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Two prior reviews highlight the scarcity and conflicting nature of available data on chronic postsurgical pain in children, reporting a wide prevalence range of 3.2% to 64% (at ≥3 months). This updated systematic review aimed to consolidate information on the prevalence of pediatric chronic postsurgical pain. A thorough literature search of full English‐text publications from April 2014 to August 2021 was conducted using Ovid MEDLINE, PubMed, and Cochrane Database of Systematic Reviews, with search terms: postoperative pain, child, preschool, pediatrics, adolescent, chronic pain. Seventeen relevant studies were identified. Most assessed chronicity once greater than 3 months duration postoperatively (82%), were predominantly prospective (71%) and conducted in inpatient settings (88%). The surgeries examined included orthopedic (scoliosis and limb), urological, laparotomy, inguinal, and cardiothoracic procedures, involving numbers ranging from 36 to 750, totaling 3137 participants/2792 completers. The studies had wide variations in median age at surgery (6 days to 16 years), the percentage of female participants (unspecified or 12.5% to 90%), and follow‐up duration (2.5 months to 9 years). Various pain, functional, psychosocial, and health‐related quality of life outcomes were documented. Chronic postsurgical pain prevalence varied widely from 2% to 100%. Despite increased data, challenges persist due to heterogeneity in definitions, patient demographics, mixed versus single surgical populations, diverse perioperative analgesic interventions, follow‐up durations and reported outcomes. Interpretation is further complicated by limited information on impact, long‐term analgesia and healthcare utilization, and relatively small sample sizes, hindering the assessment of reported associations. In some cases, preoperative pain and deformity may not have been addressed by surgery and persisting pain postoperatively may then be inappropriately termed chronic postsurgical pain. Larger‐scale, procedure‐specific data to better assess current prevalence, impact, and whether modifiable factors link to negative long‐term outcomes, would be more useful and allow targeted perioperative interventions for at‐risk pediatric surgical patients. [ABSTRACT FROM AUTHOR]

Understanding the response of species to global change requires disentangling the drivers of their distributions across landscapes. Colonization and extinction processes, shaped by the interplay of landscape‐level and local patch‐level factors, are key determinants of these distributions. However, disentangling the influence of these factors, when larger‐scale processes manifest at local scales, remains a challenge. We addressed this challenge by investigating the colonization and extinction dynamics of the aquatic plant, Hydrilla verticillata, in a complex riverine rock pool system. This system, with hundreds of rock pools experiencing varying flooding frequencies, provided a natural laboratory to examine how a single landscape‐level disturbance can differentially impact colonization and extinction depending on local patch characteristics to shape species distributions. Using 5 years of data across over 500 sites and more than 5000 surveys, we employed dynamic occupancy models to model colonization, extinction, and changes in Hydrilla patch occupancy while accounting for imperfect detection. Our results revealed that larger, infrequently flooded pools closer to the river were more likely to be colonized. In contrast, local extinction of Hydrilla was more likely in smaller pools closer to the river that flooded frequently. These findings underscore the importance of considering context‐dependence in species distribution models. The same landscape‐level disturbance (flooding) had opposing effects on colonization and extinction, with the direction and magnitude of these effects varying with local patch characteristics. Our study highlights the need for integrating local and landscape‐level factors, and considering how larger‐scale processes play out at the patch level, to understand the complex dynamics that shape species distributions. [ABSTRACT FROM AUTHOR]

Activation of the cAMP pathway is one of the common mechanisms underlying long‐term potentiation (LTP). In the Drosophila mushroom body, simultaneous activation of odour‐coding Kenyon cells (KCs) and reinforcement‐coding dopaminergic neurons activates adenylyl cyclase in KC presynaptic terminals, which is believed to trigger synaptic plasticity underlying olfactory associative learning. However, learning induces long‐term depression (LTD) at these synapses, contradicting the universal role of cAMP as a facilitator of transmission. Here, we developed a system to electrophysiologically monitor both short‐term and long‐term synaptic plasticity at KC output synapses and demonstrated that they are indeed an exception in which activation of the cAMP–protein kinase A pathway induces LTD. Contrary to the prevailing model, our cAMP imaging found no evidence for synergistic action of dopamine and KC activity on cAMP synthesis. Furthermore, we found that forskolin‐induced cAMP increase alone was insufficient for plasticity induction; it additionally required simultaneous KC activation to replicate the presynaptic LTD induced by pairing with dopamine. On the other hand, activation of the cGMP pathway paired with KC activation induced slowly developing LTP, proving antagonistic actions of the two second‐messenger pathways predicted by behavioural study. Finally, KC subtype‐specific interrogation of synapses revealed that different KC subtypes exhibit distinct plasticity duration even among synapses on the same postsynaptic neuron. Thus, our work not only revises the role of cAMP in synaptic plasticity by uncovering the unexpected convergence point of the cAMP pathway and neuronal activity, but also establishes the methods to address physiological mechanisms of synaptic plasticity in this important model. Key points: Although presynaptic cAMP increase generally facilitates synapses, olfactory associative learning in Drosophila, which depends on dopamine and cAMP signalling genes, induces long‐term depression (LTD) at the mushroom body output synapses.By combining electrophysiology, pharmacology and optogenetics, we directly demonstrate that these synapses are an exception where activation of the cAMP–protein kinase A pathway leads to presynaptic LTD.Dopamine‐ or forskolin‐induced cAMP increase alone is not sufficient for LTD induction; neuronal activity, which has been believed to trigger cAMP synthesis in synergy with dopamine input, is required in the downstream pathway of cAMP.In contrast to cAMP, activation of the cGMP pathway paired with neuronal activity induces presynaptic long‐term potentiation, which explains behaviourally observed opposing actions of transmitters co‐released by dopaminergic neurons.Our work not only revises the role of cAMP in synaptic plasticity, but also provides essential methods to address physiological mechanisms of synaptic plasticity in this important model system. [ABSTRACT FROM AUTHOR]

Adaptive platform trials (APTs) offer a promising alternative to traditional randomised controlled trials for evaluating treatments for paediatric sepsis. Randomised controlled trials, despite being the gold standard for establishing causality between interventions and outcomes, make many assumptions about disease prevalence, severity and intervention effects, which are often incorrect. As a result, the evidence for most treatments for paediatric sepsis are based on low‐quality evidence. APTs use accrued data rather than assumptions to power trial adaptations. They can assess multiple treatments simultaneously with shared research infrastructure. As such, APTs offer a more efficient, flexible and more effective way to identify optimal treatments. The proposed Paediatric Adaptive Sepsis Platform Trial, leveraging the Paediatric Research in Emergency Departments International Collaborative network's infrastructure, will evaluate resuscitation fluids, vasoactive medications, corticosteroids and antimicrobials. This trial has the potential to substantially impact clinical practice and reduce global sepsis mortality in children. [ABSTRACT FROM AUTHOR]

