RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors and the mechanism of fusion of the virus at the plasma membrane have been investigated extensively, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the TMPRSS2 inhibitor camostat, we discovered that SARS-CoV-2 entry is not dependent on dynamin but on cholesterol. ADP-ribosylation factor 6 (ARF6) has been described as a host factor for SARS-CoV-2 replication and is involved in the entry and infection of several pathogenic viruses. Using CRISPR/Cas9 genetic deletion, a modest reduction in SARS-CoV-2 uptake and infection in Huh-7 was observed. In addition, pharmacological inhibition of ARF6 with the small molecule NAV-2729 showed a dose-dependent reduction of viral infection. Importantly, NAV-2729 also reduced SARS-CoV-2 viral loads in more physiological models of infection: Calu-3 cells and kidney organoids. This highlighted a role for ARF6 in multiple cell contexts. Together, these experiments point to ARF6 as a putative target to develop antiviral strategies against SARS-CoV-2.
Assuntos
COVID-19 , Humanos , Fator 6 de Ribosilação do ADP , Antivirais/farmacologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do VírusRESUMO
OBJECTIVE: To estimate the prevalence of psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) and rheumatoid arthritis (RA) and the use of biologic agents in these diseases in Norway. METHODS: From the Norwegian Patient Registry (NPR), we identified as PsA, axSpA and RA patients ≥18 years those with ≥2 recorded episodes with diagnostic coding for index disease (L40.5, M07.0-M07.3 for PsA; M45, M46.0, M46.1, M46.8 and M46.9 for axSpA; M05-M06 for RA). We calculated the point prevalence of PsA, axSpA and RA as per the 1st of January 2017 in the Norwegian adult population (age ≥18). Dispensed disease-modifying antirheumatic drug (DMARD) prescriptions were obtained from the Norwegian Prescription Database and biologic DMARDs given in hospitals from the NPR. RESULTS: The point prevalence of PsA, axSpA, RA, and any of these diseases in total was 0.46%, 0.41%, 0.78%, and 1.56%, respectively. Among women, the prevalence of PsA, axSpA, and RA was 0.50%, 0.37%, and 1.10%, and among men 0.43%, 0.45%, and 0.46%, respectively. In 2017, 27.3% of RA patients, 25.7% of PsA patients and 35.1% of axSpA patients used biologic DMARDs. Treatment with biologics was more frequent in younger age groups in all three diseases, and became more infrequent especially after age ≥55 years. CONCLUSION: In Norway, the combined prevalence of PsA, axSpA, and RA was over 1.5%. Reflecting the good overall access to highly effective but costly biologic treatments, more than a fourth of these patients used biologic agents, which corresponds to over 0.4% of Norwegian adult population.
Assuntos
Antirreumáticos , Artrite Psoriásica , Artrite Reumatoide , Espondiloartrite Axial , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/diagnóstico , Prevalência , Fatores Biológicos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/diagnóstico , Antirreumáticos/uso terapêuticoRESUMO
OBJECTIVE: Adherence to urate-lowering therapy (ULT) in gout is challenging. This longitudinal study aimed to determine 2 year changes in beliefs about medicines during intervention with ULT. METHOD: Patients with a recent gout flare and increased serum urate received a nurse-led ULT intervention with tight control visits and a treatment target. Frequent visits at baseline and 1, 2, 3, 6, 9, 12, and 24 months included the Beliefs about Medicines Questionnaire (BMQ), and demographic and clinical variables. The BMQ subscales on necessity, concerns, overuse, harm, and the necessity-concerns differential were calculated as a measure of whether the patient perceived that necessity outweighed concerns. RESULTS: The mean serum urate reduced from 500 mmol/L at baseline to 324 mmol/L at year 2. At years 1 and 2, 85.5% and 78.6% of patients, respectively, were at treatment target. The 2 year mean ± sd BMQ scores increased for the necessity subscale from 17.0 ± 4.4 to 18.9 ± 3.6 (p < 0.001) and decreased for the concerns subscale from 13.4 ± 4.9 to 12.5 ± 2.7 (p = 0.001). The necessity-concerns differential increased from 3.52 to 6.58 (p < 0.001), with a positive change independent of patients achieving treatment targets at 1 or 2 years. BMQ scores were not significantly related to treatment outcomes 1 or 2 years later, and achieving treatment targets did not lead to higher BMQ scores. CONCLUSION: Patient beliefs about medicines improved gradually over 2 years, with increased beliefs in the necessity of medication and reduced concerns, but this improvement was unrelated to better outcomes. TRIAL REGISTRATION: ACTRN12618001372279.
