Plasma drug screening using paper spray mass spectrometry with integrated solid phase extraction.

Drug overdoses have risen dramatically in recent years. We developed a simple nontargeted method using a disposable paper spray cartridge with an integrated solid phase extraction column. This method was used to screen for ~160 fentanyl analogs, synthetic cannabinoids, other synthetic drugs, and traditional drugs of abuse in over 300 authentic overdose samples collected at emergency departments in Indianapolis. A solid phase extraction step was implemented on the paper spray cartridge to enable subnanograms per milliliter synthetic drugs screening in plasma. Analysis was performed on a quadrupole orbitrap mass spectrometer using the sequential window acquisition of all theoretical fragment ion spectra approach in which tandem mass spectrometry was performed using 7 m/z isolation windows in the quadrupole. Calibration curves with isotopically labeled internal standards were constructed for 35 of the most frequently encountered synthetic and traditional illicit drugs by US toxicology labs. Additional qualitative-only drugs in a suspect screening list were also included. Limits of detection in plasma for synthetic cannabinoids ranged from 0.1 to 0.5 and 0.1 to 0.3 ng/mL for fentanyl and its analogs and between 1 and 5 ng/mL for most other drugs. Relative matrix effects were evaluated by determining the variation of the calibration slope in 10 different lots of biofluid and found to be between 3% and 20%. The method was validated on authentic overdose samples collected from two emergency departments in Indianapolis, Indiana, from suspected or known overdoses. Commonly detected synthetic drugs included fentanyl related substances, designer benzodiazepines such as flubromazolam, and the synthetic cannabinoid 5F-PB-22.

Automated and High-Throughput Urine Drug Screening Using Paper Spray Mass Spectrometry.

Paper spray mass spectrometry (PS-MS) has been shown to be a rapid, simple and inexpensive alternative to traditional forensic drug screening methods. It can address the limitations of both immunoassays and chromatography-based techniques due to its non-reliance on sample preparation and its ability to rapidly screen for a wide array of compounds. In this study, an automated PS-MS system was employed to semi-quantitatively screen for 40 commonly abused drugs and metabolites in urine after a 15-min glucuronidase reaction. The target compounds included common prescription opioids, fentanyl and norfentanyl, stimulants including methamphetamine and cocaine, benzodiazepines and antidepressants. The enzyme, buffer and internal standard solution were combined in one spiking solution to minimize sample handling. Analysis was carried out using a commercially available automated paper spray system coupled to a triple quadrupole mass spectrometer. This method may prove useful for clinical and forensic toxicology laboratories as it allows for automated screening of complex samples for drugs without extraction, separation and sample cleanup.

Insects as Chemical Sensors: Detection of Chemical Warfare Agent Simulants and Hydrolysis Products in the Blow Fly Using LC-MS/MS.

In this work, blow flies were investigated as environmental chemical sample collectors following a chemical warfare attack (CWA). Blow flies sample the environment as they search for water and food sources and can be trapped from kilometers away using baited traps. Three species of blow flies were exposed to CWA simulants to determine the persistence and detectability of these compounds under varying environmental conditions. A liquid chromatography mass spectrometry (LC-MS/MS) method was developed to detect CWA simulants and hydrolysis products from fly guts. Flies were exposed to the CWA simulants dimethyl methylphosphonate and diethyl phosphoramidate as well as the pesticide dichlorvos, followed by treatment-dependent temperature and humidity conditions. Flies were sacrificed at intervals within a 14 day postexposure period. Fly guts were extracted and analyzed with the LC-MS/MS method. The amount of CWA simulant in fly guts decreased with time following exposure but were detectable 14 days following exposure, giving a long window of detectability. In addition to the analysis of CWA simulants, isopropyl methylphosphonic acid, the hydrolysis product of sarin, was also detected in blow flies 14 days post exposure. This work demonstrates the potential to obtain valuable samples from remote or access-restricted areas without risking lives.

The Challenges of Partnering to Promote Health through Sport.

