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BACKGROUND: Intimate partner violence (IPV) is a significant public health problem that is associated with substantial health sequelae, including traumatic injury. Surgical professional societies recommend universal intimate partner violence screening in patients presenting after trauma, but this recommendation is not uniformly implemented. We designed and implemented a quality improvement project at our institution in July 2020 to enhance intimate partner violence screening. Although screening rates improved, they remained suboptimal. Therefore, we sought to examine barriers and facilitators to intimate partner violence screening from trauma clinicians' perspectives. STUDY DESIGN: We conducted a qualitative study using in-depth, semistructured interviews to understand the perspectives and experiences of trauma clinicians conducting intimate partner violence screening. A constructivist paradigm informed our study whereby our data collection approaches aimed to understand intimate partner violence screening from the perspectives of those tasked with implementing screening within real-world clinical settings. We used thematic analysis to analyze our data and generate themes related to barriers and facilitators to screening. RESULTS: We conducted interviews with 12 resident physicians and 2 advance practice providers. We identified 6 themes, 3 reflecting facilitator themes as (1) standardized education and workflow, (2) benefits of interdisciplinary teamwork, and (3) context of screening, and 3 reflecting barrier themes as (1) lack of time, (2) language misinterpretation, and (3) perceived inappropriateness of universal screening. CONCLUSION: Trauma clinicians described multiple facilitators and barriers to screening for intimate partner violence following traumatic injury, some of which were unique to the trauma setting. Projects seeking to achieve universal screening following traumatic injury may benefit from accounting for these factors when designing interventions.
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BACKGROUND: Surgeons have come under increased scrutiny for postoperative pain management, particularly for opioid prescribing. To decrease opioid use but still provide pain control, nonopioid medications such as muscle relaxants are being used, which can be harmful in older adults. However, the prevalence of muscle relaxant prescribing, trends in use over time, and risk of prolonged use are unknown. STUDY DESIGN: Using a 20% representative Medicare sample, we conducted a retrospective analysis of muscle relaxant prescribing to patients ≥ 65 years of age. We merged patient data from Medicare Carrier, MedPAR, and Outpatient Files with Medicare Part D for the years 2013-2018. A total of 14 surgical procedures were included to represent a wide range of anatomic regions and specialties. RESULTS: The study cohort included 543,929 patients. Of the cohort, 8111 (1.5%) received a new muscle relaxant prescription at discharge. Spine procedures accounted for 12% of all procedures but 56% of postoperative prescribing. Overall, the rate of prescribing increased over the time period (1.4-2.0%, p < 0.001), with increases in prescribing primarily in the spine (7-9.6%, p < 0.0001) and orthopedic procedure groups (0.9-1.4%, p < 0.0001). Of patients discharged with a new muscle relaxant prescription, 10.7% had prolonged use. CONCLUSIONS: The use of muscle relaxants in the postoperative period for older adults is low, but increasing over time, especially in ortho and spine procedures. While pain control after surgery is crucial, surgeons should carefully consider the risks of muscle relaxant use, especially for older adults who are at higher risk for medication-related problems.
