Lisdexamfetamine-Induced Psychosis in a Patient With a Neurodevelopmental Disorder.

Individuals diagnosed with autism spectrum disorder (ASD) often experience a higher occurrence of comorbid attention deficit hyperactivity disorder (ADHD). Stimulant medications are frequently prescribed to manage ADHD. In rare instances, the use of stimulant medications has been linked to the development of psychotic symptoms. This is a case of a 13-year-old male diagnosed with ASD and comorbid ADHD, anxiety, and depression, who presented with an abrupt onset of psychosis, which manifested about a week after the initiation of lisdexamfetamine. The psychotic symptoms subsided upon discontinuation of lisdexamfetamine; however, there was a re-emergence of severe ADHD symptoms that proved resistant to non-stimulant medications. The patient experienced significant improvement without any recurrence of psychosis after being prescribed extended-release methylphenidate. Notably, there are no established clinical guidelines to assist in selecting one stimulant over another in the treatment of ADHD comorbid with ASD. The authors recommend considering the methylphenidate class of stimulants as a first-line treatment for ADHD in individuals with ASD, citing better tolerability compared to amphetamines.

The Virtual Couch: a Curriculum on the Question of the Fundamentals of Remote Psychotherapy-Pilot Study.

OBJECTIVE: With a rise in remote clinical practice related to the COVID-19 pandemic, a novel remote psychotherapy curriculum was presented to psychiatry residents and fellows to address the urgent need to teach trainees how to adapt traditional psychotherapy skills to telepsychiatry settings. METHODS: Trainees completed a survey before and after receiving the curriculum to assess remote psychotherapy skills and areas for growth. RESULTS: Eighteen trainees (24% fellows, 77% residents) completed the pre-curriculum survey, and 28 trainees (26% fellows, 74% residents) completed the post-curriculum survey. Thirty-five percent of pre-curriculum participants indicated no experience with remote psychotherapy. Technology (24%) and patient engagement (29%) were identified as the greatest challenges in providing teletherapy pre-curriculum. Content related to patient care (69%) and technology (31%) was of most interest to pre-curriculum participants and identified as most helpful post-curriculum (53% and 26%, respectively). After receiving the curriculum, most trainees planned to make internal, provider-related changes to their remote teletherapy practice. CONCLUSIONS: The remote psychotherapy curriculum was well received by psychiatry trainees who had limited experience with remote clinical practice prior to the pandemic.

The Effects of Remote Cognitive Training Combined With a Mobile App Intervention on Psychosis: Double-Blind Randomized Controlled Trial.