Interagency partnerships and collaborations underpin a settings-based approach to health promotion in all settings, including sport. This study used an online concept mapping approach to explore the challenges that Regional Sports Assemblies (RSAs) in Victoria, Australia experienced when working in partnerships to develop and deliver physical activity programs in a community sport context. Participants from nine RSAs brainstormed 46 unique partnership-related challenges that they then sorted into groups based on similarity of meaning and rated for importance and capacity to manage (6-point scale; 0 = least, 5 = most). A six cluster map (number of statements in cluster, mean cluster importance and capacity ratings)-Co-design for regional areas (4, 4.22, 2.51); Financial resources (3, 4.00, 2.32); Localised delivery challenges (4, 3.72, 2.33); Challenges implementing existing State Sporting Association (SSA) products (9, 3.58, 2.23); Working with clubs (8, 3.43, 2.99); and Partnership engagement (18, 3.23, 2.95)-was considered the most appropriate interpretation of the sorted data. The most important challenge was Lack of volunteer time (4.56). Partnerships to implement health promotion initiatives in sports settings involve multiple challenges, particularly for regional sport organisations working in partnership with community sport clubs with limited human and financial resources, to implement programs developed by national or state-based organisations.

A clinical investigation into the ability of subjects with lung disease to provide breath specimens using the EvidenzerIRL evidential breath analyser in alcohol intoxicant driving in criminal justice evidence.

The EvidenzerIRL instrument has been in use as an evidential breath analyser in the application of drink driving laws in the Republic of Ireland since 2011. The result of the analysis is used as evidence in prosecutions before the Courts in per se offences of driving under the influence of alcohol as distinct from screening results at the roadside. This study aims to assist doctors, lawyers and judges in assessing drivers' failure to provide valid evidential breath specimens. Since the introduction of the EvidenzerIRL, approximately 10% of evidential breath tests annually result in failure or refusal to provide a successful breath specimen, this is an offence under Irish road traffic laws. The presence of lung disease has been given as a reason for the driver failing to provide evidential breath specimens. The aim of this study is to assess the ability of subjects with lung disease to provide breath specimens using the EvidenzerIRL. Pulmonary function tests (PFT) were carried out on volunteers from outpatients of the pulmonary laboratory in St Vincent's University Hospital, Dublin (n = 58) and a control group with no underlying lung disease (n = 19). After the PFTs all volunteers were asked to provide breath specimens using the EvidenzerIRL. Fourteen (24%) out of 58 lung disease volunteers failed to provide a breath specimen, no one from the control group was unsuccessful. Thirteen females and one male volunteer could not successfully provide. Female volunteers were more likely to fail to provide than male volunteers. A significant difference was found between the median age of successful (62.2 years) and unsuccessful (69.2 years) lung disease volunteers. Only one PFT, percentage predicted of Forced Expiratory Volume in 1 second (FEV1), had a significant difference between the mean of successful (86.6%) and unsuccessful (66.5%) lung disease volunteers. A subject with lung disease was more likely to be successful than unsuccessful. Drivers' effort and operators' guidance through the process were found to be crucial parts to a successful outcome.

Gender equality in academic psychiatry in the UK in 2019.

AIMS AND METHOD: To investigate whether gender balance in academic psychiatry in the UK has improved since a 2005 initiative to encourage career progression for female academics in UK universities. We surveyed the gender of academic psychiatrists across the UK and compared our findings with our previous 2003 London-wide survey and with the Royal College of Psychiatrists' 2001 workforce census. RESULTS: The percentage of women in academic psychiatry posts in the UK more than doubled, from 20% in 2001 to 40% in 2019, with increases at senior lecturer (from 25 to 50%), reader/associate professor (from 29 to 48%) and professor level (from 11 to 21%). Outside London, men occupy 72% of all posts and 89% of professorial posts. Within London, men occupy 45% of all posts and 74% of professorial posts. CLINICAL IMPLICATIONS: The representation of women in academic psychiatry has improved but men continue to dominate at professorial level. Gender equality appears worse outside London. The situation is exacerbated by the diminishing availability of posts across the UK.

A clinical investigation into the ability of subjects with a lung disease to provide breath specimens using the Dräger 6510.

