Evidence, ethics and the promise of artificial intelligence in psychiatry.

Researchers are studying how artificial intelligence (AI) can be used to better detect, prognosticate and subgroup diseases. The idea that AI might advance medicine's understanding of biological categories of psychiatric disorders, as well as provide better treatments, is appealing given the historical challenges with prediction, diagnosis and treatment in psychiatry. Given the power of AI to analyse vast amounts of information, some clinicians may feel obligated to align their clinical judgements with the outputs of the AI system. However, a potential epistemic privileging of AI in clinical judgements may lead to unintended consequences that could negatively affect patient treatment, well-being and rights. The implications are also relevant to precision medicine, digital twin technologies and predictive analytics generally. We propose that a commitment to epistemic humility can help promote judicious clinical decision-making at the interface of big data and AI in psychiatry.

Third Nerve Palsy Due to Intracranial Aneurysms and Recovery after Endovascular Coiling.

INTRODUCTION: The modality of treatment of third nerve palsy (TNP) associated with intracranial aneurysms remains controversial. While treatment varies with the location of the aneurysm, microsurgical clipping of PComm aneurysms has generally been the traditional choice, with endovascular coiling emerging as a reasonable alternative. METHODS: Patients with TNP due to an intracranial aneurysm who subsequently underwent treatment at a mid-sized Canadian neurosurgical center over a 15-year period (2003-2018) were examined. RESULTS: A total of 616 intracranial aneurysms in 538 patients were treated; the majority underwent endovascular coiling with only 24 patients treated with surgical clipping. Only 37 patients (6.9%) presented with either a partial or complete TNP and underwent endovascular embolization; of these, 17 presented with a SAH secondary to intracranial aneurysm rupture. Aneurysms associated with TNP included PComm (64.9%), terminal ICA (29.7%), proximal MCA (2.7%), and basilar tip (2.7%) aneurysms. In general, smaller aneurysms and earlier treatment were provided for patients for ruptured aneurysms with a shorter mean interval to TNP recovery. In the endovascularly treated cohort initially presenting with TNP, seven presented with a complete TNP and the remaining were partial TNPs. TNP resolved completely in 20 patients (55.1%) and partially in 10 patients (27.0%). Neither time to coiling nor SAH at presentation were significantly associated with the recovery status of TNP. CONCLUSION: Endovascular coil embolization is a viable treatment modality for patients presenting with an associated cranial nerve palsy.

Paralysie du troisième nerf en raison d'un anévrisme intracrânien et rétablissement après la pose d'une bobine endovasculaire. INTRODUCTION: Les modalités de traitement de la paralysie du troisième nerf (PTN) associée aux anévrismes intracrâniens demeurent controversées. Bien que les traitements varient selon l'emplacement de l'anévrisme, le clippage (ou clipping) microchirurgical des anévrismes affectant les artères communicantes postérieures (ACP) est généralement apparu comme le choix le plus courant, la pose d'une bobine endovasculaire (endovascular coiling) ayant aussi émergé comme une option raisonnable. MÉTHODES: Nous nous sommes penchés sur les cas de patients atteints de PTN en raison d'un anévrisme intracrânien qui ont ensuite bénéficié d'un traitement dans un centre neurochirurgical canadien de taille moyenne, et ce, sur une période de 15 ans (2003 à 2018). RÉSULTATS: Au total, 616 anévrismes intracrâniens ayant affecté 538 patients ont été traités. La majorité d'entre eux ont bénéficié de la pose d'une bobine endovasculaire alors que seulement 24 patients ont été traités par clippage microchirurgical. Fait à noter, seuls 37 patients (6,9 %) ont donné à voir une PTN partielle ou totale et ont bénéficié d'une embolisation endovasculaire. De ce nombre, 17 ont donné à voir une hémorragie sous-arachnoïdienne (HSA) consécutive à une rupture d'anévrisme intracrânien. Les anévrismes associés à la PTN ont inclus les ACP (64,9 %), l'artère carotide interne terminale (29,7%), l'artère cérébrale moyenne proximale (2,7 %) et la pointe (tip) de l'artère basilaire (2,7 %). En général, un traitement plus précoce a été proposé aux patients victimes de plus petites ruptures d'anévrisme associées à des délais moyens de rétablissement plus courts à la suite d'une PTN. Dans la cohorte de patients ayant donné à voir des signes de PTN et ayant bénéficié d'un traitement endovasculaire, 7 d'entre eux étaient atteints d'une PTN complète alors que les autres étaient atteints d'une PTN partielle. Les signes de PTN ont fini par disparaître complètement chez 20 patients (55,1 %) et partiellement chez 10 autres (27,0 %). Ni les délais dans la pose d'une bobine endovasculaire ni des signes de HSA au moment de consulter n'ont été notablement associés au processus de rétablissement à la suite d'une PTN. CONCLUSION: En somme, il ressort que l'embolisation endovasculaire au moyen de bobines est une modalité de traitement viable pour les patients présentant une paralysie des nerfs crâniens.

