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Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) have distinct genetic etiologies but overlapping phenotypes. Genetic testing may be required for accurate diagnosis, which is critical for determining prognosis, screening recommendations, and treatment options. Our study aimed to compare the efficacy of germline-only versus paired (germline and tumor) genetic testing for clarifying the diagnosis in patients with features of NF2 and SWN. We performed a retrospective chart review of patients referred for NF2/SWN genetic testing at Massachusetts General Hospital from 2015 to 2020. Logistic regression analysis was performed to assess factors associated with diagnostic clarity. Overall, paired testing had 8.5 times greater odds of providing diagnostic clarity than germline-only testing (p < 0.01). Among patients who underwent paired testing, those who had analysis of two or more tumors had the greatest likelihood of gaining diagnostic clarity, with odds 13 times greater than patients who underwent germline-only testing (p < 0.01). Paired testing with analysis of one tumor significantly increased the odds of diagnostic clarity over germline-only testing by a factor of 6.5 (p < 0.01). These results have implications for genetic testing strategies and counseling patients about genetic testing utility. They also support the routine use of testing in individuals with suspected NF2 or SWN and improved insurance coverage for paired testing within this population.
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Neurofibromatoses , Neurofibromatose 1 , Neurofibromatose 2 , Neoplasias Cutâneas , Testes Genéticos , Humanos , Neurilemoma , Neurofibromatoses/diagnóstico , Neurofibromatoses/genética , Neurofibromatose 1/genética , Neurofibromatose 2/diagnóstico , Neurofibromatose 2/genética , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
During November 19-21, 2021, an indoor convention (event) in New York City (NYC), was attended by approximately 53,000 persons from 52 U.S. jurisdictions and 30 foreign countries. In-person registration for the event began on November 18, 2021. The venue was equipped with high efficiency particulate air (HEPA) filtration, and attendees were required to wear a mask indoors and have documented receipt of at least 1 dose of a COVID-19 vaccine.* On December 2, 2021, the Minnesota Department of Health reported the first case of community-acquired COVID-19 in the United States caused by the SARS-CoV-2 B.1.1.529 (Omicron) variant in a person who had attended the event (1). CDC collaborated with state and local health departments to assess event-associated COVID-19 cases and potential exposures among U.S.-based attendees using data from COVID-19 surveillance systems and an anonymous online attendee survey. Among 34,541 attendees with available contact information, surveillance data identified test results for 4,560, including 119 (2.6%) persons from 16 jurisdictions with positive SARS-CoV-2 test results. Most (4,041 [95.2%]), survey respondents reported always wearing a mask while indoors at the event. Compared with test-negative respondents, test-positive respondents were more likely to report attending bars, karaoke, or nightclubs, and eating or drinking indoors near others for at least 15 minutes. Among 4,560 attendees who received testing, evidence of widespread transmission during the event was not identified. Genomic sequencing of 20 specimens identified the SARS-CoV-2 B.1.617.2 (Delta) variant (AY.25 and AY.103 sublineages) in 15 (75%) cases, and the Omicron variant (BA.1 sublineage) in five (25%) cases. These findings reinforce the importance of implementing multiple, simultaneous prevention measures, such as ensuring up-to-date vaccination, mask use, physical distancing, and improved ventilation in limiting SARS-CoV-2 transmission, during large, indoor events..