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Medicare Part D , Dolor Postoperatorio , Humanos , Anciano , Medicare Part D/estadística & datos numéricos , Masculino , Estados Unidos , Femenino , Dolor Postoperatorio/tratamiento farmacológico , Anciano de 80 o más Años , Estudios Retrospectivos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Prescripciones de Medicamentos/estadística & datos numéricosRESUMEN
AIMS: While acute cardiovascular complications of COVID-19 are well-described, less is known about longer-term cardiac sequelae. For many individuals with cardiac signs or symptoms arising after COVID-19 infection, the aetiology remains unclear. We examined immune profiles associated with magnetic resonance imaging (MRI) abnormalities in patients with unexplained cardiac injury after COVID-19. METHODS AND RESULTS: Twenty-one participants (mean age 47 [SD 13] years, 71% female) with long COVID (n=17), raised troponin (n=2), or unexplained new-onset heart failure (n=2), who did not have pre-existing heart conditions or recent steroid/immunosuppression treatment were enrolled a mean 346 (SD 191) days after COVID-19 infection in a prospective observational study. Cardiac MRI and blood sampling for deep immunophenotyping using mass cytometry by time of flight and measurement of proteomic inflammatory markers was performed. Nine of 21 (43%) participants had MRI abnormalities (MRI(+)), including non-ischaemic patterns of late gadolinium enhancement and/or visually overt myocardial oedema in 8 people. One patient had mildly impaired biventricular function without fibrosis or oedema, and 2 had severe left ventricular impairment. MRI(+) individuals had higher blood CCL3, CCL7, FGF-23 and CD4 Th2 cells, and lower CD8 T effector memory (TEM) cells, than MRI(-). Cluster analysis revealed lower expression of inhibitory receptors PD1 and TIM3 in CD8 TEM cells from MRI(+) patients than MRI(-) patients, and functional studies of CD8 T αß cells showed higher proportions of cytotoxic granzyme B+ secreting cells upon stimulation. CD8 TEM cells and CCL7 were the strongest predictors of MRI abnormalities in a LASSO regression model (composite AUC 0.96, 95%CI 0.88-1.0). CCL7 was correlated with diffuse myocardial fibrosis/oedema detected by quantitative T1 mapping (r=0.47, p=0.04). CONCLUSION: COVID-19 related cardiac injury in symptomatic patients with non-ischaemic myocarditis-like MRI abnormalities is associated with immune dysregulation, including decreased peripheral CD8 TEM cells and increased CCL7, persisting long after the initial infection.
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The persistent failure of standard chemotherapy underscores the urgent need for innovative and targeted approaches in cancer treatment. Photodynamic therapy (PDT) has emerged as a promising photochemistry-based approach to address chemoresistance in cancer regimens. PDT not only induces cell death but also primes surviving cells, enhancing their susceptibility to subsequent therapies. This review explores the principles of PDT and discusses the concept of photodynamic priming (PDP), which augments the effectiveness of treatments like chemotherapy. Furthermore, the integration of nanotechnology for precise drug delivery at the right time and location and PDT optimization are examined. Ultimately, this study highlights the potential and limitations of PDT and PDP in cancer treatment paradigms, offering insights into future clinical applications.
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Neoplasias , Fotoquimioterapia , Humanos , Resistencia a Antineoplásicos , Protocolos Antineoplásicos , Muerte Celular , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológicoRESUMEN
The prognosis for patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) remains dismal. It is generally accepted that combination cancer therapies offer the most promise, such as Folforinox, despite their associated high toxicity. This study addresses the issue of chemoresistance by introducing a complementary dual priming approach to attenuate the DNA repair mechanism and to improve the efficacy of a type 1 topoisomerase (Top1) inhibitor. The result is a regimen that integrates drug-repurposing and nanotechnology using 3 clinically relevant FDA-approved agents (1) Top1 inhibitor (irinotecan) at subcytotoxic doses (2) benzoporphyrin derivative (BPD) as a photoactive molecule for photodynamic priming (PDP) to improve the delivery of irinotecan within the cancer cell and (3) minocycline priming (MNP) to modulate DNA repair enzyme Tdp1 (tyrosyl-DNA phosphodiesterase) activity. We demonstrate in heterotypic 3D cancer models that incorporate cancer cells and pancreatic cancer-associated fibroblasts that simultaneous targeting of Tdp1 and Top1 were significantly more effective by employing MNP and photoactivatable multi-inhibitor liposomes encapsulating BPD and irinotecan compared to monotherapies or a cocktail of dual or triple-agents. These data are encouraging and warrant further work in appropriate animal models to evolve improved therapeutic regimens.
