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1.
Artigo em Inglês | MEDLINE | ID: mdl-35535467

RESUMO

PURPOSE: This study aimsed to gather opinions from medical educators on the possibility of introducing an interview to the Korean Medical Licensing Examination (KMLE) to assess professional attributes. Specifically following topics were dealt with: the appropriate timing and tool to assess unprofessional conduct; ; the possiblity of prevention of unprofessional conduct by introducing an interview to the KMLE; and the possibility of implementation of an interview to the KMLE.. METHODS: A cross-sectional study approach based on a survey questionnaire was adopted. We analyzed 104 pieces of news about doctors' unprofessional conduct to determine the deficient professional attributes. We derived 24 items of unprofessional conduct and developed the questionnaire and surveyed 250 members of the Korean Society of Medical Education two times. Descriptive statistics, cross-tabulation analysis, and Fisher's exact test were applied to the responses. The answers to the open-ended questions were analyzed using conventional content analysis. RESULTS: In the 1st survey, 49 members (19.6%) responded. Out of 49, 24 (49.5%) responded in the 2nd survey. To assess unprofessional conduct, there was no dominant timing among basic medical education (BME), KMLE, and continuing professional development (CPD). There was no overwhelming assessment tool among written examination, objective structured clinical examination, practice observation, and interview. Response rates of "Impossible" (49.0%) and "Possible" (42.9%) suggested an interview of KMLE prevented unprofessional conduct. In terms of implementation, "Impossible" (50.0%) was selected more often than "Possible" (33.3%). CONCLUSION: Professional attributes should be assessed by various tools over the period from BME to CPD. Hence, it may be impossible to introduce an interview to assess professional attributes to theKMLE, and a system is needed such as self-regulation by the professional body rather than licensing examination.


Assuntos
Educação Médica , Licenciamento , Estudos Transversais , Humanos , República da Coreia , Inquéritos e Questionários
3.
Artigo em Inglês | MEDLINE | ID: mdl-35457440

RESUMO

Previous studies have frequently reported that those with a driver's license have better physical and cognitive functions than those without. However, there are many people in the world who do not need or who cannot have a driver's license. We hypothesized that if the non-driver's license group had the same or better physical and cognitive functioning as the driver's license group, they could lead healthy lives without the risk of functional decline or loss of functioning due to surrendering their licenses or giving up driving. The subjects were 47 community-dwelling older adults. We measured their physical function and cognitive function and performed psychological assessment via the following tests: grip strength, Timed Up and Go test, walking speed, Five Times Sit to Stand test, Functional Reach test, Two-Step Test, Mini-Mental State Examination, Trail Making Test, Modified Falls Efficacy Scale, Geriatric Depression Scale, and University of California Los Angeles Loneliness Scale. In previous studies, it has been said that having a driver's license provides good physical, cognitive, and psychological functions. However, in this study, loneliness and executive function were strongly influenced by age and sex, and no direct relationship to a driver's license was suggested. Rather, non-driver license holders may be relieved because there is no risk of accidents due to driving, and there is no possibility of a suddenly decline in physical or cognitive function due to revocation of a driver's license.


Assuntos
Condução de Veículo , Equilíbrio Postural , Idoso , Condução de Veículo/psicologia , Cognição , Humanos , Licenciamento , Projetos Piloto , Estudos de Tempo e Movimento
4.
Tidsskr Nor Laegeforen ; 142(6)2022 Apr 05.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-35383458

RESUMO

BACKGROUND: In February 2021, the Storting decided to abolish the mandatory medical certificate required for driving licence renewals for drivers over the age of 80. The decision will affect older drivers, traffic safety in general, and the everyday work of GPs in particular. MATERIALS AND METHODS: A content analysis was performed of the parliamentary debates and supporting documentation on the issue of medical certificates for older drivers, from the time of the motion in December 2020 up to the debate on when to implement the decision in May 2021. RESULTS: The majority decision was founded on an anti-discrimination argument with undertones of district politics, in which the traffic safety element was relativised. A minority argued for a traffic safety policy based on a health authority decision and with an emphasis on the added overall health value. Cognitive screening tests were unanimously rejected. INTERPRETATION: The parties that represent the majority decision framed cognitive testing in a way that suggests the decision is a reaction to these tests rather than to the medical certificate requirement as such. There was little discussion on how the decision will affect GPs' ability to identify impaired fitness to drive among the older population.


