Efficacy and Tolerability of Intranasal Midazolam Administration for Antiseizure Treatment in Adults: A Systematic Review.

OBJECTIVE: The objective of this study was to assess the efficacy and tolerability of intranasal midazolam (in-MDZ) administration for antiseizure treatment in adults. METHODS: Embase and Medline literature databases were searched. We included randomized trials and cohort studies (excluding case series) of adult patients (≥ 18 years of age) examining in-MDZ administration for epilepsy, epileptic seizures, or status epilepticus published in English between 1985 and 2022. Studies were screened for eligibility based on predefined criteria. The primary outcome was the efficacy of in-MDZ administration, and the secondary outcome was its tolerability. Extracted data included study design, patient characteristics, intervention details, and outcomes. Risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: A total of 12 studies with 929 individuals treated with in-MDZ were included. Most studies were retrospective, with their number increasing over time. Administered in-MDZ doses ranged from 2.5 to 20 mg per single dose. The mean proportion of successful seizure termination after first in-MDZ administration was 72.7% (standard deviation [SD] 18%), and the proportion of seizure recurrence or persistent seizures ranged from 61 to 75%. Most frequent adverse reactions to in-MDZ were dizziness (mean 23.5% [SD 38.6%]), confusion (one study; 17.4%), local irritation (mean 16.6% [SD 9.6%]), and sedation (mean 12.7% [SD 9.7%]). CONCLUSIONS: Administration of in-MDZ seems promising for the treatment of prolonged epileptic seizures and seizure clusters in adults. Limited evidence suggests that intranasal administration is safe. Further research is warranted because of the heterogeneity of cohorts, the variation in dosages, and the lack of uniformity in defining successful seizure termination.

Performance of large language models on advocating the management of meningitis: a comparative qualitative study.

OBJECTIVES: We aimed to examine the adherence of large language models (LLMs) to bacterial meningitis guidelines using a hypothetical medical case, highlighting their utility and limitations in healthcare. METHODS: A simulated clinical scenario of a patient with bacterial meningitis secondary to mastoiditis was presented in three independent sessions to seven publicly accessible LLMs (Bard, Bing, Claude-2, GTP-3.5, GTP-4, Llama, PaLM). Responses were evaluated for adherence to good clinical practice and two international meningitis guidelines. RESULTS: A central nervous system infection was identified in 90% of LLM sessions. All recommended imaging, while 81% suggested lumbar puncture. Blood cultures and specific mastoiditis work-up were proposed in only 62% and 38% sessions, respectively. Only 38% of sessions provided the correct empirical antibiotic treatment, while antiviral treatment and dexamethasone were advised in 33% and 24%, respectively. Misleading statements were generated in 52%. No significant correlation was found between LLMs' text length and performance (r=0.29, p=0.20). Among all LLMs, GTP-4 demonstrated the best performance. DISCUSSION: Latest LLMs provide valuable advice on differential diagnosis and diagnostic procedures but significantly vary in treatment-specific information for bacterial meningitis when introduced to a realistic clinical scenario. Misleading statements were common, with performance differences attributed to each LLM's unique algorithm rather than output length. CONCLUSIONS: Users must be aware of such limitations and performance variability when considering LLMs as a support tool for medical decision-making. Further research is needed to refine these models' comprehension of complex medical scenarios and their ability to provide reliable information.

Translation of patients' advance directives in intensive care units: are we there yet?

OBJECTIVES: This review examined studies regarding the implementation and translation of patients' advance directives (AD) in intensive care units (ICUs), focusing on practical difficulties and obstacles. METHODS: The digital PubMed and Medline databases were screened using predefined keywords to identify relevant prospective and retrospective studies published until 2022. RESULTS: Seventeen studies from the United States, Europe, and South Africa (including 149,413 patients and 1210 healthcare professionals) were identified. The highest prevalence of ADs was described in a prospective study in North America (49%), followed by Central Europe (13%), Asia (4%), Australia and New Zealand (4%), Latin America (3%), and Northern and Southern Europe (2.6%). While four retrospective studies reported limited effects of ADs, four retrospective studies, one survey and one systematic review indicated significant effects on provision of intensive care, higher rates of do-not-resuscitate orders, and care withholding in patients with ADs. Four of these studies showed shorter ICU stays, and lower treatment costs in patients with ADs. One prospective and two retrospective studies reported issues with loss, delayed or no transmission of ADs. One survey revealed that 91% of healthcare workers did not regularly check for ADs. Two retrospective studies and two survey revealed that the implementation of directives is further challenged by issues with their applicability, phrasing, and compliance by the critical care team and family members. CONCLUSIONS: Although ADs may improve intensive- and end-of-life care, insufficient knowledge, lack of awareness, poor communication between healthcare providers and patients or surrogates, lack of standardization of directives, as well as ethical and legal concerns challenge their implementation.

Sex-related differences in adult patients with status epilepticus: a seven-year two-center observation.