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Carcinoma Ductal Pancreático , Irinotecán , Minociclina , Neoplasias Pancreáticas , Fotoquimioterapia , Humanos , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Línea Celular Tumoral , Minociclina/farmacología , Minociclina/uso terapéutico , Irinotecán/farmacología , Irinotecán/uso terapéutico , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/patología , Hidrolasas Diéster Fosfóricas/metabolismo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Inhibidores de Topoisomerasa I/farmacología , Inhibidores de Topoisomerasa I/uso terapéutico , Inhibidores de Topoisomerasa I/química , Liposomas/químicaRESUMEN
BACKGROUND: Disparities in opioid prescribing by race/ethnicity have been described in many healthcare settings, with White patients being more likely to receive an opioid prescription than other races studied. As surgeons increase prescribing of nonopioid medications in response to the opioid epidemic, it is unknown whether postoperative prescribing disparities also exist for these medications, specifically gabapentinoids. METHODS: We conducted a retrospective cohort study using a 20% Medicare sample for 2013-2018. We included patients ≥66 years without prior gabapentinoid use who underwent one of 14 common surgical procedures. The primary outcome was the proportion of patients prescribed gabapentinoids at discharge among racial and ethnic groups. Secondary outcomes were days' supply of gabapentinoids, opioid prescribing at discharge, and oral morphine equivalent (OME) of opioid prescriptions. Trends over time were constructed by analyzing proportion of postoperative prescribing of gabapentinoids and opioids for each year. For trends by year by racial/ethnic groups, we ran a multivariable logistic regression with an interaction term of procedure year and racial/ethnic group. RESULTS: Of the 494,922 patients in the cohort (54% female, 86% White, 5% Black, 5% Hispanic, mean age 73.7 years), 3.7% received a new gabapentinoid prescription. Gabapentinoid prescribing increased over time for all groups and did not differ significantly among groups (P = 0.13). Opioid prescribing also increased, with higher proportion of prescribing to White patients than to Black and Hispanic patients in every year except 2014. CONCLUSIONS: We found no significant prescribing variation of gabapentinoids in the postoperative period between racial/ethnic groups. Importantly, we found that despite national attention to disparities in opioid prescribing, variation continues to persist in postoperative opioid prescribing, with a higher proportion of White patients being prescribed opioids, a difference that persisted over time.
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Analgésicos Opioides , Prescripciones de Medicamentos , Gabapentina , Dolor Postoperatorio , Pautas de la Práctica en Medicina , Humanos , Femenino , Masculino , Anciano , Analgésicos Opioides/uso terapéutico , Estudios Retrospectivos , Dolor Postoperatorio/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Gabapentina/uso terapéutico , Estados Unidos , Anciano de 80 o más Años , Prescripciones de Medicamentos/estadística & datos numéricos , Medicare/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Disparidades en Atención de Salud/tendencias , Etnicidad/estadística & datos numéricosRESUMEN
AIMS: The adaptive immune response plays an important role in atherosclerosis. In response to a high-fat/high-cholesterol (HF/HC) diet, marginal zone B (MZB) cells activate an atheroprotective programme by regulating the differentiation and accumulation of 'poorly differentiated' T follicular helper (Tfh) cells. On the other hand, Tfh cells activate the germinal centre response, which promotes atherosclerosis through the production of class-switched high-affinity antibodies. We therefore investigated the direct role of Tfh cells and the role of IL18 in Tfh differentiation in atherosclerosis. METHODS AND RESULTS: We generated atherosclerotic mouse models with selective genetic deletion of Tfh cells, MZB cells, or IL18 signalling in Tfh cells. Surprisingly, mice lacking Tfh cells had increased atherosclerosis. Lack of Tfh not only reduced class-switched IgG antibodies against oxidation-specific epitopes (OSEs) but also reduced atheroprotective natural IgM-type anti-phosphorylcholine (PC) antibodies, despite no alteration of natural B1 cells. Moreover, the absence of Tfh cells was associated with an accumulation of MZB cells with substantially reduced ability to secrete antibodies. In the same manner, MZB cell deficiency in Ldlr-/- mice was associated with a significant decrease in atheroprotective IgM antibodies, including natural anti-PC IgM antibodies. In humans, we found a positive correlation between circulating MZB-like cells and anti-OSE IgM antibodies. Finally, we identified an important role for IL18 signalling in HF/HC diet-induced Tfh. CONCLUSION: Our findings reveal a previously unsuspected role of MZB cells in regulating atheroprotective 'natural' IgM antibody production in a Tfh-dependent manner, which could have important pathophysiological and therapeutic implications.