BACKGROUND: Impairments in cognition and motivation are core features of psychosis and strong predictors of social and occupational functioning. Accumulating evidence indicates that cognitive deficits in psychosis can be improved by computer-based cognitive training programs; however, barriers include access and adherence to cognitive training exercises. Limited evidence-based methods have been established to enhance motivated behavior. In this study, we tested the effects of web-based targeted cognitive and social cognitive training (TCT) delivered in conjunction with an innovative digital smartphone app called Personalized Real-Time Intervention for Motivational Enhancement (PRIME). The PRIME app provides users with a motivational coach to set personalized goals and secure social networking for peer support. OBJECTIVE: This study investigated whether deficits in cognition and motivation in people with a psychosis spectrum disorder (N=100) can be successfully addressed with 30 hours of TCT+PRIME as compared with 30 hours of a computer games control condition (CG) plus PRIME (CG+PRIME). Here, we describe our study procedures, the feasibility and acceptability of the intervention, and the results on all primary outcomes. METHODS: In this double-blind randomized controlled trial, English-speaking participants completed all cognitive training, PRIME activities, and assessments remotely. Participants completed a diagnostic interview and remote cognitive, clinical, and self-report measures at baseline, posttraining, and at a 6-month follow-up. RESULTS: This study included participants from 27 states across the United States and 8 countries worldwide. The study population was 58% (58/100) female, with a mean age of 33.77 (SD 10.70) years. On average, participants completed more than half of the cognitive training regimen (mean 18.58, SD 12.47 hours of training), and logged into the PRIME app 4.71 (SD 1.58) times per week. The attrition rate of 22% (22/100) was lower than that reported in our previous studies on remote cognitive training. The total sample showed significant gains in global cognition (P=.03) and attention (P<.001). The TCT+PRIME participants showed significantly greater gains in emotion recognition (P<.001) and global cognition at the trend level (P=.09), although this was not statistically significant, relative to the CG+PRIME participants. The total sample also showed significant improvements on multiple indices of motivation (P=.02-0.05), in depression (P=.04), in positive symptoms (P=.04), and in negative symptoms at a trend level (P=.09), although this was not statistically significant. Satisfaction with the PRIME app was rated at 7.74 (SD 2.05) on a scale of 1 to 10, with higher values indicating more satisfaction. CONCLUSIONS: These results demonstrate the feasibility and acceptability of remote cognitive training combined with the PRIME app and that this intervention can improve cognition, motivation, and symptoms in individuals with psychosis. TCT+PRIME appeared more effective in improving emotion recognition and global cognition than CG+PRIME. Future analyses will test the relationship between hours of cognitive training completed; PRIME use; and changes in cognition, motivation, symptoms, and functioning. TRIAL REGISTRATION: ClinicalTrials.gov NCT02782442; https://clinicaltrials.gov/study/NCT02782442.

Culturing the Plastisphere: comparing methods to isolate culturable bacteria colonising microplastics.

Microplastics quickly become colonised by diverse microbial communities, known as the Plastisphere. There is growing concern that microplastics may support the enrichment and spread of pathogenic or antimicrobial resistant microorganisms, although research to support the unique role of microplastics in comparison to control particles remains inconclusive. Limitations to this research include the microbiological methods available for isolating adhered microbes. Culture-based methods provide some of the most established, accessible and cost-effective microbiological protocols, which could be extremely useful in helping to address some of the remaining key questions in Plastisphere research. Previous works have successfully cultured bacteria from plastics, but these have not yet been reviewed, nor compared in efficiency. In this study, we compared four common biofilm extraction methods (swabbing, sonication, vortexing, sonication followed by vortexing) to extract and culture a mixed community of bacteria from both microplastic (polyethylene, polypropylene and polystyrene) and control (wood and glass) particles. Biofilm extraction efficiency and viability of bacterial suspension was determined by comparing CFU/mL of four different groups of bacteria. This was verified against optical density and 16S rRNA qPCR. Overall, we found that all tested methods were able to remove biofilms, but to varying efficiencies. Sonicating particles with glass beads for 15 min, followed by vortexing for a further minute, generated the highest yield and therefore greatest removal efficiency of culturable, biofilm-forming bacteria.

Systemic Racism's Impact on Minority Children and Youth With Psychosis: Enacting Antiracist Strategies in Psychosis Care.

Psychotic disorders represent a treatable but debilitating subset of mental illnesses. Children and adolescents who are given a diagnosis of psychosis are at risk for serious sequelae that may affect cognitive and social function. Alarmingly, evidence has shown that racial differences exist in the diagnosis and progression of pathology. This article presents a conceptualization of the challenges that minority pediatric patients diagnosed with a psychotic disorder often confront, and explores practical means to antiracist care.

Exploring the potential of using simulation games for engaging with sheep farmers about lameness recognition.

