Should physician-assisted suicide (PAS) be legalised in the UK? An innovative workshop exploring medical students' perspectives.

This workshop aimed to investigate students' perspectives on physician-assisted suicide (PAS) and its potential legalisation. A two-pronged strategy was used - a goldfish bowl roleplay simulation and a facilitated group discussion. The roleplay enabled students to engage with practical and emotional challenges related to responding to a PAS request, while the discussion encouraged open dialogue on the ethical complexities of legalising PAS. Students showed nuanced changes in perspectives on PAS by actively participating in roleplay and discussions, demonstrating the potential for these approaches to promote deeper understanding.

Preferential whole blood transfusion during the early resuscitation period is associated with decreased mortality and transfusion requirements in traumatically injured patients.

Introduction: Whole blood (WB) transfusion represents a promising resuscitation strategy for trauma patients. However, a paucity of data surrounding the optimal incorporation of WB into resuscitation strategies persists. We hypothesized that traumatically injured patients who received a greater proportion of WB compared with blood product components during their resuscitative efforts would have improved early mortality outcomes and decreased transfusion requirements compared with those who received a greater proportion of blood product components. Methods: Retrospective review from our Level 1 trauma center of trauma patients during their initial resuscitation (2019-2022) was performed. WB to packed red blood cell ratios (WB:RBC) were assigned to patients based on their respective blood product resuscitation at 1, 2, 3, and 24 hours from presentation. Multivariable regression models were constructed to assess the relationship of WB:RBC to 4 and 24-hour mortality, and 24-hour transfusion requirements. Results: 390 patients were evaluated (79% male, median age of 33 years old, 48% penetrating injury rate, and a median Injury Severity Score of 27). Overall mortality at 4 hours was 9%, while 24-hour mortality was 12%. A significantly decreased 4-hour mortality was demonstrated in patients who displayed a WB:RBC≥1 at 1 hour (5.9% vs. 12.3%; OR 0.17, p=0.015), 2 hours (5.5% vs. 13%; OR 0.16, p=0.019), and 3 hours (5.5% vs. 13%, OR 0.18, p<0.01), while a decreased 24-hour mortality was displayed in those with a WB:RBC≥1 at 24 hours (7.9% vs. 14.6%, OR 0.21, p=0.01). Overall 24-hour transfusion requirements were significantly decreased within the WB:RBC≥1 cohort (12.1 units vs. 24.4 units, p<0.01). Conclusion: Preferential WB transfusion compared with a balanced transfusion strategy during the early resuscitative period was associated with a lower 4 and 24-hour mortality, as well as decreased 24-hour transfusion requirements, in trauma patients. Future prospective studies are warranted to determine the optimal use of WB in trauma. Level of evidence: Level III/therapeutic.

Halofuginone for non-hospitalized adult patients with COVID-19 a multicenter, randomized placebo-controlled phase 2 trial. The HALOS trial.

BACKGROUND: Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied. METHODS: We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization. RESULTS: From September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days. CONCLUSIONS: Among non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.

Feasibility and acceptability of the use of flash glucose monitoring encountered by Indigenous Australians with type 2 diabetes mellitus: initial experiences from a pilot study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is highly prevalent within the Indigenous Australian community. Novel glucose monitoring technology offers an accurate approach to glycaemic management, providing real-time information on glucose levels and trends. The acceptability and feasibilility of this technology in Indigenous Australians with T2DM has not been investigated. OBJECTIVE: This feasibility phenomenological study aims to understand the experiences of Indigenous Australians with T2DM using flash glucose monitoring (FGM). METHODS: Indigenous Australians with T2DM receiving injectable therapy (n = 8) who used FGM (Abbott Freestyle Libre) for 6-months, as part of a clinical trial, participated in semi-structured interviews. Thematic analysis of the interviews was performed using NVivo12 Plus qualitative data analysis software (QSR International). RESULTS: Six major themes emerged: 1) FGM was highly acceptable to the individual; 2) FGM's convenience was its biggest benefit; 3) data from FGM was a tool to modify lifestyle choices; 4) FGM needed to be complemented with health professional support; 5) FGM can be a tool to engage communities in diabetes management; and 6) cost of the device is a barrier to future use. CONCLUSIONS: Indigenous Australians with T2DM had positive experiences with FGM. This study highlights future steps to ensure likelihood of FGM is acceptable and effective within the wider Indigenous Australian community.

Associations between rapid auditory processing of speech sounds and specific verbal communication skills in autism.