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Aterosclerosis , Interleucina-18 , Humanos , Ratones , Animales , Inmunoglobulina M , Linfocitos B , Aterosclerosis/genética , Aterosclerosis/prevención & control , Colesterol , Linfocitos T Colaboradores-InductoresRESUMEN
This systematic review examines studies of traffic injury that involved linkage of police crash data and hospital data and were published from 1994 to 2023 worldwide in English. Inclusion and exclusion criteria were the basis for selecting papers from PubMed, Web of Science, and Scopus, and for identifying additional relevant papers using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and supplementary snowballing (n = 60). The selected papers were reviewed in terms of research objectives, data items and sample size included, temporal and spatial coverage, linkage methods and software tools, as well as linkage rates and most significant findings. Many studies found that the number of clinically significant road injury cases was much higher according to hospital data than crash data. Under-estimation of cases in crash data differs by road user type, pedestrian cases commonly being highly under-counted. A limited number of the papers were from low- and middle-income countries. The papers reviewed lack consistency in what was reported and how, which limited comparability.
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Accidentes de Tránsito , Heridas y Lesiones , Humanos , Accidentes de Tránsito/estadística & datos numéricos , Hospitales , Peatones , Policia , Heridas y Lesiones/epidemiología , Exactitud de los Datos , Fuentes de InformaciónRESUMEN
BACKGROUND: Embolic stroke of unknown source (ESUS) accounts for 1 in 6 ischemic strokes. Current guidelines do not recommend routine cardiac magnetic resonance (CMR) imaging in ESUS, and beyond the identification of cardioembolic sources, there are no data assessing new clinical findings from CMR in ESUS. This study aimed to assess the prevalence of new cardiac and noncardiac findings and to determine their impact on clinical care in patients with ESUS. METHODS AND RESULTS: In this prospective, multicenter, observational study, CMR imaging was performed within 3 months of ESUS. All scans were reported according to standard clinical practice. A new clinical finding was defined as one not previously identified through prior clinical evaluation. A clinically significant finding was defined as one resulting in further investigation, follow-up, or treatment. A change in patient care was defined as initiation of medical, interventional, surgical, or palliative care. From 102 patients recruited, 96 underwent CMR imaging. One or more new clinical findings were observed in 59 patients (61%). New findings were clinically significant in 48 (81%) of these patients. Of 40 patients with a new clinically significant cardiac finding, 21 (53%) experienced a change in care (medical therapy, n=15; interventional/surgical procedure, n=6). In 12 patients with a new clinically significant extracardiac finding, 6 (50%) experienced a change in care (medical therapy, n=4; palliative care, n=2). CONCLUSIONS: CMR imaging identifies new clinically significant cardiac and noncardiac findings in half of patients with recent ESUS. Advanced cardiovascular screening should be considered in patients with ESUS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04555538.
