Trends in use of intraosseous and intravenous access in out-of-hospital cardiac arrest across English ambulance services: A registry-based, cohort study.

INTRODUCTION: The optimum route for drug administration in cardiac arrest is unclear. Recent data suggest that use of the intraosseous route may be increasing. This study aimed to explore changes over time in use of the intraosseous and intravenous drug routes in out-of-hospital cardiac arrest in England. METHODS: We extracted data from the UK Out-of-Hospital Cardiac Arrest Outcomes registry. We included adult out-of-hospital cardiac arrest patients between 2015-2020 who were treated by an English Emergency Medical Service that submitted vascular access route data to the registry. The primary outcome was any use of the intraosseous route during cardiac arrest. We used logistic regression models to describe the association between time (calendar month) and intraosseous use. RESULTS: We identified 75,343 adults in cardiac arrest treated by seven Emergency Medical Service systems between January 2015 and December 2020. The median age was 72 years, 64% were male and 23% presented in a shockable rhythm. Over the study period, the percentage of patients receiving intraosseous access increased from 22.8% in 2015 to 42.5% in 2020. For each study-month, the odds of receiving any intraosseous access increased by 1.019 (95% confidence interval 1.019 to 1.020, p < 0.001). This observed effect was consistent across sensitivity analyses. We observed a corresponding decrease in use of intravenous access. CONCLUSION: In England, the use of intraosseous access in out-of-hospital cardiac arrest has progressively increased over time. There is an urgent need for randomised controlled trials to evaluate the clinical effectiveness of the different vascular access routes in cardiac arrest.

Drug routes in out-of-hospital cardiac arrest: A summary of current evidence.

Recent evidence showing the clinical effectiveness of drug therapy in cardiac arrest has led to renewed interest in the optimal route for drug administration in adult out-of-hospital cardiac arrest. Current resuscitation guidelines support use of the intravenous route for intra-arrest drug delivery, with the intraosseous route reserved for patients in whom intravenous access cannot be established. We sought to evaluate current evidence on drug route for administration of cardiac arrest drugs, with a specific focus on the intravenous and intraosseous route. We identified relevant animal, manikin, and human studies through targeted searches of MEDLINE in June 2022. Across pre-hospital systems, there is wide variation in use of the intraosseous route. Early administration of cardiac arrest drugs is associated with improved patient outcomes. Challenges in obtaining intravenous access mean that the intraosseous access may facilitate earlier drug administration. However, time from administration to the central circulation is unclear with pharmacokinetic data limited mainly to animal studies. Observational studies comparing the effect of intravenous and intraosseous drug administration on patient outcomes are challenging to interpret because of resuscitation time bias and other confounders. To date, no randomised controlled trial has directly compared the effect on patient outcomes of intraosseous compared with intravenous drug administration in cardiac arrest. The International Liaison Committee on Resuscitation has described the urgent need for randomised controlled trials comparing the intravenous and intraosseous route in adult out-of-hospital cardiac arrest. Ongoing clinical trials will directly address this knowledge gap.

Perioperative oxygen therapy: a protocol for an overview of systematic reviews and meta-analyses.

BACKGROUND: Oxygen is routinely given to patients during and after surgery. Perioperative oxygen administration has been proposed as a potential strategy to prevent and treat hypoxaemia and reduce complications, such as surgical site infections, pulmonary complications and mortality. However, uncertainty exists as to which strategies in terms of amount, delivery devices and timing are clinically effective. The aim of this overview of systematic reviews and meta-analyses is to answer the research question, 'For which types of surgery, at which stages of care, in which sub-groups of patients and delivered under what conditions are different types of perioperative oxygen therapy clinically effective?'. METHODS: We will search key electronic databases (MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, CENTRAL, Epistemonikos, PROSPERO, the INAHTA International HTA Database and DARE archives) for systematic reviews and randomised controlled trials comparing perioperative oxygen strategies. Each review will be mapped according to type of surgery, surgical pathway timepoints and clinical comparison. The highest quality reviews with the most comprehensive and up-to-date coverage of relevant literature will be chosen as anchoring reviews. Standardised data will be extracted from each chosen review, including definition of oxygen therapy, summaries of interventions and comparators, patient population, surgical characteristics and assessment of overall certainty of evidence. For clinical outcomes and adverse events, the overall pooled findings and results of subgroup and sensitivity analyses (where available) will be extracted. Trial-level data will be extracted for surgical site infections, mortality, and potential trial-level effect modifiers such as risk of bias, outcome definition and type of surgery to facilitate quantitative data analysis. This analysis will adopt a multiple indication review approach with panoramic meta-analysis using review-level data and meta-regression using trial-level data. An evidence map will be produced to summarise our findings and highlight any research gaps. DISCUSSION: There is a need to provide a panoramic overview of systematic reviews and meta-analyses describing peri-operative oxygen practice to both inform clinical practice and identify areas of ongoing uncertainty, where further research may be required. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272361.

Effects of genetic vs. environmental quality on condition-dependent morphological and life history traits in a neriid fly.

Condition is assumed to reflect both genes and environment, enabling condition-dependent signals to reveal genetic quality. However, because the phenotypic effects of variation in genetic quality could be masked by environmental heterogeneity, the contribution of genetic quality to phenotypic variation in fitness-related traits and condition-dependent signals remains unclear. We compared effects of ecologically relevant manipulations of environmental quality (nutrient dilution in the larval diet) and genetic quality (one generation of inbreeding) on male and female morphology, life history and reproductive performance in the neriid fly Telostylinus angusticollis. We found that larval diet quality had strong, positive effects on male and female body size, male secondary sexual traits, and aspects of male and female reproductive performance. By contrast, inbreeding had weak effects on most traits, and no trait showed clear and consistent effects of both environmental and genetic quality. Indeed, inbreeding effects on body size and male competitive performance were of opposite sign in rich vs. poor larval diet treatment groups. Our results suggest that environmental quality strongly affects condition, but the effects of genetic quality are subtle and environment-dependent in this species. These findings raise questions about the genetic architecture of condition and the potential for condition-dependent traits to function as signals of genetic quality.