This article discusses the importance of increasing access to new therapies for Australian children and adolescents through clinical trials. It emphasizes the need for investment and a coordinated national approach to ensure that Australian children do not fall behind their international peers. The article highlights the benefits of collaborative approaches and strategic investment in pediatric clinical trials, as well as the challenges in delivering high-quality trials in this population. It acknowledges the additional challenges faced in Australia due to distance and regulatory factors, and calls for equitable access to emerging treatments for all Australian children, regardless of their circumstances. The article concludes by emphasizing the need for national investment in pediatric clinical trial delivery in Australia. [Extracted from the article]

Warming has broad and often nonlinear impacts on organismal physiology and traits, allowing it to impact species interactions like predation through a variety of pathways that may be difficult to predict. Predictions are commonly based on short‐term experiments and models, and these studies often yield conflicting results depending on the environmental context, spatiotemporal scale, and the predator and prey species considered. Thus, the accuracy of predicted changes in interaction strength, and their importance to the broader ecosystems they take place in, remain unclear. Here, we attempted to link one such set of predictions generated using theory, modeling, and controlled experiments to patterns in the natural abundance of prey across a broad thermal gradient. To do so, we first predicted how warming would impact a stage‐structured predator–prey interaction in riverine rock pools between Pantala spp. dragonfly nymph predators and Aedes atropalpus mosquito larval prey. We then described temperature variation across a set of hundreds of riverine rock pools (n = 775) and leveraged this natural gradient to look for evidence for or against our model's predictions. Our model's predictions suggested that warming should weaken predator control of mosquito larval prey by accelerating their development and shrinking the window of time during which aquatic dragonfly nymphs could consume them. This was consistent with data collected in rock pool ecosystems, where the negative effects of dragonfly nymph predators on mosquito larval abundance were weaker in warmer pools. Our findings provide additional evidence to substantiate our model‐derived predictions while emphasizing the importance of assessing similar predictions using natural gradients of temperature whenever possible. [ABSTRACT FROM AUTHOR]

Summary: The clearance of dead and dying cells, termed efferocytosis, is a rapid and efficient process and one that is critical for organismal health. The extraordinary speed and efficiency with which dead cells are detected and engulfed by immune cells within tissues presents a challenge to researchers who wish to unravel this fascinating process, since these fleeting moments of uptake are almost impossible to catch in vivo. In recent years, the fruit fly (Drosophila melanogaster) embryo has emerged as a powerful model to circumvent this problem. With its abundance of dying cells, specialist phagocytes and relative ease of live imaging, the humble fly embryo provides a unique opportunity to catch and study the moment of cell engulfment in real‐time within a living animal. In this review, we explore the recent advances that have come from studies in the fly, and how live imaging and genetics have revealed a previously unappreciated level of diversity in the efferocytic program. A variety of efferocytic strategies across the phagocytic cell population ensure efficient and rapid clearance of corpses wherever death is encountered within the varied and complex setting of a multicellular living organism. [ABSTRACT FROM AUTHOR]

The article discusses the changing landscape of medical journals, specifically focusing on the future of the journal Pediatric Anesthesia. The author explores various drivers for change, including the rise of the internet and digital age, open science and open access, the increasing number of manuscripts and journals, and the growing complexity of science. The internet has allowed journals to move online, changing the way manuscripts are published and accessed. The author also discusses the impact of open access on the traditional economics of publishing and the need for quality and reputation in the face of an abundance of information. Despite these changes, the author believes that Pediatric Anesthesia will continue to exist in the future, emphasizing the importance of being a place of quality in an increasingly information-saturated world. [Extracted from the article]

Summary: Primary production in the Southern Ocean is dominated by diatom‐rich phytoplankton assemblages, whose individual physiological characteristics and community composition are strongly shaped by the environment, yet knowledge on how diatoms allocate cellular energy in response to ocean acidification (OA) is limited. Understanding such changes in allocation is integral to determining the nutritional quality of diatoms and the subsequent impacts on the trophic transfer of energy and nutrients.Using synchrotron‐based Fourier transform infrared microspectroscopy, we analysed the macromolecular content of selected individual diatom taxa from a natural Antarctic phytoplankton community exposed to a gradient of fCO2 levels (288–1263 µatm).Strong species‐specific differences in macromolecular partitioning were observed under OA. Large taxa showed preferential energy allocation towards proteins, while smaller taxa increased both lipid and protein stores at high fCO2.If these changes are representative of future Antarctic diatom physiology, we may expect a shift away from lipid‐rich large diatoms towards a community dominated by smaller taxa, but with higher lipid and protein stores than their present‐day contemporaries, a response that could have cascading effects on food web dynamics in the Antarctic marine ecosystem. [ABSTRACT FROM AUTHOR]

We describe a two‐year‐old boy with Dravet syndrome, a severe genetic epilepsy, who developed a generalized tonic–clonic seizure immediately following an intravenous bolus of lidocaine given for propofol pain amelioration during induction of anesthesia for emergency gastroscopy. Although lidocaine has not specifically been reported as potentiating seizures in Dravet syndrome, it is well‐established that sodium channel blockers can worsen seizures in this population. [ABSTRACT FROM AUTHOR]

Dr. Anne Marie Lynn (1949–present), Professor Emeritus of Anesthesiology, Pain Medicine, and Pediatrics at the University of Washington, Seattle, was one of the most influential women in pediatric anesthesiology of her generation. Dr. Lynn embodies the spirit of discovery and advancement that have created the practice of pediatric anesthesiology as we know it today. A pioneer in pain medicine pharmacology, particularly morphine and ketorolac, her research transformed pediatric anesthesia, pediatric pain medicine, and pediatric intensive care medicine. Through her journal articles, book chapters, national and international lectures, mentoring of residents, fellows, and faculty, and leadership in the Society for Pediatric Anesthesia, she inspired a generation of women and men physicians by demonstrating that gender should not be a barrier to undertaking roles once only held only by men. In 2017, for her many contributions, she was awarded the Society for Pediatric Anesthesia's Myron Yaster lifetime achievement award. [ABSTRACT FROM AUTHOR]

Warming can impact consumer–resource interactions through multiple mechanisms. For example, warming can both alter the rate at which predators consume prey and the rate prey develop through vulnerable life stages. Thus, the overall effect of warming on consumer–resource interactions will depend upon the strength and asymmetry of warming effects on predator and prey performance.Here, we quantified the temperature dependence of both (a) density‐dependent predation rates for two dragonfly nymph predators on a shared mosquito larval prey, via the functional response, and (b) the development rate of mosquito larval prey to a predator‐invulnerable adult stage. We united the results of these two empirical studies using a temperature‐ and density‐dependent stage‐structured predation model to predict the effects of temperature on the number of larvae that survive to adulthood.Warming accelerated both larval mosquito development and increased dragonfly consumption. Model simulations suggest that differences in the magnitude and rate of predator and prey responses to warming determined the change in magnitude of the overall effect of predation on prey survival to adulthood. Specifically, we found that depending on which predator species prey were exposed to in the model, the net effect of warming was either an overall reduction or no change in predation strength across a temperature gradient.Our results highlight a need for better mechanistic understanding of the differential effects of temperature on consumer–resource pairs to accurately predict how warming affects food web dynamics. A free plain language summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

