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1.
BMJ Open ; 14(4): e085850, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631827

RESUMO

INTRODUCTION: Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not. METHODS AND ANALYSIS: Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities. ETHICS AND DISSEMINATION: This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles.


Assuntos
Fortalecimento Institucional , Ciência da Implementação , Humanos , Cidades , Canadá , Vitória
2.
Syst Rev ; 13(1): 94, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519996

RESUMO

BACKGROUND: Social determinants of health (SDH), including "the conditions in which individuals are born, grow, work, live and age" affect child health and well-being. Several studies have synthesized evidence about the influence of SDH on childhood injury risks and outcomes. However, there is no systematic evidence about the impact of SDH on accessing care and quality of care once a child has suffered an injury. We aim to evaluate the extent to which access to care and quality of care after injury are affected by children and adolescents' SDH. METHODS: Using Cochrane methodology, we will conduct a systematic review including observational and experimental studies evaluating the association between social/material elements contributing to health disparities, using the PROGRESS-Plus framework: place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, and social capital and care received by children and adolescents (≤ 19 years of age) after injury. We will consult published literature using PubMed, EMBASE, CINAHL, PsycINFO, Web of Science, and Academic Search Premier and grey literature using Google Scholar from their inception to a maximum of 6 months prior to submission for publication. Two reviewers will independently perform study selection, data extraction, and risk of bias assessment for included studies. The risk of bias will be assessed using the ROBINS-E and ROB-2 tools respectively for observational and experimental study designs. We will analyze data to perform narrative syntheses, and if enough studies are identified, we will conduct a meta-analysis using random effects models. DISCUSSION: This systematic review will provide a synthesis of evidence on the association between SDH and pediatric trauma care (access to care and quality of care) that clinicians and policymakers can use to better tailor care systems and promote equitable access and quality of care for all children. We will share our findings through clinical rounds, conferences, and publication in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023408467.


Assuntos
Serviços Médicos de Emergência , Determinantes Sociais da Saúde , Feminino , Adolescente , Humanos , Criança , Revisões Sistemáticas como Assunto , Metanálise como Assunto , Projetos de Pesquisa
3.
Child Abuse Negl ; 149: 106645, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38241804

RESUMO

BACKGROUND: During the COVID-19 pandemic, multiple child health experts postulated that the stay-at-home orders would negatively impact child abuse and neglect. OBJECTIVES: We aimed to examine the impact of the COVID-19 pandemic on child abuse and neglect in children ages 18 and under; and review author recommendations for future emergency lockdown procedures. METHODS: We completed a systematic search of articles across five databases. Review-level studies were included if they examined any abuse or neglect related outcomes in children and youth (e.g., injuries, case openings), and were published in English. We completed quality appraisals of each included article using the Health Evidence™ tool. We categorized the findings by data source including administrative and survey data, or other data sources. We also narratively summarized reported recommendations. RESULTS: In total, 11 reviews were included. Two reviews were of strong quality, 7 moderate, and 2 were weak. Overall, studies within reviews that reported from administrative data sources demonstrated decreased child abuse and neglect outcomes compared to before the pandemic. Studies using cross-sectional data demonstrated increases. Reviews with mixed results often reported increases in emotional, neglect and psychological abuse cases and decreases physical and sexual abuse cases. CONCLUSIONS: This study found consistent results across reviews; depending on the data source and study design, child abuse and neglect outcomes either increased or decreased during the COVID-19 pandemic. Future work should enhance data collection methods for surveillance and intervention of child abuse and neglect during public health emergencies when traditional mechanisms are limited, with an increased focus on the rigor of reporting.


Assuntos
COVID-19 , Maus-Tratos Infantis , Adolescente , Humanos , Criança , Pandemias , Estudos Transversais , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Maus-Tratos Infantis/psicologia
4.
Ann Emerg Med ; 83(4): 327-339, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38142375