Assuntos
Supressores da Gota , Gota , Humanos , Gota/tratamento farmacológico , Supressores da Gota/uso terapêutico , Estudos Longitudinais , Adesão à Medicação , Inquéritos e Questionários , Exacerbação dos Sintomas , Resultado do Tratamento , Ácido Úrico/sangue , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
OBJECTIVES: Inflammatory joint disease (IJD) is associated with an increased risk of developing cardiovascular disease (CVD). Arterial stiffness is both a risk factor and a surrogate marker for CVD. This study aims to compare arterial stiffness across patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and, by extension, to explore the relationship between arterial stiffness and the estimated CVD risk by the Systematic COronary Risk Evaluation (SCORE) algorithm. METHOD: During the study period, from April 2017 to June 2018, 196 patients with IJD visited the Preventive Cardio-Rheuma Clinic in Oslo, Norway. A CVD risk stratification was performed, including the assessment of traditional risk factors and the measurement of arterial stiffness. RESULTS: Thirty-six patients (18.4%) had elevated aortic pulse wave velocity (aPWV) (≥ 10 m/s). After adjustment for age and heart rate, arterial stiffness was comparable across the IJD entities (p = 0.69). Associated factors, revealed by regression analysis, were age, blood pressure, heart rate, presence of carotid plaques, establis hed CVD, non-steroidal anti-inflammatory drugs, and statin use. Furthermore, aPWV was positively correlated with estimated CVD risk (r = 0.7, p < 0.001) and patients with a very high predicted CVD risk (SCORE ≥ 10%) had significantly higher aPWV than patients at lower CVD risk (9.2 vs 7.5 m/s, p < 0.001). CONCLUSION: The degree of arterial stiffness was comparable across the IJD entities and was highly associated with the estimated CVD risk. Our findings support the need for an increased focus on prevention of CVD in all patients with IJD.
Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Rigidez Vascular , Artrite Reumatoide/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Humanos , Análise de Onda de Pulso/efeitos adversos , Fatores de RiscoRESUMO
Objectives: This study aimed to identify the therapeutic target concentration and frequency of anti-drug antibodies (ADAbs) in golimumab-treated patients with inflammatory joint disease (IJD).Method: Associations between golimumab concentration, ADAbs, and treatment response were examined in 91 patients with IJD [41 axial spondyloarthritis (axSpA), 20 rheumatoid arthritis (RA), and 30 psoriatic arthritis (PsA)] included in the NOR-DMARD study. Treatment response was defined by Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement in axSpA, European League Against Rheumatism (EULAR) good/moderate response in RA, and improvement of ≥ 50% in modified Disease Activity index for PSoriatic Arthritis (DAPSA) (28 swollen/tender joint counts) in PsA. Serum drug concentrations and ADAbs were analysed using automated in-house assays.Results: At inclusion, 42% were biological disease-modifying anti-rheumatic drug naïve and 42% used concomitant synthetic disease-modifying anti-rheumatic drug. The median golimumab concentration was 2.2 (interquartile range 1.0-3.5) mg/L. The proportions of responders after 3 months among patients with golimumab concentration < 1.0, 1.0-3.9, and ≥ 4.0 mg/L were 19%, 49%, and 74%, respectively. A higher rate of treatment discontinuation was seen in patients with serum golimumab concentration < 1.0 compared to ≥ 1.0 mg/L (hazard ratio 3.3, 95% confidence interval 1.8-6.0, p < 0.05). ADAbs were detected in 6%, and were associated with lower drug concentrations and both reduced treatment response and drug survival.Conclusions: Golimumab concentrations ≥ 1.0 mg/L were associated with improved treatment response and better drug survival, although some patients may benefit from higher concentrations. This study suggests a rationale for dosing guided by therapeutic drug monitoring in golimumab-treated patients with IJD. The results should be confirmed in larger studies including trough samples, and the efficacy of such a strategy must be examined in randomized controlled trials.
