Wilderness Medical Society Clinical Practice Guidelines for the Treatment of Acute Pain in Austere Environments: 2024 Update.

The Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the management of pain in austere environments. Recommendations are graded based on the quality of supporting evidence as defined by criteria put forth by the American College of Chest Physicians. This is an update of the 2014 version of the "WMS Practice Guidelines for the Treatment of Acute Pain in Remote Environments" published in Wilderness & Environmental Medicine 2014; 25:41-49.

Tobacco smoking and nicotine vaping in persons with first episode psychosis.

Tobacco smoking is highly prevalent in persons with psychosis and is the leading cause of preventable mortality in this population. Less is known about tobacco smoking in persons with first episode psychosis (FEP) and there have been no estimates about the prevalence of nicotine vaping in FEP. This study reports rates of tobacco smoking and nicotine vaping in young people with FEP enrolled in Coordinated Specialty Care programs in Pennsylvania and Maryland. Using data collected from 2021 to 2023, we examined lifetime and recent smoking and vaping and compared smokers and vapers to nonusers on symptoms, functioning, and substance use. The sample included 445 participants aged 13-35 with recent psychosis onset. Assessments were collected by program staff. Overall, 28 % of participants engaged in either smoking or vaping within 30 days of the admission assessment. Smokers and vapers were disproportionately male, cannabis users, and had lower negative symptom severity than non-smokers. Vapers had higher role and social functioning. Both smoking and vaping were related to a longer time from psychosis onset to program enrollment. We compare these findings to previous studies and suggest steps for addressing smoking and vaping in this vulnerable population.

The Ethics of Risk Prediction for Psychosis and Suicide Attempt in Youth Mental Health.

OBJECTIVE: To identify potential clinical utility of polygenic risk scores (PRS) and exposomic risk scores (ERS) for psychosis and suicide attempt in youth and assess the ethical implications of these tools. STUDY DESIGN: We conducted a narrative literature review of emerging findings on PRS and ERS for suicide and psychosis as well as a literature review on the ethics of PRS. We discuss the ethical implications of the emerging findings for the clinical potential of PRS and ERS. RESULTS: Emerging evidence suggests that PRS and ERS may offer clinical utility in the relatively near future but that this utility will be limited to specific, narrow clinical questions, in contrast to the suggestion that population-level screening will have sweeping impact. Combining PRS and ERS might optimize prediction. This clinical utility would change the risk-benefit balance of PRS, and further empirical assessment of proposed risks would be necessary. Some concerns for PRS, such as those about counseling, privacy, and inequities, apply to ERS. ERS raise distinct ethical challenges as well, including some that involve informed consent and direct-to-consumer advertising. Both raise questions about the ethics of machine-learning/artificial intelligence approaches. CONCLUSIONS: Predictive analytics using PRS and ERS may soon play a role in youth mental health settings. Our findings help educate clinicians about potential capabilities, limitations, and ethical implications of these tools. We suggest that a broader discussion with the public is needed to avoid overenthusiasm and determine regulations and guidelines for use of predictive scores.

Use of SGLT2 Inhibitors Reduces Heart Failure and Hospitalization: A Multicenter, Real-World Evidence Study.

Background New research has produced evidence to support the use of diabetic drugs to prevent heart failure (HF). However, evidence of their effect in real-world clinical practice is limited. Objective The objective of this study is to establish whether real-world evidence supports clinical trial findings that use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) reduces rate of hospitalization and incidence of HF for patients with cardiovascular disease and type 2 diabetes. Methods This retrospective study used electronic medical records to compare rate of hospitalization and incidence of HF among 37,231 patients with cardiovascular disease and type 2 diabetes under treatment with SGLT2i, glucagon-like peptide-1 receptor agonist (GLP1-RA), both, or neither. Results Significant differences were found between medication class prescribed and number of hospitalizations (p < 0.0001) and incidence of HF (p < 0.0001). Post-hoc tests revealed reduced incidence of HF in the group treated with SGLT2i relative to GLP1-RA alone (p = 0.004) or neither of these key drugs (p < 0.001). No significant differences were observed between the group receiving both drug classes compared to SGLT2i alone. Discussion Results of this real-world analysis are consistent with clinical trial findings that SGLT2i therapy reduces incidence of HF. The findings also suggest the need for further points of research in demographic and socioeconomic status differences. Conclusion Real-world evidence supports clinical trial findings of SGLT2i reducing both incidence of HF and rate of hospitalization.

