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Knowledge on the genetic basis of Parkinson's disease has grown tremendously since the discovery of the first monogenic form, caused by a mutation in α-synuclein, and with the subsequent identification of multiple other causative genes and associated loci. Genetic studies provide insights into the phenotypic heterogeneity and global distribution of Parkinson's disease. By shedding light on the underlying biological mechanisms, genetics facilitates the identification of new biomarkers and therapeutic targets. Several clinical trials of genetics-informed therapies are ongoing or imminent. International programmes in populations who have been under-represented in Parkinson's disease genetics research are fostering collaboration and capacity-building, and have already generated novel findings. Many challenges remain for genetics research in these populations, but addressing them provides opportunities to obtain a more complete and equitable understanding of Parkinson's disease globally. These advances facilitate the integration of genetics into the clinic, to improve patient management and personalised medicine., Competing Interests: Declaration of interests SYL is an employee at the University of Malaya. SYL has received stipends from the International Parkinson and Movement Disorder Society (MDS) as Chair of the Asian-Oceanian Section, and Science Advances as Associate Editor (Neuroscience). He reports consultancies from the Michael J Fox Foundation (MJFF), the Aligning Science Across Parkinson's-Global Parkinson's Genetics Program (ASAP-GP2), and Neurotorium Editorial Board; honoraria for lecturing from the MDS, Lundbeck, Eisai, and Medtronic; and research grants from the Malaysian Ministry of Education Fundamental Research Grant Scheme and the MJFF. AHT is an employee at the University of Malaya. AHT has received grants from and served as a consultant for the MJFF and the ASAP-GP2. AHT has received honoraria for lecturing from the MDS and Boehringer Ingelheim. NUO is employed by the College of Medicine, University of Lagos and receives institutional research grant support from the ASAP-GP2, the MJFF, and the UK National Institute for Health and Care Research for Parkinson's disease research including Parkinson's disease genetics studies. NUO has received honoraria as speaker from the MDS. HRM is employed by University College London. HRM reports paid consultancy from Roche, Aprinoia, AI Therapeutics, and Amylyx; lecture fees and honoraria from the British Medical Journal, Kyowa Kirin, and the MDS; research grants from Parkinson's UK, the Cure Parkinson's Trust, PSP Association, Medical Research Council, and the MJFF. HRM is a co-applicant on a patent application related to C9ORF72 (method for diagnosing a neurodegenerative disease; PCT/GB2012/052140). IM reports receiving research grants from the National Institutes of Health (1R01NS112499), the MJFF, and the ASAP-GP2. IM is also a member of the MDS-PAS Executive Committee and the PDGENEration Latino Advisory Council from the Parkinson's Foundation and has received honoraria as speaker from the MDS. LML reports receiving support from the Bachmann-Strauss Dystonia & Parkinson Foundation as part of a research fellowship. She also received a travel stipend to attend the Samuel Belzberg Dystonia Symposium in 2023. JNF is an employee at Nanyang Technological University Singapore, and received the National Medical Research Council Open Fund Individual Research Grant (MOH-000559) and the Ministry of Education Academic Research Funds (MOE-T2EP30220-0005 and MOE-MOET32020-0004). ES is employed by the University of Dundee, UK and has received research funding from the MJFF, the Chief Scientist Office in Scotland, and UK Research and Innovation Medical Research Council. AJN is employed by Queen Mary University of London. AJN reports grants from Parkinson's UK, Barts Charity, Cure Parkinson's, National Institute for Health and Care Research, Innovate UK, Solvemed, the Medical College of Saint Bartholomew's Hospital Trust, Alchemab, and the MJFF. AJN reports consultancy and personal fees from AstraZeneca, AbbVie, Profile, Bial, Charco Neurotech, Alchemab, Sosei Heptares, Umedeor, and Britannia, outside the submitted work. AJN has share options in Umedeor. WL reports research grants from the National Natural Science Foundation of China and the Science Technology Department of Zhejiang Province, China. RO has received travel grants from the MDS in 2022 and 2023, and received a research grant in 2022 and travel support to attend the annual GP2 meeting in 2022 and 2023 from ASAP-GP2. ABS is employed by the National Institutes of Health. He has received grants from the MJFF, and is a member of the scientific advisory board of Cajal Neuroscience. CB is a federal employee of the National Institutes of Health (NIH) USA, specifically the National Institute on Aging. He reports receiving research grants from the MJFF and ASAP-GP2. CK is the recipient of research grants from the German Research Foundation, ASAP-GP2, and the MJFF. CK has received travel grants and faculty honoraria from the MDS, and