Data are used in healthcare quality improvement endeavors to measure and determine whether the changes made in the course of the work have made the desired impact. The methods used to analyze data in quality improvement differ slightly from those used in classical statistics. Run charts and statistical process control charts are the most common types of graphical representations used to visualize data collected for quality improvement. This review provides a basic introduction to measurement in quality improvement and explains the use of run charts and statistical process control charts with real‐life examples. [ABSTRACT FROM AUTHOR]

Introduction: This prospective study examines the test–retest reliability of touchscreen DriveSafe DriveAware (DSDA). In a future study, the authors intend assessing the usefulness of DSDA to measure progress of patients undergoing treatment for neurological conditions. Evidence of test–retest reliability is required first. Methods: Australian adults with current driver's licences (N = 39) aged 20 to 91 years (Mage = 58) recruited from a convenience sample were assessed with DSDA. The assessment was repeated 6 weeks, 6 months, and 12 months later to match planned assessments of patients undergoing neurosurgical treatment in future research. DSDA classification, DriveSafe subtest score, and DriveAware subtest scores were analysed as a whole sample, and in three age groups. Results: DSDA classification and DriveAware scores were consistent over repeated tests. DriveSafe scores increased between test 1 and 2 (p =.006), and thereafter no significant change from test 2 to 4. DriveSafe scores of older participants (70+ years) increased between test 1 and 2 more notably than younger participants' scores. No DriveSafe scores decreased over time. Conclusion: DSDA classification and DriveAware scores demonstrated test–retest reliability for all age groups. DriveSafe scores did not demonstrate test–retest reliability between test 1 and 2 for participants 70+ years. However, DriveSafe scores demonstrated test–retest reliability after test 2, possibly indicating an initial learning effect for the DriveSafe score only. The authors posit that this result may have been influenced by older adults' reduced familiarity with iPad technology at first assessment. Further longitudinal research is required to confirm whether these results are consistent in a sample population with diagnosed cognitive impairment. Future research will assess whether repeated assessment of DSDA may be useful for monitoring and screening cognitive fitness to drive in patients who have undergone neurosurgical treatment and whether declining scores may indicate cognitive changes in ability to drive. [ABSTRACT FROM AUTHOR]

We investigate binding of linoleate and other potential ligands to the recently discovered fatty acid binding site in the SARS‐CoV‐2 spike protein, using docking and molecular dynamics simulations. Simulations suggest that linoleate and dexamethasone stabilize the locked spike conformation, thus reducing the opportunity for ACE2 interaction. In contrast, cholesterol may expose the receptor‐binding domain by destabilizing the closed structure, preferentially binding to a different site in the hinge region of the open structure. We docked a library of FDA‐approved drugs to the fatty acid site using an approach that reproduces the structure of the linoleate complex. Docking identifies steroids (including dexamethasone and vitamin D); retinoids (some known to be active in vitro, and vitamin A); and vitamin K as potential ligands that may stabilize the closed conformation. The SARS‐CoV‐2 spike fatty acid site may bind a diverse array of ligands, including dietary components, and therefore provides a promising target for therapeutics or prophylaxis. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has greatly affected access to elective surgery, largely because of concerns for patients and healthcare workers. A return to normal surgery workflow depends on the prevalence and transmission of coronavirus in elective surgical patients. The aim of this study was to determine the prevalence of active SARS‐coronavirus‐2 infection during a second wave among patients admitted to hospital for elective surgery in Victoria. Methods: Prospective cohort study across eight hospitals in Victoria during July–August 2020 was conducted enrolling adults and children admitted to hospital for elective surgery or interventional procedure requiring general anaesthesia. Study outcomes included a positive polymerase chain reaction (PCR) test for SARS‐CoV‐2 in the preoperative period (primary outcome), and for those with a negative test preoperatively, the incidence of a positive PCR test for SARS‐CoV‐2 in the post‐operative period. Results: We enrolled 4965 elective adult and paediatric surgical patients from 15 July to 31 August 2020. Four patients screened negative on questionnaire but had a positive PCR test for coronavirus, resulting in a Bayesian estimated prevalence of 0.12% (95% probability interval 0–0.26%). There were no reports of healthcare worker infections linked to elective surgery during and up to 2 weeks after the study period. Conclusion: The prevalence of SARS‐CoV‐2 in asymptomatic elective surgical patients during a second wave was approximately 1 in 833. Given the very low likelihood of coronavirus transmission, and with existing current hospital capacity, recommencement of elective surgery should be considered. A coronavirus screening checklist should be mandated for surgical patients. [ABSTRACT FROM AUTHOR]

The Pediatric Perioperative Outcomes Group (PPOG) is an international collaborative of clinical investigators and clinicians within the subspecialty of pediatric anesthesiology and perioperative care which aims to use COMET (Core Outcomes Measures in Effectiveness Trials) methodology to develop core outcome sets for infants, children, and young people that are tailored to the priorities of the pediatric surgical population. Focusing on four age‐dependent patient subpopulations determined a priori for core outcome set development: (a) neonates and former preterm infants (up to 60 weeks postmenstrual age); (b) infants (>60 weeks postmenstrual age—<1 year); (c) toddlers and school age children (>1‐<13 years); and (d) adolescents (>13‐<18 years), we conducted a systematic review of outcomes reported in perioperative studies that include participants within age‐dependent pediatric subpopulations. Our review of pediatric perioperative controlled trials published from 2008 to 2018 identified 724 articles reporting 3192 outcome measures. The proportion of published trials and the most frequently reported outcomes varied across predetermined age‐groups. Outcomes related to patient comfort, particularly pain and analgesic requirement, were the most frequent domain for infants, children, and adolescents. Clinical indicators, particularly cardiorespiratory or medication‐related adverse events, were the most common outcomes for neonates and infants <60 weeks and were the second most frequent domain at all other ages. Neonates and infants <60 weeks of age were significantly under‐represented in perioperative trials. Patient‐centered outcomes, healthcare utilization, and bleeding/transfusion‐related outcomes were less often reported. In most studies, outcomes were measured in the immediate perioperative period, with the duration often restricted to the postanesthesia care unit or the first 24 postoperative hours. The outcomes identified with this systematic review will be combined with patient‐centered outcomes identified through a subsequent stakeholder engagement study to arrive at a core outcome set for each age‐specific group. [ABSTRACT FROM AUTHOR]