Moral expertise without moral elitism.

Skepticism about ethical expertise has grown common, raising concerns that bioethicists' roles are inappropriate or depend on something other than expertise in ethics. While these roles may depend on skills other than those of expertise, overlooking the role of expertise in ethics distorts our conception of moral advising. This paper argues that motivations to reject ethical expertise often stem from concerns about elitism: either an intellectualist elitism, where some privileged elite have supposedly special access in virtue of expertise in moral theory; or an authoritarian elitism, where our reliance on experts in ethics risks violation of autonomy and democracy. The paper sketches an anti-elitist conception of ethics expertise in bioethics as continuous with an anti-elitist conception of ethics expertise in common moral practice, undercutting the intellectualism, and then uses this anti-elitist conception to reject arguments that ethical expertise violates autonomy or democracy. An anti-elitist picture of ethical expertise both renders it consistent with our general moral practice and allows us to resist skeptical concerns.

Addressing Substance Use in Psychiatric Care: An Old Problem With Renewed Urgency.

Patients, clinicians, researchers, and policy makers have long called for greater integration of services for people with co-occurring mental and substance use disorders. Decades later, these services remain fragmented in psychiatry across much of the United States. Mounting deaths from drug-related overdoses call for renewed focus on bringing substance use into the center of psychiatric services. This Open Forum explores factors within the field of psychiatry, including insufficient training related to substance use, prevalent stigma surrounding substance use, and limited availability of co-occurring disorder specialists, that reinforce this divide and offers solutions for better addressing substance use disorders in psychiatric care.

Religious pluralism and the ethics of healthcare.

Democratic societies that separate church and state face major challenges in accommodating religious convictions. This applies especially to determining healthcare policies. Building on our prior work on the demands and limits of religious accommodation in democratic societies, we propose a set of ethical standards that can guide societies in meeting this challenge. In applying and defending these standards, we explore three topics: vaccine resistance, abortion, and concerns about rights to healthcare. We clarify these and other issues of religious accommodation and propose ethical standards for approaching these and other problems.

Novel ethical and policy issues in psychiatric uses of psychedelic substances.

Classic psychedelics and related substances have shown promising initial research results. However, they raise a number of relatively novel ethical and policy challenges in light of their psychoactive properties, their emergence from the unregulated "underground" settings in which they have been used, their rapid commercialization, and the means and speed with which they are moving from Schedule 1 status to legalized use. All of these issues are affected by the current limits to the evidence base on use of psychedelics. Here we survey these novel challenges, illustrating the issues raised regarding each, and offering suggestions for how to address them.

Atomistic simulation framework for molten salt vapor-liquid equilibrium prediction and its application to NaCl.

Knowledge of the vapor-liquid equilibrium (VLE) properties of molten salts is important in the design of thermal energy storage systems for solar power and nuclear energy production applications. The high temperatures involved make their experimental determination problematic, and the development of both macroscopic thermodynamic correlations and predictive molecular-based methodologies are complicated by the requirement to appropriately incorporate the chemically reacting vapor-phase species. We derive a general thermodynamic-based atomistic simulation framework for molten salt VLE prediction and show its application to NaCl. Its input quantities are temperature-dependent ideal-gas free energy data for the vapor phase reactions and density and residual chemical potential data for the liquid. If these are not available experimentally, the former may be predicted using standard electronic structure software, and the latter may be predicted by means of classical atomistic simulation methodology. The framework predicts the temperature dependence of vapor pressure, coexisting phase densities, vapor phase composition, and vaporization enthalpy. It also predicts the concentrations of vapor phase species present in minor amounts (such as the free ions), quantities that are extremely difficult to measure experimentally. We furthermore use the results to obtain an approximation to the complete VLE binodal dome and the critical properties. We verify the framework for molten NaCl, for which experimentally based density and chemical potential data are available in the literature. We then apply it to the analysis of NaCl simulation data for two commonly used atomistic force fields. The framework can be readily extended to molten salt mixtures and to ionic liquids.