In the enforcement of drink driving laws failing to provide a breath specimen for alcohol analysis at the roadside when requested by a Police Officer is an offence in many countries. Some drivers claim that a lung disease prevented their ability to be successful. This study aims to investigate the relationship between the presence of a lung disease and the ability to provide a successful breath specimen using the Dräger 6510 screening device. Sixty participants with lung disease and nineteen control participants underwent pulmonary function tests and were then tested with a Dräger 6510 screening device. Only one participant was unsuccessful using the Dräger 6510, this participant suffered from interstitial lung disease. The pulmonary function test results did not indicate if someone would be successful or how many attempts would be needed to be successful. The presence of a lung disease did not indicate if a driver would be unsuccessful however all participants were free from infection and the participants with a lung disease were stable at the time of testing. Correct instruction, subject cooperation and the technique used by the driver to provide a breath specimen were found to be important factors in the success of a breath test.

Predictors of moving on from mental health supported accommodation in England: national cohort study.

BACKGROUND: Around 60 000 people in England live in mental health supported accommodation. There are three main types: residential care, supported housing and floating outreach. Supported housing and floating outreach aim to support service users in moving on to more independent accommodation within 2 years, but there has been little research investigating their effectiveness. AIMS: A 30-month prospective cohort study investigating outcomes for users of mental health supported accommodation. METHOD: We used random sampling, accounting for relevant geographical variation factors, to recruit 87 services (22 residential care, 35 supported housing and 30 floating outreach) and 619 service users (residential care 159, supported housing 251, floating outreach 209) across England. We contacted services every 3 months to investigate the proportion of service users who successfully moved on to more independent accommodation. Multilevel modelling was used to estimate how much of the outcome and cost variations were due to service type and quality, after accounting for service-user characteristics. RESULTS: Overall 243/586 participants successfully moved on (residential care 15/146, supported housing 96/244, floating outreach 132/196). This was most likely for floating outreach service users (versus residential care: odds ratio 7.96, 95% CI 2.92-21.69, P < 0.001; versus supported housing: odds ratio 2.74, 95% CI 1.01-7.41, P < 0.001) and was associated with reduced costs of care and two aspects of service quality: promotion of human rights and recovery-based practice. CONCLUSIONS: Most people do not move on from supported accommodation within the expected time frame. Greater focus on human rights and recovery-based practice may increase service effectiveness.

Feasibility Randomised Trial Comparing Two Forms of Mental Health Supported Accommodation (Supported Housing and Floating Outreach); a Component of the QuEST (Quality and Effectiveness of Supported Tenancies) Study.

Background: Mental health supported accommodation services are implemented across England, usually organised into a 'step-down' care pathway that requires the individual to repeatedly move as they gain skills and confidence for more independent living. There have been no trials comparing the effectiveness of different types of supported accommodation, but two widely used models (supported housing and floating outreach) have been found to provide similar support. We aimed to assess the feasibility of conducting a large-scale trial comparing these two models. Methods: Individually randomised, parallel group feasibility trial in three regions of England (North London, East London, and Cheltenham and Gloucestershire). We aimed to recruit 60 participants in 15 months, referred to supported accommodation, randomly allocated on an equal basis to receive either a local supported housing or floating outreach service. We assessed referrals to the trial, participants recruited, attrition, time from recruitment to moving into either type of supported accommodation, and feasibility of masking. We conducted a process evaluation to examine our results further. Results: We screened 1,432 potential participants, of whom 17 consented to participate, with 8 agreeing to randomisation (of whom 1 was lost to attrition) and 9 participating in naturalistic follow-up. Our process evaluation indicated that the main obstacle to recruitment was staff and service user preferences for certain types of supported accommodation or for specific services. Staff also felt that randomisation compromised their professional judgement. Conclusions: Our results do not support investment in a large-scale trial in England at this time. Trial registration: UK CRN Portfolio database, Trial ID: ISRCTN19689576. Trial funding: National Institute of Health Research (RP-PG-0707-10093).

Biomarkers of oxidative stress as an assessment of the redox status of the liver in dogs.

