides an overview of the major antimicrobial weapons possessed by P. aeruginosa, captures recent advances in the field and discusses how these could be targeted as a therapeutic intervention, or potentially harnessed to combat infection.

Device Design Modifications Informed by In Vitro Testing of Bacterial Attachment Reduce Infection Rates of Cochlear Implants in Clinical Practice.

Recalcitrant chronic infections of implanted medical devices are often linked to the presence of biofilms. The prevention and treatment of medical device-associated infections is a major source of antibiotic use and driver of antimicrobial resistance globally. Lowering the incidence of infection in patients that receive implanted medical devices could therefore significantly improve antibiotic stewardship and reduce patient morbidity. Here we determined if modifying the design of an implantable medical device to reduce bacterial attachment, impacted the incidence of device-associated infections in clinical practice. Since the 1980s cochlear implants have provided long-term treatment of sensorineural hearing deficiency in hundreds of thousands of patients world-wide. Nonetheless, a relatively small number of devices are surgically explanted each year due to unresolvable infections. Features associated with the accumulation of bacteria on the Cochlear™ Nucleus® CI24RE™ model of cochlear implant devices were identified using both in vitro bacterial attachment assays and examination of explanted devices. Macro-scale design modifications that reduced bacterial attachment in vitro were incorporated into the design of the CI500™ and Profile™ series of Nucleus implant. Analyses of mandatory post-market vigilance data of 198,757 CI24RE and 123,084 CI500/Profile series implantation surgeries revealed that these design modifications correlated with significantly reduced infection rates. This study demonstrates that a design-centric approach aimed at mitigating bacterial attachment was a simple, and effective means of reducing infections associated with Cochlear Nucleus devices. This approach is likely to be applicable to improving the designs of other implantable medical devices to reduce device-associated infections.

Identification of Tse8 as a Type VI secretion system toxin from Pseudomonas aeruginosa that targets the bacterial transamidosome to inhibit protein synthesis in prey cells.

The Type VI secretion system (T6SS) is a bacterial nanomachine that delivers toxic effectors to kill competitors or subvert some of their key functions. Here, we use transposon directed insertion-site sequencing to identify T6SS toxins associated with the H1-T6SS, one of the three T6SS machines found in Pseudomonas aeruginosa. This approach identified several putative toxin-immunity pairs, including Tse8-Tsi8. Full characterization of this protein pair demonstrated that Tse8 is delivered by the VgrG1a spike complex into prey cells where it targets the transamidosome, a multiprotein complex involved in protein synthesis in bacteria that lack either one, or both, of the asparagine and glutamine transfer RNA synthases. Biochemical characterization of the interactions between Tse8 and the transamidosome components GatA, GatB and GatC suggests that the presence of Tse8 alters the fine-tuned stoichiometry of the transamidosome complex, and in vivo assays demonstrate that Tse8 limits the ability of prey cells to synthesize proteins. These data expand the range of cellular components targeted by the T6SS by identifying a T6SS toxin affecting protein synthesis and validate the use of a transposon directed insertion site sequencing-based global genomics approach to expand the repertoire of T6SS toxins in T6SS-encoding bacteria.

Bacteriophage infection of Escherichia coli leads to the formation of membrane vesicles via both explosive cell lysis and membrane blebbing.

Membrane vesicles (MVs) are membrane-bound spherical nanostructures that prevail in all three domains of life. In Gram-negative bacteria, MVs are thought to be produced through blebbing of the outer membrane and are often referred to as outer membrane vesicles (OMVs). We have recently described another mechanism of MV formation in Pseudomonas aeruginosa that involves explosive cell-lysis events, which shatters cellular membranes into fragments that rapidly anneal into MVs. Interestingly, MVs are often observed within preparations of lytic bacteriophage, however the source of these MVs and their association with bacteriophage infection has not been explored. In this study we aimed to determine if MV formation is associated with lytic bacteriophage infection. Live super-resolution microscopy demonstrated that explosive cell lysis of Escherichia coli cells infected with either bacteriophage T4 or T7, resulted in the formation of MVs derived from shattered membrane fragments. Infection by either bacteriophage was also associated with the formation of membrane blebs on intact bacteria. TEM revealed multiple classes of MVs within phage lysates, consistent with multiple mechanisms of MV formation. These findings suggest that bacteriophage infection may be a major contributor to the abundance of bacterial MVs in nature.