Southern Ocean waters are among the most vulnerable to ocean acidification. The projected increase in the CO2 level will cause changes in carbonate chemistry that are likely to be damaging to organisms inhabiting these waters. A meta‐analysis was undertaken to examine the vulnerability of Antarctic marine biota occupying waters south of 60°S to ocean acidification. This meta‐analysis showed that ocean acidification negatively affects autotrophic organisms, mainly phytoplankton, at CO2 levels above 1,000 μatm and invertebrates above 1,500 μatm, but positively affects bacterial abundance. The sensitivity of phytoplankton to ocean acidification was influenced by the experimental procedure used. Natural, mixed communities were more sensitive than single species in culture and showed a decline in chlorophyll a concentration, productivity, and photosynthetic health, as well as a shift in community composition at CO2 levels above 1,000 μatm. Invertebrates showed reduced fertilization rates and increased occurrence of larval abnormalities, as well as decreased calcification rates and increased shell dissolution with any increase in CO2 level above 1,500 μatm. Assessment of the vulnerability of fish and macroalgae to ocean acidification was limited by the number of studies available. Overall, this analysis indicates that many marine organisms in the Southern Ocean are likely to be susceptible to ocean acidification and thereby likely to change their contribution to ecosystem services in the future. Further studies are required to address the poor spatial coverage, lack of community or ecosystem‐level studies, and the largely unknown potential for organisms to acclimate and/or adapt to the changing conditions. [ABSTRACT FROM AUTHOR]

Gonadotropinoma in Klinefelter syndrome (KS) is uncommon and may be a result of protracted stimulation of gonadotrophs from lack of androgen feedback. Associations of white matter changes and increased venous thromboembolic risk have been reported and need to be considered in patients with KS. [ABSTRACT FROM AUTHOR]

Clinical outcomes are measurable changes in health, function, or quality of life that are important for evaluating the quality of care and comparing the efficacy of interventions. However, clinical outcomes and related measurement tools need to be well‐defined, relevant, and valid. In adults, Core Outcome Measures in Effectiveness Trials (COMET) methodology has been used to develop core outcome sets for perioperative care. Systematic literature reviews identified standardized endpoints (StEP) and valid measurement tools, and consensus across a broader range of relevant stakeholders was achieved via a Delphi process to establish Core Outcome Measures in Perioperative and Anaesthetic Care (COMPAC). Core outcome sets for pediatric perioperative care cannot be directly extrapolated from adult data. The type and weighting of endpoints within particular domains can be influenced by age‐dependent differences in the indications for and/or nature of surgery and medical comorbidities, and the validity and utility of many measurement tools vary significantly with developmental stage and age. The involvement of parents/carers is essential as they frequently act as surrogate responders for preverbal and developmentally delayed children, parental response may influence child outcome, and parental and/or child ranking of outcomes may differ from those of health professionals. Here, we describe the formation of the international Pediatric Perioperative Outcomes Group, which aims to identify and create validated, broadly applicable, patient‐centered outcome measures for infants, children, and young people. Methodologies parallel that of the StEP and COMPAC projects, and systematic literature searches have been performed within agreed age‐dependent subpopulations to identify reported outcomes and measurement tools. This represents the first steps for developing core outcome sets for pediatric perioperative care. [ABSTRACT FROM AUTHOR]

Early postoperative negative behaviors such as pain and emergence delirium are present in a significant number of young children undergoing surgery or diagnostic procedures after general anesthesia. Emergence delirium has been traditionally considered an immediate recovery room problem.1 However, the medium- and long-term consequences of emergence delirium have been rarely studied. [Extracted from the article]

Background: Autism Spectrum Disorder is now diagnosed in more than 1% of children in Australia and USA. Children with autism spectrum disorder may have additional health care needs, require more specialized services for their health care, or experience more difficulties during hospital attendance. Customized care for these children may assist in decreasing potentially challenging behaviours during hospitalization. The purpose of this study was to explore the experiences of children with autism spectrum disorder and their caregivers during attendance for day procedures in two hospitals in Melbourne, Australia. Further, the perceptions of their health care providers were explored. Methods: Twenty‐nine participants, including 14 health care providers and 15 caregivers of children with autism spectrum disorder, were interviewed within 72 hours of their day procedure attendance at the Royal Children's Hospital and the Royal Dental Hospital in Melbourne, Australia. Interviews were recorded digitally, then transcribed and coded. Mixed quantitative and qualitative methods (content analysis) were used. Results: Hospital attendance was often stressful. Participants identified a number of facilitating factors including good communication, clear explanations, and friendly attitudes of staff. Flexibility and individualized care of patients (such as avoiding unnecessary blood pressure measurements, and not changing into hospital gowns) were valued. Supportive aids (such as computers or special interest objects), use of social stories, and giving premedication were all considered helpful. Perceived barriers to care included prolonged waiting times for operation date as well as waiting on the day of operation, lack of private space, lack of noninvasive equipment such as cutaneous infrared thermometers, poor communication, and inadequate training of staff about autism spectrum disorder. Conclusion: Providing optimal care for children with autism spectrum disorder requires a multifaceted approach that may require changes to hospital work flow, staff training, better use of aids (such as tablet computers and social stories), and premedication. Good communication and flexibility are key areas of importance. [ABSTRACT FROM AUTHOR]

Summary: This Statistical Analysis Plan details the statistical procedures to be applied for the analysis of data for the multicenter electroencephalography study. It consists of a basic description of the study in broad terms and separate sections that detail the methods of different aspects of the statistical analysis, summarized under the following headings (a) Background; (b) Definitions of protocol violations; (c) Definitions of objectives and other terms; (d) Variables for analyses; (e) Handling of missing data and study bias; (f) Statistical analysis of the primary and secondary study outcomes; (g) Reporting of study results; and (h) References. It serves as a template for researchers interested in writing a Statistical Analysis Plan. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Randomized trials are important for generating high‐quality evidence, but are perceived as difficult to perform in the pediatric population. Thus far there has been poor characterization of the barriers to conducting trials involving children, and the variation in these barriers between countries remains undescribed. The General Anesthesia compared to Spinal anesthesia (GAS) trial, conducted in seven countries between 2007 and 2013, provides an opportunity to explore these issues. Methods: We undertook a descriptive analysis to evaluate the reasons for variation in enrollment between countries in the GAS trial, looking specifically at the number of potential subjects screened, and the subsequent application of four exclusion criteria that were applied in a hierarchical order. Results: A total of 4023 patients were screened by 28 centers in seven countries. Australia and the USA screened the most subjects, accounting for 84% of all potential trial participants. The percentage of subjects eliminated from the screened pool by each exclusion criterion varied between countries. Exclusion due to a predefined condition (H1) eliminated only 5% of potential subjects in Italy and the UK, but 37% in Canada. Exclusions due to a contraindication or a physician's refusal most impacted enrollment in Australia and the USA. The patient being "too large for spinal anesthesia" was the most commonly cited by anesthetists who refused to enroll a patient (64% of anesthetist refusals). The majority of surgeon refusals came from the USA, where surgeons preferred the patient to receive a general anesthetic. The percentage of approached parents refusing to consent ranged from a low of 3% in Italy to a high of 70% in the USA and Netherlands. The most frequently cited reason for parent refusal in all countries was a preference for general anesthesia (median: 43%, range: 32%‐67%). However, a sizeable proportion of parents in all countries had a contrasting preference for spinal anesthesia (median: 25%, range: 13%‐31%), and 23% of U.S. parents expressed concern about randomization. Conclusion: The GAS trial highlights enrollment challenges that can occur when conducting multicenter, international, pediatric studies. Investigators planning future trials should be aware of potential differences in screening processes across countries, and that exclusions by anesthetists and surgeons may vary in reason, in frequency, and by country. Furthermore, investigators should be aware that the U.S. centers encountered particularly high surgeon and parental refusal rates and that U.S. parents were uniquely concerned about randomization. Planning trials that address these difficulties should increase the likelihood of successfully recruiting subjects in pediatric trials. [ABSTRACT FROM AUTHOR]