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COVID-19/prevenção & controle , COVID-19/transmissão , Controle de Doenças Transmissíveis/métodos , Eventos de Massa , Cooperação do Paciente , SARS-CoV-2 , Humanos , Cidade de Nova Iorque/epidemiologia , Vigilância em Saúde Pública , Estados Unidos/epidemiologiaRESUMO
Free-fatty acid receptor-4 (FFA4), previously termed GPR120, is a G protein-coupled receptor (GPCR) for medium and long-chained fatty acids, agonism of which can regulate a myriad of metabolic, sensory, inflammatory, and proliferatory signals. Two alternative splice isoforms of FFA4 exist that differ by the presence of an additional 16 amino acids in the longer (FFA4-L) transcript, which has been suggested to be an intrinsically ß-arrestin-biased GPCR. Although the shorter isoform (FFA4-S) has been studied more extensively, very little is known about mechanisms of regulation or signaling of the longer isoform. Because ß-arrestin recruitment is dependent on receptor phosphorylation, in the current study, we used the endogenous agonist docosahexaenoic acid (DHA) to examine the mechanisms of FFA4-L phosphorylation, as well as DHA-dependent ß-arrestin recruitment and DHA-dependent extracellular-signal regulated kinase-1/2 (ERK1/2) signaling in human embryonic kidney 293 cells. Our results reveal differences in basal phosphorylation of the two FFA4 isoforms, and we show that DHA-mediated phosphorylation of FFA4-L is primarily regulated by G protein-coupled receptor kinase 6, whereas protein kinase-C can also contribute to agonist-induced and heterologous phosphorylation. Moreover, our data demonstrate that FFA4-L phosphorylation occurs on the distal C terminus and is directly responsible for recruitment and interactions with ß-arrestin-2. Finally, using CRISPR/Cas9 genome-edited cells, our data reveal that unlike FFA4-S, the longer isoform is unable to facilitate phosphorylation of ERK1/2 in cells that are devoid of ß-arrestin-1/2. Together, these results are the first to demonstrate phosphoregulation of FFA4-L as well as the effects of loss of phosphorylation sites on ß-arrestin recruitment and ERK1/2 activation. SIGNIFICANCE STATEMENT: Free-fatty acid receptor-4 (FFA4) is a cell-surface G protein-coupled receptor for medium and long-chained fatty acids that can be expressed as distinct short (FFA4-S) or long (FFA4-L) isoforms. Although much is known about FFA4-S, the longer isoform remains virtually unstudied. Here, we reveal the mechanisms of docosahexaenoic acid-induced phosphorylation of FFA4-L and subsequent ß-arrestin-2 recruitment and extracellular-signal regulated kinase-1/2 activity.
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Processamento Alternativo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Sistema de Sinalização das MAP Quinases , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , beta-Arrestina 2/metabolismo , Processamento Alternativo/efeitos dos fármacos , Sequência de Aminoácidos , Ácidos Docosa-Hexaenoicos/farmacologia , Quinases de Receptores Acoplados a Proteína G/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteína Quinase C/metabolismo , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: In the United States (US), Medicaid capitated managed care costs are controlled by optimizing patients' healthcare utilization. Adults in capitated plans utilize primary care providers (PCP) more than emergency departments (ED), compared to fee-for-service (FFS). Pediatric data are lacking. We aim to determine the association between US capitated and FFS Medicaid payment models and children's outpatient utilization. METHODS: This retrospective cohort compared outpatient utilization between two payment models of US Medicaid enrollees aged 1-18 years using Truven's 2014 Marketscan Medicaid database. Children enrolled > 11 months were included, and were excluded for eligibility due to disability/complex chronic condition, lack of outpatient utilization, or provider capitation penetration rate < 5% or > 95%. Negative binomial and logistic regression assessed relationships between payment model and number of visits or odds of utilization, respectively. RESULTS: Of 711,008 children, 66,980(9.4%) had FFS and 644,028(90.6%) had capitated plans. Children in capitated plans had greater odds of visits to urgent care, PCP-acute, and PCP-well-child care (aOR 1.21[95%CI 1.15-1.26]; aOR 2.07[95%CI 2.03-2.13]; aOR 1.86 [95%CI 1.82-1.91], respectively), and had lower odds of visits to EDs and specialty care (aOR 0.82 [95%CI 0.8-0.83]; aOR 0.61 [95%CI 0.59-0.62], respectively), compared to FFS. CONCLUSIONS: The majority of children in this US Medicaid population had capitated plans associated with higher utilization of acute care, but increased proportion of lower-cost sites, such as PCP-acute visits and UC. Health insurance programs that encourage capitated payment models and care through the PCP may improve access to timely acute care in lower-cost settings for children with non-complex chronic conditions.
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Assistência Ambulatorial/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Medicaid/economia , Pacientes Ambulatoriais/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Planos de Pagamento por Serviço Prestado , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Programas de Assistência Gerenciada/economia , Estudos Retrospectivos , Estados UnidosRESUMO
The description of substituents as electron donating or withdrawing leads to a perceived dominance of through-bond influences. The situation is compounded by the challenge of separating through-bond and through-space contributions. Here, we probe the experimental significance of through-space substituent effects in molecular interactions and reaction kinetics. Conformational equilibrium constants were transposed onto the Hammett substituent constant scale revealing dominant through-space substituent effects that cannot be described in classic terms. For example, NO2 groups positioned over a biaryl bond exhibited similar influences as resonant electron donors. Meanwhile, the electro-enhancing influence of OMe/OH groups could be switched off or inverted by conformational twisting. 267 conformational equilibrium constants measured across eleven solvents were found to be better predictors of reaction kinetics than calculated electrostatic potentials, suggesting utility in other contexts and for benchmarking theoretical solvation models.