Introduction: Computer simulation games are increasingly being used in agriculture as a promising tool to study, support and influence real-life farming practices. We explored the potential of using simulation games to engage with sheep farmers on the ongoing challenge of reducing lameness. Working with UK stakeholders, we developed a game in which players are challenged with identifying all the lame sheep in a simulated flock. Here, we evaluate the game's potential to act as a tool to help assess, train and understand farmers' ability to recognize the early signs of lameness. Methods: Participants in the UK were invited to play the game in an online study, sharing with us their in-game scores alongside information relating to their real-life farming experience, how they played the game, and feedback on the game. Mixed methods were used to analyze this information in order to evaluate the game. Quantitative analyses consisted of linear modeling to test for statistical relationships between participants' in-game recall (% of the total number of lame sheep that were marked as lame), and the additional information they provided. Qualitative analyses of participants' feedback on the game consisted of thematic analysis and a Likert Scale questionnaire to contextualize the quantitative results and identify additional insights from the study. Results: Quantitative analyses identified no relationships between participants' (n = 63) recall scores and their real life farming experience, or the lameness signs they looked for when playing the game. The only relationship identified was a relationship between participants' recall score and time spent playing the game. Qualitative analyses identified that participants did not find the game sufficiently realistic or engaging, though several enjoyed playing it and saw potential for future development. Qualitative analyses also identified several interesting and less-expected insights about real-life lameness recognition practices that participants shared after playing the game. Discussion: Simulation games have potential as a tool in livestock husbandry education and research, but achieving the desired levels of realism and/or engagingness may be an obstacle to realizing this. Future research should explore this potential further, aided by larger budgets and closer collaboration with farmers, stockpeople, and veterinarians.

Functional metagenomic libraries generated from anthropogenically impacted environments reveal importance of metabolic genes in biocide and antibiotic resistance.

Anthropogenic activities result in the release of antimicrobial resistant bacteria and a cocktail of antimicrobial compounds into the environment that may directly select or indirectly co-select for antimicrobial resistance (AMR). Many studies use metagenome sequencing or qPCR-based approaches to study the environmental resistome but these methods are limited by a priori knowledge. In this study, a functional metagenomic approach was used to explore biocide resistance mechanisms in two contaminated environments and a pristine site, and to identify whether potentially novel genes conferring biocide resistance also conferred resistance or reduced susceptibility to antibiotics. Resistance was predominately mediated through novel mechanisms exclusive of the well-known qac efflux genes. UDP-galactose 4-epimerase (galE) -like genes were identified in both contaminated environments and were shown to confer cross-resistance to biocides and clinically important antibiotics for the first time (to our knowledge), compared to knockout mutants. GalE -like genes were also co-located with transposons, suggesting mobilisation potential. These results show that housekeeping genes may play a significant yet underappreciated role in AMR in environmental microbiomes.

When the Supervisor Needs a Supervisor: A Case-based Guide for Developing Psychotherapy Supervisors.

Supervision of psychotherapy is recognized as fundamental for attaining competency in psychotherapy. However, there is a lack of training in "best practices" of supervisory skills, and some supervisors may lack contemporary knowledge to support supervisees adequately. Training program leadership challenged by limited time and resources to provide supervisors with the necessary education and support can benefit from additional resources for developing psychotherapy supervisors. The authors present 3 core elements of navigating supervisory challenges: training, open dialogue in supervision, and a formal program-level process. Common issues in psychotherapy supervision are then presented in a case-based format. Reflection questions are included to provide an opportunity to consider a personal approach to the case, while specific guidance based on the literature addresses critical aspects of the case examples. Complex supervisory conflicts can challenge programs, but they are normative to the learning process and promote growth in our supervisors.

The Complex Interplay Between Antibiotic Resistance and Pharmaceutical and Personal Care Products in the Environment.

Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are important environmental contaminants. Nonetheless, what drives the evolution, spread, and transmission of antibiotic resistance dissemination is still poorly understood. The abundance of ARB and ARGs is often elevated in human-impacted areas, especially in environments receiving fecal wastes, or in the presence of complex mixtures of chemical contaminants, such as pharmaceuticals and personal care products. Self-replication, mutation, horizontal gene transfer, and adaptation to different environmental conditions contribute to the persistence and proliferation of ARB in habitats under strong anthropogenic influence. Our review discusses the interplay between chemical contaminants and ARB and their respective genes, specifically in reference to co-occurrence, potential biostimulation, and selective pressure effects, and gives an overview of mitigation by existing man-made and natural barriers. Evidence and strategies to improve the assessment of human health risks due to environmental antibiotic resistance are also discussed. Environ Toxicol Chem 2023;00:1-16. © 2022 SETAC.

Does Environmental Exposure to Pharmaceutical and Personal Care Product Residues Result in the Selection of Antimicrobial-Resistant Microorganisms, and is this Important in Terms of Human Health Outcomes?

The environment plays a critical role in the development, dissemination, and transmission of antimicrobial resistance (AMR). Pharmaceuticals and personal care products (PPCPs) enter the environment through direct application to the environment and through anthropogenic pollution. Although there is a growing body of evidence defining minimal selective concentrations (MSCs) of antibiotics and the role antibiotics play in horizontal gene transfer (HGT), there is limited evidence on the role of non-antibiotic PPCPs. Existing data show associations with the development of resistance or effects on bacterial growth rather than calculating selective endpoints. Research has focused on laboratory-based systems rather than in situ experiments, although PPCP concentrations found throughout wastewater, natural water, and soil environments are often within the range of laboratory-derived MSCs and at concentrations shown to promote HGT. Increased selection and HGT of AMR by PPCPs will result in an increase in total AMR abundance in the environment, increasing the risk of exposure and potential transmission of environmental AMR to humans. There is some evidence to suggest that humans can acquire resistance from environmental settings, with water environments being the most frequently studied. However, because this is currently limited, we recommend that more evidence be gathered to understand the risk the environment plays in regard to human health. In addition, we recommend that future research efforts focus on MSC-based experiments for non-antibiotic PPCPS, particularly in situ, and investigate the effect of PPCP mixtures on AMR. Environ Toxicol Chem 2022;00:1-14. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Predicting selection for antimicrobial resistance in UK wastewater and aquatic environments: Ciprofloxacin poses a significant risk.

Antimicrobial resistance (AMR) is a threat to human and animal health, with the environment increasingly recognised as playing an important role in AMR evolution, dissemination, and transmission. Antibiotics can select for AMR at very low concentrations, similar to those in the environment, yet their release into the environment, e.g., from wastewater treatment plants, is not currently regulated. Understanding the selection risk antibiotics pose in wastewater and receiving waters is key to understanding if environmental regulation of antibiotics is required. We investigated the risk of selection occurring in UK wastewater and receiving waters by determining where measured environmental concentration data (n = 8187) for four antibiotics (ciprofloxacin, azithromycin, clarithromycin, and erythromycin) collected in England and Wales 2015-2018 (sites n = 67) exceeded selective concentration thresholds derived from complex microbial community evolution experiments undertaken previously. We show that selection for AMR by ciprofloxacin is likely to have occurred routinely in England and Wales wastewater during the 2015-2018 period, with some seasonal and regional trends. Wastewater treatment reduces the selection risk posed by ciprofloxacin significantly, but not completely, and predicted risk in surface waters remains high in several cases. Conversely, the potential risks posed by the macrolides (azithromycin, clarithromycin, and erythromycin) were lower than those posed by ciprofloxacin. Our data demonstrate further action is needed to prevent selection for AMR in wastewater, with environmental quality standards for some antibiotics required in the future, and that selection risk is not solely a concern in low/middle income countries.

Non-antibiotic pharmaceuticals promote conjugative plasmid transfer at a community-wide level.