Do LMIC providers feel that they may not realistically ever provide a high standard of care since the HIC surgeons and anesthesiologists always use newer equipment and supplies, which a LMIC hospital may never access? We would propose that the resources of the STSP industry be re-invested in the training of LMIC surgical team members toward a goal of surgery care independency, in parallel with continuing collaborative partnerships with their HIC colleagues. Why is this model for addressing deep and complex LMIC healthcare delivery issues still promoted by HIC academics, humanitarians, and organizations seeking to assist and improve surgery delivery and safety? Global surgery in the 21st century: The voice from Africa - We need a new model. [Extracted from the article]

Summary: All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long‐term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well‐designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare‐related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered. [ABSTRACT FROM AUTHOR]

Abstract: A 7‐year‐old female neutered Jack Russell Terrier was presented to Langford Vets, the University of Bristol, with a history of chronic intermittent lethargy. Investigations and clinical course were compatible with hereditary hemolysis due to a red blood cell membrane defect. Proteomics was used to explore protein alterations in the presence of a hypothesized red blood cell membrane protein deficiency. Proteomic analysis revealed downregulation of the band 3, and alpha‐ and beta‐adducin proteins, and alterations in the red blood cell proteome consistent with previous reports of changes due to the presence of reticulocytosis and ongoing hemolysis. The spectrum of protein alterations identified in the affected dog may be homologous to a band 3 protein deficiency secondary to hereditary spherocytosis, as described in people. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Understanding the duration of pediatric general anesthesia exposure in contemporary practice is important for identifying groups at risk for long general anesthesia exposures and designing trials examining associations between general anesthesia exposure and neurodevelopmental outcomes. Methods: We performed a retrospective cohort analysis to estimate pediatric general anesthesia exposure duration during 2010‐2015 using the National Anesthesia Clinical Outcomes Registry. Results: A total of 1 548 021 pediatric general anesthetics were included. Median general anesthesia duration was 57 minutes (IQR: 28‐86) with 90th percentile 145 minutes. Children aged <1 year had the longest median exposure duration (79 minutes, IQR: 39‐119) with 90th percentile 210 minutes, and 13.7% of this very young cohort was exposed for >3 hours. High ASA physical status and care at a university hospital were associated with longer exposure times. Conclusion: While the vast majority (94%) of children undergoing general anesthesia are exposed for <3 hours, certain groups may be at increased risk for longer exposures. These findings may help guide the design of future trials aimed at understanding neurodevelopmental impact of prolonged exposure in these high‐risk groups. [ABSTRACT FROM AUTHOR]

Summary: Background: There has been considerable interest in the possible adverse neurocognitive effects of exposure to general anesthesia and surgery in early childhood. Aims: The aim of this data linkage study was to investigate developmental and school performance outcomes of children undergoing procedures requiring general anesthesia in early childhood. Methods: We included children born in New South Wales, Australia of 37+ weeks’ gestation without major congenital anomalies or neurodevelopmental disability with either a school entry developmental assessment in 2009, 2012, or Grade‐3 school test results in 2008‐2014. We compared children exposed to general anesthesia aged <48 months to those without any hospitalization. Children with only 1 hospitalization with general anesthesia and no other hospitalization were assessed separately. Outcomes included being classified developmentally high risk at school entry and scoring below national minimum standard in school numeracy and reading tests. Results: Of 211 978 children included, 82 156 had developmental assessment and 153 025 had school test results, with 12 848 (15.7%) and 25 032 (16.4%) exposed to general anesthesia, respectively. Children exposed to general anesthesia had 17%, 34%, and 23% increased odds of being developmentally high risk (adjusted odds ratio [aOR]: 1.17; 95% CI: 1.07‐1.29); or scoring below the national minimum standard in numeracy (aOR: 1.34; 95% CI: 1.21‐1.48) and reading (aOR: 1.23; 95% CI: 1.12‐1.36), respectively. Although the risk for being developmentally high risk and poor reading attenuated for children with only 1 hospitalization and exposure to general anesthesia, the association with poor numeracy results remained. Conclusion: Children exposed to general anesthesia before 4 years have poorer development at school entry and school performance. While the association among children with 1 hospitalization with 1 general anesthesia and no other hospitalization was attenuated, poor numeracy outcome remained. Further investigation of the specific effects of general anesthesia and the impact of the underlying health conditions that prompt the need for surgery or diagnostic procedures is required, particularly among children exposed to long duration of general anesthesia or with repeated hospitalizations. [ABSTRACT FROM AUTHOR]

Background: There are no medications known that improve the outcome of infants with bronchiolitis. Studies have shown the management of bronchiolitis to be varied. Objectives: To describe medication use at the seven study hospitals from a recent multi-centre randomised controlled trial on hydration in bronchiolitis (comparative rehydration in bronchiolitis [CRIB]). Methods: A retrospective analysis of extant data of infants between 2 months (corrected for prematurity) and 12 months of age admitted with bronchiolitis identified through the CRIB trial. CRIB study records, medical records, pathology and radiology databases were used to collect data using a standardised form and entered in a single site database. Medications investigated included salbutamol, adrenaline, steroids, ipratropium bromide, normal saline, hypertonic saline, steroids and antibiotics. Results: There were 3456 infants available for analysis, of which 42.0% received at least one medication during hospitalisation. Medication use varied by site between 27.0 and 48.7%. The most frequently used medication was salbutamol (25.5%). Medication use in general, and salbutamol use in particular, increased by 8.2 and 9.3%, respectively, per month after 4 months of age; from 22.9 and 3.6% at 4 months to 81.4 and 68.8% at 11 months. In infants admitted to the intensive care unit (ICU) compared with those not admitted to ICU 81.6 and 39.5%, respectively, received medication at one point during the hospital stay. Conclusions: Medication was used for infants with bronchiolitis frequently and variably in Australia and New Zealand. Medication use increased with age. Better strategies for translating evidence into practice are needed. [ABSTRACT FROM AUTHOR]