BACKGROUND: Oxidative stress is associated with a diverse group of liver disorders across species. OBJECTIVES: Determine whether glutathione (GSH) concentration in plasma and red blood cells correlates with liver GSH concentration in dogs and evaluate whether other markers of systemic oxidative stress, plasma vitamin E and urine 8-isoprostanes/creatinine (F2 -IsoPs/Cr) concentrations, correlate with liver GSH. ANIMALS: Thirty-four client-owned dogs undergoing clinically indicated liver biopsy and 15 healthy control dogs. METHODS: Prospective, observational cross-sectional study. Urine and blood were collected before liver biopsy. Plasma, erythrocyte, and liver GSH were measured using high performance liquid chromatography (HPLC); vitamin E was measured by HPLC, and F2 -IsoPs/Cr was measured by gas chromatography/mass spectrometry. RESULTS: All dogs were treated at the discretion of the attending clinician (24/34 received antioxidants; 4/34 fed therapeutic liver diet), which included dogs with primary or secondary liver disease (inflammatory (n = 21), metabolic (n = 9), vascular (n = 2), and neoplastic (n = 2)). Median GSH concentrations in plasma, erythrocyte, and liver were 0.18 mg/dL (range 0.14 to 0.56 mg/dL), 56.7 mg/dL (18.3 to 79.2 mg/dL), and 181 mg/dL (39.9 to 527 mg/dL), respectively. No significant correlations were found between liver GSH and erythrocyte GSH, plasma GSH, vitamin E, or F2 -IsoPs/Cr. Dogs undergoing clinically indicated liver biopsy had significantly higher urine F2 -IsoPs/Cr than did healthy controls (5.89 vs 2.98 ng/mg; P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Erythrocyte and plasma GSH are not indicative of liver GSH concentration in dogs. In addition, dogs undergoing clinically indicated liver biopsy have evidence of increased systemic oxidative stress compared to healthy controls.

Intentions and experiences of effective practice in mental health specific supported accommodation services: a qualitative interview study.

BACKGROUND: Deinstitutionalisation in Europe has led to the development of community-based accommodation for people with mental health problems. The type, setting, and intensity of support provided vary and the costs are substantial. Yet, despite the large investment in these services, there is little clarity on their aims and outcomes or how they are regarded by staff and the clients. METHODS: We interviewed 30 staff and 30 clients from the three main types of supported accommodation in England (residential care, supported housing, floating outreach) to explore their perspectives on the purpose of these services, and the components of care considered most helpful. The interviews were coded and analysed using thematic analysis. RESULTS: There were generally consistent understandings amongst clients and staff across service types on the goals and purposes of supported accommodation services as: building independence and confidence; supporting people with their mental health; and providing safety and stability. We also noted a competing theme of anxiety about the continuity of support when clients move on from a service. Themes on the experience of what aided effective practice centred on: the supportive presence of others; incremental steps to progress; working together to avoid deskilling and dependency; feeling known and personally understood; tailoring support for social and community engagement; and building confidence through encouragement. CONCLUSIONS: The findings provide an understanding of the commonalities in service approach, and goals of clients in these services, as well as the facilitators of goal attainment. However, they also highlight a common tension between providing safe and supportive living environments, whilst also promoting independence and facilitating rehabilitative change.

Quality of life, autonomy, satisfaction, and costs associated with mental health supported accommodation services in England: a national survey.

BACKGROUND: Little research has been done into the effectiveness of mental health supported accommodation services. We did a national survey to investigate provision and costs of services and assess service user quality of life and outcomes across England. METHODS: We randomly sampled three types of services from 14 nationally representative regions-residential care, supported housing, and floating outreach-and recruited up to ten service users per service. Service quality and costs and service users' quality of life, autonomy, and satisfaction with care were assessed in a standardised manner with validated tools and compared by multilevel modelling. FINDINGS: 619 service users were recruited from 22 residential care, 35 supported housing, and 30 floating outreach services. Those in residential care and supported housing had more severe mental health problems than those in floating outreach. 348 (57%) were assessed as being at risk of severe self-neglect and 229 (37%) as being vulnerable to exploitation in the previous 2 years. Residential care was most expensive but provided for people with the greatest needs. The mean annual budget was £466 687 for residential care (range £276 000-777 920), compared with £365 452 for supported housing (£174 877-818 000), and £172 114 for floating outreach (£17 126-491 692). Quality of care was best in supported housing. People in supported housing and floating outreach were more socially included but experienced more crime than those in residential care. After adjustment for service quality and service user sociodemographic and clinical factors, quality of life was similar for service users in residential care and supported housing (mean difference -0·138, 95% CI -0·402 to 0·126, p=0·306) and lower for those in floating outreach than in residential care (-0·424, -0·734 to -0·114, p=0·007). However, autonomy was greater for those in supported housing than for those in residential care (0·145, 0·010 to 0·279, p=0.035). Satisfaction with care was similar across services. INTERPRETATION: Supported housing might be cost-effective, but the benefits need to be weighed against the risks associated with increased autonomy. FUNDING: National Institute for Health Research.