Parental breeding age effects on descendants' longevity interact over 2 generations in matrilines and patrilines.

Individuals within populations vary enormously in mortality risk and longevity, but the causes of this variation remain poorly understood. A potentially important and phylogenetically widespread source of such variation is maternal age at breeding, which typically has negative effects on offspring longevity. Here, we show that paternal age can affect offspring longevity as strongly as maternal age does and that breeding age effects can interact over 2 generations in both matrilines and patrilines. We manipulated maternal and paternal ages at breeding over 2 generations in the neriid fly Telostylinus angusticollis. To determine whether breeding age effects can be modulated by the environment, we also manipulated larval diet and male competitive environment in the first generation. We found separate and interactive effects of parental and grand-parental ages at breeding on descendants' mortality rate and life span in both matrilines and patrilines. These breeding age effects were not modulated by grand-parental larval diet quality or competitive environment. Our findings suggest that variation in maternal and paternal ages at breeding could contribute substantially to intrapopulation variation in mortality and longevity.

Sexual competition and the evolution of condition-dependent ageing.

Increased individual resources (condition) can be correlated with either increased or decreased longevity. While variation in resource acquisition and allocation can account for some of this variation, the general conditions that select for either pattern remain unclear. Previous models suggest that nonlinearity of payoffs from investment in reproduction (e.g., male secondary sexual traits) can select for high-condition individuals that sacrifice longevity to increase reproductive opportunity. However, it remains unclear what mating systems or patterns of sexual competition might select for such life-history strategies. We used a model of condition-dependent investment to explore how expected payoffs from increased expression of secondary sexual traits affect optimal investment in lifespan. We find that nonlinearity of these payoffs results in a negative relationship between condition and lifespan under two general conditions: first, when there are accelerating marginal benefits from increasing investment; second, when individuals that invest minimally in secondary sexual trait expression can still achieve matings. In the second scenario, the negative relationship occurs due to selection on low-condition individuals to extend lifespan at the cost of secondary sexual trait expression. Our findings clarify the potential role of sexual selection in shaping patterns of condition-dependent ageing, and highlight the importance of considering the strategies of both low- and high-condition individuals when investigating patterns of condition-dependent ageing.

Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence.

BACKGROUND: Altered expression of mRNA splicing factors occurs with ageing in vivo and is thought to be an ageing mechanism. The accumulation of senescent cells also occurs in vivo with advancing age and causes much degenerative age-related pathology. However, the relationship between these two processes is opaque. Accordingly we developed a novel panel of small molecules based on resveratrol, previously suggested to alter mRNA splicing, to determine whether altered splicing factor expression had potential to influence features of replicative senescence. RESULTS: Treatment with resveralogues was associated with altered splicing factor expression and rescue of multiple features of senescence. This rescue was independent of cell cycle traverse and also independent of SIRT1, SASP modulation or senolysis. Under growth permissive conditions, cells demonstrating restored splicing factor expression also demonstrated increased telomere length, re-entered cell cycle and resumed proliferation. These phenomena were also influenced by ERK antagonists and agonists. CONCLUSIONS: This is the first demonstration that moderation of splicing factor levels is associated with reversal of cellular senescence in human primary fibroblasts. Small molecule modulators of such targets may therefore represent promising novel anti-degenerative therapies.

Ontogenetic timing as a condition-dependent life history trait: High-condition males develop quickly, peak early, and age fast.

Within-population variation in ageing remains poorly understood. In males, condition-dependent investment in secondary sexual traits may incur costs that limit ability to invest in somatic maintenance. Moreover, males often express morphological and behavioral secondary sexual traits simultaneously, but the relative effects on ageing of investment in these traits remain unclear. We investigated the condition dependence of male life history in the neriid fly Telostylinus angusticollis. Using a fully factorial design, we manipulated male early-life condition by varying nutrient content of the larval diet and, subsequently, manipulated opportunity for adult males to interact with rival males. We found that high-condition males developed more quickly and reached their reproductive peak earlier in life, but also experienced faster reproductive ageing and died sooner than low-condition males. By contrast, interactions with rival males reduced male lifespan but did not affect male reproductive ageing. High-condition in early life is therefore associated with rapid ageing in T. angusticollis males, even in the absence of damaging male-male interactions. Our results show that abundant resources during the juvenile phase are used to expedite growth and development and enhance early-life reproductive performance at the expense of late-life performance and survival, demonstrating a clear link between male condition and ageing.

Implicit policies about relations between personality traits and behavioral effectiveness in situational judgment items.

This paper develops the concept of implicit trait policy (ITP), which is a variant of the accentuation effect described by Tajfel (1957). ITPs are implicit beliefs about causal relations between personality traits and behavioral effectiveness. Studies reported here tested the hypotheses (a) that personality traits affect ITPs so that agreeable people, for instance, believe the relation between agreeableness and effectiveness is more strongly positive than disagreeable people do and (b) that ITPs can predict behavior that expresses associated personality traits. Two studies with undergraduate research participants supported the first hypothesis for traits of agreeableness and extraversion (the average correlation between traits and associated ITPs was .31 for agreeableness and .37 for extraversion) but not for conscientiousness. A 3rd study with student participants found that individual differences in ITPs for agreeableness predicted agreeable behavior (the average correlation was .33) in simulated work settings. These results suggest that ITPs may be useful for predicting work behavior that expresses personality traits even though ITPs may not be strongly correlated with the personality traits themselves.