Introduction: The ability to rapidly process speech sounds is integral not only for processing other's speech, but also for auditory processing of one's own speech, which allows for maintenance of speech accuracy. Deficits in rapid auditory processing have been demonstrated in autistic individuals, particularly those with language impairment. We examined rapid auditory processing for speech sounds in relation to performance on a battery of verbal communication measures to determine which aspects of verbal communication were associated with cortical auditory processing in a sample of individuals with autism. Methods: Participants were 57 children and adolescents (40 male and 17 female) ages 5-18 who were diagnosed with an Autism Spectrum Disorder (ASD). Rapid auditory processing of speech sounds was measured via a magnetoencephalographic (MEG) index of the quality of the auditory evoked response to the second of two differing speech sounds ("Ga" / "Da") presented in rapid succession. Verbal communication abilities were assessed on standardized clinical measures of overall expressive and receptive language, vocabulary, articulation, and phonological processing. Associations between cortical measures of left- and right-hemisphere rapid auditory processing and verbal communication measures were examined. Results: Rapid auditory processing of speech sounds was significantly associated with speech articulation bilaterally (r = 0.463, p = 0.001 for left hemisphere and r = 0.328, p = 0.020 for right hemisphere). In addition, rapid auditory processing in the left hemisphere was significantly associated with overall expressive language abilities (r = 0.354, p = 0.013); expressive (r = 0.384, p = 0.005) vocabulary; and phonological memory (r = 0.325, p = 0.024). Phonological memory was found to mediate the relationship between rapid cortical processing and receptive language. Discussion: These results demonstrate that impaired rapid auditory processing for speech sounds is associated with dysfunction in verbal communication in ASD. The data also indicate that intact rapid auditory processing may be necessary for even basic communication skills that support speech production, such as phonological memory and articulatory control.

17q25.3 copy number changes: association with neurodevelopmental disorders and cardiac malformation.

Copy number variants (CNVs) have been identified as common genomic variants that play a significant role in inter-individual variability. Conversely, rare recurrent CNVs have been found to be causal for many disorders with well-established genotype-phenotype relationships. However, the phenotypic implications of rare non-recurrent CNVs remain poorly understood. Herein, we re-investigated 18,542 cases reported from chromosomal microarray at Greenwood Genetic Center from 2010 to 2022 and identified 15 cases with CNVs involving the 17q25.3 region. We report the detailed clinical features of these subjects, and compare with the cases reported in the literature to determine genotype-phenotype correlations for a subset of genes in this region. The CNVs in the 17q25.3 region were found to be rare events, with a prevalence of 0.08% (15/18542) observed in our cohort. The CNVs were dispersed across the entire 17q25.3 region with variable breakpoints and no smallest region of overlap. The subjects presented with a wide range of clinical features, with neurodevelopmental disorders (autism spectrum disorder, intellectual disability, developmental delay) being the most common features (80%), then expressive language disorder (33%), and finally cardiovascular malformations (26%). The association of CNVs involving the critical gene-rich region of 17q25.3 with neurodevelopmental disorders and cardiac malformation, implicates several genes as plausible drivers for these events.

Language Abilities are Associated with Both Verbal and Nonverbal Intelligence in Children on the Autism Spectrum.

Intellectual abilities factor into levels of functioning used to characterize autism. Language difficulties are highly prevalent in autism and may impact performance on measures of intellectual abilities. As such, nonverbal tests are often prioritized in classifying intelligence in those with language difficulties and autism. However, the relationship between language abilities and intellectual performance is not well characterized, and the superiority of tests with nonverbal instructions is not well established. The current study evaluates verbal and nonverbal intellectual abilities in the context of language abilities in autism and the potential benefit of tests with nonverbal instructions. Participants were 55 children and adolescents on the autism spectrum who underwent a neuropsychological evaluation as part of a study examining language functioning in autism. Correlation analyses were performed to examine relations between expressive and receptive language abilities. Language abilities (CELF-4) were significantly correlated with all measures of both verbal (WISC-IV VCI) and nonverbal intelligence scores (WISC-IV PRI and Leiter-R). There were no significant differences between nonverbal intelligence measures with verbal or nonverbal instructions. We further discuss the role of assessment of language abilities in interpreting results of intelligence testing in populations with higher prevalence of language difficulties.

Continuity of care for patients with dementia during COVID-19 pandemic: flexibility and integration between in-person and remote visits.

Introduction: During the pandemic, the Cognitive Disorders Unit of San Raffaele Hospital (Milan, Italy) offered patients the opportunity to undergo neuropsychological evaluations and cognitive training through telemedicine. Method: We conducted an investigation to assess how patients responded to this option and to determine if telemedicine could ensure continuity of care. Results: Between October 2019 and May 2022, a total of 5,768 telemedicine appointments and 8,190 in-person outpatient appointments were conducted, resulting in an increase in the rate of telemedicine activity from 16.81% in January 2020 to 23.21% in May 2022. Peaks in telemedicine activity reached 85.64% in May 2020 and 83.65% in February 2021, both representing a significant portion of the total activity. Interestingly, there was a notable positive correlation between telemedicine activity and the worsening of the Italian pandemic (r = 0.433, p = 0.027). Discussion: During the peaks of contagion, the total number of visits remained stable, highlighting that telemedicine effectively served as a valuable and efficient tool to ensure continuity of care for vulnerable patients. This was evident from the integration of remote visits with in-person appointments.