Model-informed drug repurposing: A pharmacometric approach to novel pathogen preparedness, response and retrospection.

During a pandemic caused by a novel pathogen (NP), drug repurposing offers the potential of a rapid treatment response via a repurposed drug (RD) while more targeted treatments are developed. Five steps of model-informed drug repurposing (MIDR) are discussed: (i) utilize RD product label and in vitro NP data to determine initial proof of potential, (ii) optimize potential posology using clinical pharmacokinetics (PK) considering both efficacy and safety, (iii) link events in the viral life cycle to RD PK, (iv) link RD PK to clinical and virologic outcomes, and optimize clinical trial design, and (v) assess RD treatment effects from trials using model-based meta-analysis. Activities which fall under these five steps are categorized into three stages: what can be accomplished prior to an NP emergence (preparatory stage), during the NP pandemic (responsive stage) and once the crisis has subsided (retrospective stage). MIDR allows for extraction of a greater amount of information from emerging data and integration of disparate data into actionable insight.

Optimizing vancomycin dosage regimens in relation to high-flux haemodialysis.

Objectives: To develop a population pharmacokinetic (PK) model for vancomycin in adults receiving high-flux haemodialysis (HFHD) in an effort to optimize vancomycin dosing in this population. Methods: A population PK model using NONMEM was developed using retrospective data collected from 48 vancomycin courses administered to patients (n = 37) receiving HFHD. Fixed-dose [1.5 g loading dose (LD), 1 g maintenance dose (MD)], literature-adapted weight-based (WBL; 20 mg/kg LD, 10 mg/kg MD) and hospital-adapted weight-based (WBH; 25-30 mg/kg LD, 20-25 mg/kg MD) dosage regimens were then simulated using the Monte Carlo method. The PTA was an AUC24/MIC ≥400 with success being a PTA ≥90%. Results: The data were best described using a two-compartment model. It was observed that fixed-dose and WBL dosage regimens resulted in a PTA ≤90% for most days. The WBH dosing achieved a PTA ≥90% on most days, but there were supratherapeutic concentrations with repeated dosing of vancomycin. If HFHD was delayed by 48-72 h after the LD, the PTA would fall below 90%. A dose-optimized regimen was developed: 30 mg/kg LD and 10 mg/kg MD given on HFHD days. An additional dose of 500 mg or 1 g was administered 24 h after the LD if HFHD occurred 48-72 h post-LD. This dose-optimized regimen afforded a PTA ≥90% on all days of therapy and achieved clinically acceptable pre-haemodialysis concentrations. Conclusions: Current vancomycin dosage regimens used clinically do not achieve a PTA ≥90% for most days of therapy for people receiving HFHD. A dose-optimized regimen was developed, which could be implemented in clinical practice.

Psychedelic microdosing benefits and challenges: an empirical codebook.