RESUMO

STUDY OBJECTIVE: Our primary objectives were to identify clinical practice guideline recommendations for children with acute mild traumatic brain injury (mTBI) presenting to an emergency department (ED), appraise their overall quality, and synthesize the quality of evidence and the strength of included recommendations. METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and medical association websites from January 2012 to May 2023 for clinical practice guidelines with at least 1 recommendation targeting pediatric mTBI populations presenting to the ED within 48 hours of injury for any diagnostic or therapeutic intervention in the acute phase of care (ED and inhospital). Pairs of reviewers independently assessed overall clinical practice guideline quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The quality of evidence on recommendations was synthesized using a matrix based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Evidence-to-Decision framework. RESULTS: We included 11 clinical practice guidelines, of which 6 (55%) were rated high quality. These included 101 recommendations, of which 34 (34%) were based on moderate- to high-quality evidence, covering initial assessment, initial diagnostic imaging, monitoring/observation, therapeutic interventions, discharge advice, follow-up, and patient and family support. We did not identify any evidence-based recommendations in high-quality clinical practice guidelines for repeat imaging, neurosurgical consultation, or hospital admission. Lack of strategies and tools to aid implementation and editorial independence were the most common methodological weaknesses. CONCLUSIONS: We identified 34 recommendations based on moderate- to high-quality evidence that may be considered for implementation in clinical settings. Our review highlights important areas for future research. This review also underlines the importance of providing strategies to facilitate the implementation of clinical practice guideline recommendations for pediatric mTBI.


Assuntos
Concussão Encefálica , Humanos , Criança , Concussão Encefálica/diagnóstico , Concussão Encefálica/terapia , Serviço Hospitalar de Emergência
5.
Can J Nurs Res ; 56(1): 109-116, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38115698

RESUMO

BACKGROUND: The Period of PURPLE Crying Program® (PURPLE) is a universal parent education program that is delivered by nurses and health care providers to all parents/caregivers of newborns in British Columbia (B.C.). The aim of the program is to reduce the incidence of Traumatic Head Injury -Child Maltreatment (THI-CM), a form of child physical abuse. OBJECTIVE: To determine if the PURPLE program had an impact on the rate of physical abuse hospitalizations for children less than or equal to 24 months of age in B.C. since implementation in 2009. METHODS: The analysis measured physical abuse hospitalization rates for the period January 1, 1999 to December 31, 2019 and excluded any cases of confirmed Traumatic Head Injury-Child Maltreatment. Data were divided into pre-implementation period January, 1999 to December, 2008, and post-implementation period January, 2009 to December, 2019. Data were obtained from the Discharge Abstract Database and B.C. THI-CM Surveillance System to capture information on infant child abuse. Poisson regression and ANCOVA was applied to model the change in rates pre and post program implementation. RESULTS: Physical abuse hospitalization rates decreased by 30% post-implementation period (95% CI: -14%, 57%, p = 0.1561). The decreasing linear trend in the post-implementation period was significantly different than the increasing linear trend in the pre-implementation period (F1,17 = 4.832, p = 0.042). CONCLUSIONS: Nurses' role in engaging parents in conversations about PURPLE messages over multiple timepoints within a structured universal program model resulted in a decrease in physical abuse hospitalization rates since the implementation of PURPLE.


Assuntos
Traumatismos Craniocerebrais , Pais , Abuso Físico , Humanos , Lactente , Recém-Nascido , Colúmbia Britânica/epidemiologia , Cuidadores , Traumatismos Craniocerebrais/epidemiologia , Hospitalização , Pais/educação , Abuso Físico/prevenção & controle , Incidência
6.
Biomolecules ; 13(10)2023 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-37892154

RESUMO

Hypoxic-ischaemic encephalopathy (HIE) is an important cause of morbidity and mortality globally. Although mild therapeutic hypothermia (TH) may improve outcomes in selected babies, the mechanism of action is not fully understood. A proteomics discovery study was carried out to analyse proteins in the plasma of newborns with HIE. Proteomic analysis of plasma from 22 newborns with moderate-severe HIE that had initially undergone TH, and relative controls including 10 newborns with mild HIE who did not warrant TH and also cord blood from 10 normal births (non-HIE) were carried out using the isobaric Tandem Mass Tag (TMT®) 10plexTM labelling with tandem mass spectrometry. A total of 7818 unique peptides were identified in all TMT10plexTM samples, translating to 3457 peptides representing 405 proteins, after applying stringent filter criteria. Apart from the unique protein signature from normal cord blood, unsupervised analysis revealed several significantly regulated proteins in the TH-treated moderate-severe HIE group. GO annotation and functional clustering revealed various proteins associated with glucose metabolism: the enzymes fructose-bisphosphate aldolase A, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase 1, phosphoglycerate kinase 1, and pyruvate kinase PKM were upregulated in newborns with favourable (sHIE+) outcomes compared to newborns with unfavourable (sHIE-) outcomes. Those with favourable outcomes had normal MR imaging or mild abnormalities not predictive of adverse outcomes. However, in comparison to mild HIE and the sHIE- groups, the sHIE+ group had the additional glucose metabolism-related enzymes upregulated, including triosephosphate isomerase, α-enolase, 6-phosphogluconate dehydrogenase, transaldolase, and mitochondrial glutathione reductase. In conclusion, our plasma proteomic study demonstrates that TH-treated newborns with favourable outcomes have an upregulation in glucose metabolism. These findings may open new avenues for more effective neuroprotective therapy.


