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1.
EClinicalMedicine ; 72: 102629, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38745967

RESUMO

Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 103/µL at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].

2.
J Med Internet Res ; 25: e49016, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37971792

RESUMO

BACKGROUND: Cancer indeed represents a significant public health challenge, and unplanned extubation of peripherally inserted central catheter (PICC-UE) is a critical concern in patient safety. Identifying independent risk factors and implementing high-quality assessment tools for early detection in high-risk populations can play a crucial role in reducing the incidence of PICC-UE among patients with cancer. Precise prevention and treatment strategies are essential to improve patient outcomes and safety in clinical settings. OBJECTIVE: This study aims to identify the independent risk factors associated with PICC-UE in patients with cancer and to construct a predictive model tailored to this group, offering a theoretical framework for anticipating and preventing PICC-UE in these patients. METHODS: Prospective data were gathered from January to December 2022, encompassing patients with cancer with PICC at Xiangya Hospital, Central South University. Each patient underwent continuous monitoring until the catheter's removal. The patients were categorized into 2 groups: the UE group (n=3107) and the non-UE group (n=284). Independent risk factors were identified through univariate analysis, the least absolute shrinkage and selection operator (LASSO) algorithm, and multivariate analysis. Subsequently, the 3391 patients were classified into a train set and a test set in a 7:3 ratio. Utilizing the identified predictors, 3 predictive models were constructed using the logistic regression, support vector machine, and random forest algorithms. The ultimate model was selected based on the receiver operating characteristic (ROC) curve and TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) synthesis analysis. To further validate the model, we gathered prospective data from 600 patients with cancer at the Affiliated Hospital of Qinghai University and Hainan Provincial People's Hospital from June to December 2022. We assessed the model's performance using the area under the curve of the ROC to evaluate differentiation, the calibration curve for calibration capability, and decision curve analysis (DCA) to gauge the model's clinical applicability. RESULTS: Independent risk factors for PICC-UE in patients with cancer were identified, including impaired physical mobility (odds ratio [OR] 2.775, 95% CI 1.951-3.946), diabetes (OR 1.754, 95% CI 1.134-2.712), surgical history (OR 1.734, 95% CI 1.313-2.290), elevated D-dimer concentration (OR 2.376, 95% CI 1.778-3.176), targeted therapy (OR 1.441, 95% CI 1.104-1.881), surgical treatment (OR 1.543, 95% CI 1.152-2.066), and more than 1 catheter puncture (OR 1.715, 95% CI 1.121-2.624). Protective factors were normal BMI (OR 0.449, 95% CI 0.342-0.590), polyurethane catheter material (OR 0.305, 95% CI 0.228-0.408), and valved catheter (OR 0.639, 95% CI 0.480-0.851). The TOPSIS synthesis analysis results showed that in the train set, the composite index (Ci) values were 0.00 for the logistic model, 0.82 for the support vector machine model, and 0.85 for the random forest model. In the test set, the Ci values were 0.00 for the logistic model, 1.00 for the support vector machine model, and 0.81 for the random forest model. The optimal model, constructed based on the support vector machine, was obtained and validated externally. The ROC curve, calibration curve, and DCA curve demonstrated that the model exhibited excellent accuracy, stability, generalizability, and clinical applicability. CONCLUSIONS: In summary, this study identified 10 independent risk factors for PICC-UE in patients with cancer. The predictive model developed using the support vector machine algorithm demonstrated excellent clinical applicability and was validated externally, providing valuable support for the early prediction of PICC-UE in patients with cancer.


Assuntos
Extubação , Cateterismo Venoso Central , Neoplasias , Humanos , Cateterismo Venoso Central/efeitos adversos , Catéteres , Aprendizado de Máquina , Neoplasias/terapia , Estudos Prospectivos , Fatores de Risco
3.
J Med Internet Res ; 25: e45602, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37540546

RESUMO

BACKGROUND: Developing Internet+home care (IHC) services is a promising way to address the problems related to population aging, which is an important global issue. However, IHC services are in their infancy in China. Limited studies have investigated the willingness and demand of nurses in municipal hospitals to provide IHC services. OBJECTIVE: This study aims to investigate the willingness and demand of nurses in municipal hospitals in China to provide IHC services and analyze the factors to promote IHC development in China. METHODS: This cross-sectional study used multistage sampling to recruit 9405 nurses from 10 hospitals in 5 regions of China. A self-designed questionnaire with good reliability and validity was used to measure nurses' willingness and demand for providing IHC services. Data analysis used the chi-square test, Welch t test, binary logistic regression analysis, and multiple linear regression analysis. RESULTS: Nurses were highly willing to provide IHC services and preferred service distances of <5 km and times from 8 AM to 6 PM. An individual share >60% was the expected service pay sharing. Job title, educational level, monthly income, and marital status were associated with nurses' willingness to provide IHC services in binary logistic regression analysis. Supervising nurses were 1.177 times more likely to express a willingness to provide IHC services than senior nurses. Nurses with a bachelor's degree had a 1.167 times higher likelihood of expressing willingness to provide IHC services than those with a junior college education or lower. Married nurses were 1.075 times more likely to express a willingness than unmarried nurses. A monthly income >¥10,000 increased the likelihood of nurses' willingness to provide IHC services, by 1.187 times, compared with an income <¥5000. Nurses' total mean demand score for IHC services was 17.38 (SD 3.67), with the highest demand being privacy protection. Multiple linear regression analysis showed that job title, monthly income, and educational level were associated with nurses' demand for IHC services. Supervising nurses (B=1.058, P<.001) and co-chief nurses or those with higher positions (B=2.574, P<.001) reported higher demand scores than senior nurses. Monthly incomes of ¥5000 to ¥10,000 (B=0.894, P<.001) and >¥10,000 (B=1.335, P<.001), as well as a bachelor's degree (B=0.484, P=.002) and at least a master's degree (B=1.224, P=.02), were associated with higher demand scores compared with a monthly income <¥5000 and junior college education or lower, respectively. CONCLUSIONS: Nurses in municipal hospitals showed a high willingness and demand to provide IHC services, with differences in willingness and demand by demographic characteristics. Accordingly, government and hospitals should regulate the service period, service distance, and other characteristics according to nurses' willingness and demand and establish relevant laws and regulations to ensure the steady and orderly development of IHC services.