Abstract: DNA metabarcoding is an efficient method for measuring biodiversity, but the process of initiating long‐term DNA‐based monitoring programmes, or integrating with conventional programs, is only starting. In marine ecosystems, plankton surveys using the continuous plankton recorder (CPR) have characterized biodiversity along transects covering millions of kilometres with time‐series spanning decades. We investigated the potential for use of metabarcoding in CPR surveys. Samples (n = 53) were collected in two Southern Ocean transects and metazoans identified using standard microscopic methods and by high‐throughput sequencing of a cytochrome c oxidase subunit I marker. DNA increased the number of metazoan species identified and provided high‐resolution taxonomy of groups problematic in conventional surveys (e.g., larval echinoderms and hydrozoans). Metabarcoding also generally produced more detections than microscopy, but this sensitivity may make cross‐contamination during sampling a problem. In some samples, the prevalence of DNA from large plankton such as krill masked the presence of smaller species. We investigated adding a fixed amount of exogenous DNA to samples as an internal control to allow determination of relative plankton biomass. Overall, the metabarcoding data represent a substantial shift in perspective, making direct integration into current long‐term time‐series challenging. We discuss a number of hurdles that exist for progressing DNA metabarcoding from the current snapshot studies to the requirements of a long‐term monitoring programme. Given the power and continually increasing efficiency of metabarcoding, it is almost certain this approach will play an important role in future plankton monitoring. [ABSTRACT FROM AUTHOR]

Background: Intranasal phenylephrine is commonly used to vasoconstrict the nasal mucosa, reducing bleeding associated with nasotracheal intubation or endoscopic sinus surgery. There are few data quantifying either absorption pharmacokinetics or phenylephrine concentration effect on blood pressure in children. Methods: Published observations of plasma concentration and blood pressure changes after phenylephrine nasal administration (0.1 mL kg-1, 0.25% or 0.5%) in children (n = 52, 2-12 years, 10-40 kg) were pooled with those in adults (23-81 years) given phenylephrine 2.5% (n = 10) and 10% (n = 10) eyedrops. Further pharmacokinetic (PK) data were available from healthy volunteers given oral phenylephrine 10 mg alone, with blood for concentration assay taken at 5, 15, 30, 45 minutes and 1, 2, 3, 6 hours (n = 28). Intravenous time-concentration data were available from four healthy volunteers given phenylephrine 1 mg and who had blood taken for assay on 17 occasions over the subsequent 4 hours. Data were analyzed using an integrated pharmacokinetic-pharmacodynamic (PK-PD) model using nonlinear mixed-effects models. Allometry, scaled to a 70-kg person, was used for PK size standardization. Effect was described using an EMAX model. Results: A two-compartment model was used to fit PK data while an additional compartment, linked by an equilibration half-time (T1/2keo), was used to describe effect. PK parameter estimates for the nasal formulation were clearance (CL) 160 L h-1, central volume of distribution (V1) 13.3 L, intercompartment clearance (Q) 25.3 L h-1, peripheral volume of distribution (V2) 225 L, absorption half-time (Tabs) 6.2 minutes, absorption lag time (Tlag) 1.5 minutes, and bioavailability (F) 0.183. Bioavailability and absorption of the ophthalmic solution were concentration dependent (F 0.13, Tabs 5.5 minutes for 2.5% solution; F 0.15, Tabs 9.6 minutes for 10% solution). Absorption of the oral formulation was slow (Tabs 48 minutes) with poor bioavailability (F 0.0128). The pediatric PD interrogation revealed a baseline mean arterial pressure of 60 mm Hg, a maximum effect (EMAX) of 25 mm Hg, and an EC50 of 10.3 µg L-1. The effect on vasculature was immediate and T1/2keo was not estimable. Conclusion: Absorption of phenylephrine through the nasal mucosa was rapid and similar to the ophthalmic formulation. Bioavailability was also similar to the ophthalmic formulation. The maximum effect (EMAX) in children was half that in adults (EMAX 50 mm Hg). [ABSTRACT FROM AUTHOR]

Aim: We aimed to examine the impact of weather on hospital admissions with bronchiolitis in Australia and New Zealand.Methods: We collected data for inpatient admissions of infants aged 2-12 months to seven hospitals in four cities in Australia and New Zealand from 2009 until 2011. Correlation of hospital admissions with minimum daily temperature, wind speed, relative humidity and rainfall was examined using linear, Poisson and negative binomial regression analyses as well as general estimated equation models. To account for possible lag between exposure to weather and admission to hospital, analyses were conducted for time lags of 0-4 weeks.Results: During the study period, 3876 patients were admitted to the study hospitals. Hospital admissions showed strong seasonality with peaks in wintertime, onset in autumn and offset in spring. The onset of peak incidence was preceded by a drop in temperature. Minimum temperature was inversely correlated with hospital admissions, whereas wind speed was directly correlated. These correlations were sustained for time lags of up to 4 weeks. Standardised correlation coefficients ranged from -0.14 to -0.54 for minimum temperature and from 0.18 to 0.39 for wind speed. Relative humidity and rainfall showed no correlation with hospital admissions in our study.Conclusion: A decrease in temperature and increasing wind speed are associated with increasing incidence of bronchiolitis hospital admissions in Australia and New Zealand. [ABSTRACT FROM AUTHOR]

Capillary malformations ( CM) cause significant psychosocial complications. Pulsed dye laser ( PDL) treatment at 6-12-weekly intervals under general anaesthesia ( GA) commencing in infants at 6 months of age remains the standard of care in order to achieve maximal improvement prior to school age. The safety of repeated GA in children is controversial. Shortening the time between treatments increases the number that can be delivered prior to 6 months of age, thus reducing the number of subsequent treatments needed under GA. We investigated the safety and effectiveness of more frequent PDL treatment of CM in infancy via a pilot, prospective patient-controlled study of 10 patients. Using 595 nm (Vbeam) PDL, the entire CM was treated initially, then half the CM randomly allocated to 2-weekly and half to 3-monthly intervals for two further treatments. Photographs of the CM taken 3 months after treatment completion were evaluated by an independent, blinded dermatologist. Nine infants completed the study. Three infants (33%) had more improvement on the 2-weekly treated side and four (44%) had more improvement on the 3-monthly treated side. Two patients (22%) showed no difference between sides. Treatments were well tolerated without complications. We conclude that 2-weekly PDL treatments of CM in infants aged under 6 months is effective and well tolerated without adverse effects. Our preliminary data suggest a possible superior efficacy with 3-monthly treatment intervals; however, larger studies are warranted for stronger evidence. More frequent non- GA treatment of CM in infants should be further investigated to decrease the risk of repeated GA exposure in young children. [ABSTRACT FROM AUTHOR]