stipends as Deputy Editor of Movement Disorders and Science Advances, as well as a member of the Science Committee of the Else Kroener Fresenius Foundation. CK serves as a medical advisor to Centogene, Takeda, and Retromer Therapeutics, and has received speakers' honoraria from Bial and Desitin. AAA, KL, TST, YWT, SBC, JCEO, and NB declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Until recently, about three-quarters of all monogenic Parkinson's disease (PD) studies were performed in European/White ancestry, thereby severely limiting our insights into genotype-phenotype relationships at a global scale., Objective: To identify the multi-ancestry spectrum of monogenic PD., Methods: The first systematic approach to embrace monogenic PD worldwide, The Michael J. Fox Foundation Global Monogenic PD Project, contacted authors of publications reporting individuals carrying pathogenic variants in known PD-causing genes. In contrast, the Global Parkinson's Genetics Program's Monogenic Network took a different approach by targeting PD centers underrepresented or not yet represented in the medical literature., Results: In this article, we describe combining both efforts in a merger project resulting in a global monogenic PD cohort with the buildup of a sustainable infrastructure to identify the multi-ancestry spectrum of monogenic PD and enable studies of factors modifying penetrance and expressivity of monogenic PD., Conclusions: This effort demonstrates the value of future research based on team science approaches to generate comprehensive and globally relevant results. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Importance: Survival for children with out-of-hospital cardiac arrest (OHCA) remains poor despite improvements in adult OHCA survival., Objective: To characterize the frequency of and factors associated with adverse safety events (ASEs) in pediatric OHCA., Design, Setting, and Participants: This population-based retrospective cohort study examined patient care reports from 51 emergency medical services (EMS) agencies in California, Georgia, Oregon, Pennsylvania, Texas, and Wisconsin for children younger than 18 years with an OHCA in which resuscitation was attempted by EMS personnel between 2013 and 2019. Medical record review was conducted from January 2019 to April 2022 and data analysis from October 2022 to February 2023., Main Outcomes and Measure: Severe ASEs during the patient encounter (eg, failure to give an indicated medication, 10-fold medication overdose)., Results: A total of 1019 encounters of EMS-treated pediatric OHCA were evaluated; 465 patients (46%) were younger than 12 months. At least 1 severe ASE occurred in 610 patients (60%), and 310 patients (30%) had 2 or more. Neonates had the highest frequency of ASEs. The most common severe ASEs involved epinephrine administration (332 [30%]), vascular access (212 [19%]), and ventilation (160 [14%]). In multivariable logistic regression, the only factor associated with severe ASEs was young age. Neonates with birth-related and non-birth-related OHCA had greater odds of a severe ASE compared with adolescents (birth-related: odds ratio [OR], 7.0; 95% CI, 3.1-16.1; non-birth-related: OR, 3.4; 95% CI, 1.2-9.6)., Conclusions and Relevance: In this large geographically diverse cohort of children with EMS-treated OHCA, 60% of all patients experienced at least 1 severe ASE. The odds of a severe ASE were higher for neonates than adolescents and even higher when the cardiac arrest was birth related. Given the national increase in out-of-hospital births and ongoing poor outcomes of OHCA in young children, these findings represent an urgent call to action to improve care delivery and training for this population.

Background: Most episodic ataxias (EA) are autosomal dominantly inherited and characterized by recurrent attacks of ataxia and other paroxysmal and non-paroxysmal features. EA is often caused by pathogenic variants in the CACNA1A, KCNA1, PDHA1, and SLC1A3 genes, listed as paroxysmal movement disorders (PxMD) by the MDS Task Force on the Nomenclature of Genetic Movement Disorders. Little is known about the genotype-phenotype correlation of the different genetic EA forms., Methods: We performed a systematic review of the literature to identify individuals affected by an episodic movement disorder harboring pathogenic variants in one of the four genes. We applied the standardized MDSGene literature search and data extraction protocol to summarize the clinical and genetic features. All data are available via the MDSGene protocol and platform on the MDSGene website (https://www.mdsgene.org/)., Results: Information on 717 patients (CACNA1A: 491, KCNA1: 125, PDHA1: 90, and SLC1A3: 11) carrying 287 different pathogenic variants from 229 papers was identified and summarized. We show the profound phenotypic variability and overlap leading to the absence of frank genotype-phenotype correlation aside from a few key 'red flags'., Conclusion: Given this overlap, a broad approach to genetic testing using a panel or whole exome or genome approach is most practical in most circumstances., (© 2023 European Academy of Neurology.)