Multiple holins contribute to extracellular DNA release in Pseudomonas aeruginosa biofilms.

Bacterial biofilms are composed of aggregates of cells encased within a matrix of extracellular polymeric substances (EPS). One key EPS component is extracellular DNA (eDNA), which acts as a 'glue', facilitating cell-cell and cell-substratum interactions. We have previously demonstrated that eDNA is produced in Pseudomonas aeruginosa biofilms via explosive cell lysis. This phenomenon involves a subset of the bacterial population explosively lysing, due to peptidoglycan degradation by the endolysin Lys. Here we demonstrate that in P. aeruginosa three holins, AlpB, CidA and Hol, are involved in Lys-mediated eDNA release within both submerged (hydrated) and interstitial (actively expanding) biofilms, albeit to different extents, depending upon the type of biofilm and the stage of biofilm development. We also demonstrate that eDNA release events determine the sites at which cells begin to cluster to initiate microcolony formation during the early stages of submerged biofilm development. Furthermore, our results show that sustained release of eDNA is required for cell cluster consolidation and subsequent microcolony development in submerged biofilms. Overall, this study adds to our understanding of how eDNA release is controlled temporally and spatially within P. aeruginosa biofilms.

Pseudomonas aeruginosa is capable of natural transformation in biofilms.

Natural transformation is a mechanism that enables competent bacteria to acquire naked, exogenous DNA from the environment. It is a key process that facilitates the dissemination of antibiotic resistance and virulence determinants throughout bacterial populations. Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that produces large quantities of extracellular DNA (eDNA) that is required for biofilm formation. P. aeruginosa has a remarkable level of genome plasticity and diversity that suggests a high degree of horizontal gene transfer and recombination but is thought to be incapable of natural transformation. Here we show that P. aeruginosa possesses homologues of all proteins known to be involved in natural transformation in other bacterial species. We found that P. aeruginosa in biofilms is competent for natural transformation of both genomic and plasmid DNA. Furthermore, we demonstrate that type-IV pili (T4P) facilitate but are not absolutely essential for natural transformation in P. aeruginosa.

Physician Support for Non-Physician Advanced Practice Providers for Persons With Cardiopulmonary Disease.

BACKGROUND: The use of non-physician advanced practice providers (NPAPP) has increased in the United States to offset shortages in the physician workforce. Yet there are still gaps in some locations where there is little to no access to quality health care. This study sought to identify whether physicians perceived a workforce gap and their level of interest in hiring an NPAPP with cardiopulmonary expertise to fill the perceived gap. METHODS: An American Association for Respiratory Care (AARC)-led workgroup surveyed 1,401 physicians in 6 different specialties. The survey instrument contained 32 closed-ended questions and 4 open-ended questions. RESULTS: 74% of the 1,401 physician respondents agreed or strongly agreed that there will be a future need for an NPAPP with cardiopulmonary expertise. Respondents from sleep, pediatrics, pulmonary, and critical care were most likely to indicate that there is a current need for an NPAPP. A majority of respondents perceived that the specialized NPAPP would improve efficiency and productivity (74%), patient experience (73%), and patient outcomes (72%). Interest in adding this NPAPP did not increase when participants were told to presume authority for hiring, budget, and reimbursement. CONCLUSIONS: These results indicate that there is both a need for and an interest in hiring an NPAPP with cardiopulmonary expertise. Having an NPAPP would boost physician efficiency and productivity, improve the patient care experience, and provide benefits that other clinicians are not trained to provide to persons with cardiopulmonary disease. Results suggest there should be continued efforts to develop the NPAPP role to add value for physicians and patients alike.

