Subtle variation in sepsis-III definitions markedly influences predictive performance within and across methods.

Early detection of sepsis is key to ensure timely clinical intervention. Since very few end-to-end pipelines are publicly available, fair comparisons between methodologies are difficult if not impossible. Progress is further limited by discrepancies in the reconstruction of sepsis onset time. This retrospective cohort study highlights the variation in performance of predictive models under three subtly different interpretations of sepsis onset from the sepsis-III definition and compares this against inter-model differences. The models are chosen to cover tree-based, deep learning, and survival analysis methods. Using the MIMIC-III database, between 867 and 2178 intensive care unit admissions with sepsis were identified, depending on the onset definition. We show that model performance can be more sensitive to differences in the definition of sepsis onset than to the model itself. Given a fixed sepsis definition, the best performing method had a gain of 1-5% in the area under the receiver operating characteristic (AUROC). However, the choice of onset time can cause a greater effect, with variation of 0-6% in AUROC. We illustrate that misleading conclusions can be drawn if models are compared without consideration of the sepsis definition used which emphasizes the need for a standardized definition for sepsis onset.

Antidepressants for the prevention of depression following first-episode psychosis (ADEPP): study protocol for a multi-centre, double-blind, randomised controlled trial.

BACKGROUND: Depressive episodes are common after first-episode psychosis (FEP), affecting more than 40% of people, adding to individual burden, poor outcomes, and healthcare costs. If the risks of developing depression were lower, this could have a beneficial effect on morbidity and mortality, as well as improving outcomes. Sertraline is a selective serotonin reuptake inhibitor and a common first-line medication for the treatment of depression in adults. It has been shown to be safe when co-prescribed with antipsychotic medication, and there is evidence that it is an effective treatment for depression in established schizophrenia. We present a protocol for a multi-centre, double-blind, randomised, placebo-controlled clinical trial called ADEPP that aims to investigate the efficacy and cost-effectiveness of sertraline in preventing depression after FEP. METHODS: The recruitment target is 452 participants between the ages of 18 and 65 years who are within 12 months of treatment initiation for FEP. Having provided informed consent, participants will be randomised to receive either 50 mg of sertraline daily or matched placebo for 6 months, in addition to treatment as usual. The primary outcome measure will be a comparison of the number of new cases of depression between the treatment and placebo arms over the 6-month intervention phase. Secondary outcomes include suicidal behaviour, anxiety, rates of relapse, functional outcome, quality of life, and resource use. DISCUSSION: The ADEPP trial will test whether the addition of sertraline following FEP is a clinically useful, acceptable, and cost-effective way of improving outcomes following FEP. TRIAL REGISTRATION: ISRCTN12682719 registration date 24/11/2020.

Altruism or self-interest in tomorrow's veterinarians? A metric conjoint experiment and cluster analysis.

Introduction: Altruism is considered a trait of veterinary and other health professionals, but the level of altruism in the veterinary profession is unknown. We designed a metric conjoint experiment to reveal other-orientation (an individual's caring concern for the wellbeing of others) and self-interest. We draw on the 'Theory of Other-Orientation', which states that individuals' decision-making heuristics can be impacted by their other-orientation independent of their self-interest. In patient-focused contexts, highly other-oriented or altruistic (veterinary) professionals may care too much for others and suffer immediate or cumulative financial and personal costs of such caring. At the same time, other-orientation can enhance job-related attitudes and outcomes, such as job satisfaction. Methods: In a metric conjoint experiment, Australian final-year veterinary, science, nursing, entrepreneurship, and engineering students rated eight job scenarios with orthogonally arranged high and low levels of three job characteristics (n = 586) to provide observed measures of other-orientation and self-interest. Results: A two-way MANOVA showed other-orientation or self-interest differed per discipline, but not gender. Veterinary (and engineering) respondents were less other-oriented than nursing respondents. Veterinary (and entrepreneurship) respondents were more self-interested than nursing respondents. K-Means cluster analysis confirmed four distinct profile groupings-altruistic/self-sacrificing, 'both other-self', self-interested and selfish-aligning with the discourse in the literature. Human nursing respondents stood out for the most members (50%) in the 'both other-self' profile compared to veterinary respondents (28%). Respondents of one of three veterinary schools stood out for the most members (19%) in the altruistic/self-sacrificing group. Discussion: Our metric conjoint experiment illustrates an alternative to 'self-report' items with Likert-scaled responses. Our finding of the 'both other-self' group adds to the literature, which considers that other-orientation and self-interest are separate constructs that are difficult to co-exist in individuals. This mix of traits is deemed helpful by organizational psychology scholars, for sustainability and wellbeing, especially for healthcare professionals involved in high-frequency and intense, patient-focused interactions. Our findings highlight the need for more research on the potential role of other-orientation and self-interest in veterinary school admissions processes, the hidden or taught curricula, job-related attitudes and beliefs, and wellbeing and professional sustainability in the veterinary sector.