Assuntos
Acidentes de Trânsito , Condução de Veículo , Acidentes de Trânsito/prevenção & controle , Humanos , Licenciamento , Programas de Rastreamento , Testes Neuropsicológicos
5.
BMJ Open ; 12(4): e059312, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35418439

RESUMO

OBJECTIVE: To identify and prioritise the research needed to help Nepali agencies develop an improved road safety system. DESIGN: Delphi study. SETTING: Nepal. PARTICIPANTS: Stakeholders from government institutions, academia, engineering, healthcare and civil society were interviewed to identify knowledge gaps and research questions. Participants then completed two rounds of ranking and a workshop. RESULTS: A total of 93 participants took part in interviews and two rounds of ranking. Participants were grouped with others sharing expertise relating to each of the five WHO 'pillars' of road safety: (1) road safety management; (2) safer roads; (3) safer vehicles; (4) safer road users and (5) effective postcrash response. Interviews yielded 1019 research suggestions across the five pillars. Two rounds of ranking within expert groups yielded consensus on the important questions for each pillar. A workshop involving all participants then led to the selection of 6 questions considered the most urgent: (1) How can implementing agencies be made more accountable? (2) How should different types of roads, and roads in different geographical locations, be designed to make them safer for all road users? (3) What vehicle fitness factors lead to road traffic crashes? (4) How can the driver licensing system be improved to ensure safer drivers? (5) What factors lead to public vehicle crashes and how can they be addressed? and (6) What factors affect emergency response services getting to the patient and then getting them to the right hospital in the best possible time? CONCLUSIONS: The application of the Delphi approach is useful to enable participants representing a range of institutions and expertise to contribute to the identification of road safety research priorities. Outcomes from this study provide Nepali researchers with a greater understanding of the necessary focus for future road safety research.


Assuntos
Condução de Veículo , Acidentes de Trânsito/prevenção & controle , Técnica Delfos , Humanos , Licenciamento , Nepal , Pesquisa , Segurança
6.
Artigo em Inglês | MEDLINE | ID: mdl-35409647

RESUMO

The Environmental Impact Assessment (EIA) is a legal and administrative tool aimed to identify, predict, and interpret the impact of a project or activity on the environment and human health. The EIA also evaluates the accuracy of the predictions and audits the effectiveness of the established preventive measures. Regarding the sanitation sector, efficiency of wastewater treatments and sanitation networks determine the pollutant level of the discharged liquid effluents and the subsequent impact on the environment and human health. This problematic makes necessary to assess how proper the regulatory follow-ups of sanitation projects is. This paper evaluates the performance of the Chilean EIA System concerning to sanitation projects. Taking into account that the more restrictive Environmental Impact Study (EIS) and more permissive Environmental Impact Declaration (EID) are the ways for projects' entry to the EIA System in Chile, 5336 sanitation projects submitted to EIA between 1994 and 2019 were complied. A representative sample of 76 projects (15 entered as EIS and 61 as EID) was analyzed by using a principal coordinate analysis (PCoA) through 14 selected performance indicators. Observed weaknesses have led to propose improvement opportunities of the EIA focused on the follow-ups after the environmental license is obtained, such as creation of a simplified sanctioning procedure, decentralization of decision-making, deadline establishment in each stage, and unified direct link for each project. These proposals seek to improve the effectiveness of monitoring and possible sanctions to early identify impacts of sanitation projects on the environment and human health. This paper introduces a robust methodology for evaluation criteria focused on the follow-ups analysis, which can be used in other countries that consider respectful sanitation projects have direct social and environmental benefits leading to long-term indirect cultural and economic values.