ChpC controls twitching motility-mediated expansion of Pseudomonas aeruginosa biofilms in response to serum albumin, mucin and oligopeptides.

Twitching motility-mediated biofilm expansion occurs via coordinated, multi-cellular collective behaviour to allow bacteria to actively expand across surfaces. Type-IV pili (T4P) are cell-associated virulence factors which mediate twitching motility via rounds of extension, surface attachment and retraction. The Chp chemosensory system is thought to respond to environmental signals to regulate the biogenesis, assembly and twitching motility function of T4P. In other well characterised chemosensory systems, methyl-accepting chemotaxis proteins (MCPs) feed environmental signals through a CheW adapter protein to the histidine kinase CheA to modulate motility. The Pseudomonas aeruginosa Chp system has an MCP PilJ and two CheW adapter proteins, PilI and ChpC, that likely interact with the histidine kinase ChpA to feed environmental signals into the system. In the current study we show that ChpC is involved in the response to host-derived signals serum albumin, mucin and oligopeptides. We demonstrate that these signals stimulate an increase in twitching motility, as well as in levels of 3'-5'-cyclic adenosine monophosphate (cAMP) and surface-assembled T4P. Interestingly, our data shows that changes in cAMP and surface piliation levels are independent of ChpC but that the twitching motility response to these environmental signals requires ChpC. Furthermore, we show that protease activity is required for the twitching motility response of P. aeruginosa to environmental signals. Based upon our data we propose a model whereby ChpC feeds these environmental signals into the Chp system, potentially via PilJ or another MCP, to control twitching motility. PilJ and PilI then modulate T4P surface levels to allow the cell to continue to undergo twitching motility. Our study is the first to link environmental signals to the Chp chemosensory system and refines our understanding of how this system controls twitching motility-mediated biofilm expansion in P. aeruginosa.

Reducing poverty among children: Evidence from state policy simulations.

State approaches to reducing child poverty vary considerably. We exploit this state-level variation to estimate what could be achieved in terms of child poverty if all states adopted the most generous or inclusive states' policies. Specifically, we simulate the child poverty reductions that would occur if every state were as generous or inclusive as the most generous or inclusive state in four key policies: Supplemental Nutrition Assistance Program (SNAP), state Earned Income Tax Credits (EITC), Temporary Assistance for Needy Families (TANF), and state Child Tax Credits (CTC). We find that adopting the most generous or inclusive state EITC policy would have the largest impact on child poverty, reducing it by 1.2 percentage points, followed by SNAP, TANF, and lastly state CTC. If all states were as generous or inclusive as the most generous or inclusive state in all four policies, the child poverty rate would decrease by 2.5 percentage points, and five and a half million children would be lifted out of poverty.

Causalities of war: The connection between type VI secretion system and microbiota.

Microbiota niches have space and/or nutrient restrictions, which has led to the coevolution of cooperation, specialisation, and competition within the population. Different animal and environmental niches contain defined resident microbiota that tend to be stable over time and offer protection against undesired intruders. Yet fluxes can occur, which alter the composition of a bacterial population. In humans, the microbiota are now considered a key contributor to maintenance of health and homeostasis, and its alteration leads to dysbiosis. The bacterial type VI secretion system (T6SS) transports proteins into the environment, directly into host cells or can function as an antibacterial weapon by killing surrounding competitors. Upon contact with neighbouring cells, the T6SS fires, delivering a payload of effector proteins. In the absence of an immunity protein, this results in growth inhibition or death of prey leading to a competitive advantage for the attacker. It is becoming apparent that the T6SS has a role in modulating and shaping the microbiota at multiple levels, which is the focus of this review. Discussed here is the T6SS, its role in competition, key examples of its effect upon the microbiota, and future avenues of research.

The Pseudomonas aeruginosa T6SS Delivers a Periplasmic Toxin that Disrupts Bacterial Cell Morphology.