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Anticorpos Monoclonais , Artropatias , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Espondiloartrite Axial/tratamento farmacológico , Humanos , Artropatias/tratamento farmacológico , Masculino , Resultado do TratamentoRESUMO
Numerous studies are published on the benefits of electric hand dryers vs paper towels (PT) for drying hands after washing. Data are conflicting and lacking key variables needed to assess infection risks. We provide a rapid scoping review on hand-drying methods relative to hygiene and health risks. Controlled vocabulary terms and keywords were used to search PubMed (1946-2018) and Embase (1947-2018). Multiple researchers independently screened abstracts for relevance using predetermined criteria and created a quality assessment scoring system for relative study comparisons. Of 293 papers, 23 were included in the final analysis. Five studies did not compare multiple methods; however, 2 generally favoured electric dryers (ED); 7 preferred PT; and 9 had mixed or statistically insignificant results (among these, 3 contained scenarios favourable to ED, 4 had results supporting PT, and the remaining studies had broadly conflicting results). Results were mixed among and within studies and many lacked consistent design or statistical analysis. The breadth of data does not favour one method as being more hygienic. However, some authors extended generalizable recommendations without sufficient scientific evidence. The use of tools in quantitative microbial risk assessment is suggested to evaluate health exposure potentials and risks relative to hand-drying methods. We found no data to support any human health claims associated with hand-drying methods. Inconclusive and conflicting results represent data gaps preventing the advancement of hand-drying policy or practice recommendations.
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Higiene das Mãos/instrumentação , Higiene das Mãos/métodos , Eletricidade , Mãos/microbiologia , Humanos , PapelRESUMO
BACKGROUND: New technology adoption is common in health care, but it may elicit frustration if end users are not sufficiently considered in their design or trained in their use. These frustrations may contribute to burnout. OBJECTIVE: This study aimed to evaluate and quantify health care workers' frustration with technology and its relationship with emotional exhaustion, after controlling for measures of work-life integration that may indicate excessive job demands. METHODS: This was a cross-sectional, observational study of health care workers across 31 Michigan hospitals. We used the Safety, Communication, Operational Reliability, and Engagement (SCORE) survey to measure work-life integration and emotional exhaustion among the survey respondents. We used mixed-effects hierarchical linear regression to evaluate the relationship among frustration with technology, other components of work-life integration, and emotional exhaustion, with adjustment for unit and health care worker characteristics. RESULTS: Of 15,505 respondents, 5065 (32.7%) reported that they experienced frustration with technology on at least 3-5 days per week. Frustration with technology was associated with higher scores for the composite Emotional Exhaustion scale (r=0.35, P<.001) and each individual item on the Emotional Exhaustion scale (r=0.29-0.36, P<.001 for all). Each 10-point increase in the frustration with technology score was associated with a 1.2-point increase (95% CI 1.1-1.4) in emotional exhaustion (both measured on 100-point scales), after adjustment for other work-life integration items and unit and health care worker characteristics. CONCLUSIONS: This study found that frustration with technology and several other markers of work-life integration are independently associated with emotional exhaustion among health care workers. Frustration with technology is common but not ubiquitous among health care workers, and it is one of several work-life integration factors associated with emotional exhaustion. Minimizing frustration with health care technology may be an effective approach in reducing burnout among health care workers.
