Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine "matalafi".

The leaf homogenate of Psychotria insularum is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism Saccharomyces cerevisiae (baker's yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use. Bioactivity-guided fractionation of the homogenate identified two flavonol glycosides, rutin and nicotiflorin, each binding iron in an ion-dependent molecular networking metabolomics analysis. Translating results to mammalian immune cells and traditional application, the iron chelator activity of the P. insularum homogenate or rutin decreased proinflammatory and enhanced anti-inflammatory cytokine responses in immune cells. Together, the synergistic power of combining traditional knowledge with chemical genomics, metabolomics, and bioassay-guided fractionation provided molecular insight into a relatively understudied Samoan traditional medicine and developed methodology to advance ethnobotany.

How do Healthcare Workers 'Do' Guidelines? Exploring How Policy Decisions Impacted UK Healthcare Workers During the First Phase of the COVID-19 Pandemic.

We describe how COVID-19-related policy decisions and guidelines impacted healthcare workers (HCWs) during the UK's first COVID-19 pandemic phase. Guidelines in healthcare aim to streamline processes, improve quality and manage risk. However, we argue that during this time the guidelines we studied often fell short of these goals in practice. We analysed 74 remote interviews with 14 UK HCWs over 6 months (February-August 2020). Reframing guidelines through Mol's lens of 'enactment', we reveal embodied, relational and material impacts that some guidelines had for HCWs. Beyond guideline 'adherence', we show that enacting guidelines is an ongoing, complex process of negotiating and balancing multilevel tensions. Overall, guidelines: (1) were inconsistently communicated; (2) did not sufficiently accommodate contextual considerations; and (3) were at times in tension with HCWs' values. Healthcare policymakers should produce more agile, acceptable guidelines that frontline HCWs can enact in ways which make sense and are effective in their contexts.

Perspectives on COVID-19 testing policies and practices: a qualitative study with scientific advisors and NHS health care workers in England.

BACKGROUND: As COVID-19 death rates have risen and health-care systems have experienced increased demand, national testing strategies have come under scrutiny. Utilising qualitative interview data from a larger COVID-19 study, this paper provides insights into influences on and the enactment of national COVID-19 testing strategies for health care workers (HCWs) in English NHS settings during wave one of the COVID-19 pandemic (March-August 2020). Through the findings we aim to inform learning about COVID-19 testing policies and practices; and to inform future pandemic diagnostic preparedness. METHODS: A remote qualitative, semi-structured longitudinal interview method was employed with a purposive snowball sample of senior scientific advisors to the UK Government on COVID-19, and HCWs employed in NHS primary and secondary health care settings in England. Twenty-four interviews from 13 participants were selected from the larger project dataset using a key term search, as not all of the transcripts contained references to testing. Framework analysis was informed by the non-adoption, abandonment, scale-up, spread, and sustainability of patient-facing health and care technologies implementation framework (NASSS) and by normalisation process theory (NPT). RESULTS: Our account highlights tensions between the communication and implementation of national testing developments; scientific advisor and HCW perceptions about infectiousness; and uncertainties about the responsibility for testing and its implications at the local level. CONCLUSIONS: Consideration must be given to the implications of mass NHS staff testing, including the accuracy of information communicated to HCWs; how HCWs interpret, manage, and act on testing guidance; and the influence these have on health care organisations and services.

Remote Scene Size-up Using an Unmanned Aerial Vehicle in a Simulated Mass Casualty Incident.