Assuntos
Asfixia , Proteômica , Lactente , Humanos , Recém-Nascido , Metabolismo dos Carboidratos , Espectrometria de Massas em Tandem , Peptídeos
7.
J Immunother Cancer ; 11(10)2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37857526

RESUMO

BACKGROUND: Post-translational modification of proteins has the potential to alter the ability of T cells to recognize major histocompatibility complex (MHC) class -I and class-II restricted antigens, thereby resulting in altered immune responses. One such modification is carbamylation (homocitrullination) that results in the formation of homocitrulline (Hcit) residues in a non-enzymatic reaction of cyanate with the lysine residues in the polypeptide chain. Homocitrullination occurs in the tumor microenvironment and CD4-mediated immune responses to Hcit epitopes can target stressed tumor cells and provide a potent antitumor response in mouse models. METHODS: Homocitrullinated peptides were identified and assessed in vitro for HLA-A2 binding and in vivo in human leukocyte antigen (HLA) transgenic mouse models for immunogenicity. CD8 responses were assessed in vitro for cytotoxicity and in vivo tumor therapy. Human tumor samples were analyzed by targeted mass spectrometry for presence of homocitrullinated peptides. RESULTS: Homocitrullinated peptides from aldolase and cytokeratin were identified, that stimulated CD8-mediated responses in vivo. Modified peptides showed enhanced binding to HLA-A2 compared with the native sequences and immunization of HLA-A2 transgenic mice generated high avidity modification specific CD8 responses that killed peptide expressing target cells. Importantly, in vivo the homocitrullinated aldolase specific response was associated with efficient CD8 dependent antitumor therapy of the aggressive murine B16 tumor model indicating that this epitope is naturally presented in the tumor. In addition, the homocitrullinated aldolase epitope was also detected in human tumor samples. CONCLUSION: This is the first evidence that homocitrullinated peptides can be processed and presented via MHC-I and targeted for tumor therapy. Thus, Hcit-specific CD8 T-cell responses have potential in the development of future anticancer therapy.


Assuntos
Linfócitos T CD8-Positivos , Antígeno HLA-A2 , Camundongos , Humanos , Animais , Antígenos de Histocompatibilidade Classe II/metabolismo , Vacinação , Camundongos Transgênicos , Peptídeos , Antígenos de Histocompatibilidade Classe I , Epitopos , Processamento de Proteína Pós-Traducional , Aldeído Liases/metabolismo
8.
BMJ Open Sport Exerc Med ; 9(3): e001645, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37780130

RESUMO

Video analysis is a useful tool for injury surveillance in rugby union. There are few video analysis studies in the professional female game, with most studies published in the male elite/professional settings. Moreover, there is a sparsity of literature in youth rugby settings. The following narrative review outlines the strengths and limitations of the current video analysis literature for injury surveillance in youth rugby union, highlights the importance of video analysis for youth rugby player safety and welfare, and discusses recommendations for using video analysis to inform player safety in youth rugby.

9.
Artigo em Inglês | MEDLINE | ID: mdl-37510600

RESUMO

(1) Background: Residential fires represent the third leading cause of unintentional injuries globally. This study aims to offer an overview and a longitudinal evaluation of the HomeSafe program implemented in Surrey in 2008 and to assess its effectiveness in mitigating fire-related outcomes. (2) Methods: Data were collected over a 12-year period (2008-2019). Assessed outcomes comprised frequency of fire incidents, residential fires, casualties, functioning smoke alarms, and contained fires. The effectiveness of each initiative was determined by comparing the specific intervention group outcome and the city-wide outcome to the pre-intervention period. (3) Results: This study targeted 120,349 households. HomeSafe achieved overwhelming success in decreasing fire rates (-80%), increasing functioning smoke alarms (+60%), increasing the percentage of contained fires (+94%), and decreasing fire casualties (-40%). The study findings confirm that the three most effective HomeSafe initiatives were firefighters' visits of households, inspections and installations of smoke alarms, and verifications of fire crew alarms at fire incidents. Some initiatives were less successful, including post-door hangers (+12%) and package distribution (+15%). (4) Conclusions: The HomeSafe program effectively decreased the occurrence and magnitude of residential fires. Lessons learned should be transferred to similar contexts to implement an evidence-based, consistent, and systematic approach to sustainable fire prevention initiatives.