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Peripheral intravenous (PIV) catheters are commonly used in pediatric medical-surgical orthopedic and neurology populations but are at risk of dislodgement with subsequent infiltration of fluids and/or medications. This quality improvement project sought to decrease the incidence of infiltration by creating an educational awareness program for both staff nurses and families using the S.T.I.C.K. mnemonic bundle. Rates of PIV catheter infiltration on a pediatric medical-surgical orthopedic and neurology unit were found to decrease when staff nurses utilized the S.T.I.C.K. mnemonic bundle while managing PIV catheter care for pediatric medical-surgical orthopedic and neurology patients.
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OBJECTIVE: To assess healthcare utilization patterns associated with high (≥3 visits/year) urgent care utilization. STUDY DESIGN: Retrospective analysis of 2 723 792 children who were less than 19 years of age in the 2013 Marketscan Medicaid database. Healthcare utilization categorized as inpatient, emergency department, urgent care, well-child primary care provider (PCP), acute PCP, and specialist visits was documented for 4 groups. We hypothesized that children with high urgent care utilization would have decreased utilization at other sites of care. Multivariable logistic models compared the odds of high urgent care utilization. RESULTS: Of children in the study population, 92.0% had no urgent care visits; 4.7% had 1; 1.5% had 2; and 1.0% had ≥3. Patient attributes of high urgent care utilization were: ages 1-2 years (aOR = 2.32, 95% CI: 2.18-2.36, reference group: 13-18 years), presence of a complex chronic condition (CCC) (aOR = 1.98, 95% CI: 1.88-2.07, reference group: no CCC) and no CCC but ≥3 chronic conditions (aOR = 2.85, 95% CI: 2.73-2.97, reference group: no CCC, no chronic conditions). High urgent care utilization was associated with ≥5 PCP visits for acute care (aOR = 1.16, 95% CI: 1.11-1.20, reference group: 0 visits), and ≥3 emergency department visits (aOR = 2.15, 95% CI: 2.10-2.23, reference group: 0 visits). CONCLUSIONS: Increased urgent care utilization was associated with an increase in overall healthcare utilization. Even though those with higher urgent care utilization had more visits for acute care, patients continued to see their PCP for both well-child and acute care visits.
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Assistência Ambulatorial/estatística & dados numéricos , Medicaid , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Atenção Primária à Saúde/estatística & dados numéricos , Estudos Retrospectivos , Estados UnidosRESUMO
Pollination syndromes are suites of floral traits presumed to reflect adaptations to attract and utilize a "primary" type of animal pollinator. However, syndrome traits may also function to deter "secondary" flower visitors that reduce plant fitness through their foraging activities. Here we use the hummingbird-pollinated plant species Mimulus cardinalis as a model to investigate the potential deterrent effects of classic bird syndrome traits on bumble bee foragers. To establish that M. cardinalis flowers elicit an avoidance response in bees, we assessed the choice behavior of individual foragers on a mixed experimental array of M. cardinalis and its bee-pollinated sister species M. lewisii. As expected, bees showed a strong preference against M. cardinalis flowers (only 22% of total bee visits were to M. cardinalis), but surprisingly also showed a high degree of individual specialization (95.2% of total plant transitions were between conspecifics). To determine M. cardinalis floral traits that discourage bee visitation, we then assessed foraging responses of individuals to M. cardinalis-like and M. lewisii-like floral models differing in color, orientation, reward, and combinations thereof. Across experiments, M. cardinalis-like trait combinations consistently produced a higher degree of flower avoidance behavior and individual specialization than expected based on bee responses to each trait in isolation. We then conducted a series of flower discrimination experiments to assess the ability of bees to utilize traits and trait combinations associated with each species. Relative to M. lewisii-like alternatives, M. cardinalis-like traits alone had a minimal effect on bee foraging proficiency but together increased the time bees spent searching for rewarding flowers from 1.49 to 2.65 s per visit. Collectively, our results show that M. cardinalis flowers impose foraging costs on bumble bees sufficient to discourage visitation and remarkably, generate such costs through synergistic color-orientation and color-reward trait interactions. Floral syndromes therefore represent complex adaptations to multiple pollinator groups, rather than simply the primary pollinator.