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Esgotamento Profissional , Frustração , Estudos Transversais , Pessoal de Saúde , Humanos , Satisfação no Emprego , Reprodutibilidade dos Testes , Inquéritos e Questionários , TecnologiaRESUMO
Objectives: Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes catalysing the conversion of arginine residues to citrulline, which may constitute a risk factor in rheumatoid arthritis (RA) pathogenesis. We investigated PAD activation by serum (PADAct) in early RA, and the associations between PAD activation and disease characteristics, treatment response, and progression of radiographic damage.Method: Sera from disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients (n = 225), classified according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and healthy controls (n = 63) were analysed for PAD4 activating capacity at 0, 3, 12, and 24 months using a high-performance liquid chromatography fluorometric method. Associations for PADAct were evaluated by Mann-Whitney U and chi-squared tests. Changes in PADAct levels were compared using the Wilcoxon signed-rank test.Results: PADAct positivity occurred in 42% (n = 95) of the patients and was more prevalent in anti-citrullinated protein antibody (ACPA)-positive vs ACPA-negative patients (47% vs 20%, p = 0.002), but not in rheumatoid factor (RF)-positive vs RF-negative patients (44% vs 38%, p = 0.49). PADAct-positive were younger than PADAct-negative patients [mean ± sd 48.7 ± 13.5 vs 53.2 ± 13.7 years, p = 0.011]. Median [25th, 75th percentile] PADAct levels were higher in patients than in controls (8768 [7491, 11 393] vs 7046 [6347, 7906], p < 0.0001) and decreased after initiation of DMARD treatment, but were not associated with treatment response or progression of radiographic damage after 2 years of follow-up.Conclusion: Serum capacity to activate PAD4 was associated with ACPA and RF positivity and earlier disease onset in early RA patients, and decreased after initiation of DMARD treatment, indicating that anti-PAD treatment could potentially be beneficial in RA.
Assuntos
Artrite Reumatoide/enzimologia , Proteína-Arginina Desiminase do Tipo 4/metabolismo , Adulto , Idoso , Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína-Arginina Desiminase do Tipo 4/antagonistas & inibidores , Proteína-Arginina Desiminase do Tipo 4/sangue , Fator Reumatoide/sangueRESUMO
Background: Whether health care provider burnout contributes to lower quality of patient care is unclear. Purpose: To estimate the overall relationship between burnout and quality of care and to evaluate whether published studies provide exaggerated estimates of this relationship. Data Sources: MEDLINE, PsycINFO, Health and Psychosocial Instruments (EBSCO), Mental Measurements Yearbook (EBSCO), EMBASE (Elsevier), and Web of Science (Clarivate Analytics), with no language restrictions, from inception through 28 May 2019. Study Selection: Peer-reviewed publications, in any language, quantifying health care provider burnout in relation to quality of patient care. Data Extraction: 2 reviewers independently selected studies, extracted measures of association of burnout and quality of care, and assessed potential bias by using the Ioannidis (excess significance) and Egger (small-study effect) tests. Data Synthesis: A total of 11 703 citations were identified, from which 123 publications with 142 study populations encompassing 241 553 health care providers were selected. Quality-of-care outcomes were grouped into 5 categories: best practices (n = 14), communication (n = 5), medical errors (n = 32), patient outcomes (n = 17), and quality and safety (n = 74). Relations between burnout and quality of care were highly heterogeneous (I2 = 93.4% to 98.8%). Of 114 unique burnout-quality combinations, 58 indicated burnout related to poor-quality care, 6 indicated burnout related to high-quality care, and 50 showed no significant effect. Excess significance was apparent (73% of studies observed vs. 62% predicted to have statistically significant results; P = 0.011). This indicator of potential bias was most prominent for the least-rigorous quality measures of best practices and quality and safety. Limitation: Studies were primarily observational; neither causality nor directionality could be determined. Conclusion: Burnout in health care professionals frequently is associated with poor-quality care in the published literature. The true effect size may be smaller than reported. Future studies should prespecify outcomes to reduce the risk for exaggerated effect size estimates. Primary Funding Source: Stanford Maternal and Child Health Research Institute.