Assuntos
Bombeiros , Incêndios , Humanos , Equipamentos de Proteção , Incêndios/prevenção & controle , Fumaça , Canadá
10.
Front Public Health ; 11: 1180968, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37325315

RESUMO

[This corrects the article DOI: 10.3389/fpubh.2022.938091.].

11.
BMC Public Health ; 23(1): 1211, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349745

RESUMO

BACKGROUND: Concerns regarding health equity (HE) and the built environment (BE) are well established in the Canadian urban context. Transport and injury prevention professionals across sectors, such as transportation and public health, are involved in designing and implementing BE interventions that enhance the safety of vulnerable road users (VRUs). Results from a larger study examining barriers and facilitators to BE change are used to illustrate how transport and injury prevention professionals perceive HE concerns in their work in five Canadian municipalities. Broadening our understanding of how HE influences the professional BE change context is crucial when advocating for modifications that enhance the safety of equity-deserving VRUs and groups who experience marginalization. METHODS: Interview and focus group data were gathered from transport and injury prevention professionals working in policy/decision-making, transport, police services, public health, non-profit organizations, schools/school boards, community associations, and private sectors across five Canadian urban municipalities: Vancouver, Calgary, Peel Region, Toronto, and Montréal. Data were analyzed using thematic analysis (TA) to illustrate how equity considerations were perceived and applied in participants' BE change work. RESULTS: The results of this study illustrate transport and injury prevention professionals' awareness of the varying needs of VRUs, as well as the inadequacies of current BEs in the Canadian urban context and consultation processes utilized to guide change. Participants emphasized the importance of equitable community consultation strategies, as well as specific BE changes that would support the health and safety of VRUs. Overall, the results highlight how HE concerns inform transport and injury prevention professionals' BE change work in the Canadian urban context. CONCLUSION: For professionals working in urban Canadian transport and injury prevention sectors HE concerns influenced their perspectives of the BE and BE change. These results illustrate a growing need for HE to guide BE change work and consultation processes. Further, these results contribute to ongoing efforts in the Canadian urban context to ensure that HE is at the forefront of BE policy change and decision-making, while promoting existing strategies to ensure that the BE, and related decision-making processes, are accessible and informed by a HE lens.


Assuntos
Equidade em Saúde , Humanos , Cidades , Canadá , Formulação de Políticas , Meios de Transporte
13.
Inj Prev ; 29(5): 407-411, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37295929

RESUMO

BACKGROUND: Injuries resulting from collisions between a bicyclist and driver are preventable and have high economic, personal and societal costs. Studying the language choices used by police officers to describe factors responsible for child bicyclist-motor vehicle collisions may help shift prevention efforts away from vulnerable road users to motorists and the environment. The overall aim was to investigate how police officers attribute blame in child (≤18 years) bicycle-motor vehicle collision scenarios. METHODS: A document analysis approach was used to analyse Alberta Transportation police collision reports from Calgary and Edmonton (2016-2017). Collision reports were categorised by the research team according to perceived blame (child, driver, both, neither, unsure). Content analysis was then used to examine police officer language choices. A narrative thematic analysis of the individual, behavioural, structural and environmental factors leading to collision blame was then conducted. RESULTS: Of 171 police collision reports included, child bicyclists were perceived to be at fault in 78 reports (45.6%) and adult drivers were perceived at fault in 85 reports (49.7%). Child bicyclists were portrayed through language choices as being irresponsible and irrational, leading to interactions with drivers and collisions. Risk perception issues were also mentioned frequently in relation to poor decisions made by child bicyclists. Most police officer reports discussed road user behaviours, and children were frequently blamed for collisions. CONCLUSIONS: This work provides an opportunity to re-examine perceptions of factors related to motor vehicle and child bicyclist collisions with a view to prevention.