Assuntos
Meio Ambiente , Saneamento , Chile , Seguimentos , Humanos , Licenciamento
7.
BMC Public Health ; 22(1): 649, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35382791

RESUMO

BACKGROUND: The toll associated with road traffic crashes (RTC) is high, and the burden of injury is disproportionately borne by pedestrians and motor riders, particularly in developing countries. This study synthesized the factors associated with motorcycle-related RTC in Africa. METHODS: The PICO framework and the PRISMA guidelines for conducting reviews were incorporated in searching, screening, and reporting the findings. Advanced search in five electronic databases (Google Scholar, PubMed Central, Scopus, CINAHL, and Embase) yielded 2552 titles and 22 from manual search, filtered for 2016 to 2022 (to generate 1699) and then further for primary studies (854). Through the title, abstract and full-text screening, 22 were appropriate for this review. Data extraction was done by the two researchers independently, and the results were compared. Convergent synthesis was adopted to integrate results, transformed into a narrative, and analyzed using thematic synthesis. RESULTS: The four main themes identified were the rider-related, non-rider-related factors, prevalence and severity of injuries from RTC, and the measures to reduce RTC. The behavioral factors associated with RTC were alcohol use, smoking, use of illicit drugs, tiredness of rider, poor knowledge on traffic regulations, more than one pillow rider, lack of rider license, non-observance of traffic regulations, and non-use of personal protective equipment. Road traffic crashes were common among younger age and male gender. Other factors identified included poor road network, unplanned stoppage by police, unlawful vehicular packing, increased urbanization, and slippery floors. CONCLUSION: There is the need to institute multi-sectoral measures that target riders' behavior change. Coordinated efforts should target governments, enforcement authorities, and regulatory bodies to enforce enactment that ensures safe use of roads.


Assuntos
Motocicletas , Ferimentos e Lesões , Acidentes de Trânsito/prevenção & controle , África/epidemiologia , Humanos , Licenciamento , Masculino , Polícia , Ferimentos e Lesões/epidemiologia
8.
JAMA Netw Open ; 5(4): e228780, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35467733

RESUMO

Importance: Despite US graduated driver licensing laws, young novice driver crash rates remain high. Study findings suggest comprehensive license policy that mandates driver education including behind-the-wheel (BTW) training may reduce crashes postlicensure. However, only 15 states mandate BTW training. Objective: To identify differences in licensing and crash outcomes for drivers younger than 18 years who are subject to comprehensive licensing requirements (graduated driver licensing, driver education, and BTW training) vs those aged 18 to 24 years who are exempt from these requirements. Design, Setting, and Participants: This prospective, population-based cohort study used Ohio licensing data to define a cohort of 2018 license applicants (age 16-24 years, n = 136 643) and tracked licensed driver (n = 129 897) crash outcomes up to 12 months postlicensure. The study was conducted from January 1, 2018, to December 31, 2019, and data analysis was performed from October 7, 2019, to February 11, 2022. Main Outcomes and Measures: Licensing examination performance and population-based, police-reported crash rates in the first 2 months and 12 months postlicensure across age groups, sex, and census tract-level sociodemographic variables were measured. Poisson regression models compared newly licensed driver crash rates, with reference to individuals licensed at 18 years, while controlling for census tract-level sociodemographic factors, time spent in the learner permit period, and licensing examination performance measures. Results: Of 136 643 novice drivers, 69 488 (50.9%) were male and 67 152 (49.1%) were female. Mean (SD) age at enrollment (age at first on-road examination) was 17.7 (2.1) years. License applicants aged 16 and 17 years performed best on license examinations (15 466 [21.6%] and 5112 [30.9%] failing vs 7981 [37.5%] of applicants aged 18 years). Drivers licensed at 18 years had the highest crash rates of all those younger than 25 years. Compared with drivers licensed at 18 years, crash rates were 27% lower in individuals aged 16 years and 14% lower in those aged 17 years during the first 2 months postlicensure when controlling for socioeconomic status, time spent in learner permit status, and license examination performance measures (adjusted relative risk [aRR] at age 16 years: 0.73; 95% CI, 0.67-0.80; age 17 years: aRR, 0.86; 95% CI, 0.77-0.96). At 12 months postlicensure, crash rates were 19% lower for individuals licensed at age 16 years (aRR, 0.81; 95%, CI, 0.77-0.85) and 6% lower at age 17 years (aRR, 0.94; 95% CI, 0.89-0.99) compared with individuals aged 18 years. Conclusions and Relevance: In Ohio, drivers younger than 18 years who are subject to graduated driver licensing and driver education, including BTW training requirements, had lower crash rates in the first year postlicensure compared with those aged 18 years, with controls applied. These findings suggest that it may be fruitful for future work to reconsider the value of mandated driver license policies, including BTW training, and to examine reasons for delayed licensure and barriers to accessing training.