BACKGROUND: Microdosing psychedelics is the practice of consuming very low, sub-hallucinogenic doses of a psychedelic substance, such as lysergic acid diethylamide (LSD) or psilocybin-containing mushrooms. According to media reports, microdosing has grown in popularity, yet the scientific literature contains minimal research on this practice. There has been limited reporting on adverse events associated with microdosing, and the experiences of microdosers in community samples have not been categorized. METHODS: In the present study, we develop a codebook of microdosing benefits and challenges (MDBC) based on the qualitative reports of a real-world sample of 278 microdosers. RESULTS: We describe novel findings, both in terms of beneficial outcomes, such as improved mood (26.6%) and focus (14.8%), and in terms of challenging outcomes, such as physiological discomfort (18.0%) and increased anxiety (6.7%). We also show parallels between benefits and drawbacks and discuss the implications of these results. We probe for substance-dependent differences, finding that psilocybin-only users report the benefits of microdosing were more important than other users report. CONCLUSIONS: These mixed-methods results help summarize and frame the experiences reported by an active microdosing community as high-potential avenues for future scientific research. The MDBC taxonomy reported here informs future research, leveraging participant reports to distil the highest-potential intervention targets so research funding can be efficiently allocated. Microdosing research complements the full-dose literature as clinical treatments are developed and neuropharmacological mechanisms are sought. This framework aims to inform researchers and clinicians as experimental microdosing research begins in earnest in the years to come.

Patterns of use and appropriateness of antibiotics prescribed to patients receiving haemodialysis: an observational study.

BACKGROUND: There are limited published data on the types and appropriateness of oral and intravenous (IV) antibiotics prescribed to patients receiving haemodialysis. This information is critical to optimise antibiotic prescribing. Therefore this study aims to describe the patterns of use and the appropriateness of oral and IV antibiotics prescribed to patients receiving haemodialysis. METHODS: This was a prospective, observational study across four community and two hospital inpatient haemodialysis units in Melbourne, Australia. Data were collected from July 2014 to January 2015 from participants. Antibiotic regimens prescribed were compared with nationally available antibiotic guidelines and then classified as being either appropriate, inappropriate or not assessable by an expert multidisciplinary team using the National Antimicrobial Prescribing Survey tool. RESULTS: Overall, 114 participants consented to this study where 55.3% (63/114) received antibiotics and 235 antibiotic regimens were prescribed at a rate of 69.1 antibiotic regimens/100 patient-months. The most common oral antibiotics prescribed were amoxycillin/clavulanic acid and cephalexin. The most common IV antibiotics prescribed were vancomycin, piperacillin/tazobactam, cephazolin and ceftriaxone. The percentage of inappropriate antibiotic regimens prescribed were 34.9% (15/43) in the community setting and 22.1% (40/181) in the hospital setting. Furthermore, 29.4% (30/102) of oral and 20.5% (25/122) of IV antibiotic regimens were inappropriate with incorrect dosing as the primary reason. CONCLUSION: Although this study is limited by the sample size, it describes the high antibiotic exposure that patients receiving haemodialysis experience. Of concern is inappropriate dose and frequency being a major issue. This requires interventions focused on the quality use of medicines and antimicrobial stewardship aspects of prescribing in this population.

Reviewing HIV-Related Research in Emerging Economies: The Role of Government Reviewing Agencies.

Little research has explored the possible effects of government institutions in emerging economies on ethical reviews of multinational research. We conducted semi-structured, in-depth telephone interviews with 15 researchers, Research Ethics Committees (RECs) personnel, and a government agency member involved in multinational HIV Prevention Trials Network (HPTN) research in emerging economies. Ministries of Health (MOH) or other government agencies often play pivotal roles as facilitators or barriers in the research ethics approval process. Government agency RECs reviewing protocols may face particular challenges, as they can lack resources, be poorly organized, have inconsistent review processes and limited expertise, and use differing definitions of national interests, including upholding national reputation and avoiding potential exploitation and stigma of the country's population. The MOH/governmental review body may be affected by power dynamics and politics in study reviews; may consider issues both related and unrelated to research ethics as understood elsewhere; and may prioritize particular diseases, treatments, or interventions over other topics/types of research. Poor communication and deeply-rooted tensions may exist between sponsor and host countries, impeding optimal interactions and reviews. Investigators must understand and plan for the potential effects of governmental agencies on multinational collaborative research, including preserving adequate time for agency review, and contacting these agencies beforehand to address issues that may arise. Better understanding of these issues can aid and advance appropriate global scientific collaboration.