Assuntos
Esgotamento Profissional/epidemiologia , Qualidade da Assistência à Saúde , Esgotamento Profissional/psicologia , Pessoal de Saúde/psicologia , Humanos , Qualidade da Assistência à Saúde/estatística & dados numéricosRESUMO
BACKGROUND: Emotional exhaustion (EE) in health care workers is common and consequentially linked to lower quality of care. Effective interventions to address EE are urgently needed. OBJECTIVE: This randomized single-exposure trial examined the efficacy of a gratitude letter-writing intervention for improving health care workers' well-being. METHODS: A total of 1575 health care workers were randomly assigned to one of two gratitude letter-writing prompts (self- vs other focused) to assess differential efficacy. Assessments of EE, subjective happiness, work-life balance, and tool engagement were collected at baseline and 1-week post intervention. Participants received their EE score at baseline and quartile benchmarking scores. Paired-samples t tests, independent t tests, and correlations explored the efficacy of the intervention. Linguistic Inquiry and Word Count software assessed the linguistic content of the gratitude letters and associations with well-being. RESULTS: Participants in both conditions showed significant improvements in EE, happiness, and work-life balance between the intervention and 1-week follow-up (P<.001). The self-focused (vs other) instruction conditions did not differentially predict improvement in any of the measures (P=.91). Tool engagement was high, and participants reporting higher motivation to improve their EE had higher EE at baseline (P<.001) and were more likely to improve EE a week later (P=.03). Linguistic analyses revealed that participants high on EE at baseline used more negative emotion words in their letters (P=.005). Reduction in EE at the 1-week follow-up was predicted at the level of a trend by using fewer first-person (P=.06) and positive emotion words (P=.09). No baseline differences were found between those who completed the follow-up assessment and those who did not (Ps>.05). CONCLUSIONS: This single-exposure gratitude letter-writing intervention appears to be a promising low-cost, brief, and meaningful tool to improve the well-being of health care workers.
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Emoções/fisiologia , Pessoal de Saúde/normas , Angústia Psicológica , Estudos de Coortes , Feminino , Humanos , Internet , Masculino , Estudos ProspectivosRESUMO
BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Infliximab/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Anticorpos Monoclonais/efeitos adversos , Método Duplo-Cego , Substituição de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Safety climate is an important marker of patient safety attitudes within health care units, but the significance of intra-unit variation of safety climate perceptions (safety climate strength) is poorly understood. This study sought to examine the standard safety climate measure (percent positive response (PPR)) and safety climate strength in relation to length of stay (LOS) of very low birth weight (VLBW) infants within California neonatal intensive care units (NICUs). METHODS: Observational study of safety climate from 2073 health care providers in 44 NICUs. Consistent perceptions among a NICU's respondents, i.e., safety climate strength, was determined via intra-unit standard deviation of safety climate scores. The relation between safety climate PPR, safety climate strength, and LOS among VLBW (< 1500 g) infants was evaluated using log-linear regression. Secondary outcomes were infections, chronic lung disease, and mortality. RESULTS: NICUs had safety climate PPRs of 66 ± 12%, intra-unit standard deviations 11 (strongest) to 23 (weakest), and median LOS 60 days. NICUs with stronger climates had LOS 4 days shorter than those with weaker climates. In interaction modeling, NICUs with weak climates and low PPR had the longest LOS, NICUs with strong climates and low PPR had the shortest LOS, and NICUs with high PPR (both strong and weak) had intermediate LOS. Stronger climates were associated with lower odds of infections, but not with other secondary outcomes. CONCLUSIONS: Safety climate strength is independently associated with LOS and moderates the association between PPR and LOS among VLBW infants. Strength and PPR together provided better prediction than PPR alone, capturing variance in outcomes missed by PPR. Evaluations of NICU safety climate consider both positivity (PPR) and consistency of responses (strength) across individuals.
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Unidades de Terapia Intensiva Neonatal , Tempo de Internação/estatística & dados numéricos , Segurança do Paciente/normas , Feminino , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal/normas , Masculino , Cultura OrganizacionalRESUMO
BACKGROUND: Quality improvement efforts are inextricably linked to the readiness of healthcare workers to take them on. The current study aims to clarify the nature and measurement of Improvement Readiness (IR) by 1) examining the psychometric properties of a novel IR scale, 2) assessing relationships between IR and other safety culture domains 3) exploring whether IR differs by healthcare worker demographic factors, and 4) examining linguistic differences in word type use between high and low scoring IR work settings from their free text responses. METHODS: Of 13,040 eligible healthcare workers across a large academic health system, 10,627 (response rate 81%) completed the 5-item IR scale, demographics, safety culture scales, and two open-ended questions. Psychometric analyses, correlations and ANOVAs tested the properties of IR. Linguistic Inquiry Word Count software assessed comments from open-ended questions. RESULTS: The IR scale exhibited strong psychometric properties and a one factor model fit the data well (Cronbach's alpha = .93; RMSEA = .07; CFI = 99; TLI = .99). IR scores differed significantly by role, shift, shift length, and years in specialty. IR correlated significantly and in expected directions with safety culture scales. Linguistic analyses revealed that people in low versus high IR work settings used significantly more words in their responses, and specifically more past tense verbs (e.g., "ignored"), negative emotion words (e.g., "upset"), and first person singular ("I"). Workers from high IR work settings used significantly more positive emotions words (e.g., "grateful") and social words (e.g., "team"). CONCLUSION: The IR scale exhibits strong psychometric properties, is associated with better safety and teamwork climate, lower burnout, and predicts linguistic differences in high versus low IR groups.