Assuntos
Ciclismo , Polícia , Adulto , Humanos , Criança , Ciclismo/lesões , Acidentes de Trânsito/prevenção & controle , Veículos Automotores , Alberta
14.
Front Public Health ; 11: 1126066, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124817

RESUMO

Objectives: This study explored how demographic characteristics, life experiences, and firefighting exposures have an impact on cancer among female firefighters, and described the types and biologic characteristics of cancers as reported by women in the fire service. Methods: The online survey was available from June 2019 to July 2020. Questions related to demographic characteristics, lifestyle factors, firefighting exposures, and cancer diagnoses. Descriptive analyses characterized variables by the presence or absence of cancer. Qualitative data provided insight into both firefighting and cancer experiences among women. Results: There were 1,344 female firefighter respondents from 12 different countries, 256 of whom provided information on their cancer diagnosis. North American respondents made up 92% of the total. Those with cancer were older, had been in the fire service longer, had more career fires and toxic exposures, and were less likely to still be in active service. They also reported more tobacco use, and more full-term pregnancies. There were no differences in family history of cancer between the two groups. The average age at diagnosis was 39.0 years. The major types of cancer reported included breast (25.4%), cervical (21.1%), melanoma (20.7%), base cell/skin (16.4%), and uterine (14.8%). The cancer was detected when seeking medical attention for symptoms (42.1%), during routine health screening (29.8%), and during specific cancer screening (28.1%). The stage of cancer was reported by 44.5%, and 30.9% included the histopathological grade. Treatments included surgery (72.7%), chemotherapy (14.8%), radiotherapy (13.7%), and observation (13.7%). Challenges associated with cancer included psychosocial (33.2%), financial (18.8%), physical (6.6%), and spiritual (6.3%). Concerns about reporting a cancer experience to their employer included the desire to keep health information private (11.3%), a feeling of vulnerability (7.4%), and being perceived as weak (7.0%). Lack of support from their employer or insurer was also noted. Conclusion: Female firefighters experienced a wide variety of different types of cancers which may come earlier than similar cancers in the public. These findings can help inform resource allocation, the development of new policies, and the need for broader presumptive coverage to support female firefighters diagnosed with cancer.


Assuntos
Bombeiros , Melanoma , Gravidez , Feminino , Humanos , Adulto , Confiabilidade dos Dados , Emoções , Seguradoras
15.
Inj Prev ; 29(5): 367-370, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37230734

RESUMO

BACKGROUND: Unintentional injuries are a leading cause of children's hospitalisations and death globally and are thus a pressing public health concern. Fortunately, they are largely preventable, and understanding children's perspectives on safe and dangerous outdoor play can help educators and researchers identify ways to mitigate the likelihood of their occurrence. Problematically, children's perspectives are rarely included in injury prevention scholarship. In this study, we acknowledge children's right to have their voices heard by exploring the perspectives on safe and dangerous play and injury of 13 children in Metro Vancouver, Canada. METHODS: We employed tenets of risk and sociocultural theory and a child-centred community-based participatory research approach to injury prevention. We conducted unstructured interviews with children aged 9-13 years old. RESULTS: Through our thematic analysis, we identified two themes: (1) 'little' and 'big' injuries and (2) risk and danger. CONCLUSION: Our results suggest children differentiate between 'little' and 'big' injuries by reflecting on the potential loss of opportunities for play with friends. Further, they suggest children avoid play they perceive as dangerous, but enjoy 'risk-seeking' because it is thrilling and provides them with opportunities to push their physical and mental capabilities. Child educators and injury prevention researchers can use our findings to inform their communications with children and make play spaces more accessible to, fun and safe for children.


Assuntos
Lesões Acidentais , Exame Físico , Humanos , Criança , Adolescente , Jogos e Brinquedos , Pesquisa Qualitativa , Canadá
16.
Neurobiol Dis ; 182: 106140, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37120095