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Accidente Cerebrovascular Embólico , Embolia Intracraneal , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Prevalencia , Estudios Prospectivos , Imagen por Resonancia Magnética , Embolia Intracraneal/diagnóstico por imagen , Embolia Intracraneal/epidemiología , Factores de RiesgoRESUMEN
INTRODUCTION: Road safety has been a long-enduring policy concern in Australia, with significant financial burden of road trauma and evident socioeconomic disparities. Transport injuries disproportionately impact individuals in remote areas, those in lower socioeconomic situations, and Aboriginal and Torres Strait Islander populations. There is a lack of insight into transport injuries in Aboriginal and Torres Strait Islander communities, absence of Indigenous perspective in published research and limited utilisation of linked data assets to address the inequity. Aim 1 is to determine the breadth, cost and causal factors of serious injury from road traffic crashes in South Australia (SA) and New South Wales (NSW) with a focus on injury prevention. Aim 2 is to identify enablers and barriers to compensation schemes for Aboriginal and Torres Strait Islander patients in SA and NSW. METHODS AND ANALYSIS: This study will be guided by an Aboriginal and Torres Strait Islander Governance Group, applying Knowledge Interface Methodology and Indigenous research principles to ensure Indigenous Data Sovereignty and incorporation of informed perspectives. A mixed-method approach will be undertaken to explore study aims including using big data assets and mapping patient journey. CONCLUSION: The results of this study will provide valuable insights for the development of focused injury prevention strategies and policies tailored to Aboriginal and Torres Strait Islander communities. By addressing the specific needs and challenges faced by these communities, the study aims to enhance road safety outcomes and promote equitable access to healthcare and compensation for affected individuals and their families.
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Accidentes de Tránsito , Aborigenas Australianos e Isleños del Estrecho de Torres , Atención a la Salud , Humanos , Nueva Gales del Sur/epidemiología , Australia del Sur/epidemiología , Proyectos de InvestigaciónRESUMEN
We created a concise nurse-driven delirium reduction workflow with the aim of reducing delirium rates and length of stay for hospitalized adults. Our nurse-driven workflow included five evidence-based daytime "sunrise" interventions (patient room lights on, blinds up, mobilization/out-of-bed, water within patient's reach and patient awake) and five nighttime "turndown" interventions (patient room lights off, blinds down, television off, noise reduction and pre-set bedtime). Interventions were also chosen because fidelity could be quickly monitored twice daily without patient interruption from outside the room. To evaluate the workflow, we used an interrupted time series study design between 06/01/17 and 05/30/22 to determine if the workflow significantly reduced the unit's delirium rate and average length of stay. Our workflow is feasible to implement and monitor and initially significantly reduced delirium rates but not length of stay. However, the reduction in delirium rates were not sustained following the emergence of the COVID-19 pandemic.
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Delirio , Humanos , Delirio/prevención & control , Análisis de Series de Tiempo Interrumpido , Pandemias , Flujo de Trabajo , Unidades de Cuidados IntensivosRESUMEN
BACKGROUND: While injuries can impact on children's educational achievements (with threats to their development and employment prospects), these risks are poorly quantified. This population-based longitudinal study investigated the impact of an injury-related hospital admission on Welsh children's academic performance. METHODS: The Secure Anonymised Information Linkage databank, 55 587 children residing in Wales from 2006 to 2016 who had an injury hospital admission (58.2% males; 16.8% born in most deprived Wales area; 80.1% one injury hospital admission) were linked to data from the Wales Electronic Cohort for Children. The primary outcome was the Core Subject Indicator reflecting educational achievement at key stages 2 (school years 3-6), 3 (school years 7-9) and 4 (school years 10-11). Covariates in models included demographic, birth, injury and school characteristics. RESULTS: Educational achievement of children was negatively associated with: pedestrian injuries (adjusted risk ratio, (95% CIs)) (0.87, (0.83 to 0.92)), cyclist (0.96, (0.94 to 0.99)), high fall (0.96, (0.94 to 0.97)), fire/flames/smoke (0.85, (0.73 to 0.99)), cutting/piercing object (0.96, (0.93 to 0.99)), intentional self-harm (0.86, (0.82 to 0.91)), minor traumatic brain injury (0.92, (0.86 to 0.99)), contusion/open wound (0.93, (0.91 to 0.95)), fracture of vertebral column (0.78, (0.64 to 0.95)), fracture of femur (0.88, (0.84 to 0.93)), internal abdomen/pelvic haemorrhage (0.82, (0.69 to 0.97)), superficial injury (0.94, (0.92 to 0.97)), young maternal age (<18 years: 0.91, (0.88 to 0.94); 19-24 years: 0.94, (0.93 to 0.96)); area based socioeconomic status (0.98, (0.97 to 0.98)); moving to a more deprived area (0.95, (0.93 to 0.97)); requiring special educational needs (0.46, (0.44 to 0.47)). Positive associations were: being female (1.04, (1.03 to 1.06)); larger pupil school sizes and maternal age 30+ years. CONCLUSION: This study highlights the importance on a child's education of preventing injuries and implementing intervention programmes that support injured children. Greater attention is needed on equity-focused educational support and social policies addressing needs of children at risk of underachievement, including those from families experiencing poverty. VIBES-JUNIOR STUDY PROTOCOL: http://dx.doi.org/10.1136/bmjopen-2018-024755.