Assuntos
Condução de Veículo , Licenciamento , Acidentes de Trânsito/prevenção & controle , Adolescente , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos
9.
Nat Biotechnol ; 40(4): 439, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35379964

Assuntos
Licenciamento
10.
Lancet ; 399(10335): 1602-1603, 2022 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-35358422
11.
Air Med J ; 41(1): 11-13, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35248329

Assuntos
Licenciamento , Humanos
12.
J Adolesc Health ; 70(5): 751-756, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35260285

RESUMO

PURPOSE: Driving licensure remains a major developmental milestone for adolescents as they become more independent to access important health, education, and employment opportunities. Today, more teens are delaying driving licensure than before. We investigated associations of delayed licensure with health, education, and employment 4 years after high school. METHODS: We analyzed data from all seven annual assessments (W1-W7) of the NEXT Generation Health Study, a nationally representative cohort survey starting at 10th grade (W1, 2009-2010). The independent variable was delaying driving licensure (DDL [delaying ≥1 year] vs. No-DDL), defined as participants receiving driver licensure ≥1 year after the initial legal eligibility time until W7. Outcome variables were self-reported health, education, and employment at W7. Covariates included sex, race/ethnicity, family affluence, parental education, and urbanicity. Multinomial logistic regressions were conducted considering complex survey features. RESULTS: No-DDL versus DDL was associated with a higher likelihood of (1) excellent (adjusted odds ratio [AOR] = 2.06, p < .001), good (AOR = 1.74, p < .001), and fair (AOR = 1.34, p = .008) health compared with poor health; (2) completing a 4-year college or graduate school [AOR = 2.71, p < .001] and tech/community college [AOR = 1.92, p = .004] compared with high school or less; and (3) working ≥30 hours/week (AOR = 7.63, p = .011) and working <30 hours/week (AOR = 1.54, p = .016) compared with not working. DISCUSSION: Among emerging adults, no delay in driving licensure was associated with better self-reported health, higher education, and more working hours four years after leaving high school. Although earlier driving licensure increases driving exposure and risk, avoiding DDL appears to provide advantages for health, education, and employment during early adulthood.


Assuntos
Condução de Veículo , Adolescente , Adulto , Escolaridade , Emprego , Humanos , Licenciamento , Instituições Acadêmicas
13.
Transl Vis Sci Technol ; 11(3): 20, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35297979

RESUMO

Purpose: As the prevalence of age-related visual field disorders and the number of older drivers are rising, clear criteria on visual field requirements for driving are important. This article explores the predictive value of the Esterman visual field in relation to the outcome of an on-road driving test. Methods: A retrospective chart review was performed for driver's license applicants who, based on their visual field, performed an on-road driving test. Cases (N = 101) with a failed on-road driving test were matched with 101 controls with a passed outcome. The Esterman visual field was divided in regions, and the number of points missed per region was counted. Logistic regression models and receiver operating characteristic (ROC) curves were computed for each region. Results: Most regions presented a significantly increased odds for failing the driving test when more points were missed. The odds ratio for the whole visual field was 2.52 (95% confidence interval, 1.53-4.14, P < 0.001) for all the participants. However, ROC curves failed to reveal distinct fail-pass criteria based on the number of points missed, as revealed by a large amount of overlap between cases and controls. Conclusions: These findings confirm the relation between visual field damage and impaired driving performance. However, the Esterman visual field results were not conclusive for predicting the driving performance of the individual driver with visual field defects. Translational Relevance: In our group of participants, the number of on-road driving tests cannot be further reduced by a more detailed definition of fail-pass criteria, based on the Esterman visual field test.