Business Intentions of Australian Veterinary Students-My Business or Yours? A Cluster Analysis.

Little is known about veterinary entrepreneurial predisposition. Yet entrepreneurship and intrapreneurship (entrepreneurial behaviour of employees) foster business innovation and growth and support wealth creation and employment in both privately and corporately owned businesses which deliver contemporary veterinary services. We used responses from 515 final-year students in Australian entrepreneurship, nursing, and veterinary programs to capture entrepreneurial intention (EI), outcome expectations (OE-sb), entrepreneurial self-efficacy (ESE), and corporate/large organisation work intentions (CWIs). Veterinary respondents stood out for their high EI and high OE-sb, but low financial ESE and low CWI. Proportions of veterinary, entrepreneurship, and nursing respondents differed markedly across distinct cluster profiles representing entrepreneurial, intrapreneurial, both entrepreneurial and intrapreneurial, indifferent, and corporate employment intentions and attributes. Post hoc analysis revealed proportional cluster membership differences for respondents from different veterinary schools. Our findings raise questions regarding (1) the effectiveness of veterinary business curricula competencies which focus on expense management and (2) the implications of the mismatch of motivations and goals of new veterinary sector entrants whose low intent to work in a corporate environment is at odds with increasing corporate ownership of veterinary practices. To inform curricular change, we recommend further research to evaluate the relative impact of individual factors, admissions factors, and the formal or hidden curricula on entrepreneurial intention in veterinary final-year students.

Novel and emerging treatments for major depression.

Depression is common, costly, debilitating, and associated with increased risk of suicide. It is one of the leading global public health problems. Although existing available pharmacological treatments can be effective, their onset of action can take up to 6 weeks, side-effects are common, and recovery can require treatment with multiple different agents. Although psychosocial interventions might also be recommended, more effective treatments than those currently available are needed for people with moderate or severe depression. In the past 10 years, treatment trials have developed and tested many new targeted interventions. In this Review, we assess novel and emerging biological treatments for major depressive disorder, evaluate their putative brain and body mechanisms, and highlight how close each might be to clinical use.

Integrated rapid-cycle comparative effectiveness trials using flexible point of care randomisation in electronic health record systems.

Whilst the Randomised Controlled Trial remains the gold standard for deriving robust causal estimates of treatment efficacy, too often a traditional design proves prohibitively expensive or cumbersome when it comes to assessing questions regarding the comparative effectiveness of routinely used treatments. As a result, patients experience variation in practice as clinicians lack the evidence needed to personalise treatments effectively. This variation may be classified as unwarranted, where existing evidence is ignored, or legitimate where in the absence of evidence, clinicians rely on experience, expert opinion, and inferred principles from basic science to make decisions. We argue that within the right ethical and technological framework, legitimate variation can be transformed into a mechanism for evidence generation and learning. Learning Health Systems which harness existing variation in practice, represent a novel approach for generating evidence from everyday clinical practice. The development of these systems has gained traction due to the increased availability of modern Electronic Health Record Systems. However, despite their promise, overcoming hurdles to successfully integrating clinical trials within Learning Health Systems has proven challenging. This article describes the origins of integrated clinical trials and explores two main barriers to their further implementation - how best to obtain informed consent from patients to participate in routine comparative effectiveness research, and how to automate and integrate randomisation into a clinical workflow. Having described these barriers, we present a potential solution in the form of a research pipeline using a novel form of flexible point-of-care randomisation to allow clinicians and patients to participate in studies where there is clinical equipoise.