INTRODUCTION: The scene-size-up is a crucial first step in the response to a mass casualty incident (MCI). Unmanned aerial vehicles (UAV) may potentially enhance the scene-size-up with real-time visual feedback during chaotic, evolving or inaccessible events. We performed this study to test the feasibility of paramedics using UAV video from a simulated MCI to identify scene hazards, initiate patient triage, and designate key operational locations. METHODS: We simulated an MCI, including 15 patients plus 4 hazards, on a college campus. A UAV surveyed the scene, capturing video of all patients, hazards, surrounding buildings and streets. We invited attendees of a provincial paramedic meeting to participate. Participants received a lecture on Sort-Assess-Lifesaving Interventions-Treatment/Transport (SALT) Triage and MCI scene management principles. Next, they watched the UAV video footage. We directed participants to sort patients according to SALT Triage Step One, identify injuries, and to localize the patients within the campus. Additionally, we asked them to select a start point for SALT Triage Step Two, identify and locate hazards, and designate locations for an Incident Command Post, Treatment Area, Transport Area and Access/Egress routes. The primary outcome was the number of correctly allocated triage scores. RESULTS: Ninety-six individuals participated. Mean age was 35 years (SD 11); 46% (44) were female and 49% (47) were Primary Care Paramedics. Most participants (79; 82%) correctly sorted at least 12 of 15 patients. Increased age was associated with decreased triage accuracy [-0.04(-0.07, -0.01); p = 0.031]. Fifty-two (54%) correctly localized 12 or more patients to a 27 × 20m grid area. Advanced paramedic certification, and local residency were associated with improved patient localization [2.47(0.23,4.72); p = 0.031], [3.36(1.10,5.61); p = 0.004]. The majority of participants (70; 81%) chose an acceptable location to start SALT Triage Step Two and 75 (78%) identified at least 3 of 4 hazards. Approximately half (53; 56%) of participants appropriately designated 4 or more of 5 key operational areas. CONCLUSION: This study demonstrates the ability of UAV technology to remotely facilitate the scene size-up in an MCI. Additional research is required to further investigate optimal strategies to deploy UAVs in this context.

'All the stars were aligned'? The origins of England's National Institute for Health Research.

BACKGROUND: In 2006, the research and development (R&D) activity of England's national healthcare system, the National Health Service, was reformed. A National Institute for Health Research (NIHR) was established within the Department of Health, the first body to manage this activity as an integrated system, unlocking significant increases in government funding. This article investigates how the NIHR came to be set up, and why it took the form it did. Our goal was a better understanding of 'how we got here'. METHODS: We conducted oral history interviews with 38 key witnesses, held a witness seminar, and examined published and unpublished documents. RESULTS: We conclude that the most important forces shaping the origin of NIHR were the growing impact of evidence-based medicine on service policies, the growth of New Public Management ways of thinking, economic policies favouring investment in health R&D and buoyant public funding for healthcare. We note the strong two-way interaction between the health research system and the healthcare system - while beneficial for the use of research, challenges for healthcare (such as stop-go funding) could also produce challenges for health research. CONCLUSIONS: Understanding how and why England came to have a centralised health service research system alongside a long-established funder of biomedical research (the Medical Research Council) helps us interpret the significance of the English health research experience for other countries and helps English policy-makers better understand their present options. Learning lessons from the features of the English health research system calls for an understanding of the processes which shaped it. Firstly, the publicly funded, nationally organised character of healthcare promoted government interest in evidence-based medicine, made research prioritisation simpler and helped promote the implementation of findings. Secondly, the essential role of leadership by a group who valued research for its health impact ensured that new management methods (such as metrics and competitive tendering) were harnessed to patient benefit, rather than as an end in themselves. A policy window of government willingness to invest in R&D for wider economic goals and buoyant funding of the health system were also effectively exploited.

Characterisation of the biological response of Saccharomyces cerevisiae to the loss of an allele of the eukaryotic initiation factor 4A.

The translation initiation machinery is emerging as an important target for therapeutic intervention, with potential in the treatment of cancer, viral infections, and muscle wasting. Amongst the targets for pharmacological control of translation initiation is the eukaryotic initiation factor 4A (eIF4A), an RNA helicase that is essential for cap-dependent translation initiation. We set out to explore the system-wide impact of a reduction of functional eIF4A. To this end, we investigated the effect of deletion of TIF1, one of the duplicate genes that produce eIF4A in yeast, through synthetic genetic array interactions and system-wide changes in GFP-tagged protein abundances. We show that there is a biological response to deletion of the TIF1 gene that extends through the proteostasis network. Effects of the deletion are apparent in processes as distributed as chromatin remodelling, ribosome biogenesis, amino acid metabolism, and protein trafficking. The results from this study identify protein complexes and pathways that will make ideal targets for combination therapies with eIF4A inhibitors.