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Abelhas/fisiologia , Aves/fisiologia , Flores/anatomia & histologia , Fenótipo , Polinização , Animais , Flores/genética , PlantasRESUMO
PURPOSE: Hodgkin Lymphoma (HL) is highly curable with well-established treatment regimens; however, the impact on patient's health-related quality of life (HRQL) from diagnosis through survivorship is unclear. This systematic review aimed to describe the available literature on HRQL in HL, assess the quality of these studies, identify gaps in the literature and recommend further areas of research. METHODS: Following PRISMA guidelines, we performed a systematic review to include studies assessing the HRQL in HL patients. Articles identified through database searches were screened and data extracted. Quality was evaluated using a 6-point scale, adapted from published HRQL systematic reviews. RESULTS: Sixty five articles published between 1986 and 2015 met inclusion criteria. These included 53 (82 %) cross-sectional studies; 12 (18 %) longitudinal studies, including three embedded in randomized trials; and three additional longitudinal studies that began assessment at diagnosis. Study sample sizes of HL patients varied considerably with only five (42 %) longitudinal studies including more than 50 patients. Multidimensional HRQL was assessed in 45 studies, single HRQL domains in 22 studies, and symptoms, including fatigue, in 28 studies. CONCLUSIONS: The majority of studies employed a cross-sectional design, enrolling HL survivors at least 10 years after the completion of therapy. Emphasis on HRQL following therapy may inform initial treatment decisions and long-term survivorship goals. We recommend that future research include prospective, longitudinal randomized designs across both treatment and time.
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Adaptação Psicológica , Doença de Hodgkin/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Estudos Transversais , Humanos , Estudos Prospectivos , Fatores Socioeconômicos , Sobreviventes/psicologiaRESUMO
Adaptive management (AM) is being employed in a number of programs in the United States to guide actions to restore aquatic ecosystems because these programs are both expensive and are faced with significant uncertainties. Many of these uncertainties are associated with prioritizing when, where, and what kind of actions are needed to meet the objectives of enhancing ecosystem services and recovering threatened and endangered species. We interviewed nine large-scale aquatic ecosystem restoration programs across the United States to document the lessons learned from implementing AM. In addition, we recorded information on ecological drivers (e.g., endangered fish species) for the program, and inferred how these drivers reflected more generic ecosystem services. Ecosystem services (e.g., genetic diversity, cultural heritage), albeit not explicit drivers, were either important to the recovery or enhancement of the drivers, or were additional benefits associated with actions to recover or enhance the program drivers. Implementing programs using AM lessons learned has apparently helped achieve better results regarding enhancing ecosystem services and restoring target species populations. The interviews yielded several recommendations. The science and AM program must be integrated into how the overall restoration program operates in order to gain understanding and support, and effectively inform management decision-making. Governance and decision-making varied based on its particular circumstances. Open communication within and among agency and stakeholder groups and extensive vetting lead up to decisions. It was important to have an internal agency staff member to implement the AM plan, and a clear designation of roles and responsibilities, and long-term commitment of other involved parties. The most important management questions and information needs must be identified up front. It was imperative to clearly identify, link and continually reinforce the essential components of an AM plan, including objectives, constraints, uncertainties, hypotheses, management actions, decision criteria and triggers, monitoring, and research. Some employed predictive models and the results of research on uncertainties to vet options for actions. Many relied on best available science and professional judgment to decide if adjustments to actions were needed. All programs emphasized the need to be nimble enough to be responsive to new information and make necessary adjustments to management action implementation. We recommend that ecosystem services be explicit drivers of restoration programs to facilitate needed funding and communicate to the general public and with the global efforts on restoring and conserving ecosystems.