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Rendimiento Académico , Heridas y Lesiones , Humanos , Gales/epidemiología , Femenino , Niño , Masculino , Heridas y Lesiones/epidemiología , Rendimiento Académico/estadística & datos numéricos , Estudios Longitudinales , Hospitalización/estadística & datos numéricos , Almacenamiento y Recuperación de la Información , Adolescente , PreescolarRESUMEN
OBJECTIVE: To elicit and summarise collective expert opinion on contemporary child product safety risks, challenges and priorities. METHODS: An online survey targeted international experts from a cross-section of product safety fields. RESULTS: Fifty-five experts participated, representing 1,137 years of product safety experience, from a broad range of fields including industry risk management, product assessment and testing, policy and regulation, research, paediatric medicine, advocacy and product liability. Participants identified the leading product safety hazards across all age brackets as falls, drowning and chemical hazards, with variance in specific age brackets, particularly the threat to breathing hazards for infants. The leading products of concern to experts were electrical connection/distribution products, primarily button batteries and lithium-ion batteries, infant furnishing products and household furniture. Product safety priorities and challenges were identified under five themes: regulatory, surveillance, industry, consumer and product-specific. CONCLUSIONS: The gains in knowledge, insight and understanding from experts on contemporary child product safety risks and issues should inform policy and future research. IMPLICATIONS FOR PUBLIC HEALTH: There are significant consequences of unsafe consumer products on population health, and the results are timely as we face new product safety issues emerging from e-commerce, the digital transition and innovative product technologies.
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Ahogamiento , Niño , Lactante , Humanos , Encuestas y Cuestionarios , ElectricidadRESUMEN
BACKGROUND: Few hospitals have built surveillance for diagnostic errors into usual care or used comparative quantitative and qualitative data to understand their diagnostic processes and implement interventions designed to reduce these errors. OBJECTIVES: To build surveillance for diagnostic errors into usual care, benchmark diagnostic performance across sites, pilot test interventions, and evaluate the program's impact on diagnostic error rates. METHODS AND ANALYSIS: Achieving diagnostic excellence through prevention and teamwork (ADEPT) is a multicenter, real-world quality and safety program utilizing interrupted time-series techniques to evaluate outcomes. Study subjects will be a randomly sampled population of medical patients hospitalized at 16 US hospitals who died, were transferred to intensive care, or had a rapid response during the hospitalization. Surveillance for diagnostic errors will occur on 10 events per month per site using a previously established two-person adjudication process. Concurrent reviews of patients who had a qualifying event in the previous week will allow for surveys of clinicians to better understand contributors to diagnostic error, or conversely, examples of diagnostic excellence, which cannot be gleaned from medical record review alone. With guidance from national experts in quality and safety, sites will report and benchmark diagnostic error rates, share lessons regarding underlying causes, and design, implement, and pilot test interventions using both Safety I and Safety II approaches aimed at patients, providers, and health systems. Safety II approaches will focus on cases where diagnostic error did not occur, applying theories of how people and systems are able to succeed under varying conditions. The primary outcome will be the number of diagnostic errors per patient, using segmented multivariable regression to evaluate change in y-intercept and change in slope after initiation of the program. ETHICS AND DISSEMINATION: The study has been approved by the University of California, San Francisco Institutional Review Board (IRB), which is serving as the single IRB. Intervention toolkits and study findings will be disseminated through partners including Vizient, The Joint Commission, and Press-Ganey, and through national meetings, scientific journals, and publications aimed at the general public.