BACKGROUND: Conflicting findings exist regarding the influence of sex on the development, treatment, course, and outcome of status epilepticus (SE). Our study aimed to investigate sex-related disparities in adult SE patients, focusing on treatment, disease course, and outcome at two Swiss academic medical centers. METHODS: In this retrospective study, patients treated for SE at two Swiss academic care centers from Basel and Geneva from 2015 to 2021 were included. Primary outcomes were return to premorbid neurologic function, death during hospital stay and at 30 days. Secondary outcomes included characteristics of treatment and disease course. Associations with primary and secondary outcomes were assessed using multivariable logistic regression. Analysis using propensity score matching was performed to account for the imbalances regarding age between men and women. RESULTS: Among 762 SE patients, 45.9% were women. No sex-related differences were found between men and women, except for older age and lower frequency of intracranial hemorrhages in women. Compared to men, women had a higher median age (70 vs. 66, p = 0.003), had focal nonconvulsive SE without coma more (34.9% vs. 25.5%; p = 0.005) and SE with motor symptoms less often (52.3% vs. 63.6%, p = 0.002). With longer SE duration (1 day vs. 0.5 days, p = 0.011) and a similar proportion of refractory SE compared to men (36.9% vs. 36.4%, p = 0.898), women were anesthetized and mechanically ventilated less often (30.6% vs. 42%, p = 0.001). Age was associated with all primary outcomes in the unmatched multivariable analyses, but not female sex. In contrast, propensity score-matched multivariable analyses revealed decreased odds for return to premorbid neurologic function for women independent of potential confounders. At hospital discharge, women were sent home less (29.7% vs. 43.7%, p < 0.001) and to nursing homes more often (17.1% vs. 10.0%, p = 0.004). CONCLUSIONS: This study identified sex-related disparities in the clinical features, treatment modalities, and outcome of adult patients with SE with women being at a disadvantage, implying that sex-based factors must be considered when formulating strategies for managing SE and forecasting outcomes.

First-Response ABCDE Management of Status Epilepticus: A Prospective High-Fidelity Simulation Study.

Respiratory infections following status epilepticus (SE) are frequent, and associated with higher mortality, prolonged ICU stay, and higher rates of refractory SE. Lack of airway protection may contribute to respiratory infectious complications. This study investigates the order and frequency of physicians treating a simulated SE following a systematic Airways-Breathing-Circulation-Disability-Exposure (ABCDE) approach, identifies risk factors for non-adherence, and analyzes the compliance of an ABCDE guided approach to SE with current guidelines. We conducted a prospective single-blinded high-fidelity trial at a Swiss academic simulator training center. Physicians of different affiliations were confronted with a simulated SE. Physicians (n = 74) recognized SE and performed a median of four of the five ABCDE checks (interquartile range 3-4). Thereof, 5% performed a complete assessment. Airways were checked within the recommended timeframe in 46%, breathing in 66%, circulation in 92%, and disability in 96%. Head-to-toe (exposure) examination was performed in 15%. Airways were protected in a timely manner in 14%, oxygen supplied in 69%, and antiseizure drugs (ASDs) administered in 99%. Participants' neurologic affiliation was associated with performance of fewer checks (regression coefficient -0.49; p = 0.015). We conclude that adherence to the ABCDE approach in a simulated SE was infrequent, but, if followed, resulted in adherence to treatment steps and more frequent protection of airways.

Prolonged mechanical ventilation in patients with terminated status epilepticus and outcome: An observational cohort study.

OBJECTIVE: Classical clinical characteristics associated with successful or unsuccessful extubation are unreliable in neurocritically ill patients, and attempts to predict successful extubation in this context have failed. We aimed to investigate the frequency of mechanical ventilation (MV) in adult patients in status epilepticus (SE) and its clinical associations, to identify predictors at SE onset of prolonged postictal MV, and to determine the associated outcomes with prolonged MV. METHODS: From 2012 to 2018, SE patients treated in intensive care units at a Swiss academic care center were included. Multivariable Poisson regression adjusting for potential confounders, such as continuously administered anesthetics, was performed to identify risks for postictal MV for >24 h after SE and its association with no return to neurologic function and death. Linear regression was performed to identify correlations between the durations of administered specific anesthetics and postictal MV. RESULTS: Of 262 patients, 42% were ventilated, with 24% being on ventilators for >24 h after SE. Patients with prolonged postictal MV were extubated at a median of 7 days, with 56% not being extubated on the day of successful weaning from MV because of altered consciousness and/or lack of airway-protective reflexes. After extubation, noninvasive ventilation and reintubation were rarely needed. Prolonged postictal MV was associated with increased risk for death independent of potential confounders, including fatal etiology of SE, age, SE severity, and use of anesthetics (relative risk for every additional day = 2.7, p = .024). At SE onset, decreased consciousness and presumed fatal etiology predicted prolonged postictal MV. Anesthetics were associated with prolonged MV, but linear regression could not identify significant correlations. SIGNIFICANCE: Our data reveal that prolonged postictal MV is frequent and an independent risk factor for death. Extubation is often delayed for days despite sufficient weaning from the ventilator and altered airway-protective reflexes in only few patients. Studies need to investigate whether more rigorous extubation strategies improve outcome.