Inflammation and Brain Structure in Schizophrenia and Other Neuropsychiatric Disorders: A Mendelian Randomization Study.

Importance: Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction in a range of neuropsychiatric disorders. Objective: To investigate the relationship between inflammation and changes in brain structures in vivo and to explore a transcriptome-driven functional basis with relevance to mental illness. Design, Setting, and Participants: This study used multistage linked analyses, including mendelian randomization (MR), gene expression correlation, and connectivity analyses. A total of 20 688 participants in the UK Biobank, which includes clinical, genomic, and neuroimaging data, and 6 postmortem brains from neurotypical individuals in the Allen Human Brain Atlas (AHBA), including RNA microarray data. Data were extracted in February 2021 and analyzed between March and October 2021. Exposures: Genetic variants regulating levels and activity of circulating interleukin 1 (IL-1), IL-2, IL-6, C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were used as exposures in MR analyses. Main Outcomes and Measures: Brain imaging measures, including gray matter volume (GMV) and cortical thickness (CT), were used as outcomes. Associations were considered significant at a multiple testing-corrected threshold of P < 1.1 × 10-4. Differential gene expression in AHBA data was modeled in brain regions mapped to areas significant in MR analyses; genes were tested for biological and disease overrepresentation in annotation databases and for connectivity in protein-protein interaction networks. Results: Of 20 688 participants in the UK Biobank sample, 10 828 (52.3%) were female, and the mean (SD) age was 55.5 (7.5) years. In the UK Biobank sample, genetically predicted levels of IL-6 were associated with GMV in the middle temporal cortex (z score, 5.76; P = 8.39 × 10-9), inferior temporal (z score, 3.38; P = 7.20 × 10-5), fusiform (z score, 4.70; P = 2.60 × 10-7), and frontal (z score, -3.59; P = 3.30 × 10-5) cortex together with CT in the superior frontal region (z score, -5.11; P = 3.22 × 10-7). No significant associations were found for IL-1, IL-2, CRP, or BDNF after correction for multiple comparison. In the AHBA sample, 5 of 6 participants (83%) were male, and the mean (SD) age was 42.5 (13.4) years. Brain-wide coexpression analysis showed a highly interconnected network of genes preferentially expressed in the middle temporal gyrus (MTG), which further formed a highly connected protein-protein interaction network with IL-6 (enrichment test of expected vs observed network given the prevalence and degree of interactions in the STRING database: 43 nodes/30 edges observed vs 8 edges expected; mean node degree, 1.4; genome-wide significance, P = 4.54 × 10-9). MTG differentially expressed genes that were functionally enriched for biological processes in schizophrenia, autism spectrum disorder, and epilepsy. Conclusions and Relevance: In this study, genetically determined IL-6 was associated with brain structure and potentially affects areas implicated in developmental neuropsychiatric disorders, including schizophrenia and autism.

Persistent Childhood and Adolescent Anxiety and Risk for Psychosis: A Longitudinal Birth Cohort Study.

BACKGROUND: Persistent anxiety in childhood and adolescence could represent a novel treatment target for psychosis, potentially targeting activation of stress pathways and secondary nonresolving inflammatory response. Here, we examined the association between persistent anxiety through childhood and adolescence with individuals with psychotic experiences (PEs) or who met criteria for psychotic disorder (PD) at age 24 years. We also investigated whether C-reactive protein mediated any association. METHODS: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were available in 8242 children at age 8 years, 7658 at age 10 years, 6906 at age 13 years, and 3889 at age 24 years. The Development and Well-Being Assessment was administered to capture child and adolescent anxiety. We created a composite score of generalized anxiety at ages 8, 10, and 13. PEs and PD were assessed at age 24, derived from the Psychosis-like Symptoms Interview. The mean of C-reactive protein at ages 9 and 15 years was used as a mediator. RESULTS: Individuals with persistent high levels of anxiety were more likely to develop PEs (odds ratio 2.02, 95% CI 1.26-3.23, p = .003) and PD at age 24 (odds ratio 4.23, 95% CI 2.27-7.88, p < .001). The mean of C-reactive protein at ages 9 and 15 mediated the associations of persistent anxiety with PEs (bias-corrected estimate -0.001, p = .013) and PD (bias-corrected estimate 0.001, p = .003). CONCLUSIONS: Persistent high levels of anxiety through childhood and adolescence could be a risk factor for psychosis. Persistent anxiety is potentially related to subsequent psychosis via activation of stress hormones and nonresolving inflammation. These results contribute to the potential for preventive interventions in psychosis, with the novel target of early anxiety.

Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder.

OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. METHODS: In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. RESULTS: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. CONCLUSIONS: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.

Descriptors of Sepsis Using the Sepsis-3 Criteria: A Cohort Study in Critical Care Units Within the U.K. National Institute for Health Research Critical Care Health Informatics Collaborative.

OBJECTIVES: To describe the epidemiology of sepsis in critical care by applying the Sepsis-3 criteria to electronic health records. DESIGN: Retrospective cohort study using electronic health records. SETTING: Ten ICUs from four U.K. National Health Service hospital trusts contributing to the National Institute for Health Research Critical Care Health Informatics Collaborative. PATIENTS: A total of 28,456 critical care admissions (14,332 emergency medical, 4,585 emergency surgical, and 9,539 elective surgical). MEASUREMENTS AND MAIN RESULTS: Twenty-nine thousand three hundred forty-three episodes of clinical deterioration were identified with a rise in Sequential Organ Failure Assessment score of at least 2 points, of which 14,869 (50.7%) were associated with antibiotic escalation and thereby met the Sepsis-3 criteria for sepsis. A total of 4,100 episodes of sepsis (27.6%) were associated with vasopressor use and lactate greater than 2.0 mmol/L, and therefore met the Sepsis-3 criteria for septic shock. ICU mortality by source of sepsis was highest for ICU-acquired sepsis (23.7%; 95% CI, 21.9-25.6%), followed by hospital-acquired sepsis (18.6%; 95% CI, 17.5-19.9%), and community-acquired sepsis (12.9%; 95% CI, 12.1-13.6%) (p for comparison less than 0.0001). CONCLUSIONS: We successfully operationalized the Sepsis-3 criteria to an electronic health record dataset to describe the characteristics of critical care patients with sepsis. This may facilitate sepsis research using electronic health record data at scale without relying on human coding.

The acute effects of alcohol on state rumination in the laboratory.

RATIONALE: Rumination is a repetitive, negative, self-focused thinking style associated with various forms of psychopathology. Recent studies suggest that rumination increases craving for alcohol and predicts harmful drinking and alcohol-related problems. However, the acute effects of alcohol on rumination have not been previously studied. It is proposed that alcohol may reduce ruminative thinking through decreasing negative mood. OBJECTIVES: In the present study, we aimed to test the previously unexplored effects of acute alcohol consumption on rumination in a hazardous drinking population. METHODS: We conducted a randomised placebo-controlled laboratory study to examine the effect of low (0.4 g kg-1) and high doses (0.8 g kg-1) of alcohol on state rumination compared to placebo. Participants completed a rumination induction task prior to receiving drinks. We then measured state rumination and mood at repeated time points; 30 min, 60 min and 90 min post-drinks consumption. RESULTS: We found a significant decrease in state rumination in the low-dose alcohol group compared to placebo at 30 min post-alcohol consumption, but no difference was observed between the high-dose alcohol and placebo groups. Mediation analysis provided evidence for an indirect effect of alcohol on state rumination through concurrent changes in negative mood. CONCLUSIONS: These findings suggest that acute alcohol consumption can regulate negative mood and concurrently rumination, providing preliminary evidence for the role of rumination in alcohol use disorders. Rumination may be a treatment target in alcohol use disorders.

Personal digital health hubs for multiple conditions.