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Atenção à Saúde/normas , Melhoria de Qualidade , Adulto , Análise de Variância , Atitude do Pessoal de Saúde , Estudos Transversais , Feminino , Humanos , Masculino , Psicometria , Gestão da Segurança , Inquéritos e QuestionáriosRESUMO
The zebrafish ( Danio rerio) provides a powerful model for analyzing genetic contributors to cancer. Multiple zebrafish lines with cancer-associated genetic mutations develop soft tissue sarcomas that are histologically consistent with malignant peripheral nerve sheath tumor (MPNST). The goal of this study was to determine the phenotype of soft tissue sarcomas in a brca2-mutant/ tp53-mutant zebrafish line using immunohistochemical markers that are commonly expressed in mammalian MPNST. We classified 70 soft tissue sarcomas from a brca2-mutant/ tp53-mutant zebrafish cohort as MPNST, undifferentiated sarcoma, or other tumor based on histologic features. The expression of S100, CD57, and glial fibrillary acidic protein (GFAP) was analyzed in nonneoplastic neural tissues and tumor specimens by immunohistochemistry. Each marker was expressed in nonneoplastic neural tissues. In MPNST, S100 and CD57 were widely expressed in neoplastic cells, with greater consistency observed for CD57 expression. In undifferentiated sarcomas, results were variable and correlated to anatomic location. Coelomic undifferentiated sarcomas often exhibited widespread CD57 expression but limited S100 expression. In comparison, ocular undifferentiated sarcomas exhibited limited expression of both CD57 and S100. Overall, CD57 and S100 expression was significantly higher in MPNST than in undifferentiated sarcomas. GFAP was not expressed in any of the tumors. This study identified commercially available antibodies that are useful for analyzing S100, CD57, and GFAP expression in zebrafish. This study further shows a correlation between degree of histologic differentiation and expression of these markers in soft tissue sarcomas from brca2-mutant/ tp53-mutant zebrafish and suggests that these cancers are derived from the neural crest with differentiation toward myelinating Schwann cells.
Assuntos
Proteína BRCA2/metabolismo , Doenças dos Peixes/patologia , Crista Neural , Sarcoma/veterinária , Proteína Supressora de Tumor p53/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra , Animais , Proteína BRCA2/genética , Biomarcadores Tumorais , Antígenos CD57/genética , Antígenos CD57/metabolismo , Regulação Neoplásica da Expressão Gênica , Genótipo , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Mutação , Neurilemoma/metabolismo , Proteínas S100/genética , Proteínas S100/metabolismo , Sarcoma/etiologia , Sarcoma/patologia , Proteína Supressora de Tumor p53/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
BACKGROUND: Organizations that encourage the respectful expression of diverse spiritual views have higher productivity and performance, and support employees with greater organizational commitment and job satisfaction. Within healthcare, there is a paucity of studies which define or intervene on the spiritual needs of healthcare workers, or examine the effects of a pro-spirituality environment on teamwork and patient safety. Our objective was to describe a novel survey scale for evaluating spiritual climate in healthcare workers, evaluate its psychometric properties, provide benchmarking data from a large faith-based healthcare system, and investigate relationships between spiritual climate and other predictors of patient safety and job satisfaction. METHODS: Cross-sectional survey study of US healthcare workers within a large, faith-based health system. RESULTS: Seven thousand nine hundred twenty three of 9199 eligible healthcare workers across 325 clinical areas within 16 hospitals completed our survey in 2009 (86% response rate). The spiritual climate scale exhibited good psychometric properties (internal consistency: Cronbach α = .863). On average 68% (SD 17.7) of respondents of a given clinical area expressed good spiritual climate, although assessments varied widely (14 to 100%). Spiritual climate correlated positively with teamwork climate (r = .434, p < .001) and safety climate (r = .489, p < .001). Healthcare workers reporting good spiritual climate were less likely to have intentions to leave, to be burned out, or to experience disruptive behaviors in their unit and more likely to have participated in executive rounding (p < .001 for each variable). CONCLUSIONS: The spiritual climate scale exhibits good psychometric properties, elicits results that vary widely by clinical area, and aligns well with other culture constructs that have been found to correlate with clinical and organizational outcomes.