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Hospitales , Pacientes Internos , Humanos , Estudios Prospectivos , Hospitalización , Errores Diagnósticos , Estudios Multicéntricos como AsuntoRESUMEN
Unabated activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome is linked with the pathogenesis of various inflammatory disorders. Polo-like kinase 1 (PLK1) has been widely studied for its role in mitosis. Here, using both pharmacological and genetic approaches, we demonstrate that PLK1 promoted NLRP3 inflammasome activation at cell interphase. Using an unbiased proximity-dependent biotin identification (Bio-ID) screen for the PLK1 interactome in macrophages, we show an enhanced proximal association of NLRP3 with PLK1 upon NLRP3 inflammasome activation. We further confirmed the interaction between PLK1 and NLRP3 and identified the interacting domains. Mechanistically, we show that PLK1 orchestrated the microtubule-organizing center (MTOC) structure and NLRP3 subcellular positioning upon inflammasome activation. Treatment with a selective PLK1 kinase inhibitor suppressed IL-1ß production in in vivo inflammatory models, including LPS-induced endotoxemia and monosodium urate-induced peritonitis in mice. Our results uncover a role of PLK1 in regulating NLRP3 inflammasome activation during interphase and identify pharmacological inhibition of PLK1 as a potential therapeutic strategy for inflammatory diseases with excessive NLRP3 inflammasome activation.
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Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Ratones , Inflamasomas/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas de Ciclo Celular/genética , Interleucina-1beta/genética , Ratones Endogámicos C57BL , Quinasa Tipo Polo 1RESUMEN
This cross-sectional study used time series forecasting to estimate excess firearm mortality in the US during the COVID-19 pandemic.
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COVID-19 , Armas de Fuego , Heridas por Arma de Fuego , Humanos , Urbanización , Pandemias , Heridas por Arma de Fuego/epidemiologíaRESUMEN
Written instructions improve patient comprehension of discharge instructions but are often provided only in English even for patients with a non-English language preference (NELP). We implemented standardized written discharge instructions in English, Spanish, and Chinese for hospital medicine patients at an urban academic medical center. Using an interrupted time series analysis, we assessed the impact on medication-related postdischarge questions for patients with English, Spanish, or Chinese language preferences. Of 4013 patients, â¼15% had NELP. Preintervention, Chinese-preferring patients had a 5.6 percentage point higher probability of questions (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI]: 1.08, 2.21) compared to English-preferring patients; Spanish-preferring and English-preferring patients had similar rates of questions. Postintervention, English-preferring and Spanish-preferring patients had no significant change; Chinese-preferring patients had a significant 10.9 percentage point decrease in the probability of questions (aOR = 0.38, 95% CI: 0.21, 0.69) thereby closing the disparity. Language-concordant written discharge instructions may reduce disparities in medication-related postdischarge questions for patients with NELP.