The ethics of molecular memory modification.

Novel molecular interventions have recently shown the potential to erase, enhance and alter specific long-term memories. Unique features of this form of memory modification call for a close examination of its possible applications. While there have been discussions of the ethics of memory modification in the literature, molecular memory modification (MMM) can provide special insights. Previously raised ethical concerns regarding memory enhancement, such as safety issues, the 'duty to remember', selfhood and personal identity, require re-evaluation in light of MMM. As a technology that exploits the brain's updating processes, MMM helps correct the common misconception that memory is a static entity by demonstrating how memory is plastic and subject to revision even in the absence of external manipulation. Furthermore, while putatively safer than other speculative technologies because of its high specificity, MMM raises notable safety issues, including potential insidious effects on the agent's emotions and personal identity. Nonetheless, MMM possesses characteristics of a more permissible form of modification, not only because it is theoretically safer, but because its unique mechanism of action requires a heightened level of cooperation from the agent. Discussions of memory modification must consider the specific mechanisms of action, which can alter the weight and relevance of various ethical concerns. MMM also highlights the need for conceptual accuracy regarding the term 'enhancement'; this umbrella term will have to be differentiated as new technologies are applied to a widening array of purposes.

The Influence of Using Novel Predictive Technologies on Judgments of Stigma, Empathy, and Compassion among Healthcare Professionals.

BACKGROUND: Our objective was to evaluate whether the description of a machine learning (ML) app or brain imaging technology to predict the onset of schizophrenia or alcohol use disorder (AUD) influences healthcare professionals' judgments of stigma, empathy, and compassion. METHODS: We randomized healthcare professionals (N = 310) to one vignette about a person whose clinician seeks to predict schizophrenia or an AUD, using a ML app, brain imaging, or a psychosocial assessment. Participants used scales to measure their judgments of stigma, empathy, and compassion. RESULTS: Participants randomized to the ML vignette endorsed less anger and more fear relative to the psychosocial vignette, and the brain imaging vignette elicited higher pity ratings. The brain imaging and ML vignettes evoked lower personal responsibility judgments compared to the psychosocial vignette. Physicians and nurses reported less empathy than clinical psychologists. CONCLUSIONS: The use of predictive technologies may reinforce essentialist views about mental health and substance use that may increase specific aspects of stigma and reduce others.

Predictive care: a protocol for a computational ethnographic approach to building fair models of inpatient violence in emergency psychiatry.

INTRODUCTION: Managing violence or aggression is an ongoing challenge in emergency psychiatry. Many patients identified as being at risk do not go on to become violent or aggressive. Efforts to automate the assessment of risk involve training machine learning (ML) models on data from electronic health records (EHRs) to predict these behaviours. However, no studies to date have examined which patient groups may be over-represented in false positive predictions, despite evidence of social and clinical biases that may lead to higher perceptions of risk in patients defined by intersecting features (eg, race, gender). Because risk assessment can impact psychiatric care (eg, via coercive measures, such as restraints), it is unclear which patients might be underserved or harmed by the application of ML. METHODS AND ANALYSIS: We pilot a computational ethnography to study how the integration of ML into risk assessment might impact acute psychiatric care, with a focus on how EHR data is compiled and used to predict a risk of violence or aggression. Our objectives include: (1) evaluating an ML model trained on psychiatric EHRs to predict violent or aggressive incidents for intersectional bias; and (2) completing participant observation and qualitative interviews in an emergency psychiatric setting to explore how social, clinical and structural biases are encoded in the training data. Our overall aim is to study the impact of ML applications in acute psychiatry on marginalised and underserved patient groups. ETHICS AND DISSEMINATION: The project was approved by the research ethics board at The Centre for Addiction and Mental Health (053/2021). Study findings will be presented in peer-reviewed journals, conferences and shared with service users and providers.