Adaptation of the Quality Indicator for Rehabilitative Care (QuIRC) for use in mental health supported accommodation services (QuIRC-SA).

BACKGROUND: No standardised tools for assessing the quality of specialist mental health supported accommodation services exist. To address this, we adapted the Quality Indicator for Rehabilitative care-QuIRC-that was originally developed to assess the quality of longer term inpatient and community based mental health facilities. The QuIRC, which is completed by the service manager and gives ratings of seven domains of care, has good psychometric properties. METHODS: Focus groups with staff of the three main types of supported accommodation in the UK (residential care, supported housing and floating outreach services) were carried out to identify potential amendments to the QuIRC. Additional advice was gained from consultation with three expert panels, two of which comprised service users with lived experience of mental health and supported accommodation services. The amended QuIRC (QuIRC-SA) was piloted with a manager of each of the three service types. Item response variance, inter-rater reliability and internal consistency were assessed in a random sample of 52 services. Factorial structure and discriminant validity were assessed in a larger random sample of 87 services. RESULTS: The QuIRC-SA comprised 143 items of which only 18 items showed a narrow range of response and five items had poor inter-rater reliability. The tool showed good discriminant validity, with supported housing services generally scoring higher than the other two types of supported accommodation on most domains. Exploratory factor analysis showed that the QuIRC-SA items loaded onto the domains to which they had been allocated. CONCLUSIONS: The QuIRC-SA is the first standardised tool for quality assessment of specialist mental health supported accommodation services. Its psychometric properties mean that it has potential for use in research as well as audit and quality improvement programmes. A web based application is being developed to make it more accessible which will produce a printable report for the service manager about the performance of their service, comparison data for similar services and suggestions on how to improve service quality.

Development and psychometric properties of the client's assessment of treatment scale for supported accommodation (CAT-SA).

BACKGROUND: Patient-Reported Outcome Measures (PROMs) are important for evaluating mental health services. Yet, no specific PROM exists for the large and diverse mental health supported accommodation sector. We aimed to produce and validate a PROM specifically for supported accommodation services, by adapting the Client's Assessment of Treatment Scale (CAT) and assessing its psychometric properties in a large sample. METHODS: Focus groups with service users in the three main types of mental health supported accommodation services in the United Kingdom (residential care, supported housing and floating outreach) were conducted to adapt the contents of the original CAT items and assess the acceptability of the modified scale (CAT-SA). The CAT-SA was then administered in a survey to service users across England. Internal consistency was assessed using Cronbach's alpha. Convergent validity was tested through correlations with subjective quality of life and satisfaction with accommodation, as measured by the Manchester Short Assessment of Quality of Life (MANSA). RESULTS: All seven original items of the CAT were regarded as relevant to appraisals of mental health supported accommodation services, with only slight modifications to the wording required. In the survey, data were obtained from 618 clients. The internal consistency of the CAT-SA items was 0.89. Mean CAT-SA scores were correlated with the specific accommodation item on the MANSA (r s = 0.37, p ˂ .001). CONCLUSIONS: The content of the CAT-SA has relevance to service users living in mental health supported accommodation. The findings from our large survey show that the CAT-SA is acceptable across different types of supported accommodation and suggest good psychometric properties. The CAT-SA appears a valid and easy to use PROM for service users in mental health supported accommodation services.

Foreword--as per verse: the queer in the clinic in the poem.

This essay introduces a series of poems by six authors: Rafael Campo, Susan Holbrook, Katie Price, Trish Salah, Qwo-Li Driskill, and Brian Teare. I argue that the poems demonstrate that a queer bioethics, whether literary or medical, must dispense with commonplace assumptions about the ways in which selves, especially queer selves, are represented in language. Instead, poetry's sound-sense and avoidance of language-as-usual can serve as an analogy for modes of approach, analysis, and even recognition that do not receive official sanction; the non-linear modes of reading required by contemporary poetry can serve as methodological models for a queer bioethics.