Aim: To identify specific activities associated with high cognitive load during simulated pediatric out-of-hospital cardiac arrest (POHCA) resuscitation using physiological monitoring with functional near-infrared spectroscopy (fNIRS)., Methods: We recruited teams of emergency medical services (EMS) responders from fire departments located throughout the Portland, OR metropolitan area to participate in POHCA simulations. Teams consisted of both paramedics and emergency medical technicians (EMTs), with one paramedic serving as the person in charge (PIC). The PIC was outfitted with the OctaMon to collect fNIRS signals from the prefrontal cortex. Signals reported changes in oxygenated and deoxygenated hemoglobin concentrations, which were used to determine moments of increased cognitive activity. Increased cognitive activity was determined by significant increases in oxygenated hemoglobin and decreases in deoxygenated hemoglobin. Significant changes in fNIRS signals were associated with specific concurrent clinical tasks recorded by two independent researchers using video review., Results: We recorded cognitive activity of EMS providers in 18 POHCA simulations. We found that a proportion of PIC's experienced relatively high cognitive load during medication administration, defibrillation, and rhythm checks compared to other events., Conclusion: EMS providers commonly experienced increased cognitive activity during key resuscitation tasks that were related to safely coordinating team members around calculating and administering medications, defibrillation, and rhythm and pulse checks. Understanding more about activities that require high cognitive demand can inform future interventions that reduce cognitive load., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: This methodological intersection article demonstrates a method to measure cognitive load in clinical simulations. Researchers have hypothesized that high levels of cognitive load reduce performance and increase errors. This phenomenon has been studied primarily by experimental designs that measure responses to predetermined stimuli and self-reports that reduce the experience to a summative value. Our goal was to develop a method to identify clinical activities with high cognitive burden using physiologic measures., Methods: Teams of emergency medical responders were recruited from local fire departments to participate in a scenario with a shockable pediatric out-of-hospital cardiac arrest (POHCA) patient. The scenario was standardized with the patient being resuscitated after receiving high-quality CPR and 3 defibrillations. Each team had a person in charge (PIC) who wore a functional near-infrared spectroscopy (fNIRS) device that recorded changes in oxygenated and deoxygenated hemoglobin concentration in their prefrontal cortex (PFC), which was interpreted as cognitive activity. We developed a data processing pipeline to remove nonneural noise (e.g., motion artifacts, heart rate, respiration, and blood pressure) and detect statistically significant changes in cognitive activity. Two researchers independently watched videos and coded clinical tasks corresponding to detected events. Disagreements were resolved through consensus, and results were validated by clinicians., Results: We conducted 18 simulations with 122 participants. Participants arrived in teams of 4 to 7 members, including one PIC. We recorded the PIC's fNIRS signals and identified 173 events associated with increased cognitive activity. [Defibrillation] (N = 34); [medication] dosing (N = 33); and [rhythm checks] (N = 28) coincided most frequently with detected elevations in cognitive activity. [Defibrillations] had affinity with the right PFC, while [medication] dosing and [rhythm checks] had affinity with the left PFC., Conclusions: FNIRS is a promising tool for physiologically measuring cognitive load. We describe a novel approach to scan the signal for statistically significant events with no a priori assumptions of when they occur. The events corresponded to key resuscitation tasks and appeared to be specific to the type of task based on activated regions in the PFC. Identifying and understanding the clinical tasks that require high cognitive load can suggest targets for interventions to decrease cognitive load and errors in care., (© 2023. The Author(s).)

