Clathrin-mediated endocytosis (CME) is a well-studied mechanism to internalize plasma membrane proteins; however, to endocytose such cargo, most eukaryotic cells also use alternative clathrin-independent endocytic (CIE) pathways, which are less well characterized. The budding yeast Saccharomyces cerevisiae, a widely used model for studying CME, was recently shown to have a CIE pathway that requires the GTPase Rho1, the formin Bni1, and their regulators. Nevertheless, in both yeast and mammalian cells, the mechanisms underlying cargo selection in CME and CIE are only beginning to be understood. For CME in yeast, particular α-arrestins contribute to recognition of specific cargos and promote their ubiquitylation by recruiting the E3 ubiquitin protein ligase Rsp5. Here, we show that the same α-arrestin–cargo pairs promote internalization through the CIE pathway by interacting with CIE components. Notably, neither expression of Rsp5 nor its binding to α-arrestins is required for CIE. Thus, α-arrestins are important for cargo selection in both the CME and CIE pathways, but function by distinct mechanisms in each pathway.
Summary Background Clinical evidence shows that pediatric anesthesia patients are subject to a higher rate of life‐threatening medical errors than their adult counterparts. Medication error in adult anesthesia is estimated to occur to 1 in 133 anesthetic administrations, but such a figure has not been determined for pediatric anesthesia patients. Individual studies of medication error in pediatric anesthesia have ranged from rates of 0.01% to 1.92% of anesthetic uses. The present study is a systematic review that employs a meta‐analytic estimate to determine the rate of medication error in pediatric anesthesia. Methods A systematic review of the literature on pediatric anesthesia medication error was conducted using Medline, Cochrane Database, PROSPERO, and Clinicaltrials.gov. A meta‐analytic estimate was used to determine the medication error rate for all of the included studies. Subgroup sensitivity analysis was used to evaluate possible sources of heterogeneity in included studies. Results Of the 433 initially screened records, 13 studies met inclusion criteria. Meta‐analytic estimate of medication error rate across all studies was 0.08% (95% CI 0.05%‐0.10%), or 1 out of 1250 anesthetics. Ten different countries were represented in the studies. Sample size of anesthetics reported on ranged from 296 to 2 316 635. Data collecting periods ranged from 3 months to 15 years. Six included studies individually reported higher rates of medication error in patients under 1 year of age. Conclusion The present systematic review revealed a medication error rate of 1 per 1250 anesthetic administrations in pediatric anesthesia. This result is significantly lower than would be expected given reported rates of medication error in adult anesthesia, which raises questions regarding the validity of research methods and reporting of medication error in pediatric anesthesia. Future investigations of medication error should employ methodologies other than self‐reporting of error, such as retrospective chart review.
Informed consent for pediatric anesthesia challenges practitioners to navigate complex ethical, medical, and legal ambiguities. A patient's status as a minor does not negate the importance of his or her participation in the decision-making process but, rather, necessitates a nuanced evaluation of age and development to involve the patient to an appropriate extent. Given the complexities involved with pediatric informed consent in anesthesia practice and research, it is important to understand the experience of key stakeholders involved. For this review, we searched Medline, the Cochrane database, PROSPERO, and Clinicaltrials.gov for studies involving pediatric anesthesia informed consent. Inclusion and exclusion criteria were designed to select for studies that included issues related to informed consent as primary outcomes. The following data were extracted from included studies: title, authors, date of publication, study type, intervention, data collection method, participant type (ie, parent, pediatric patient, anesthesia provider), number of participants, pediatric patient age range, and primary outcome measures. Twenty-two articles were included for final review: studies of informed consent in pediatric anesthesia span many aspects of informed consent. Parental understanding has been studied most often (7/22 studies), followed by parental preferences (5/22 studies) and provider-related outcomes (5/22 studies) such as time spent interacting with patients, subjective reporting on amount of training related to informed consent, and provider satisfaction with the informed consent process. Outcomes pertaining to pediatric patients themselves constitute the smallest number of studies, including child anxiety (1/22), child understanding (1/22), and child refusal (1/22). Among the parties involved, parents have been most frequently identified as the subjects of these studies (2719/3805 subjects across all included studies, or 71% of all subjects). Pediatric patients are the least frequently involved subjects of studies that investigate informed consent in pediatric anesthesia (493/3805, or 13% of all subjects). Anesthesia providers and investigators have been study subjects (593/3805, or 16% of all subjects) for a range of topics including time spent interacting with patient, nature of informed consent conversation in relation to trainee status, satisfaction with informed consent process, and priorities for informed consent content. The aim of the present narrative review is to summarize the work that has been done on informed consent for pediatric anesthesia.
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