Does Point-of-Care Ultrasonography Improve Clinical Outcomes in Emergency Department Patients With Undifferentiated Hypotension? An International Randomized Controlled Trial From the SHoC-ED Investigators.

STUDY OBJECTIVE: Point-of-care ultrasonography protocols are commonly used in the initial management of patients with undifferentiated hypotension in the emergency department (ED). There is little published evidence for any mortality benefit. We compare the effect of a point-of-care ultrasonography protocol versus standard care without point-of-care ultrasonography for survival and clinical outcomes. METHODS: This international, multicenter, randomized controlled trial recruited from 6 centers in North America and South Africa and included selected hypotensive patients (systolic blood pressure <100 mm Hg or shock index >1) randomized to early point-of-care ultrasonography plus standard care versus standard care without point-of-care ultrasonography. Diagnoses were recorded at 0 and 60 minutes. The primary outcome measure was survival to 30 days or hospital discharge. Secondary outcome measures included initial treatment and investigations, admissions, and length of stay. RESULTS: Follow-up was completed for 270 of 273 patients. The most common diagnosis in more than half the patients was occult sepsis. We found no important differences between groups for the primary outcome of survival (point-of-care ultrasonography group 104 of 136 patients versus standard care 102 of 134 patients; difference 0.35%; 95% binomial confidence interval [CI] -10.2% to 11.0%), survival in North America (point-of-care ultrasonography group 76 of 89 patients versus standard care 72 of 88 patients; difference 3.6%; CI -8.1% to 15.3%), and survival in South Africa (point-of-care ultrasonography group 28 of 47 patients versus standard care 30 of 46 patients; difference 5.6%; CI -15.2% to 26.0%). There were no important differences in rates of computed tomography (CT) scanning, inotrope or intravenous fluid use, and ICU or total length of stay. CONCLUSION: To our knowledge, this is the first randomized controlled trial to compare point-of-care ultrasonography to standard care without point-of-care ultrasonography in undifferentiated hypotensive ED patients. We did not find any benefits for survival, length of stay, rates of CT scanning, inotrope use, or fluid administration. The addition of a point-of-care ultrasonography protocol to standard care may not translate into a survival benefit in this group.

A traumatic tale of two cities: does EMS level of care and transportation model affect survival in patients with trauma at level 1 trauma centres in two neighbouring Canadian provinces?

BACKGROUND: Two distinct Emergency Medical Services (EMS) systems exist in Atlantic Canada. Nova Scotia operates an Advanced Emergency Medical System (AEMS) and New Brunswick operates a Basic Emergency Medical System (BEMS). We sought to determine if survival rates differed between the two systems. METHODS: This study examined patients with trauma who were transported directly to a level 1 trauma centre in New Brunswick or Nova Scotia between 1 April 2011 and 31 March 2013. Data were extracted from the respective provincial trauma registries; the lowest common Injury Severity Score (ISS) collected by both registries was ISS≥13. Survival to hospital and survival to discharge or 30 days were the primary endpoints. A separate analysis was performed on severely injured patients. Hypothesis testing was conducted using Fisher's exact test and the Student's t-test. RESULTS: 101 cases met inclusion criteria in New Brunswick and were compared with 251 cases in Nova Scotia. Overall mortality was low with 93% of patients surviving to hospital and 80% of patients surviving to discharge or 30 days. There was no difference in survival to hospital between the AEMS (232/251, 92%) and BEMS (97/101, 96%; OR 1.98, 95% CI 0.66 to 5.99; p=0.34) groups. Furthermore, when comparing patients with more severe injuries (ISS>24) there was no significant difference in survival (71/80, 89% vs 31/33, 94%; OR 1.96, 95% CI 0.40 to 9.63; p=0.50). CONCLUSION: Overall survival to hospital was the same between advanced and basic Canadian EMS systems. As numbers included are low, individual case benefit cannot be excluded.