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Conservação dos Recursos Naturais/métodos , Ecossistema , Recuperação e Remediação Ambiental/métodos , Animais , Organismos Aquáticos , Espécies em Perigo de Extinção , Monitoramento Ambiental , Política Ambiental , Peixes , Modelos Teóricos , Estados UnidosRESUMO
The UK is a diverse society where individuals regularly interact with speakers with different accents. Whilst there is a growing body of research on the impact of speaker accent on comprehension in people with aphasia, there is none which explores their ability to identify accents. This study investigated the ability of this group to identify the geographical origins of a speaker. Age-matched participants with and without aphasia listened to 120 audio recordings of five speakers each of six accents, reading aloud four sentences each. Listeners were asked to make a forced-choice decision about the geographical origin of the speaker. Adults with aphasia were significantly less accurate than control participants at identifying accents but both groups made the same pattern of errors. Adults with aphasia who are able to identify a new speaker as being from a particular place may draw on this information to help them "tune in" to the accent.
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Afasia/fisiopatologia , Afasia/terapia , Terapia da Linguagem/métodos , Idioma , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Comunicação/fisiopatologia , Transtornos da Comunicação/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Psicológico/fisiologia , Inteligibilidade da Fala/fisiologia , Percepção da Fala/fisiologia , Reino UnidoRESUMO
We performed a prospective study to determine if the pretest probability of a positive loop-mediated isothermal amplification test is greater when there are more signs and symptoms of GAS pharyngitis. Patients were enrolled if a clinician obtained a GAS RADT. The McIsaac score was calculated. The prevalence of positive LAMP and RADT results increased as the McIsaac score increased. The calculated sensitivity of LAMP was superior to RADT.
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Faringite , Infecções Estreptocócicas , Humanos , Estudos Prospectivos , Sensibilidade e Especificidade , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/epidemiologia , Faringite/diagnóstico , Streptococcus pyogenes/genéticaRESUMO
Objectives: People with substance use disorders (SUD) are suggested to have higher risk of hospitalization, intubation, or death from coronavirus disease 2019 (COVID-19), although data are mixed. Little is known about other COVID-19-related complications in this group. We compared morbidity and mortality among individuals with and without SUD who were admitted to an urban safety net hospital with COVID-19 early in the pandemic, contemporaneous to other published studies on this subject. Methods: We performed a retrospective study of patients ⩾18 years old admitted with COVID-19 from March 16th to April 8th, 2020. SUD included alcohol, opioid, cocaine, amphetamine, and benzodiazepine use disorders and was identified using diagnostic codes, free text clinical documentation, and urine drug screens. The primary outcome was inpatient mortality. Secondary outcomes included clinical complications (eg, secondary infections, venous thromboembolism) and resource utilization (eg, mechanical ventilation, length of stay). We used multivariable regression to assess the relationship between SUD and mortality. Results: Of 409 patients, the mean age was 56 years and 13.7% had SUD. Those with SUD were more likely to be male, have experienced homelessness, have pulmonary disease or hepatitis C, or use tobacco or cannabis. After multivariable analysis, SUD was not associated with mortality (aOR 1.03; 95% CI, 0.31-3.10). Secondary outcomes were also similar between groups. Conclusions: Our findings suggest that persons with and without SUD have similar COVID-19-related outcomes. Previously reported increased COVID-19 complications may be from medical comorbidities.
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OBJECTIVES: The Australian aged-care sector employees are diverse, with a wide range of training backgrounds and work experience. Compassion and person-centred care (PCC) are essential for quality care. Effective training is required to facilitate compassion and PCC in the diverse workforce. METHODS: Eligible staff members (n = 732) participated in a 3-hour training activity using an aged simulation training suit. Training sessions were offered at eight ACH Group residential care sites. During the training, staff were required to complete functional daily tasks while wearing the suit. Pre- and post-training questionnaires were used to assess change in staff members' self-assessment of compassion and PCC. The Compassion Competence Scale and the Person-centred Care Assessment Tool were used to assess compassion and PCC. RESULTS: In total, 160 (22%) staff members participated in the evaluation of the training. Overall, participants reported significant improvements in self-reported compassion (p < 0.01) and PCC after the training (p < 0.001), compassionate communication (p < 0.001) and insight (p < 0.001), and ability to personalise care (p < 0.001) and in recognising patients' environmental accessibility (p < 0.01). CONCLUSIONS: The simulation activity improved aspects of compassion and person-centred care for the aged-care workforce. Further research is required to understand whether these changes are reflected in daily practice.