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Cuidados Posteriores , Alta del Paciente , Humanos , Lenguaje , Comprensión , HospitalesRESUMEN
Importance: In response to the opioid epidemic, recommendations from some pain societies have encouraged surgeons to embrace multimodal pain regimens with the intent of reducing opioid use in the postoperative period, including by prescribing gabapentinoids. Objective: To describe trends in postoperative prescribing of both gabapentinoids and opioids after a variety of surgical procedures by examining nationally representative Medicare data and further understand variation by procedure. Design, Setting, and Participants: This serial cross-sectional study of gabapentinoid prescribing from January 1, 2013, through December 31, 2018, used a 20% US Medicare sample. Gabapentinoid-naive patients 66 years or older undergoing 1 of 14 common noncataract surgical procedures performed in older adults were included. Data were analyzed from April 2022 to April 2023. Exposure: One of 14 common surgical procedures in older adults. Main Outcomes and Measures: Rate of postoperative prescribing of gabapentinoids and opioids, defined as a prescription filled between 7 days before the procedure and 7 days after discharge from surgery. Additionally, concomitant prescribing of gabapentinoids and opioids in the postoperative period was assessed. Results: The total study cohort included 494â¯922 patients with a mean (SD) age of 73.7 (5.9) years, 53.9% of whom were women and 86.0% of whom were White. A total of 18â¯095 patients (3.7%) received a new gabapentinoid prescription in the postoperative period. Of those receiving a new gabapentinoid prescription, 10â¯956 (60.5%) were women and 15 529 (85.8%) were White. After adjusting for age, sex, race and ethnicity, and procedure type in each year, the rate of new postoperative gabapentinoid prescribing increased from 2.3% (95% CI, 2.2%-2.4%) in 2014 to 5.2% (95% CI, 5.0%-5.4%) in 2018 (P < .001). While there was variation between procedure types, almost all procedures saw an increase in both gabapentinoid and opioid prescribing. In this same period, opioid prescribing increased from 56% (95% CI, 55%-56%) to 59% (95% CI, 58%-60%) (P < .001). Concomitant prescribing also increased from 1.6% (95% CI, 1.5%-1.7%) in 2014 to 4.1% (95% CI, 4.0%-4.3%) in 2018 (P < .001). Conclusions and Relevance: The findings of this cross-sectional study of Medicare beneficiaries suggest that new postoperative gabapentinoid prescribing increased without a subsequent downward trend in the proportion of patients receiving postoperative opioids and a near tripling of concurrent prescribing. Closer attention needs to be paid to postoperative prescribing for older adults, especially when using multiple types of medications, which can have adverse drug events.
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Analgésicos Opioides , Medicare , Humanos , Femenino , Anciano , Estados Unidos , Masculino , Analgésicos Opioides/uso terapéutico , Estudios Transversales , Estudios Retrospectivos , Pautas de la Práctica en Medicina , Dolor/tratamiento farmacológico , Prescripciones de MedicamentosRESUMEN
Background: Balancing autonomy and supervision during medical residency is important for trainee development while ensuring patient safety. In the modern clinical learning environment, tension exists when this balance is skewed. This study aimed to understand the current and ideal states of autonomy and supervision, then describe the factors that contribute to imbalance from both trainee and attending perspectives. Methods: A mixed-methods design included surveys and focus groups of trainees and attendings at three institutionally affiliated hospitals between May 2019-June 2020. Survey responses were compared using chi-square tests or Fisher's exact tests. Open-ended survey and focus group questions were analyzed using thematic analysis. Results: Surveys were sent to 182 trainees and 208 attendings; 76 trainees (42%) and 101 attendings (49%) completed the survey. Fourteen trainees (8%) and 32 attendings (32%) participated in focus groups. Trainees perceived the current culture to be significantly more autonomous than attendings; both groups described an "ideal" culture as more autonomous than the current state. Focus group analysis revealed five core contributors to the balance of autonomy and supervision: attending-, trainee-, patient-, interpersonal-, and institutional-related factors. These factors were found to be dynamic and interactive with each other. Additionally, we identified a cultural shift in how the modern inpatient environment is impacted by increased hospitalist attending supervision and emphasis on patient safety and health system improvement initiatives. Conclusions: Trainees and attendings agree that the clinical learning environment should favor resident autonomy and that the current environment does not achieve the ideal balance. There are several factors contributing to autonomy and supervision, including attending-, resident-, patient-, interpersonal-, and institutional-related. These factors are complex, multifaceted, and dynamic. Cultural shifts towards supervision by primarily hospitalist attendings and increased attending accountability for patient safety and systems improvement outcomes further impacts trainee autonomy.