The Use and Ethics of Digital Twins in Medicine.

Digital Health Technologies (DHTs) are currently the subject of much debate both in terms of their technological frontiers as well as their ethical, legal and societal implications (ELSI). Regulation of such technologies as medical devices currently lacks behind their level of adoption. Digital Twins are the next evolution step of such DHTs and provide an opportunity to anticipate and act on ELSI before adoption again leaps before the necessary review. This paper introduces the concept and use cases of digital twins in medicine, then frames the debate through the lens of related technologies, machine learning and personalized medicine, and maps ethical challenges stemming from those. Finally, we lay out how digital twins may change and challenge the future practice of medicine.

Small Nucleolar Derived RNAs as Regulators of Human Cancer.

In the past decade, RNA fragments derived from full-length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally via association with the RNA-induced silencing complex (RISC). In this review, we have summarized the literature connecting sdRNAs to cancer gene regulation. SdRNAs possess miRNA-like functions and are able to fill the role of tumor-suppressing or tumor-promoting RNAs in a tissue context-dependent manner. Indeed, there are many miRNAs that are actually derived from snoRNA transcripts, meaning that they are truly sdRNAs and as such are included in this review. As sdRNAs are frequently discarded from ncRNA analyses, we emphasize that sdRNAs are functionally relevant gene regulators and likely represent an overlooked subclass of miRNAs. Based on the evidence provided by the papers reviewed here, we propose that sdRNAs deserve more extensive study to better understand their underlying biology and to identify previously overlooked biomarkers and therapeutic targets for a multitude of human cancers.

Exploring how pregnant women in a remote northern community select a delivery location.

OBJECTIVE: To explore the perspectives and preferences of pregnant women receiving prenatal care in a rural community regarding delivery location. DESIGN: Exploratory qualitative research project. SETTING: The La Ronge Medical Clinic in northern Saskatchewan. PARTICIPANTS: Pregnant women of any parity aged 18 years or older who attended the clinic for prenatal care from March 1, 2018, to March 31, 2019, were invited to participate. The closest obstetric and surgical services are 240 km away. METHODS: This project was undertaken using semistructured interviews. The interviews were audiorecorded, transcribed, and analyzed using an inductive thematic analysis, taking into consideration both saturation and analyst triangulation. The investigators and researchers on this project were family medicine residents and faculty in a remote medical clinic. MAIN FINDINGS: The factors that played a substantial role in influencing the patients' decisions regarding delivery location included access to medical services, proximity to home community, perceptions of medical care providers, and some unique features of local hospitals. The participants largely believed they maintained their autonomy in selecting their preferred delivery location while seeking input from their prenatal care providers and families. CONCLUSION: Pregnant women in this rural community consider many factors when deciding on their delivery location. These findings can be taken into consideration by physicians when discussing with their rural patients the risks and benefits of delivery in both rural and urban centres. Barriers to local delivery should be addressed, while maintaining a woman's autonomy to choose where she gives birth.

The use of artificial intelligence applications in medicine and the standard required for healthcare provider-patient briefings-an exploratory study.

Introduction: Digital Health Technologies (DHTs) are currently being funneled through legacy regulatory processes that are not adapted to the unique particularities of this new technology class. In the absence of adequate regulation of DHTs, the briefing of a patient by their healthcare provider (HCP) as a component of informed consent can present the last line of defense before potentially harmful technologies are employed on a patient. Methods: This exploratory study utilizes a case vignette of a machine learning-based technology for the diagnosis of ischemic heart disease that is presented to a group of medical students, physicians, and bioethicists. What constitutes the necessary standard and content of the HCP-patient briefings is explored using a survey (N = 34). Whether participants actually provide a sufficient HCP-patient briefing is evaluated based on audio recordings. Results and Conclusions: We find that participants deem artificial intelligence use in medical context should be declared to patients and argue that the explanation should currently follow the standard required of other experimental procedures. Further, since our study provides indications that implementation of HCP-patient briefings lacks behind the identified standard, opportunities for incorporation of training on the use of DHTs into medical curricula and continuous training schedules should be considered.

Creation of a Student-Run Medical Education Podcast: Tutorial.