The genetic architecture in Saccharomyces cerevisiae that contributes to variation in drug response to the antifungals benomyl and ketoconazole.

The genetic basis of variation in drug response was investigated in individual Saccharomyces cerevisiae strains that exhibited different susceptibility to two antifungal agents: benomyl and ketoconazole. Following dose-response screening of 25 strains, 4 were selected on the basis of resistance or sensitivity relative to the standard laboratory strain BY. UWOPS87-2421 and L-1374 were respectively resistant and sensitive to benomyl; DBVPG6044 and Y12 were respectively resistant and sensitive to ketoconazole. We used advanced intercross lines and next generation sequencing-bulk segregant analysis to characterise the quantitative trait loci (QTL) underpinning drug responses after drug selection. Drug response was controlled by multiple QTL, ranging from a minimum of 5 to a maximum of 60 loci, almost all of which were not the primary drug target. For each drug, the resistant and the sensitive strain exhibited a number of shared loci, but also had strain-specific QTL. In our analysis, it was possible to estimate genetic effect of QTL, and a number of those shared between resistant and sensitive strains exhibited variable effect on the response phenotype. Thus, drug responses arise as a result of different genetic architectures, depending on the genetic background of the individual strain in question.

Delays to initial reduction attempt are associated with higher failure rates in anterior shoulder dislocation: a retrospective analysis of factors affecting reduction failure.

INTRODUCTION: Little is understood about the relationship between delay to treatment and initial reduction success for anterior shoulder dislocation. Our study examines whether delays to initial treatment, from injury and hospital presentation, are associated with higher reduction failure rates for anterior shoulder dislocation. METHODS: A retrospective database and chart review was performed for patients undergoing intravenous sedation for attempted reduction of anterior shoulder dislocation in the emergency department (ED). Stepwise regression analysis was performed to identify predictors of reduction failure. Key variables analysed were the duration of the wait in the ED, the interval between the time of injury and first intervention and the interval from time of injury to arrival at the ED. Possible confounding variables analysed included age, gender, dose of sedative agent, qualifications of the reducing physician and whether the dislocated shoulder was recurrent. RESULTS: The duration of the intervals from injury to first reduction attempt and from arrival at the ED to first reduction attempt were both independent predictors of a higher reduction failure rate (OR=1.07, 95% CI 1.02 to 1.13; OR=1.19, 95% CI 1.05 to 1.34). Every interval of 10 min increased the odds of a failed reduction attempt by 7% and 19%, respectively. Overall, shoulder reduction was successful during the initial sedation event in 97 cases (92%) and unsuccessful in nine cases (8%). CONCLUSIONS: Delays to first reduction attempt either from the time of injury or within the ED are associated with a lower reduction success rate for anterior shoulder dislocations.

Laparoscopic myomectomy: clinical outcomes and comparative evidence.

Laparoscopic myomectomy is a common surgical treatment for symptomatic uterine leiomyomas. Proponents of the laparoscopic approach to myomectomy propose that the advantages include shorter length of hospital stay and recovery time. Others suggest longer operative time, greater blood loss, increased risk of recurrence, risk of uterine rupture in future pregnancies, and potential dissemination of cells with use of morcellation. This review outlines techniques for performance of laparoscopic myomectomy and critically appraises the available evidence for operative data, short-term and long-term complications, and reproductive outcomes.

GnRH agonist trigger and a freeze-all strategy to prevent ovarian hyperstimulation syndrome: a retrospective study of OHSS risk and pregnancy rates.