'Problem patients and physicians' failures': What it means for doctors to counsel vaccine hesitant patients in Switzerland.

This article reports on our qualitative inquiry into the meanings biomedically trained doctors in Switzerland attach to treating vaccine hesitant (VH) and underimmunized patients. With support from social science literature on 'good' and 'bad' patients and doctors, we explore how both doctors and patients cross the boundaries of these conceptual categories in situations involving vaccine hesitancy and underimmunization. The doctors we interviewed (N = 20) and observed (N = 16 observations, subsample of 6 doctors from the interview sample) described how they screened, measured, and diagnosed patients' levels of vaccine hesitancy. Our results emphasize the meanings doctors associated with counseling hesitant patients, especially while managing their own professional responsibilities, legitimacy, and reputations among colleagues and patients. Doctors' discourses constructed the figure of 'problem patients,' characterized through their (potential) non-adherence to vaccination recommendations, desire for lengthy consultations and individualized counseling, and dogmatic ideologies running contra to biomedicine. Discussions around the dilemmas faced by doctors in vaccination consultations brings to the fore several key, yet underdiscussed, paradoxes concerning VH, patient-doctor relationships, and the constructs of 'good'/'bad' doctors and patients. These paradoxes revolve around expectations in Western societies for 'good' patients to be autonomous health-information seekers and active participants in clinical encounters, which research shows to be the case for many VH and underimmunizing individuals. However, in the eyes of many vaccination advocates and proponents of biomedical approaches, VH patients become 'bad' patients thru their risk of non-adherence, which has implications for the population at large. In these consultations, doctors find themselves conflicted around the expectations to promote vaccination while, at the same time, being active listeners and good communicators with those who question their biomedical training and legitimacy. Understanding these paradoxes highlights the need to better support HCPs in addressing VH in clinical practice.

Determinants of vaccine hesitancy in Switzerland: study protocol of a mixed-methods national research programme.

INTRODUCTION: Vaccine hesitancy is a complex public health issue referring to concerns about the safety, efficacy or need for vaccination. Relatively little is known about vaccine hesitancy in Switzerland. This ongoing study (2017-2021) focuses on biomedical and complementary and alternative medicine (CAM) providers and their patients since healthcare professionals play important roles in vaccination decision-making. This national research programme seeks to assess the sociocultural determinants of vaccine hesitancy regarding childhood and human papillomavirus vaccines in Switzerland. We aim to provide a detailed characterisation of vaccine hesitancy, including CAM and biomedical perspectives, patient-provider interactions, and sociocultural factors, to establish the mediating effects of vaccine hesitancy on underimmunisation, and to design an intervention to improve vaccination communication and counselling among physicians, parents and adolescents. METHODS AND ANALYSIS: Our transdisciplinary team employs a sequential exploratory mixed-methods study design. We have established a network of more than 150 medical providers across Switzerland, including more than 40 CAM practitioners. For the qualitative component, we conduct interviews with parents, youth, and biomedical and CAM providers and observations of vaccination consultations and school vaccination information sessions. For the quantitative component, a sample of 1350 parents of young children and 722 young adults (15-26 years) and their medical providers respond to questionnaires. We measure vaccine hesitancy with the Parent Attitudes about Childhood Vaccines 15-item survey and review vaccination certificates to assess vaccination status. We administer additional questions based on findings from qualitative research, addressing communication with medical providers, vaccine information sources and perceptions of risk control vis-à-vis vaccine-preventable diseases. The questionnaires capture sociodemographics, political views, religion and spirituality, and moral foundations. ETHICS AND DISSEMINATION: The study was approved by the local ethics committee. The results will be published in peer-reviewed journals and disseminated to healthcare professionals, researchers and the public via conferences and public presentations.

"We treat humans, not herds!": A qualitative study of complementary and alternative medicine (CAM) providers' individualized approaches to vaccination in Switzerland.

Complementary and alternative medicine (CAM) providers' roles in parents' decision-making about vaccinations for their children have only recently begun receiving research attention, despite studies showing CAM to be used by 25-50% of the population in Western countries. This article examines how CAM practitioners discuss vaccinations with parents in Switzerland, with a focus on childhood vaccinations and human papillomavirus (HPV) vaccinations. We describe how the CAM providers we interviewed (N = 17) and observed during vaccination consultations (N = 18 observations with 5 providers) employed individualized approaches to vaccination. Triangulation of qualitative evidence from interviews and observations allowed us to analyze their discourses and descriptions of experiences (i.e. what they said) and their practices in situ (i.e. what they did). Evidence gathered shows that practitioners framed vaccination decisions as choices at individual and family levels rather than focusing on public health benefits and consequences. They articulated their perspectives in terms of personal clinical experiences and parents' wishes, concerns, and contexts. Such findings challenge recurring narratives depicting CAM providers as categorically anti-vaccination and suggest that approaches to address vaccine hesitancy in clinical practice could benefit from communication and relational approaches similar to those demonstrated by participants in this study. Such approaches include taking time to understand parents' wishes, involving them in vaccination decisions, and taking their concerns seriously.