RESUMO

The rare A673T variant was the first variant found within the amyloid precursor protein (APP) gene conferring protection against Alzheimer's disease (AD). Thereafter, different studies have discovered that the carriers of the APP A673T variant show reduced levels of amyloid beta (Aß) in the plasma and better cognitive performance at high age. Here, we analyzed cerebrospinal fluid (CSF) and plasma of APP A673T carriers and control individuals using a mass spectrometry-based proteomics approach to identify differentially regulated targets in an unbiased manner. Furthermore, the APP A673T variant was introduced into 2D and 3D neuronal cell culture models together with the pathogenic APP Swedish and London mutations. Consequently, we now report for the first time the protective effects of the APP A673T variant against AD-related alterations in the CSF, plasma, and brain biopsy samples from the frontal cortex. The CSF levels of soluble APPß (sAPPß) and Aß42 were significantly decreased on average 9-26% among three APP A673T carriers as compared to three well-matched controls not carrying the protective variant. Consistent with these CSF findings, immunohistochemical assessment of cortical biopsy samples from the same APP A673T carriers did not reveal Aß, phospho-tau, or p62 pathologies. We identified differentially regulated targets involved in protein phosphorylation, inflammation, and mitochondrial function in the CSF and plasma samples of APP A673T carriers. Some of the identified targets showed inverse levels in AD brain tissue with respect to increased AD-associated neurofibrillary pathology. In 2D and 3D neuronal cell culture models expressing APP with the Swedish and London mutations, the introduction of the APP A673T variant resulted in lower sAPPß levels. Concomitantly, the levels of sAPPα were increased, while decreased levels of CTFß and Aß42 were detected in some of these models. Our findings emphasize the important role of APP-derived peptides in the pathogenesis of AD and demonstrate the effectiveness of the protective APP A673T variant to shift APP processing towards the non-amyloidogenic pathway in vitro even in the presence of two pathogenic mutations.


Assuntos
Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Humanos , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/metabolismo , Heterozigoto , Encéfalo/metabolismo
17.
CMAJ Open ; 11(1): E160-E168, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36787989

RESUMO

BACKGROUND: Poisoning, from substances such as illicit drugs, prescribed and over-the-counter medications, alcohol, pesticides, gases and household cleaners, is the leading cause of injury-related death and the second leading cause for injury-related hospital admission in British Columbia. We examined the health and economic costs of poisoning in BC for 2016, using a societal perspective, to support public health policies aimed at minimizing losses to society. METHODS: Costs by intent, sex and age group were calculated in Canadian dollars using a classification and costing framework based on existing provincial injury data combined with data from the published literature. Direct cost components included fatal poisonings, hospital admissions, emergency department visits, ambulance attendance without transfer to hospital and calls to the British Columbia Drug and Poison Information Centre (BC DPIC) not resulting in ambulance attendance, emergency care or transfer to hospital. Indirect costs, measured as loss of earnings and informal caregiving costs, were also calculated. RESULTS: We estimate that poisonings in BC totalled $812.5 million in 2016 with $108.9 million in direct health care costs and $703.6 million in indirect costs. Unintentional poisoning injuries accounted for 84% of total costs, 46% of direct costs and 89% of indirect costs. Males accounted for higher proportions of direct costs for all patient dispositions except hospital admissions. Patients aged 25-64 years accounted for higher proportions of direct costs except for calls to BC DPIC, where proportions were highest for children younger than 15 years. INTERPRETATION: Hospital care expenditures represented the largest direct cost of poisoning, and lost productivity following death represented the largest indirect cost. Quantifying and understanding the financial burden of poisoning has implications not only for government and health care, but also for society, employers, patients and families.


Assuntos
Custos de Cuidados de Saúde , Gastos em Saúde , Masculino , Criança , Humanos , Colúmbia Britânica/epidemiologia , Hospitalização , Hospitais
18.
Health Rep ; 33(7): 3-12, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35862068

RESUMO

Background: There has been increasing scrutiny of opioid prescribing following injury because of concerns that prescribed opioids may contribute to addiction and overdose. This study aimed to better understand the relationship between injury, opioids prescribed before and after injury, and non-medical drug poisoning. Data and methods: Working age (15 to 65 years old) residents of British Columbia's Fraser Health region with an injury that involved an emergency department visit were included. Factors examined included the prescription of opioid and opioid agonist therapy (OAT) medications before and after injury, age, sex, work-related injuries, and socioeconomic status, as well as how they were associated with non-medical drug poisoning risk and post-injury prescriptions. Results: Opioid-naive individuals (those without an opioid prescription captured before their injury) who were prescribed OAT medication-a marker of opioid use disorder-following their injury had a higher risk of subsequent non-medical drug poisoning (Hazard ratio (HR): 21.4 to 22.4 compared with opioid-naive individuals without an opioid or OAT prescription). Post-injury opioid prescription in these individuals increased poisoning risk (HR: 1.27 compared with those without a prescription). Being of male sex (HR: 1.80), being younger (HR: 0.76 for every 10-year increase in age) and living in the lowest-income neighbourhoods (HR: 1.44 compared with the middle quintile) increased poisoning risk. Compared with injuries sustained outside of work, work-related injuries reduced risk (HR: 0.62). Interpretation: Among a cohort of British Columbians visiting emergency departments following an injury, opioid prescribing in patients who were opioid-naive appears to be a minor contributor to non-medical drug poisoning, particularly when compared with other patient factors, such as being male, being younger and having a low socioeconomic status.