Objectives To describe the rate of intensive care unit (ICU) admission, type of ventilation support provided and risk factors for ICU admission in infants with bronchiolitis. Design Retrospective review of hospital records and Australia and New Zealand Paediatric Intensive Care (ANZPIC) registry data for infants 2-12 months old admitted with bronchiolitis. Setting Seven Australian and New Zealand hospitals. These infants were prospectively identified through the comparative rehydration in bronchiolitis (CRIB) study between 2009 and 2011. Results Of 3884 infants identified, 3589 charts were available for analysis. Of 204 (5.7%) infants with bronchiolitis admitted to ICU, 162 (79.4%) received ventilation support. Of those 133 (82.1%) received non-invasive ventilation (high flow nasal cannula [HFNC] or continuous positive airway pressure [CPAP]) 7 (4.3%) received invasive ventilation alone and 21 (13.6%) received a combination of ventilation modes. Infants with comorbidities such as chronic lung disease (OR 1.6 [95% CI 1.0-2.6]), congenital heart disease (OR 2.3 [1.5-3.5]), neurological disease (OR 2.2 [1.2-4.1]) or prematurity (OR 1.5 [1.0-2.1]), and infants 2-6 months of age (OR 1.5 [1.1-2.0]) were more likely to be admitted to ICU. Respiratory syncitial virus positivity did not increase the likelihood of being admitted to ICU (OR 1.1 [95% CI 0.8-1.4]). HFNC use changed from 13/53 (24.5% [95% CI 13.7-38.3]) patient episodes in 2009 to 39/91 (42.9% [95% CI 32.5-53.7]) patient episodes in 2011. Conclusion Admission to ICU is an uncommon occurrence in infants admitted with bronchiolitis, but more common in infants with comorbidities and prematurity. The majority are managed with non-invasive ventilation, with increasing use of HFNC. [ABSTRACT FROM AUTHOR]

Objective Bronchiolitis is the most common lower respiratory tract infection in infants and the leading cause of hospitalisation. We aimed to assess whether intravenous hydration ( IVH) was more cost-effective than nasogastric hydration ( NGH) as a planned secondary economic analysis of a randomised trial involving 759 infants (aged 2-12 months) admitted to hospital with a clinical diagnosis of bronchiolitis and requiring non-oral hydration. No Australian cost data exist to aid clinicians in decision-making around interventions in bronchiolitis. Methods Cost data collections included hospital and intervention-specific costs. The economic analysis was reduced to a cost-minimisation study, focusing on intervention-specific costs of IVH versus NGH, as length of stay was equal between groups. All analyses are reported as intention to treat. Results Intervention costs were greater for IVH than NGH ($113 vs $74; cost difference of $39 per child). The intervention-specific cost advantage to NGH was robust to inter-site variation in unit prices and treatment activity. Conclusion Intervention-specific costs account for <10% of total costs of bronchiolitis admissions, with NGH having a small cost saving across all sites. [ABSTRACT FROM AUTHOR]

We previously observed that adults with Lennox-Gastaut syndrome ( LGS) show abnormal functional connectivity among cognitive networks, suggesting that this may contribute to impaired cognition. Herein we report network reorganization following seizure remission in a child with LGS who underwent functional magnetic resonance imaging ( fMRI) before and after resection of a cortical dysplasia. Concurrent electroencephalography ( EEG) was acquired during presurgical fMRI. Presurgical and postsurgical functional connectivity were compared using (1) graph theoretical analyses of small-world network organization and node-wise strength; and (2) seed-based analyses of connectivity within and between five functional networks. To explore the specificity of these postsurgical network changes, connectivity was further compared to nine children with LGS who did not undergo surgery. The presurgical EEG- fMRI revealed diffuse activation of association cortex during interictal discharges. Following surgery and seizure control, functional connectivity showed increased small-world organization, stronger connectivity in subcortical structures, and greater within-network integration/between-network segregation. These changes suggest network improvement, and diverged sharply from the comparison group of nonoperated children. Following surgery, this child with LGS achieved seizure control and showed extensive reorganization of networks that underpin cognition. This case illustrates that the epileptic process of LGS can directly contribute to abnormal network organization, and that this network disruption may be reversible. [ABSTRACT FROM AUTHOR]

The crux of their argument is to "never conclude there is "no difference" or "no association" just because a I P i value is larger than a threshold such as.05, or equivalently, because a confidence interval includes zero. A crucial step is to ask authors not to conclude a result is "positive" or "negative" purely around a I P i value threshold, I or i bound of a 95% confidence interval. Some have suggested a I P i value around.05 shows "weak evidence", while a I P i value <.01 shows "strong evidence" and a I P i value <.001 shows "very strong evidence." Thus, the I conclusions i drawn about the overall relevance of the results must be based on the I P i value ( I if i they report a I P i value), the effect size, I and i the bounds of the 95% confidence intervals, rather than simply whether or not the I P i value is greater or smaller than.05. [Extracted from the article]

Background During the brain growth spurt, anesthetic drugs can cause cellular and behavioral changes in the developing brain. The aim of this study was to determine the neuroprotective effect of erythropoietin after isoflurane anesthesia in rat pups. Methods A total of 42, 7-day-old Wistar rats were divided into three groups. Control group ( GC; n = 14): Rats breathed 100% oxygen for 6 h; Isoflurane group ( GI; n = 14): Rats were exposed to 1.5% isoflurane in 100% oxygen for 6 h; Isoflurane + erythropoietin group ( GIE; n = 14): 1000 IU·kg−1 (intraperitoneal; IP) Erythropoietin was administered after isoflurane anesthesia. Each group was divided into two groups for pathology and learning and memory tests. Silver, caspase-3, and fluoro-jade C staining were used for detecting apoptotic cells in frontal cortex, striatum, hippocampus, thalamus, and amygdala. Morris water maze was used to evaluate learning and memory. Results There was a significant increase in apoptotic cell count after isoflurane anesthesia in the frontal cortex when compared with control group (29.0 ± 9.27 vs 3.28 ± 0.75 [ P = 0.002], 20.85 ± 10.94 vs 2.0 ± 0.81 [ P = 0.002] and 24.57 ± 10.4 vs 5.14 ± 0.69 [ P = 0.024] with silver, caspase-3, and fluoro-jade C staining, respectively). The apoptotic cell count in the frontal cortex was significantly higher in GIE than GC with caspase-3 staining (9.14 ± 3.13 vs 2.0 ± 0.81, P = 0.002). The apoptotic cell count in GIE was significantly reduced in the frontal cortex when compared with GI (4.0 ± 0.81 vs 29.0 ± 9.27 [ P = 0.002], 9.14 ± 3.13 vs 20.85 ± 10.94 [ P = 0.04] and 4.0 ± 1.63 vs 24.57 ± 10.4 [ P = 0.012] with silver, caspase-3, and fluoro-jade C staining, respectively). Conclusions A total of 1000 IU·kg−1 IP erythropoietin diminished isoflurane-induced neuroapoptosis. Further experimental studies have to be planned to reveal the optimal dose and timing of erythropoietin before adaptation to clinical practice. [ABSTRACT FROM AUTHOR]