AIMS: To analyse the data from all controlled ovarian hyperstimulation antagonist cycles that used an agonist trigger and a freeze-all strategy to quantify the risk of ovarian hyperstimulation syndrome (OHSS) and subsequent pregnancy rates. MATERIALS AND METHODS: A retrospective study of all women attending fertility clinics at IVF Australia, Sydney, undergoing controlled ovarian hyperstimulation (COH) using an antagonist protocol that had a subsequent gonadotropin-releasing hormone (GnRH) agonist trigger and freezing of all oocytes or embryos. The primary outcome measure was to determine the rate of OHSS. The secondary outcome measure was the clinical pregnancy rate. RESULTS: We collected data for 123 women. 25.2% were undergoing oocyte freezing and 74.8% underwent embryo freezing. There were no cases of OHSS, either early or late onset. The pregnancy rate was 31.7% after the first frozen cycle transfer with a cumulative pregnancy rate of 50% after two frozen embryo transfers. CONCLUSION: Our results support the hypothesis that a GnRH agonist trigger and a freeze-all approach prevents OHSS with a good pregnancy rate.

Fascia iliaca block for pain relief from proximal femoral fracture in the emergency department: a review of the literature.

OBJECTIVES: to determine the efficacy of the fascia iliaca block in providing analgesia to patients with a proximal femoral fracture in the emergency department. METHODS: EMBASE, PubMed, CINAHL and Google Scholar were searched. Free text keywords for population, intervention and outcome were identified to create a search string. The reference lists from articles identified in the primary electronic search were hand searched. Potentially eligible studies were identified based on review of the title and abstract. If eligibility was unclear from the title and abstract, the full text was examined. Randomised controlled trials comparing the fascia iliaca block with standard analgesia were included. A standardised appraisal of the methodological quality of the studies was performed. RESULTS: 39 articles were identified, of which 13 were duplicates. Of the remaining 26, 15 were relevant to the question and suitable for further sorting. There was one conference poster presenting data, which were later published as an audit, and so was considered to be a duplicate. Of the 14 remaining papers, 2 were randomised controlled trials, 6 were cohort studies and 3 were reports of audit of practice. There were 3 abstracts of conference poster or paper submissions, which were descriptions of reviews or service development projects rather than primary studies. The two randomised controlled trials showed statistically significant superior or equal pain relief between the fascia iliaca block and other forms of acute pain relief. CONCLUSIONS: the fascia iliaca block could have an important role in first-line pain control for patients presenting to the emergency department with a proximal femoral fracture. There is potential to reform the acute management of this common group of patients.

Weather factors associated with paediatric croup presentations to an Australian emergency department.

We examined if croup presentations to the emergency department (ED) were associated with weather changes in a warm temperate climate. We collected data on all 729 cases with an ED discharge or admission diagnosis of croup over a 798 day time period. We obtained detailed climatic records from the New South Wales Meteorological Office for the same time period. Only one daily variable, ground temperature at 9:00, was significantly associated with the number of croup attendances (linear regression -0.2062; 95% CI -0.272 to -0.138). There was a stronger correlation (-0.426; 95% CI -0.684 to -0.072) between the calculated mean monthly temperature and the monthly number of croup admissions. Even in this milder climate, croup is associated with cooler weather. We are unable to conclude that hospital attendances for croup are caused by changes in temperature alone, as other factors such as the prevalence of viral illness also follow a seasonal, and therefore, temperature-related pattern.

Emergency department use: is frequent use associated with a lack of primary care provider?

OBJECTIVE: To determine if having a primary care provider is an important factor in frequency of emergency department (ED) use. DESIGN: Analysis of a central computerized health network database. SETTING: Three EDs in southern New Brunswick. PARTICIPANTS: All ED visits during 1 calendar year to an urban regional hospital (URH), an urban urgent care centre (UCC), and a rural community hospital (RCH) were captured. MAIN OUTCOME MEASURES: Patients with and without listed primary care providers were compared in terms of number of visits to the ED. A logistic regression analysis was used to determine factors predictive of frequent attendance. RESULTS: In total, 48 505, 41 004, and 27 900 visits were made to the URH, UCC, and RCH, respectively, in 2009. The proportion of patients with listed primary care providers was 36.6% for the URH, 37.1% for the UCC, and 89.4% for the RCH. Among ED patients at all sites, frequent attenders (4 or more visits to an ED in 1 year) were significantly more likely (59.6% vs 45.1%, P < .001) to have listed primary care providers. Other factors that predicted frequent use included attendance at a rural ED, female sex, and older age. CONCLUSION: This study characterizes attendance rates for 3 EDs in southern New Brunswick. Our findings highlight interesting differences between urban and rural ED populations, and suggest that frequent use of the ED might not be related to lack of a listed primary care provider.