Multimorbidity is the presence of more than one chronic disease condition in an individual. Health-related, socioeconomic, cultural and environmental factors, as well as patient behaviour, all influence the outcomes of multimorbidity. Addressing these complex and often interacting biopsychosocial factors therefore requires a shift in treatment from a physical damage model towards person-centred integrated care with increased patient agency. Education influences behaviour and can be used to empower patients and their carers with greater agency, thus allowing greater responsibility for and control over the management of patient care. In this paper we reflect on our own learning as a community of health practitioners from different disciplines. Recognizing the increasing importance of patient agency in driving the evolution of health care, we describe the concept of a web-based personal digital health hub for integrated patient care. Informed by collaboration between patient, health and education communities, we share our early experience in the implementation of a health hub around a cohort of patients with hip fractures. We also describe a vision for future health care based on the co-creation of digital health hubs centred on patients' and carers' needs. The health hub could allow important advances and efficiencies to be achieved in workforce practice and education; patient and carer engagement in self-care; and the collection of patient-reported health data required for ongoing research and improvements in health care.

La multimorbidité est la présence de plus d'une maladie chronique chez un individu. L'aboutissement de la multimorbidité est influencé par des facteurs sanitaires, socio-économiques, culturels et environnementaux. Aborder ces facteurs biopsychosociaux complexes et souvent interdépendants requiert donc un changement de traitement, qui consiste à s'éloigner d'un modèle axé sur les dommages physiques pour se rapprocher d'un modèle de soins intégré et centré sur la personne, allié à une meilleure implication du patient. L'éducation a un impact sur le comportement et peut être utilisée pour renforcer la capacité d'agir des patients et de leurs soignants, ce qui permettra de conférer plus de responsabilités et un meilleur contrôle de la gestion des soins aux patients. Dans ce document, nous réfléchissons à notre propre apprentissage en tant que communauté de professionnels de la santé issus de différentes disciplines. Nous reconnaissons l'importance croissante de l'implication du patient pour stimuler l'évolution des soins de santé, et imaginons un concept de centre de santé numérique et personnalisé via site Web pour la prise en charge intégrée des patients. Grâce à la collaboration entre patients, professionnels de la santé et structures pédagogiques, nous partageons nos premières expériences en matière de mise en œuvre d'un centre de santé regroupant des patients présentant des fractures de la hanche. Nous dévoilons également notre vision d'avenir pour les soins de santé, qui repose sur la cocréation de centres de santé numériques adaptés aussi bien aux besoins des patients qu'à ceux des soignants. Ce concept pourrait faire progresser l'enseignement et la pratique pour les professionnels du secteur, mais aussi améliorer leur efficacité; favoriser la participation des patients et soignants dans les soins auto-administrés; et enfin, permettre la collecte des données fournies par les patients, et nécessaires à la poursuite des recherches et améliorations dans le domaine des soins de santé.

La multimorbilidad es la presencia de más de una enfermedad crónica en un individuo. Los factores medioambientales, culturales, socioeconómicos y los relacionados con la salud, así como el comportamiento de los pacientes, influyen en los resultados de la multimorbilidad. Por lo tanto, se requiere un cambio en el tratamiento desde el modelo de daño físico hacia una atención integrada y centrada en el individuo con una mayor participación del paciente para abordar estos factores biopsicosociales complejos y a menudo interactivos. La educación influye en el comportamiento y se puede utilizar para que los pacientes y sus cuidadores tengan más capacidad de acción, lo que permite una mayor responsabilidad y control sobre la gestión de la atención al paciente. En este documento reflexionamos sobre nuestro propio aprendizaje como comunidad de profesionales de la salud de diferentes disciplinas. Se describe el concepto de un centro de salud virtual personalizado para la atención integrada del paciente, al reconocer la creciente relevancia de la participación y la acción del paciente en el proceso de evolución de la atención médica. Gracias a la colaboración entre las comunidades de pacientes, de salud y de educación, compartimos nuestra experiencia inicial sobre el establecimiento de un centro de salud en torno a una cohorte de pacientes con fracturas de cadera. Asimismo, describimos una visión de la futura atención médica basada en la creación conjunta de centros de salud virtuales que se centran en las necesidades de los pacientes y de los cuidadores. El centro de salud permitiría alcanzar importantes avances y mejoras en la práctica y la educación de la fuerza de trabajo; en el compromiso de los pacientes y los cuidadores con el autocuidado de la salud; y en la recopilación de los datos sobre la salud que los pacientes comunican y que se requieren para la investigación y las mejoras continuas en la atención médica.