Background Near-infrared spectroscopy ( NIRS) provides an assessment of cerebral oxygenation and tissue hemoglobin concentration. Aim The aim of this study was to investigate whether the cerebral oxygenation and hemoglobin concentration measured with NIRS could predict outcomes after pediatric cardiac surgery. Method We conducted a retrospective observational study in 399 patients who underwent pediatric cardiac surgery. Associations were determined between postoperative outcome and preoperative and postoperative cerebral tissue oxygenation index ( TOI), postoperative normalized tissue hemoglobin index ( nTHI), concentration changes in oxygenated hemoglobin (Δ[HbO2]) and deoxygenated hemoglobin (Δ[ HHb]). Results Thirty-nine children had major postoperative morbidity and 12 died. Using Spearman's correlation analysis, postoperative lower TOI and higher Δ[ HHb] were associated with longer stays in the Intensive Care Unit ( ICU) ( r = −0.48, P < 0.001, r = 0.31, P < 0.001, respectively) and longer duration of intubation ( r = −0.48, P < 0.001, r = 0.31, P < 0.001, respectively) and higher probability of death determined by the Risk Adjusted Classification for Congenital Heart Surgery ( RACHS-1) ( r = −0.39, P < 0.001, r = 0.23, P < 0.001, respectively). In multivariate regression analysis, postoperative TOI was independently associated with major morbidity and mortality and Δ[ HHb] was independently associated with major morbidity. In receiver operating characteristic analysis, postoperative TOI and Δ[ HHb] predicted major morbidity (Area under the curve [ AUC] = 0.72, 0.68, respectively) and mortality ( AUC = 0.81, 0.69, respectively). Conclusion Lower TOI or higher [ HHb] at the end of surgery and higher RACHS-1 category predicted worse outcomes. [ABSTRACT FROM AUTHOR]

Background Several clinical and surgical factors can influence the occurrence of allogeneic blood transfusion ( ABT) during oncologic neurosurgery. Objectives To identify the potential predictive factors of ABT during craniotomy for the removal of brain tumors in children and the potential impact of intraoperative ABT on early postoperative outcome. Methods A retrospective study was performed in all pediatric patients younger than 18 years who underwent craniotomy for brain tumor removal from December 2009 to December 2012 in our institution. Pre-, intra-, and postoperative data were collected from medical and stored electronic anesthesia records. The predictors of intraoperative ABT were determined using multivariate logistic regression. Results A total of 110 patients were included. Twenty-seven patients (25%) received intraoperative ABT with a volume of 16 ± 8 ml·kg−1. On multivariate analysis, an age <4 years, a duration of surgery >270 min, and a preoperative hemoglobin <12.2 g·dl−1 were independently associated with the need for intraoperative ABT. We did not show any significant difference concerning postoperative early outcome and length of stay between the transfused and non-transfused patients except for the duration of postoperative mechanical ventilation that was significantly higher in the transfused group ( P = 0.04). Conclusion In children, craniotomy for brain tumor removal is at risk of intraoperative ABT. An age <4 years, a duration of surgery >270 min, and a preoperative hemoglobin <12.2 g·dl−1 are the main factors associated with intraoperative ABT during this surgery. [ABSTRACT FROM AUTHOR]

Background Exposure to some anesthetic agents during the fetal period has been shown to induce neurodegeneration or learning deficits in animal models. Sevoflurane is one of the most prevalent general anesthetics; however, the influence of sevoflurane at a clinically relevant concentration on the developing fetal brain remains unknown. Objective We investigated whether a single sevoflurane exposure during the fetal period would affect neuronal development and learning/memory ability in mice. Methods Pregnant mice at gestational day 17 were anesthetized with 1.5% sevoflurane in 50% oxygen for 6 h. Mice in the control group were exposed in 50% oxygen without sevoflurane. Pups of some mice in both groups subsequently were delivered early by cesarean section and whole fetal brains were excised. The rest of the pups were delivered naturally at gestational day 20 and were maintained for 8 weeks. The mRNA expression levels of caspase-3, brain derived neurotrophic factor ( BDNF), nerve growth factor ( NGF), and LIM kinase-1 ( LIMK-1) were measured in fetal whole brain and 8-week-old hippocampus sections. Synaptophysin protein in adult hippocampus was assessed immunochemically. In addition, 8-week-old mice were subjected to the radial maze test. Results No significant difference between sevoflurane and control groups regarding mRNA expression levels of all targets was seen, nor was there an obvious change in synaptophysin protein expression. The results of the maze test revealed that the each-day performance ratios (the rate of errors) of the sevoflurane group were not altered as compared with the control group. Conclusions These results suggest that the exposure during late pregnancy to a clinically relevant concentration of sevoflurane does not affect neuronal development and learning/memory ability of offspring mice. [ABSTRACT FROM AUTHOR]

Preclinical evidence suggests that anesthetic agents harm the developing brain thereby causing long-term neurocognitive impairments. It is not clear if these findings apply to humans, and retrospective epidemiological studies thus far have failed to show definitive evidence that anesthetic agents are harmful to the developing human brain. Aim The aim of this systematic review was to summarize the preclinical studies published over the past decade, with a focus on methodological issues, to facilitate the comparison between different preclinical studies and inform better design of future trials. Method The literature search identified 941 articles related to the topic of neurotoxicity. As the primary aim of this systematic review was to compare methodologies applied in animal studies to inform future trials, we excluded a priori all articles focused on putative mechanism of neurotoxicity and the neuroprotective agents. Forty-seven preclinical studies were finally included in this review. Results Methods used in these studies were highly heterogeneous-animals were exposed to anesthetic agents at different developmental stages, in various doses and in various combinations with other drugs, and overall showed diverse toxicity profiles. Physiological monitoring and maintenance of physiological homeostasis was variable and the use of cognitive tests was generally limited to assessment of specific brain areas, with restricted translational relevance to humans. Conclusion Comparison between studies is thus complicated by this heterogeneous methodology and the relevance of the combined body of literature to humans remains uncertain. Future preclinical studies should use better standardized methodologies to facilitate transferability of findings from preclinical into clinical science. [ABSTRACT FROM AUTHOR]