The type VI secretion system (T6SS) is crucial in interbacterial competition and is a virulence determinant of many Gram-negative bacteria. Several T6SS effectors are covalently fused to secreted T6SS structural components such as the VgrG spike for delivery into target cells. In Pseudomonas aeruginosa, the VgrG2b effector was previously proposed to mediate bacterial internalization into eukaryotic cells. In this work, we find that the VgrG2b C-terminal domain (VgrG2bC-ter) elicits toxicity in the bacterial periplasm, counteracted by a cognate immunity protein. We resolve the structure of VgrG2bC-ter and confirm it is a member of the zinc-metallopeptidase family of enzymes. We show that this effector causes membrane blebbing at midcell, which suggests a distinct type of T6SS-mediated growth inhibition through interference with cell division, mimicking the impact of ß-lactam antibiotics. Our study introduces a further effector family to the T6SS arsenal and demonstrates that VgrG2b can target both prokaryotic and eukaryotic cells.

Complete Genome Sequence of Pseudomonas aeruginosa Reference Strain PAK.

We report the complete genome of Pseudomonas aeruginosa strain PAK, a strain which has been instrumental in the study of a range of P. aeruginosa virulence and pathogenesis factors and has been used for over 50 years as a laboratory reference strain.

Systemic glucocorticoid usage in dogs under primary veterinary care in the UK: prevalence and risk factors.

Glucocorticoids are widely used in primary care veterinary practices. The study aimed to quantify the usage of systemic glucocorticoids (SGC) in dogs in the UK using primary care treatment records recorded during 2013 in the VetCompass Programme. From a study population of 455 557 dogs, 28 472 dogs (6.2 per cent, 95 per cent CI 6.2 to 6.3) received a total of 50 971 SGC therapy events in 2013. Prednisolone represented the most frequently used oral preparation (27 362 events, 90.0 per cent of oral events). Dexamethasone sodium phosphate was the most commonly used injectable agent (12 796 events, 62.7 per cent of injectable events). The most common breed treated was Staffordshire Bull Terriers (2236/28 472 dogs, 7.9 per cent, 95 per cent CI 7.5 to 8.2) and within-breed prevalence of SGC usage was 2236/32 635, 6.9 per cent, 95 per cent CI 6.6 to 7.1. The most commonly treated age group was dogs older than eight years (8931/28472, 31.4 per cent) and the most commonly treated bodyweight group was 10.01-20.0 kg (7918/28 472, 27.8 per cent). Dexamethasone and prednisolone were the most commonly prescribed SGC. Short-acting and intermediate-acting injectable SGC were more commonly used compared with long-acting injectable SGC. Older and medium size dogs were most likely to receive SGC and certain breeds appeared predisposed. These data can provide a useful benchmark for glucocorticoid usage and highlight the benefits from 'Big Data' analyses.

Importance of flagella in acute and chronic Pseudomonas aeruginosa infections.

Pseudomonas aeruginosa is an environmental microorganism and a causative agent of diverse acute and chronic, biofilm-associated infections. Advancing research-based knowledge on its adaptation to conditions within the human host is bound to reveal novel strategies and targets for therapeutic intervention. Here, we investigated the traits that P. aeruginosa PA14 as well as a virulence attenuated ΔlasR mutant need to survive in selected murine infection models. Experimentally, the genetic programs that the bacteria use to adapt to biofilm-associated versus acute infections were dissected by passaging transposon mutant libraries through mouse lungs (acute) or mouse tumours (biofilm-infection). Adaptive metabolic changes of P. aeruginosa were generally required during both infection processes. Counter-selection against flagella expression was observed during acute lung infections. Obviously, avoidance of flagella-mediated activation of host immunity is advantageous for the wildtype bacteria. For the ΔlasR mutant, loss of flagella did not confer a selective advantage. Apparently, other pathogenesis mechanisms are active in this virulence attenuated strain. In contrast, the infective process of P. aeruginosa in the chronic biofilm model apparently required expression of flagellin. Together, our findings imply that the host immune reactions against the infectious agent are very decisive for acuteness and duration of the infectious disease. They direct disease outcome.