POCUS literature primer: key papers on POCUS in cardiac arrest and shock.

OBJECTIVE: The objective of this study is to identify the top five most influential papers published on the use of point-of-care ultrasound (POCUS) in cardiac arrest and the top five most influential papers on the use of POCUS in shock in adult patients. METHODS: An expert panel of 14 members was recruited from the Canadian Association of Emergency Physicians (CAEP) Emergency Ultrasound Committee and the Canadian Ultrasound Fellowship Collaborative. The members of the panel are ultrasound fellowship trained or equivalent, are engaged in POCUS research, and are leaders in POCUS locally and nationally in Canada. A modified Delphi process was used, consisting of three rounds of sequential surveys and discussion to achieve consensus on the top five most influential papers for the use of POCUS in cardiac arrest and shock. RESULTS: The panel identified 39 relevant papers on POCUS in cardiac arrest and 42 relevant papers on POCUS in shock. All panel members participated in all three rounds of the modified Delphi process, and we ultimately identified the top five most influential papers on POCUS in cardiac arrest and also on POCUS in shock. Studies include descriptions and analysis of safe POCUS protocols that add value from a diagnostic and prognostic perspective in both populations during resuscitation. CONCLUSION: We have developed a reading list of the top five influential papers on the use of POCUS in cardiac arrest and shock to better inform residents, fellows, clinicians, and researchers on integrating and studying POCUS in a more evidence-based manner.

RéSUMé: OBJECTIF: L'objectif de cette étude est d'identifier les cinq articles les plus influents publiés sur l'utilisation de l'échographie au point de soin (POCUS) dans l'arrêt cardiaque et les cinq articles les plus influents sur l'utilisation de POCUS dans le choc chez les patients adultes. MéTHODES: Un comité d'experts composé de 14 membres a été recruté par le Comité d'échographie d'urgence de l'Association canadienne des médecins d'urgence (ACMU) et le Canadian Ultrasound Fellowship Collaborative. Les membres du comité sont formés en échographie ou l'équivalent, participent à la recherche sur le POCUS et sont des chefs de file du POCUS à l'échelle locale et nationale au Canada. Un processus Delphi modifié a été utilisé, consistant en trois séries de sondages séquentiels et de discussions pour parvenir à un consensus sur les cinq articles les plus influents pour l'utilisation de POCUS dans les arrêts cardiaques et les chocs. RéSULTATS: Le panel a identifié 39 articles pertinents sur le POCUS en arrêt cardiaque et 42 articles pertinents sur le POCUS en état de choc. Tous les membres du panel ont participé aux trois cycles du processus Delphi modifié, et nous avons finalement identifié les cinq articles les plus influents sur le POCUS en arrêt cardiaque et aussi sur le POCUS en état de choc. Les études comprennent des descriptions et des analyses de protocoles POCUS sûrs qui ajoutent de la valeur d'un point de vue diagnostique et pronostique dans les deux populations pendant la réanimation. CONCLUSION: Nous avons dressé une liste de lecture des cinq principaux articles influents sur l'utilisation du POCUS en cas d'arrêt cardiaque et de choc afin de mieux informer les résidents, les boursiers, les cliniciens et les chercheurs sur l'intégration et l'étude du POCUS d'une manière plus factuelle.

Management of antipsychotics in primary care: Insights from healthcare professionals and policy makers in the United Kingdom.