Rapprochement and Reform: Overcoming Factionalism in Policy Making for Serious Mental Illness.

This article traces the history of factionalism in policy making and advocacy for persons with serious mental illness from deinstitutionalization to the present. The authors draw on deliberative democratic theory to illustrate how factionalist advocacy causes advocates and policy makers to fail in their duties to represent and develop policy in support of people with serious mental illness. The authors discuss how this factionalism has bred distrust and undermined efforts to address the needs of people with serious mental illness. They propose the formation of a Public Mental Health Policy Commission, guided by principles of deliberative democracy, to overcome factionalism and to improve policy making to meet the needs of people with serious mental illness. The commission must include a diverse array of stakeholders, especially individuals with lived experience of serious mental illness.

Force-Field-Based Computational Study of the Thermodynamics of a Large Set of Aqueous Alkanolamine Solvents for Post-Combustion CO2 Capture.

The ability to predict the thermodynamic properties of amine species in CO2-loaded aqueous solutions, including their deprotonation (pKa) and carbamate to bicarbonate reversion (pKc) equilibrium constants and their corresponding standard reaction enthalpies, is of critical importance for the design of improved carbon capture solvents. In this study, we used isocoulombic forms of both reactions to determine these quantities for a large set of aqueous alkanolamine solvent systems. Our hybrid approach involves using classical molecular dynamics simulations with the general amber force field (GAFF) and semi-empirical AM1-BCC charges (GAFF/AM1-BCC) in the solution phase, combined with high-level composite quantum chemical ideal-gas calculations. We first determined a new force field (FF) for the hydronium ion (H3O+) by matching to the single experimental pKa data point for the well-known monoethanolamine system at 298.15 K. We then used this FF to predict the pKa values for 76 other amines at 298.15 K and for all 77 amines at elevated temperatures. Additionally, we indirectly relate the H3O+ hydration free energy to that of H+ and provide expressions for intrinsic hydration free energy and enthalpy of the proton. Using the derived H3O+ FF, we predicted the pKa values of a diverse set of alkanolamines with an overall average absolute deviation of less than 0.72 pKa units. Furthermore, the derived H3O+ FF is able to predict the protonation enthalpy of these amines when used with the GAFF. We also predicted the carbamate reversion constants of the primary and secondary amine species in the data set and their corresponding standard heats of reaction, which we compared with the scarcely available experimental data, which are often subject to significant uncertainty. Finally, we also described the influence of electronic and steric effects of different molecular fragments/groups on the stabilities of the carbamates.

Religious Accommodation in Bioethics and the Practice of Medicine.

Debates about the ethics of health care and medical research in contemporary pluralistic democracies often arise partly from competing religious and secular values. Such disagreements raise challenges of balancing claims of religious liberty with claims to equal treatment in health care. This paper proposes several mid-level principles to help in framing sound policies for resolving such disputes. We develop and illustrate these principles, exploring their application to conscientious objection by religious providers and religious institutions, accommodation of religious priorities in biomedical research, and treatment of patients' religious views in doctor-patient encounters. Given that no sound set of guiding principles yields precise solutions for every policy dispute, we explore how morally sound democracies might deliberatively resolve such policy issues, following our proposed principles. Taken together and carefully interpreted, these principles may help in guiding difficult decision making in the indefinitely large realm where government, medical providers, and patients encounter problems concerning religion and medicine.

Uterotonic agents for first-line treatment of postpartum haemorrhage: a network meta-analysis.

BACKGROUND: Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH. OBJECTIVES: To identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies. SELECTION CRITERIA: All randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Seven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty). AUTHORS' CONCLUSIONS: The available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.