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Benchmarking , Recursos Humanos em Hospital/psicologia , Psicometria , Espiritualidade , Adulto , Estudos Transversais , Feminino , Humanos , Satisfação no Emprego , Masculino , Cultura Organizacional , Segurança do Paciente , Inquéritos e Questionários , Estados UnidosRESUMO
Background and Objective Teamwork may affect clinical care in the neonatal intensive care unit (NICU) setting. The objective of this study was to assess teamwork climate across NICUs and to test scale-level and item-level associations with health care-associated infection (HAI) rates in very low-birth-weight (VLBW) infants. Methods Cross-sectional study of the association between HAI rates, defined as any bacterial or fungal infection during the birth hospitalization, among 6,663 VLBW infants cared for in 44 NICUs between 2010 and 2012. NICU HAI rates were correlated with teamwork climate ratings obtained in 2011 from 2,073 of 3,294 eligible NICU health professionals (response rate 63%). The relation between HAI rates and NICU teamwork climate was assessed using logistic regression models including NICU as a random effect. Results Across NICUs, 36 to 100% (mean 66%) of respondents reported good teamwork. HAI rates were significantly and independently associated with teamwork climate (odds ratio, 0.82; 95% confidence interval, 0.73-0.92, p = 0.005), such that the odds of an infant contracting a HAI decreased by 18% with each 10% rise in NICU respondents reporting good teamwork. Conclusion Improving teamwork may be an important element in infection control efforts.
Assuntos
Infecção Hospitalar/epidemiologia , Processos Grupais , Unidades de Terapia Intensiva Neonatal , Cultura Organizacional , Equipe de Assistência ao Paciente , Atitude do Pessoal de Saúde , Estudos Transversais , Feminino , Humanos , Incidência , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Segurança do Paciente , Inquéritos e QuestionáriosAssuntos
Natimorto , Feminino , Humanos , Modelos Logísticos , Gravidez , Prognóstico , Fatores de Risco , Natimorto/epidemiologiaRESUMO
BACKGROUND: As the first objective of caring for patients is to do no harm, patient safety is a priority in delivering clinical care. An essential component of safe care in a clinical department is its safety climate. Safety climate correlates with safety-specific behaviour, injury rates, and accidents. Safety climate in healthcare can be assessed by the Safety Attitudes Questionnaire (SAQ), which provides insight by scoring six dimensions: Teamwork Climate, Job Satisfaction, Safety Climate, Stress Recognition, Working Conditions and Perceptions of Management. The objective of this study was to assess the psychometric properties of the Dutch language version of the SAQ in a variety of clinical departments in Dutch hospitals. METHODS: The Dutch version (SAQ-NL) of the SAQ was back translated, and analyzed for semantic characteristics and content. From October 2010 to November 2015 SAQ-NL surveys were carried out in 17 departments in two university and seven large non-university teaching hospitals in the Netherlands, prior to a Crew Resource Management human factors intervention. Statistical analyses were used to examine response patterns, mean scores, correlations, internal consistency reliability and model fit. Cronbach's α's and inter-item correlations were calculated to examine internal consistency reliability. RESULTS: One thousand three hundred fourteen completed questionnaires were returned from 2113 administered to health care workers, resulting in a response rate of 62 %. Confirmatory Factor Analysis revealed the 6-factor structure fit the data adequately. Response patterns were similar for professional positions, departments, physicians and nurses, and university and non-university teaching hospitals. The SAQ-NL showed strong internal consistency (α = .87). Exploratory analysis revealed differences in scores on the SAQ dimensions when comparing different professional positions, when comparing physicians to nurses and when comparing university to non-university hospitals. CONCLUSIONS: The SAQ-NL demonstrated good psychometric properties and is therefore a useful instrument to measure patient safety climate in Dutch clinical work settings. As removal of one item resulted in an increased reliability of the Working Conditions dimension, revision or deletion of this item should be considered. The results from this study provide researchers and practitioners with insight into safety climate in a variety of departments and functional positions in Dutch hospitals.