BACKGROUND: Podcasting has become a popular medium for medical education content. Educators and trainees of all levels are turning to podcasts for high-quality, asynchronous content. Although numerous medical education podcasts have emerged in recent years, few student-run podcasts exist. Student-run podcasts are a novel approach to supporting medical students. Near-peer mentoring has been shown to promote medical students' personal and professional identity formation. Student-run podcasts offer a new medium for delivering near-peer advice to medical students in an enduring and accessible manner. OBJECTIVE: This paper describes the creation of the UnsCripted Medicine Podcast-a student-run medical education podcast produced at the University of Cincinnati College of Medicine. METHODS: The planning and preparatory phases spanned 6 months. Defining a target audience and establishing a podcast mission were key first steps. Efforts were directed toward securing funding; obtaining necessary equipment; and navigating the technical considerations of recording, editing, and publishing a podcast. In order to ensure that high professionalism standards were met, key partnerships were created with faculty from the College of Medicine. RESULTS: The UnsCripted Medicine Podcast published 53 episodes in its first 2 years. The number of episodes released per month ranges from 0 to 5, with a mean of 2.0 episodes. The podcast has a Twitter account with 217 followers. The number of listeners who subscribed to the podcast via Apple Podcasts grew to 86 in the first year and then to 218 in the second year. The show has an average rating of 4.8 (out of 5) on Apple Podcasts, which is based on 24 ratings. The podcast has hosted 70 unique guests, including medical students, resident physicians, attending physicians, nurses, physicians' family members, graduate medical education leadership, and educators. CONCLUSIONS: Medical student-run podcasts are a novel approach to supporting medical students and fostering professional identity formation. Podcasts are widely available and convenient for listeners. Additionally, podcast creators can publish content with lower barriers of entry compared to those of other forms of published content. Medical schools should consider supporting student podcast initiatives to allow for near-peer mentoring, augment the community, facilitate professional identity formation, and prepare the rising physician workforce for the technological frontier of medical education and practice.

Complement testing in the clinical laboratory.

The complement system is the human's first line of defense against microbial pathogens because of its important housekeeping and infection/inflammation roles. It is composed of a series of soluble and cell-bound proteins that are activated in a cascade effect, similar to the coagulation pathways. There are different pattern recognizing molecules that activate the complement system in response to stimuli or threats, acting through three initiation pathways: classical, lectin, and alternative. All three activation pathways converge at the C3 component and share the terminal pathway. The main outputs of the complement system action are lytic killing of microbes, the release of pro-inflammatory anaphylatoxins, and opsonization of targets. Laboratory testing is relevant in the setting of suspected complement deficiencies, as well as in the emerging number of diseases related to dysregulation (over-activation) of complement. Most common assays measure complement lytic activity and the different complement component concentrations. Specialized testing includes the evaluation of autoantibodies against complement components, activation fragments, and genetic studies. In this review, we cover laboratory testing for complement and the conditions with complement involvement, as well as current challenges in the field.

Use of continuous intercostal nerve blockade is associated with improved outcomes in patients with multiple rib fractures.

BACKGROUND: Rib fractures are common among trauma patients and may result in significant morbidity and mortality. There are numerous treatment options, but ideal management is unclear. Delivery of local anesthetic via an analgesia catheter for continuous intercostal nerve blockade offers an attractive potential option for management of patients with rib fractures. METHODS: We performed a single-center, retrospective case-control analysis of trauma patients with multiple rib fractures from 2016 to 2018, comparing patients managed with continuous intercostal nerve blockade with standard care. Matching was performed in a 2:1 ratio by Injury Severity Score, age, and gender. Respiratory morbidity potentially secondary to rib fractures, including unplanned intubation, failure of extubation, need for tracheostomy, pneumonia, or mortality, were all identified and included. Potential complications due to catheter insertion were identified to be recorded. The primary outcome of interest was 30-day hospital-free days. RESULTS: Nine hundred and thirty-three patients were eligible for analysis, with 48 managed using intercostal blockade compared with 96 matching controls. No complications of intercostal blockade were identified during the study period. Controls demonstrated fewer rib fractures (6.60±4.11 vs. 9.3±3.73, p=0.001) and fewer flail segments (0.8±1.76 vs. 2.0±2.94, p=0.02). Those managed with intercostal blockade demonstrated significantly more 30-day hospital-free days (15.9±6.43 vs. 13.2±9.94, p=0.048), less incidence of pneumonia (4.2% vs. 16.7%, p=0.03), and lower hospital mortality (2.1% vs. 13.5%, p=0.03). When adjusting for number of rib fractures and number of flail segments, use of continuous intercostal nerve blockade was significantly associated with lower hospital mortality (OR 0.10; 95% CI 0.01 to 0.91), pneumonia (OR 0.15; 95% CI 0.03 to 0.76), or need for tracheostomy (OR 0.23; 95% CI 0.06 to 0.83). DISCUSSION: The addition of continuous intercostal nerve blockade may help to improve outcomes in patients with multiple rib fractures compared with standard care alone. LEVEL OF EVIDENCE: Therapeutic/care management; level IV.