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Empatia , Treinamento por Simulação , Idoso , Austrália , Comunicação , Humanos , Assistência Centrada no Paciente , Recursos HumanosRESUMO
OBJECTIVE: With a growing emphasis on personalised care, there is a need for effective workforce training to enable person-centred care (PCC) in aged care practice. The Australian aged care workforce is very diverse; thus, tools to evaluate compassion and PCC training need to reflect an understanding of these concepts relevant to the Australian context. There are currently no tools validated for use in aged care settings in Australia. METHODS: Two existing compassion and PCC questionnaires were modified for an Australian audience using cognitive interviews with aged care workers. The reliability of the modified questionnaires was assessed. RESULTS: The modified questionnaires were found to have acceptable inter-reliability and test-retest intra-class correlation for the subscales and overall. However, the investigation also found low Cohen's kappa values between the test and retest responses for the individual items, subscales and overall, and had low inter-class correlation for individual items, indicating poor inter-rater agreement. High inter-item correlation scores also suggest the questions encapsulate overly similar constructs. CONCLUSIONS: While further investigation of the psychometric properties of the new items is needed, these modified questionnaires may offer a method of assessing and re-assessing compassion and PCC using language that is understandable to the Australian aged care workforce. Tools to accurately measure Australian aged care staff perceptions of compassion and their ability to deliver PCC are important to improve the quality of care provided in aged care and facilitate the delivery of PCC in aged care settings.
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Empatia , Assistência Centrada no Paciente , Idoso , Austrália , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Early identification of patients at risk for severe coronavirus disease 2019 (COVID-19) is crucial for appropriate triage and determination of need for closer monitoring. Few studies have examined laboratory trends in COVID-19 infection and sought to quantify the degree to which laboratory values affect mortality. We conducted a retrospective cohort (n = 407) study of hospitalized patients with COVID-19 early in the course of the pandemic, from March 16th to April 8th, 2020 and compared baseline to repeat laboratory testing 72 hours into admission. The primary outcome was death. We found that rises of 25 mg/L C-reactive protein, 50 units/L lactate dehydrogenase, and 100 ng/mL ferritin were associated with 23%, 28%, and 1% increased odds of death, respectively. In contrast, changes in fibrinogen, D-dimer, white blood cell count, and creatinine in the first few days of hospital admission were not associated with mortality. These quantitative findings may assist clinicians in determining the risk of potential clinical decline in patients with COVID-19 and influence early management.
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COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , Hospitalização , HospitaisRESUMO
Respiratory disorders are a leading cause of acute care visits by children. Data establishing the reliability of telemedicine in evaluating children with respiratory concerns are limited. The overall objective of this pilot study was to evaluate the use of telemedicine to evaluate children with respiratory concerns. We performed a pilot prospective cohort study of children 12 to 71 months old presenting to the emergency department (ED) with lower respiratory tract signs and symptoms. Three examinations were performed simultaneously-one by the ED clinician with the patient, one by a remote ED clinician using telemedicine, and one by the child's parent. We evaluated measures of agreement between (a) the local and remote clinicians, (b) the local clinician and the parent, and (c) the parent and the remote clinician. Twenty-eight patients were enrolled (84 paired examinations). Except for heart rate, all examination findings evaluated (general appearance, capillary refill time, grunting, nasal flaring, shortness of breath, retractions, impression of respiratory distress, respiratory rate, and temperature) had acceptable or excellent agreement between raters. In this pilot study, we found that telemedicine respiratory examinations of young children are feasible and reliable, using readily available platforms and equipment.
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OBJECTIVES: To establish statewide consensus priorities for safer in-person school for children with medical complexity (CMC) during the coronavirus disease 2019 (COVID-19) pandemic using a rapid, replicable, and transparent priority-setting method. METHODS: We adapted the Child Health and Nutrition Research Initiative Method, which allows for crowdsourcing ideas from diverse stakeholders and engages technical experts in prioritizing these ideas using predefined scoring criteria. Crowdsourcing surveys solicited ideas from CMC families, school staff, clinicians and administrators through statewide distribution groups/listservs using the prompt: "It is safe for children with complex health issues and those around them (families, teachers, classmates, etc.) to go to school in-person during the COVID-19 pandemic if/when " Ideas were aggregated and synthesized into a unique list of candidate priorities. Thirty-four experts then scored each candidate priority against 5 criteria (equity, impact on COVID-19, practicality, sustainability, and cost) using a 5-point Likert scale. Scores were weighted and predefined thresholds applied to identify consensus priorities. RESULTS: From May to June 2021, 460 stakeholders contributed 1166 ideas resulting in 87 candidate priorities. After applying weighted expert scores, 10 consensus CMC-specific priorities exceeded predetermined thresholds. These priorities centered on integrating COVID-19 safety and respiratory action planning into individualized education plans, educating school communities about CMC's unique COVID-19 risks, using medical equipment safely, maintaining curricular flexibility, ensuring masking and vaccination, assigning seats during transportation, and availability of testing and medical staff at school. CONCLUSIONS: Priorities for CMC, identified by statewide stakeholders, complement and extend existing recommendations. These priorities can guide implementation efforts to support safer in-person education for CMC.