Assuntos
Overdose de Drogas , Traumatismos Ocupacionais , Adolescente , Adulto , Idoso , Analgésicos Opioides , Canadá , Estudos de Coortes , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos Ocupacionais/complicações , Traumatismos Ocupacionais/tratamento farmacológico , Padrões de Prática Médica , Prescrições , Estudos Retrospectivos , Adulto Jovem
19.
Artigo em Inglês | MEDLINE | ID: mdl-35564830

RESUMO

Globally, residential fires constitute a substantial public health problem, causing major fire-related injury morbidity and mortality. This review examined the literature on residential fire prevention interventions relevant to Indigenous communities and assessed their effectiveness on mitigating fire incidents and their associated human and economic burden. Electronic databases including MEDLINE, EMBASE, CENTRAL, and Web of Science Core Collection were reviewed for studies on fire prevention interventions published after 1990 and based on the 4E's of injury prevention approaches (Education, Enforcement, Engineering, and Engagement). The grey literature and sources including indigenous organizational websites were also searched for eligible studies. Two authors independently screened, selected, and extracted data, in consultation with experts in the field. Outcomes measured included enhanced safety knowledge and practices, decreased residential fires incidents, reduced fire-related injuries and deaths, and lowered costs for healthcare needs. After removing duplicates, screening titles and abstracts, and assessing full texts, 81 articles were included in this review. Of the included studies, 29.1% implemented educational interventions within a variety of settings, including schools, community centres and homes, and included healthcare professionals and firefighters to raise awareness and the acquisition of fire safety skills. Engineering and environmental modifications were adopted in 20.2% of the studies with increased smoke alarm installations being the leading effective intervention followed by sprinkler inspections. Moreover, engagement of household members in hands-on safety training proved to be effective in enhancing household knowledge, fire safety decisions and practices. More importantly, effective outcomes were obtained when multi-faceted fire safety interventions were adopted, e.g., environmental modification and educational interventions, which together markedly reduced fire incidents and associated injuries. This review reveals the dearth of fire prevention evidence gathered directly within Indigenous communities. Nonetheless, relevant fire prevention recommendations can be made, calling for the adoption of combined and context-sensitive fire prevention interventions tailored to targeted Indigenous and vulnerable communities through multiple approaches and measures. Follow-ups and longitudinal studies are critical for accurate evaluation of the long-term outcomes and impacts on preventing residential fires.


Assuntos
Bombeiros , Instituições Acadêmicas , Humanos , Fumaça
20.
Front Public Health ; 10: 861762, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35615035

RESUMO

Objectives: This study explored how demographic characteristics, life experiences, and firefighting experiences have an impact on work-related injuries among female firefighters, and described events surrounding such work-related injuries. Methods: This online survey was available from June 2019 to July 2020. Questions related to demographic characteristics, life experiences, firefighting experiences, and work-related injuries. Descriptive analyses characterized variables by the presence or absence of work-related injury, injury severity, job assignment, and country of residence. Results: There were 1,160 active female firefighter survey respondents from the US and Canada, 64% of whom reported having at least one work-related injury. US respondents made up 67% of the total but 75% of the injured sample. Injured respondents were older, had been in the fire service longer, and had a greater number of fires and toxic exposures than non-injured respondents. Heavier weight, tobacco use, and alcohol consumption were more common among injured respondents. The two most common contributing factors to work-related injuries were human error and firefighter fatigue. Among respondents who reported an injury-related time loss claim, 69% were wearing protective equipment when injured, and 9% of the injuries directly resulted in new policy implementation. Conclusions: These findings can help inform resource allocation, and development of new policies and safety protocols, to reduce the number of work-related injuries among female firefighters.


Assuntos
Bombeiros , Traumatismos Ocupacionais , Canadá/epidemiologia , Fadiga , Feminino , Humanos , Traumatismos Ocupacionais/epidemiologia , Inquéritos e Questionários , Estados Unidos/epidemiologia
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