Importance: Mortality from pediatric out-of-hospital cardiac arrest (OHCA) is high and has not improved in decades, unlike adult mortality. The low frequency of pediatric OHCA and weight-based medication and equipment needs may lead to lower quality of pediatric resuscitation compared with adults., Objective: To compare the quality of pediatric and adult resuscitation from OHCA in a controlled simulation environment and to evaluate whether teamwork, knowledge, experience, and cognitive load are associated with resuscitation performance., Design, Setting, and Participants: This cross-sectional in-situ simulation study was conducted between September 2020 and August 2021 in the metropolitan area of Portland, Oregon, and included engine companies from fire-based emergency services (EMS) agencies., Exposures: Participating EMS crews completed 4 simulation scenarios presented in random order: (1) adult female with ventricular fibrillation; (2) adult female with pulseless electrical activity; (3) school-aged child with ventricular fibrillation; and (4) infant with pulseless electrical activity. All patients were pulseless on EMS arrival. Data were captured by the research team in real time during the scenarios., Main Outcomes and Measures: The primary outcome was defect-free care, which included correct cardiopulmonary resuscitation depth, rate, and compression to ventilation ratio, time to bag-mask ventilation, and time to defibrillation, if applicable. Outcomes were determined by direct observation by an experienced physician. Secondary outcomes included additional time-based interventions and the use of correct medication doses and equipment size. We measured teamwork using the clinical teamwork scale, cognitive load with the National Aeronautics and Space Administration task load index (NASA-TLX), and knowledge using advanced life support resuscitation tests., Results: Among the 215 clinicians (39 crews) who participated in 156 simulations, 200 (93%) were male, and the mean (SD) age was 38.7 (0.6) years. No pediatric shockable scenario was defect free and only 5 pediatric nonshockable scenarios (12.8%) were defect free, while 11 (28.2%) adult shockable scenarios and 27 adult nonshockable scenarios (69.2%) were defect free. The mental demand subscale of the NASA-TLX was higher in the pediatric compared with the adult scenarios (mean [SD] pediatric score, 59.1 [20.7]; mean [SD] adult score, 51.4 [21.1]; P = .01). Teamwork scores were not associated with defect-free care., Conclusions and Relevance: In this simulation study of OHCA, resuscitation quality was significantly lower for pediatric than adult resuscitation. Mental demand may have been a contributor.

Aim: Neonatal cardiopulmonary arrests are rare but serious events. There is limited information on compliance to best-practice guidelines due to rarity, but deviations can have dire consequences. This research aimed to characterize compliance with and deviations from Neonatal Resuscitation Program (NRP) guidelines and their association with teamwork., Methods: We observed Emergency Medical Service (EMS) teams responding to standardized neonatal resuscitation simulations following a precipitous home delivery. A Clinical expert evaluated teamwork during simulations using the Clinical Teamwork Scale (CTS™). A neonatologist evaluated technical performance in blinded video review according to NRP guidelines. We report the types, counts, and severity of observed deviations. Logistic regression tested the association of CTS™ factors with the occurrence of deviations., Results: Forty-five (45) teams of 265 EMS personnel from fire and transport agencies participated in the simulations. Eighty-seven percent (39/45) of teams were rated as having good teamwork according to CTS™. Nearly all teams (44 of 45) delayed or did not perform one or more of the initial steps of dry, warm, or stimulate; delayed bag-valve mask ventilation (BVM); or performed continuous compressions instead of the recommended 3:1 compression-to-ventilation ratio. Logistic regression revealed an 82% ( p  < 0.04) decrease in the odds of airway errors for each level of improvement in teams' decision-making., Conclusion: Drying, warming, and stimulating, and ventilation tailored to the physiologic needs of infants continue to be top priorities in neonatal care for out-of-hospital settings. EMS teamwork is good and higher quality of decision-making appears to decrease the odds of ventilation errors., (© 2022 The Author(s).)

Purpose: To determine whether a brief leadership curriculum including high-fidelity simulation can improve leadership skills among resident physicians., Method: This was a double-blind, randomized controlled trial among obstetrics-gynecology and emergency medicine (EM) residents across 5 academic medical centers from different geographic areas of the United States, 2015-2017. Participants were assigned to 1 of 3 study arms: the Leadership Education Advanced During Simulation (LEADS) curriculum, a shortened Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) curriculum, or as active controls (no leadership curriculum). Active controls were recruited from a separate site and not randomized to limit any unintentional introduction of materials from leadership curricula. The LEADS curriculum was developed in partnership with the Council on Resident Education in Obstetrics and Gynecology and Council of Residency Directors in Emergency Medicine as a novel way to provide a leadership toolkit. Both LEADS and the abbreviated TeamSTEPPS were designed as six 10-minute interactive web-based modules.The primary outcome of interest was the leadership performance score from the validated Clinical Teamwork Scale instrument measured during standardized high-fidelity simulation scenarios. Secondary outcomes were 9 key components of leadership from the detailed leadership evaluation measured on 5-point Likert scales. Both outcomes were rated by a blinded clinical video reviewer., Results: One hundred ten obstetrics-gynecology and EM residents participated in this 2-year trial. Participants in both LEADS and TeamSTEPPS had statistically significant improvement in leadership scores from "average" to "good" ranges both immediately and at the 6-month follow-up, while controls remained unchanged in the "average" category throughout the study. There were no differences between LEADS and TeamSTEPPS curricula with respect to the primary outcome., Conclusions: Residents who participated in a brief structured leadership training intervention had improved leadership skills that were maintained at 6-month follow-up., (Copyright © 2021 by the Association of American Medical Colleges.)