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COVID-19/prevenção & controle , Controle de Infecções/métodos , Múltiplas Afecções Crônicas , Segurança , Instituições Acadêmicas , Adolescente , Adulto , Criança , Saúde da Criança , Consenso , Crowdsourcing , Feminino , Política de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Participação dos Interessados , Wisconsin , Adulto JovemRESUMO
Reactive oxygen species (ROS), including hydrogen peroxide (H(2)O(2)), have recently been shown to be generated upon agonism of several members of the G protein-coupled receptor (GPCR) superfamily, including ß(2)-adrenergic receptors (ß(2)ARs). Previously, we have demonstrated that inhibition of intracellular ROS generation mitigates ß(2)AR signaling, suggesting that ß(2)AR-mediated ROS generation is capable of feeding back to regulate receptor function. Given that ROS, specifically H(2)O(2), are able to post-translationally oxidize protein cysteine sulfhydryls to cysteine-sulfenic acids, the goal of the current study was to assess whether ROS are capable of S-sulfenating ß(2)AR. Using a modified biotin-switch assay that is selective for cysteine-sulfenic acids, our results demonstrate for the first time that H(2)O(2) treatment facilitates S-sulfenation of transiently overexpressed ß(2)AR in human embryonic kidney 293 cells. It is noteworthy that stimulation of cells with the ß-agonist isoproterenol produces both dose- and time-dependent S-sulfenation of ß(2)AR, an effect that is receptor-dependent, and demonstrates that receptor-generated ROS are also capable of oxidizing the ß(2)AR. Receptor-dependent S-sulfenation was inhibited by the chemoselective sulfenic acid alkylator dimedone and the cysteine antioxidant N-acetyl-l-cysteine. Moreover, our results reveal that receptor oxidation occurs in cells that endogenously express physiologically relevant levels of ß(2)AR, because treatment of human alveolar epithelial A549 cells with either H(2)O(2) or the ß(2)-selective agonist formoterol promoted receptor S-sulfenation. These findings provide the first evidence, to our knowledge, that a mammalian GPCR can be oxidized by S-sulfenation and signify an important first step toward shedding light on the overlooked role of ROS in the regulation of ß(2)AR function.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Peróxido de Hidrogênio/metabolismo , Isoproterenol/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Alquilação , Bioensaio , Biotina/metabolismo , Cicloexanonas/farmacologia , Cisteína/análogos & derivados , Cisteína/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Etanolaminas/farmacologia , Fumarato de Formoterol , Células HEK293 , Humanos , Oxirredução , Alvéolos Pulmonares , Receptores Adrenérgicos beta 2/química , Transdução de Sinais/efeitos dos fármacos , Ácidos Sulfênicos/química , Ácidos Sulfênicos/metabolismo , Fatores de TempoRESUMO
Massachusetts is one of the epicenters of the opioid epidemic and has been severely impacted by injection-related viral and bacterial infections. A recent increase in newly diagnosed human immunodeficiency virus (HIV) infections among persons who inject drugs in the state highlights the urgent need to address and bridge the overlapping epidemics of opioid use disorder (OUD) and injection-related infections. Building on an established relationship between the Massachusetts Department of Public Health and Boston Medical Center, the Infectious Diseases section has contributed to the development and implementation of a cohesive response involving ambulatory, inpatient, emergency department, and community-based services. We describe this comprehensive approach including the rapid delivery of antimicrobials for the prevention and treatment of HIV, sexually transmitted diseases, systemic infections such as endocarditis, bone and joint infections, as well as curative therapy for chronic hepatitis C virus in a manner that is accessible to patients on the addiction-recovery continuum. We also provide an overview of programs that provide access to medications for OUD, harm reduction services including overdose education, and distribution of naloxone. Finally, we outline lessons learned to inform initiatives in other settings.