BACKGROUND: Horizontal gene transfer (HGT) plays a critical role in the spread of antibiotic resistance and the evolutionary shaping of bacterial communities. Conjugation is the most well characterized pathway for the spread of antibiotic resistance, compared to transformation and transduction. While antibiotics have been found to induce HGT, it remains unknown whether non-antibiotic pharmaceuticals can facilitate conjugation at a microbial community-wide level. RESULTS: In this study, we demonstrate that several commonly consumed non-antibiotic pharmaceuticals (including carbamazepine, ibuprofen, naproxen and propranolol), at environmentally relevant concentrations (0.5 mg/L), can promote the conjugative transfer of IncP1-α plasmid-borne antibiotic resistance across entire microbial communities. The over-generation of reactive oxygen species in response to these non-antibiotic pharmaceuticals may contribute to the enhanced conjugation ratios. Cell sorting and 16S rRNA gene amplicon sequencing analyses indicated that non-antibiotic pharmaceuticals modulate transconjugant microbial communities at both phylum and genus levels. Moreover, microbial uptake ability of the IncP1-α plasmid was also upregulated under non-antibiotic pharmaceutical exposure. Several opportunistic pathogens, such as Acinetobacter and Legionella, were more likely to acquire the plasmid conferring multidrug resistance. CONCLUSIONS: Considering the high possibility of co-occurrence of pathogenic bacteria, conjugative IncP1-α plasmids and non-antibiotic pharmaceuticals in various environments (e.g., activated sludge systems), our findings illustrate the potential risk associated with increased dissemination of antibiotic resistance promoted by non-antibiotic pharmaceuticals in complex environmental settings. Video abstract.

Heightened risk factors in the midst of the pandemic: Supporting individuals with psychosis during COVID-19.

PURPOSE: This article aims to describe distinct vulnerabilities to the psychosocial stress from coronavirus disease 2019 (COVID-19) on individuals with psychosis and provide practical ways to reduce the vulnerabilities. CONCLUSION: Societal changes and stress have come in the wake of the COVID-19. Individuals with psychosis are more susceptible to stress, cognitive biases, and lack social support. Practitioners working with individuals with psychosis are in a unique position to offer ways to reduce risk. PRACTICE IMPLICATIONS: Care during the pandemic requires practitioners to pay particular attention to magnified risk factors to individuals with psychosis and create a plan to offer adjunct support.

Antifungal Exposure and Resistance Development: Defining Minimal Selective Antifungal Concentrations and Testing Methodologies.

This scoping review aims to summarise the current understanding of selection for antifungal resistance (AFR) and to compare and contrast this with selection for antibacterial resistance, which has received more research attention. AFR is an emerging global threat to human health, associated with high mortality rates, absence of effective surveillance systems and with few alternative treatment options available. Clinical AFR is well documented, with additional settings increasingly being recognised to play a role in the evolution and spread of AFR. The environment, for example, harbours diverse fungal communities that are regularly exposed to antifungal micropollutants, potentially increasing AFR selection risk. The direct application of effect concentrations of azole fungicides to agricultural crops and the incomplete removal of pharmaceutical antifungals in wastewater treatment systems are of particular concern. Currently, environmental risk assessment (ERA) guidelines do not require assessment of antifungal agents in terms of their ability to drive AFR development, and there are no established experimental tools to determine antifungal selective concentrations. Without data to interpret the selective risk of antifungals, our ability to effectively inform safe environmental thresholds is severely limited. In this review, potential methods to generate antifungal selective concentration data are proposed, informed by approaches used to determine antibacterial minimal selective concentrations. Such data can be considered in the development of regulatory guidelines that aim to reduce selection for AFR.

Dawning of a new ERA: Environmental Risk Assessment of antibiotics and their potential to select for antimicrobial resistance.