Assuntos
Condução de Veículo , Testes de Campo Visual , Humanos , Licenciamento , Estudos Retrospectivos , Transtornos da Visão/diagnóstico , Campos Visuais
14.
Milbank Q ; 100(1): 284-313, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35257415

RESUMO

Policy Points Pharmaceutical trade organizations and media outlets in the United States regularly point to compulsory licensing-or even its threat-as the mechanism that peer countries use to control the price of prescription drugs. Our comparative analysis shows that compulsory licensing is not frequently employed in high-income countries outside the United States as a direct response to drug prices. When its use is threatened, a license is rarely issued and even less often does it lead to a price discount. Accordingly, compulsory licensing is unlikely to contribute to price discrepancies between the United States and other developed nations. In fact, of the 21 compulsory licensing petitions we identified outside the United States, over one-third were made by pharmaceutical companies themselves and only three were threatened by a government authority. CONTEXT: Compulsory licensing is a practice whereby national authorities can license a third party to produce a patented product, such as a pharmaceutical drug, effectively enabling the production of a generic before the original patent expires. The policy was designed-and has historically been used-to improve access to essential medicines in low-income countries and during public health crises. Although it was not intended to impact drug prices directly, the threat of compulsory licensing may indeed contribute to lower drug prices in high-income countries outside the United States. Our study sought to determine the plausibility of this claim. METHODS: We compiled a comprehensive database of compulsory licensing episodes in the United States and 17 comparator nations over the 20 years following the 2001 Doha Declaration, and we recorded the motivation and outcome of each instance. Our search began with publicly available reports compiled by organizations specializing in pharmaceutical intellectual property, expanded to a query of legal proceedings in Westlaw, and concluded with a comprehensive literature review on PubMed. FINDINGS: This strategy yielded 45 unique episodes of compulsory licensing, 24 in the United States and 21 outside. A minority (24%) of petitions outside the United States were motivated by high prices, and in all countries, only three cases were clearly associated with a price discount. CONCLUSIONS: We found no evidence to suggest that compulsory licensing is either frequently threatened or successfully implemented by countries outside the United States to secure price discounts for the most expensive pharmaceuticals, those that are newly patented and just entering the market.


Assuntos
Países em Desenvolvimento , Custos de Medicamentos , Países Desenvolvidos , Indústria Farmacêutica , Medicamentos Genéricos , Licenciamento , Estados Unidos
16.
BMJ Open Ophthalmol ; 7(1): e000904, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295687

RESUMO

Aims: To provide an overview of how the European visual field standards for driving (specified in Commission Directive 2009/113/EC) are applied and determine whether individuals with visual field defects are treated equally across Europe. Methods: One ophthalmic expert from each of 32 European countries was invited to participate in an electronic survey. They were presented with threshold and Esterman perimetry results of 15 cases of visual field defects and asked to classify each case as either passed or failed in reference to their national standards. The results were compared with the European Driving Test Group 1 (EDT1), which is a new perimetry algorithm that adheres to the recommendations by the Eyesight Working Group. Fleiss' kappa was used to determine the inter-rater agreement. Results: Twenty-five countries responded. Three of 15 cases were passed by all. Full agreement on a failed case was not reached. Denmark graded most leniently and passed 12 cases. Bulgaria, Romania and Slovakia graded most strictly and passed five cases. The Fleiss' kappa score was 0.52 (95% CI 0.49 to 0.55). Only Slovenia was in full agreement with the EDT1. Fifteen countries endorsed specific perimetric tests for assessing fitness to drive. Five of these also defined pass/fail criteria. Conclusion: The directive fails to establish a uniform approach to the visual field requirements, as evident by moderate pass/fail agreement between the national experts. Because the visual standards for driving are enforced differently, identical visual field loss can result in either revocation or approval of a driving license.