Conceptualising fairness: three pillars for medical algorithms and health equity.

OBJECTIVES: Fairness is a core concept meant to grapple with different forms of discrimination and bias that emerge with advances in Artificial Intelligence (eg, machine learning, ML). Yet, claims to fairness in ML discourses are often vague and contradictory. The response to these issues within the scientific community has been technocratic. Studies either measure (mathematically) competing definitions of fairness, and/or recommend a range of governance tools (eg, fairness checklists or guiding principles). To advance efforts to operationalise fairness in medicine, we synthesised a broad range of literature. METHODS: We conducted an environmental scan of English language literature on fairness from 1960-July 31, 2021. Electronic databases Medline, PubMed and Google Scholar were searched, supplemented by additional hand searches. Data from 213 selected publications were analysed using rapid framework analysis. Search and analysis were completed in two rounds: to explore previously identified issues (a priori), as well as those emerging from the analysis (de novo). RESULTS: Our synthesis identified 'Three Pillars for Fairness': transparency, impartiality and inclusion. We draw on these insights to propose a multidimensional conceptual framework to guide empirical research on the operationalisation of fairness in healthcare. DISCUSSION: We apply the conceptual framework generated by our synthesis to risk assessment in psychiatry as a case study. We argue that any claim to fairness must reflect critical assessment and ongoing social and political deliberation around these three pillars with a range of stakeholders, including patients. CONCLUSION: We conclude by outlining areas for further research that would bolster ongoing commitments to fairness and health equity in healthcare.

Reoperation in adult patients with recurrent glioblastoma: A matched cohort analysis.

Background: Despite maximal safe cytoreductive surgery and postoperative adjuvant therapies, glioblastoma (GBM) inevitably recurs and leads to deterioration of neurological status and eventual death. There is no consensus regarding the benefit of repeat resection for enhancing survival or quality of life in patients with recurrent GBM. We aimed to examine if reoperation for GBM recurrence incurs a survival benefit as well as examine its complication profile. Methods: We performed a single-center retrospective chart review on all adult patients who underwent resection of supratentorial GBM between January 1, 2008 and December 1, 2013 at our center. Patients with repeat resection were manually matched for age, sex, tumor location, and Karnofsky Performance Status (KPS) with patients who underwent single resection to compare overall survival (OS), and postoperative morbidity. Results: Of 237 patients operated with GBM, 204 underwent single resection and 33 were selected for repeat surgical resections. In a matched analysis there was no difference in the OS between groups (17.8 ± 17.6 months vs 17 ± 13.5 months, P = .221). In addition, repeat surgical resection had a higher rate of postoperative neurological complications compared to the initial surgery. Conclusions: When compared with matched patients who underwent a single surgical resection, patients undergoing repeat surgical resection did not show significant increase in OS and may have incurred more neurological complications related to the repeat resection. Further studies are required to assess which patients would benefit from repeat surgical resection and optimize timing of the repeat resection in selected patients.

Removing a Disabled Person from Her Treasured Independent Living.

Ms. X is a person with cerebral palsy and schizophrenia. She has intractable bedsores that are a result of her immobility and to poor wound care related to her delusional thinking. Despite intensive community support, the wounds have worsened to the point that she has needed multiple hospitalizations to prevent systemic sepsis, a life-threatening condition. She is capable of placement decisions and wishes for independence at home but is incapable of making wound care decisions and does not appreciate that immediately returning home from the hospital, instead of going into a special care facility, would likely result in sepsis. The resulting dilemma about discharge planning highlights the complexity involved in weighing concerns around mental illness and capacity for treatment and placement of care. The extent of the care that is required and available in a community or health care system and the slow but relatively certain progression of the symptoms also make the decision challenging. Two commentaries take very different approaches in exploring the question whether Ms. X should be supported to go home or to a special care facility.

Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities.

RATIONALE: Microdosing psychedelics - the practice of consuming small, sub-hallucinogenic doses of substances such as LSD or psilocybin - is gaining attention in popular media but remains poorly characterized. Contemporary studies of psychedelic microdosing have yet to report the basic psychiatric descriptors of psychedelic microdosers. OBJECTIVES: To examine the practices and demographics of a population of psychedelic microdosers - including their psychiatric diagnoses, prescription medications, and recreational substance use patterns - to develop a foundation on which to conduct future clinical research. METHODS: Participants (n = 909; Mage = 26.9, SD = 8.6; male = 83.2%; White/European = 79.1%) recruited primarily from the online forum Reddit completed an anonymous online survey. Respondents who reported using LSD, psilocybin, or both for microdosing were grouped and compared with non-microdosing respondents using exploratory odds ratio testing on demographic variables, rates of psychiatric diagnoses, and past-year recreational substance use. RESULTS: Of microdosers, most reported using LSD (59.3%; Mdose = 13 mcg, or 11.3% of one tab) or psilocybin (25.9%; Mdose = 0.3 g of dried psilocybin mushrooms) on a one-day-on, two-days-off schedule. Compared with non-microdosers, microdosers were significantly less likely to report a history of substance use disorders (SUDs; OR = 0.17 (95% CI: 0.05-0.56)) or anxiety disorders (OR = 0.61 (95% CI: 0.41-0.91)). Microdosers were also more likely to report recent recreational substance use compared with non-microdosers (OR = 5.2 (95% CI: 2.7-10.8)). CONCLUSIONS: Well-designed randomized controlled trials are needed to evaluate the safety and tolerability of this practice in clinical populations and to test claims about potential benefits.

Microdosing psychedelics: personality, mental health, and creativity differences in microdosers.

RATIONALE: Microdosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses. OBJECTIVES: This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity. METHODS: In this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity. RESULTS: Current and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = - 0.92) and negative emotionality (p = 0.009, r = - 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls. CONCLUSIONS: These findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.

Vancomycin dosing in chronic high-flux haemodialysis: a systematic review.

The aim of this study was to systematically evaluate whether non-weight-based dosing (non-WBD) or weight-based dosing (WBD) of vancomycin leads to a higher proportion of patients achieving the pharmacokinetic/pharmacodynamic target. Studies from January 1985 to February 2017 were identified through Cochrane, MEDLINE and Embase databases. Those conducted in adults with end-stage renal disease receiving high-flux haemodialysis (HD) and intravenous vancomycin were included. The primary outcome was the proportion of patients with a pre-HD vancomycin concentration of 15-20 mg/L and/or an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) ratio ≥400. Of the 3948 studies screened, 5 met the inclusion criteria. The proportion of patients with pre-HD concentrations between 15-20 mg/L were 35% (non-WBD) and 13% (WBD) post-loading dose. During maintenance dosing, the proportion of patients with pre-HD concentrations between 15-20 mg/L were 37% (non-WBD) and 50-67% (WBD). The proportion of pre-HD concentrations <15 mg/L was greater in the non-WBD group post-loading dose but was similar between the non-WBD and WBD group during maintenance dosing. One study reported that all patients had an AUC/MIC ≥ 400 for micro-organisms with an MIC ≤ 1 mg/L for weight-based maintenance dosing. The limited data suggest that WBD may be preferential as there was a smaller proportion of pre-HD concentrations falling below 15 mg/L. However, larger well-designed studies of higher quality are required to provide guidance for vancomycin dosing in the high-flux HD setting. Future research should focus on reporting AUC/MIC ratios and exploring clinical outcomes in this patient population.