Assuntos
Idioma , Segurança do Paciente , Gestão da Segurança/organização & administração , Inquéritos e Questionários/normas , Traduções , Adulto , Atitude do Pessoal de Saúde , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Corpo Clínico Hospitalar/psicologia , Países Baixos , Segurança do Paciente/normas , Psicometria/instrumentação , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: The goal of this study was to implement an evidence-based teamwork system to improve communication and teamwork skills among health care professionals (TeamSTEPPS) into an academic interventional ultrasound program and to assess safety and team-work climate across team members both before and after implementation. MATERIALS AND METHODS: Members of a change team (including master trainers) selected specific tools available within TeamSTEPPS to implement into an academic interventional ultrasound service. Tools selected were based on preimplementation survey data obtained from team members (n = 64: 11 attending faculty physicians, 12 clinical abdominal imaging fellows or residents, 17 sonographers, 19 nurses, and five technologist aides or administrative personnel). The survey included teamwork climate and safety climate domains from the Safety Attitudes Questionnaire. Four months after implementation, respondents were resurveyed and post-implementation data were collected. RESULTS: Teamwork climate scores improved from a mean of 67.9 (SD, 12.8) before implementation to a mean of 87.8 (SD, 14.1) after implementation (t = -7.6; p < 0.001). Safety climate scores improved from a mean of 76.5 (SD, 12.8) before implementation to a mean of 88.3 (SD, 13.4) after implementation (t = -4.6; p < 0.001). In particular, teamwork items about "input being well received" and "speaking up" were the most responsive to the intervention. CONCLUSION: The implementation of TeamSTEPPS tools was associated with statistically significant improvements in safety and teamwork metrics in an academic interventional ultrasound practice. The most notable improvements were seen in communication among team members and role clarification. We think that this model, which has been successfully implemented in many nonradiologic areas in medical care, is also applicable in imaging practice.
Assuntos
Centros Médicos Acadêmicos/organização & administração , Procedimentos Clínicos/organização & administração , Guias como Assunto , Equipe de Assistência ao Paciente/organização & administração , Melhoria de Qualidade/organização & administração , Gestão da Segurança/organização & administração , Ultrassonografia de Intervenção/normas , North Carolina , Avaliação de Programas e Projetos de SaúdeRESUMO
AIMS: In the present study, we conducted a quantitative microbial risk assessment forecasting the exposure to Campylobacter jejuni contaminated surfaces during preparation of chicken fillets and how using a disinfectant-wipe intervention to clean a contaminated work area decreases the risk of infection following the preparation of raw chicken fillet in a domestic kitchen. METHODS AND RESULTS: Using a Monte Carlo simulation of the risk of transferring Camp. jejuni strain A3249, from various surfaces to hands and subsequently transferring it to the mouth was forecasted. The use of a disinfectant-wipe intervention to disinfect contaminated surface area was also assessed. Several assumptions were used as input parameters in the classical Beta-Poisson model to determine the risk of infection. The disinfectant-wipe intervention reduced the risk of Camp. jejuni infection by 2-3 orders on all fomites. CONCLUSIONS: The use of disinfectant wipes after the preparation of raw chicken meat reduces the risk of Camp. jejuni infections. SIGNIFICANCE AND IMPACT OF THE STUDY: This risk assessment shows that the use of disinfectant wipes to decontaminate surface areas after chicken preparation reduces the annual risk of Camp. jejuni infections up to 99·2%, reducing the risk from 2 : 10 to 2 : 1000.