Innovations to improve access to musculoskeletal care.

Innovation is a form of realising a new way of doing something, often ignoring traditional wisdom, in order to meet new challenges. Globally, particularly in emerging economies, the high burden of musculoskeletal conditions and their contribution to multimorbidity continue to rise, as does the gap for services to deliver essential care. There is a growing need to find solutions to this challenge and deliver person-centred and integrated care, wherein empowering patients with the capacity for self-management is critical. Whilst there is an abundance of information available online to support consumer education, the number of sources for credible medical information is diluted by uninformed anecdotal social media solutions. Even with the provision of high-quality information, behavioural change does not necessarily follow, and more robust educational approaches are required. In this chapter, we examine innovation, its management and the strategic directions required to improve musculoskeletal healthcare at macro (policy), meso (service delivery) and micro (clinical practice) levels. We discuss the critical role of consumer agency (patients and their families/carers) in driving innovation and the need to leverage this through empowerment by education. We provide a snapshot of real-world examples of innovative practices including capacity building in consumer and interprofessional musculoskeletal education and practice; recommendations to transform the access and delivery of integrated, person-centred care; and initiatives in musculoskeletal care and implementation of models of care, enabled by digital health solutions including telehealth, remote monitoring, artificial intelligence, blockchain technology and big data. We provide emerging evidence for how innovation can support systems' strengthening and build capacity to support improved access to 'right' musculoskeletal care, and explore some of the ways to best manage innovations. We conclude with recommended systematic steps to establish required leadership, collaboration, research, networking, dissemination, implementation and evaluation of future innovations in musculoskeletal health and care.

The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study.

Rationale: There is conflicting evidence on harm related to exposure to supraphysiologic PaO2 (hyperoxemia) in critically ill patients.Objectives: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to ICUs in five United Kingdom university hospitals.Methods: A retrospective cohort of ICU admissions between January 31, 2014, and December 31, 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative was studied. Multivariable logistic regression modeled death in ICU by exposure to hyperoxemia.Measurements and Main Results: Subsets with oxygen exposure windows of 0 to 1, 0 to 3, 0 to 5, and 0 to 7 days were evaluated, capturing 19,515, 10,525, 6,360, and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mm Hg) divided by the hours of potential exposure (24, 72, 120, or 168 h). An association was found between exposure to hyperoxemia and ICU mortality for exposure windows of 0 to 1 days (odds ratio [OR], 1.15; 95% compatibility interval [CI], 0.95-1.38; P = 0.15), 0 to 3 days (OR 1.35; 95% CI, 1.04-1.74; P = 0.02), 0 to 5 days (OR, 1.5; 95% CI, 1.07-2.13; P = 0.02), and 0 to 7 days (OR, 1.74; 95% CI, 1.11-2.72; P = 0.02). However, a dose-response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation.Conclusions: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose-response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.

A holistic understanding of the effect of stress on adolescent well-being: A conditional process analysis.

Although traditional assumptions tend to conceptualize stress as inherently dysfunctional, psychological theory suggests that it is not intrinsically maladaptive. Contemporary models emphasize that the stress response can be differentiated into both negative and positive aspects, known as distress and eustress. Research examining the differential effect of positive and negative stress on adolescent well-being is limited and has been hindered by a lack of appropriate measurement tools. The aim of the present study was to utilize the recently developed Adolescent Distress-Eustress Scale to provide a balanced understanding of the impact of stress on positive mental health, holistically considering the effect of both distress and eustress on adolescent well-being. One thousand eighty-one Australian adolescents (Mage = 15.14, 54.03% female) completed an online survey composed of the Adolescent Distress-Eustress Scale alongside measures of well-being, self-efficacy, psychological ill-being, physical activity, and daytime sleepiness. Conditional process analysis suggested that distress exerted no direct influence on well-being, with the observed negative relationship fully mediated by psychological and behavioural variables. Contrastingly, eustress was both directly related to increased well-being and exerted an indirect effect through relationships with mediating variables. These results demonstrate that stress can have profoundly positive consequences. Theoretical contributions, implications for practice, and perspectives for future research are discussed.