Assuntos
Condução de Veículo , Campos Visuais , Humanos , Licenciamento , Transtornos da Visão/diagnóstico , Testes de Campo Visual/efeitos adversos
17.
BMC Public Health ; 22(1): 513, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35296294

RESUMO

BACKGROUND: Road traffic crashes (RTCs) are among the eight-leading causes of death globally. Strategies and policies have been put in place by many countries to reduce RTCs and to prevent RTCs and related injuries/deaths. METHODS: In this review, we searched the following databases Ovid Medline, Embase, Cochrane Database of Systematic Reviews, Epistemonikos, Web of Science, and LILACS for reviews matching our inclusion criteria between periods January 1950 and March 2020. We did not apply language or publication restrictions in the searches. We, however, excluded reviews that focused primarily on injury prevention and reviews that looked at crashes not involving a motor vehicle. RESULTS: We identified 35 systematic reviews matching our inclusion criteria and most of the reviews (33/35) included studies strictly from high-income countries. Most reviews were published before 2015, with only 5 published between 2015 and 2020. Methodological quality varied between reviews. Most reviews focused on enforcement intervention. There was strong evidence that random breath testing, selective breath testing, and sobriety checkpoints were effective in reducing alcohol-related crashes and associated fatal and nonfatal injuries. Other reviews found that sobriety checkpoints reduced the number of crashes by 17% [CI: (- 20, - 14)]. Road safety campaigns were found to reduce the numbers of RTCs by 9% [CI: (- 11, - 8%)]. Mass media campaigns indicated some median decrease in crashes across all studies and all levels of crash severity was 10% (IQR: 6 to 14%). Converting intersections to roundabouts was associated with a reduction of 30 to 50% in the number of RTCs resulting in injury and property damage. Electronic stability control measure was found to reduce single-vehicle crashes by - 49% [95% CI: (- 55, - 42%)]. No evidence was found to indicate that post-license driver education is effective in preventing road traffic injuries or crashes. CONCLUSION: There were many systematic reviews of varying quality available which included studies that were conducted in high-income settings. The overview has found that behavioural based interventions are very effective in reducing RTCs.


Assuntos
Acidentes de Trânsito , Licenciamento , Acidentes de Trânsito/prevenção & controle , Bases de Dados Factuais , Humanos , Aplicação da Lei , Revisões Sistemáticas como Assunto
18.
BMC Med Educ ; 22(1): 216, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35354466

RESUMO

BACKGROUND: Compared to other road users, ambulance drivers are at a higher accident risk while driving with warning lights and sirens. No standard exists for training or education for emergency medical service employees driving ambulances. Training programs should positively influence knowledge. However, knowledge gain can be influenced by several different factors. This study developed a knowledge test for ambulance drivers to determine influencing factors on knowledge and its gain by simulator-based training. METHODS: Two parallel knowledge test forms with 20 questions each were designed in several steps and tested on up to 174 participants. Questionnaires were used to study associated and influencing factors, such as objective experience, subjective attitudes, personality, motivation and demographic data. RESULTS: Test construction showed good overall parallelism of the two tests as well as reliability and sensitivity. There was no correlation between subjective and objective knowledge gain, but participants with higher subjective knowledge gain showed a higher variation in objective knowledge. Younger age, higher qualification, higher number of license classes, fewer traffic violations, and more traffic safety trainings were positively associated with knowledge, whereas less yearly driving mileage, more traffic safety trainings, and higher risk sensitivity positively influenced knowledge gain through the training. CONCLUSION: Knowledge and its gain through training are very low. Reasons for the lack of predictive power of some variables, such as motivation, personality and attitudes, are discussed. This study presents a new tool for testing knowledge on driving with warning lights and sirens. It shows the need for objective testing and for further research in this special area.