Antibiotics and antimicrobials are used, misused and overused in human and veterinary medicine, animal husbandry and aquaculture. These compounds can persist in both human and animal waste and then enter the environment through a variety of mechanisms. Though generally measured environmental concentrations (MECs) of antibiotics in aquatic systems are significantly lower than point of therapeutic use concentrations, there is increasing evidence that suggests these concentrations may still enrich antimicrobial resistant bacteria. In light of this evidence, a rigorous and standardised novel methodology needs to be developed which can perform environmental risk assessment (ERA) of antimicrobials in terms of their selective potential as well as their environmental impact, to ensure that diffuse and point source discharges are safe. This review summarises and critically appraises the current methodological approaches that study selection at below point of therapeutic use, or sub-inhibitory, concentrations of antibiotics. We collate and compare selective concentration data generated to date. We recommend how these data can be interpreted in line with current ERA guidelines; outlining and describing novel concepts unique to risk assessment of AMR (such as direct selection of AMR or increased persistence of AMR). We consolidate terminology used thus far into a single framework that could be adopted moving forward, by proposing predicted no effect concentrations for resistance (PNECRs) and predicted no effect concentrations for persistence (PNECPs) be determined in AMR risk assessment. Such a framework will contribute to antibiotic stewardship and by extension, protection of human health, food security and the global economy.

The 'SELection End points in Communities of bacTeria' (SELECT) Method: A Novel Experimental Assay to Facilitate Risk Assessment of Selection for Antimicrobial Resistance in the Environment.

BACKGROUND: Antimicrobial resistance (AMR) is one of the most significant health threats to society. A growing body of research demonstrates selection for AMR likely occurs at environmental concentrations of antibiotics. However, no standardized experimental approaches for determining selective concentrations of antimicrobials currently exist, preventing appropriate environmental and human health risk assessment of AMR. OBJECTIVES: We aimed to design a rapid, simple, and cost-effective novel experimental assay to determine selective effect concentrations of antibiotics and to generate the largest experimental data set of selective effect concentrations of antibiotics to date. METHODS: Previously published methods and data were used to validate the assay, which determines the effect concentration based on reduction of bacterial community (wastewater) growth. Risk quotients for test antibiotics were generated to quantify risk. RESULTS: The assay (SELection End points in Communities of bacTeria, or the SELECT method) was used to rapidly determine selective effect concentrations of antibiotics. These were in good agreement with quantitative polymerase chain reaction effect concentrations determined within the same experimental system. The SELECT method predicted no effect concentrations were minimally affected by changes in the assay temperature, growth media, or microbial community used as the inoculum. The predicted no effect concentrations for antibiotics tested ranged from 0.05µg/L for ciprofloxacin to 1,250µg/L for erythromycin. DISCUSSION: The lack of evidence demonstrating environmental selection for AMR, and of associated human health risks, is a primary reason for the lack of action in the mitigation of release of antibiotics into the aquatic environment. We present a novel method that can reliably and rapidly fill this data gap to enable regulation and subsequent mitigation (where required) to lower the risk of selection for, and human exposure to, AMR in aquatic environments. In particular, ciprofloxacin and, to a lesser extent, azithromycin, cefotaxime, and trimethoprim all pose a significant risk for selection of AMR in the environment. https://doi.org/10.1289/EHP6635.

Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration.

Determining the selective potential of antibiotics at environmental concentrations is critical for designing effective strategies to limit selection for antibiotic resistance. This study determined the minimal selective concentrations (MSCs) for macrolide and fluoroquinolone antibiotics included on the European Commission's Water Framework Directive's priority hazardous substances Watch List. The macrolides demonstrated positive selection for ermF at concentrations 1-2 orders of magnitude greater (>500 and <750 µg/L) than measured environmental concentrations (MECs). Ciprofloxacin illustrated positive selection for intI1 at concentrations similar to current MECs (>7.8 and <15.6 µg/L). This highlights the need for compound specific assessment of selective potential. In addition, a sub-MSC selective window defined by the minimal increased persistence concentration (MIPC) is described. Differential rates of negative selection (or persistence) were associated with elevated prevalence relative to the no antibiotic control below the MSC. This increased persistence leads to opportunities for further selection over time and risk of human exposure and environmental transmission.