INTRODUCTION: Antipsychotic medication is increasingly prescribed to patients with serious mental illness. Patients with serious mental illness often have cardiovascular and metabolic comorbidities, and antipsychotics independently increase the risk of cardiometabolic disease. Despite this, many patients prescribed antipsychotics are discharged to primary care without planned psychiatric review. We explore perceptions of healthcare professionals and managers/directors of policy regarding reasons for increasing prevalence and management of antipsychotics in primary care. METHODS: Qualitative study using semi-structured interviews with 11 general practitioners (GPs), 8 psychiatrists, and 11 managers/directors of policy in the United Kingdom. Data was analysed using thematic analysis. RESULTS: Respondents reported competency gaps that impaired ability to manage patients prescribed antipsychotic medications, arising from inadequate postgraduate training and professional development. GPs lacked confidence to manage antipsychotic medications alone; psychiatrists lacked skills to address cardiometabolic risks and did not perceive this as their role. Communication barriers, lack of integrated care records, limited psychology provision, lowered expectation towards patients with serious mental illness by professionals, and pressure to discharge from hospital resulted in patients in primary care becoming 'trapped' on antipsychotics, inhibiting opportunities to deprescribe. Organisational and contractual barriers between services exacerbate this risk, with socioeconomic deprivation and lack of access to non-pharmacological interventions driving overprescribing. Professionals voiced fears of censure if a catastrophic event occurred after stopping an antipsychotic. Facilitators to overcome these barriers were suggested. CONCLUSIONS: People prescribed antipsychotics experience a fragmented health system and suboptimal care. Several interventions could be taken to improve care for this population, but inadequate availability of non-pharmacological interventions and socioeconomic factors increasing mental distress need policy change to improve outcomes. The role of professionals' fear of medicolegal or regulatory censure inhibiting antipsychotic deprescribing was a new finding in this study.

Factors associated with frequent buprenorphine / naloxone initiation in a national survey of Canadian emergency physicians.

OBJECTIVE: To identify individual and site-related factors associated with frequent emergency department (ED) buprenorphine/naloxone (BUP) initiation. BUP initiation, an effective opioid use disorder (OUD) intervention, varies widely across Canadian EDs. METHODS: We surveyed emergency physicians in 6 Canadian provinces from 2018 to 2019 using bilingual paper and web-based questionnaires. Survey domains included BUP-related practice, demographics, attitudes toward BUP, and site characteristics. We defined frequent BUP initiation (the primary outcome) as at least once per month, high OUD prevalence as at least one OUD patient per shift, and high OUD resources as at least 3 out of the following 5 resources: BUP initiation pathways, BUP in ED, peer navigators, accessible addiction specialists, and accessible follow-up clinics. We excluded responses from sites with <50% participation (to minimize non-responder bias) and those missing the primary outcome. We used univariate analysis to identify associations between frequent BUP initiation and factors of interest, stratifying by OUD prevalence. RESULTS: We excluded 3 responses for missing BUP initiation frequency and 9 for low response rate at one ED. Of the remaining 649 respondents from 34 EDs, 374 (58%) practiced in metropolitan areas, 384 (59%) reported high OUD prevalence, 312 (48%) had high OUD resources, and 161 (25%) initiated BUP frequently. Age, gender, board certification and years in practice were not associated with frequent BUP initiation. Site-specific factors were associated with frequent BUP initiation (high OUD resources [OR 6.91], high OUD prevalence [OR 4.45], and metropolitan location [OR 2.39],) as were individual attitudinal factors (willingness, confidence, and responsibility to initiate BUP.) Similar associations persisted in the high OUD prevalence subgroup. CONCLUSIONS: Individual attitudinal and site-specific factors were associated with frequent BUP initiation. Training to increase physician confidence and increasing OUD resources could increase BUP initiation and benefit ED patients with OUD.

Closing the regulatory regress: GMP accreditation in stem cell laboratories.

Contemporary biomedical research is conducted amidst regimes of national and transnational regulation. Regulation, like rules generally, cannot specify all the practicalities of their application. Regulations for biomedical research impose considerable constraints on laboratories and others. In principle, there is a never-ending regress whereby scientists have to provide increasingly more guarantees that protocols have been followed, standards reached and maintained, and rules adhered to. In practice, regulatory regress is not the actual outcome, as actors find ways of establishing closure for all practical purposes. Based on ethnographic case studies of two sites of biomedical work--the UK Stem Cell Bank and an anonymous laboratory working with primary human foetal material--this article documents the possibility of regulatory regress and strategies aimed at its closure.