Assuntos
Ambulâncias , Condução de Veículo , Acidentes de Trânsito/prevenção & controle , Humanos , Licenciamento , Reprodutibilidade dos Testes
19.
J Immunother Cancer ; 10(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35296558

RESUMO

BACKGROUND: Novel therapies are needed to improve outcomes for women diagnosed with ovarian cancer. Oncolytic viruses are multifunctional immunotherapeutic biologics that preferentially infect cancer cells and stimulate inflammation with the potential to generate antitumor immunity. Herein we describe Parapoxvirus ovis (Orf virus (OrfV)), an oncolytic poxvirus, as a viral immunotherapy for ovarian cancer. METHODS: The immunotherapeutic potential of OrfV was tested in the ID8 orthotopic mouse model of end-stage epithelial ovarian carcinoma. Immune cell profiling, impact on secondary lesion development and survival were evaluated in OrfV-treated mice as well as in Batf3 knockout, mice depleted of specific immune cell subsets and in mice where the primary tumor was removed. Finally, we interrogated gene expression datasets from primary human ovarian tumors from the International Cancer Genome Consortium database to determine whether the interplay we observed between natural killer (NK) cells, classical type 1 dendritic cells (cDC1s) and T cells exists and influences outcomes in human ovarian cancer. RESULTS: OrfV was an effective monotherapy in a murine model of advanced-stage epithelial ovarian cancer. OrfV intervention relied on NK cells, which when depleted abrogated antitumor CD8+ T-cell responses. OrfV therapy was shown to require cDC1s in experiments with BATF3 knockout mice, which do not have mature cDC1s. Furthermore, cDC1s governed antitumor NK and T-cell responses to mediate antitumor efficacy following OrfV. Primary tumor removal, a common treatment option in human patients, was effectively combined with OrfV for optimal therapeutic outcome. Analysis of human RNA sequencing datasets revealed that cDC1s correlate with NK cells in human ovarian cancer and that intratumoral NK cells correlate positively with survival. CONCLUSIONS: The data herein support the translational potential of OrfV as an NK stimulating immunotherapeutic for the treatment of advanced-stage ovarian cancer.


Assuntos
Terapia Viral Oncolítica , Vírus Oncolíticos , Vírus do Orf , Neoplasias Ovarianas , Animais , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Células Matadoras Naturais , Licenciamento , Camundongos , Vírus do Orf/genética , Vírus do Orf/metabolismo , Ovinos
20.
J Adolesc Health ; 70(5): 757-762, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35125263

RESUMO

PURPOSE: This study examines the relative risk of death among crash-involved teenage drivers in relation to the number and ages of passengers present. METHODS: We performed cross-sectional analysis of police-reported crashes in the United States in years 2016-2019 to estimate rate ratios for death among drivers aged 16-17 years by passenger composition (no passengers, one teen, ≥two teens, teens and adults aged 20-34 years, adults aged 20-34 years only, ≥one adult aged 35-64 years). Models were adjusted for confounding and effect modification related to driver, crash, and environmental factors. RESULTS: Crash-involved teen drivers carrying ≥2 teen passengers were twice as likely to die as teens driving alone. The driver was seven times as likely to die when carrying a mix of teen and young adult passengers compared with teens driving alone. Teen drivers' risk of death was lowest in the presence of an adult passenger aged 35-64 years. Carrying one teen passenger presents greater risk of death than driving alone for male teen drivers but not for females. DISCUSSION: When teen drivers crash, they are more likely to die if they are carrying teen and/or young adult passengers than if they are driving alone or with a mature adult. The results support the current graduated licensing policies restricting young novice drivers from carrying teenage passengers. Results also help to clarify why previous studies have found that young passengers are associated with increased risk of fatal crashes, but not nonfatal crashes: it appears that passengers may have an effect on crash severity.


Assuntos
Acidentes de Trânsito , Condução de Veículo , Adolescente , Estudos Transversais , Feminino , Humanos , Licenciamento , Masculino , Risco , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
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