Assuntos
Serviços Hospitalares de Assistência Domiciliar , Hospitais Municipais , Enfermeiras e Enfermeiros , Telemedicina , Humanos , China/epidemiologia , Estudos Transversais , Reprodutibilidade dos Testes , Inquéritos e Questionários
4.
JAMA Oncol ; 9(9): 1230-1237, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37440217

RESUMO

Importance: The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease. Objective: To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted). Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months. Interventions: Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×103/µL [to convert to ×109/µL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy. Main Outcomes and Measurements: The primary end point was blinded, independent central review-assessed PFS in the intention-to-treat population. Results: A total of 384 patients were randomized (255 niraparib [66.4%]; median [range] age, 53 [32-77] years; 129 placebo [33.6%]; median [range] age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio [HR], 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events. Conclusion and Relevance: This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting. Trial Registration: ClinicalTrials.gov Identifier: NCT03709316.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Intervalo Livre de Progressão , Indazóis/efeitos adversos , Método Duplo-Cego , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
5.
Nat Commun ; 14(1): 3542, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37336884

RESUMO

PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. Despite lacking catalytic activity, alteration in their expression level is associated with several aggressive cancers. Here, we elucidate the molecular details of key PEAK signaling interactions with the adapter proteins CrkII and Grb2 and the scaffold protein 14-3-3. Our findings rationalize why the dimerization of PEAK proteins has a crucial function in signal transduction and provide biophysical and structural data to unravel binding specificity within the PEAK interactome. We identify a conserved high affinity 14-3-3 motif on PEAK3 and demonstrate its role as a molecular switch to regulate CrkII binding and signaling via Grb2. Together, our studies provide a detailed structural snapshot of PEAK interaction networks and further elucidate how PEAK proteins, especially PEAK3, act as dynamic scaffolds that exploit adapter proteins to control signal transduction in cell growth/motility and cancer.


Assuntos
Proteínas 14-3-3 , Proteínas do Citoesqueleto , Transdução de Sinais , Movimento Celular , Proliferação de Células , Transdução de Sinais/fisiologia , Proteínas do Citoesqueleto/metabolismo , Proteínas 14-3-3/metabolismo
6.
Sci Total Environ ; 893: 164897, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37329915

RESUMO

The carbon stocks (Corg stocks) in mangrove sediments and the distribution and source changes of sedimented organic matter in Qinglan Bay are not understood as the mangrove forests decrease. In this paper, we collected two sediment cores in the interior mangrove and 37 surface sediment samples from mangrove-fringe, tidal flat and subtidal habitats and then analysed the total organic carbon (TOC), total nitrogen (TN), and the stable organic carbon isotope (δ13C) and nitrogen isotope (δ15N) in the sediment samples to obtain the organic matter sources and carbon stocks in two different mangrove sediment cores from Qinglan Bay. The δ13C and TOC/TN values showed that mangrove plants and algae were the main sources of organic matter. Relatively high contributions of mangrove plants (>50 %) were distributed in the mangrove areas in Wenchang estuary, the northern region of Bamen Bay and the eastern side of the Qinglan tidal inlet. The enriched δ15N values might be related to anthropogenic nutrient inputs, including increased aquaculture wastewater, human sewage and ship wastewater. The Corg stocks in cores Z02 and Z03 were 357.79 Mg C ha-1 and 265.78 Mg C ha-1, respectively. This Corg stock difference might have been related to the salinity and the benthos activities. The high Corg stock values measured in Qinglan Bay were caused by the mangrove maturity and stand age. The total Corg storage of the mangrove ecosystem in Qinglan Bay was estimated to be approximately 263.93 Gg C. This study contributes to organic carbon stocks and sources of sedimented organic matter in global mangroves.

7.
J Occup Health ; 65(1): e12398, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37038325

RESUMO

OBJECTIVES: As the coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide, nucleic acid detection is a key step in controlling it. Psychological issues and job burnout of nurses working in nucleic acid sampling roles for long periods have become apparent. This study aimed to explore the effects of mindfulness decompression therapy on mental health and job burnout in front-line nurses working in nucleic acid sampling during the pandemic. METHODS: Nucleic acid sampling frontline nurses who were positive for burnout on both the Symptom Checklist-90 (SCL-90) and the Maslach Burnout Inventory-General Scale (MBI-GS) were selected as the participants. Frontline nurses in the nucleic acid testing area who received routine psychological nursing intervention from June 2020 to April 2021 were used as the control group. Nurses who received both routine psychological nursing and mindfulness decompression therapy from May 2021 to December 2021 formed the "mindfulness" subject group. We compared the two groups' primary outcome measures of SCL-90 and MBI-GS scores. RESULTS: Before the intervention, there were no significant differences between the two groups in general data, SCL-90 scores, and MBI-GS scores. After the mindfulness decompression therapy, according to SCL-90 and MBI-GS scales, psychological distress and job burnout of nurses in the mindfulness group were significantly better than those in the control group. CONCLUSION: Mindfulness decompression therapy can effectively improve mental health and relieve job burnout in frontline nurses in nucleic acid sampling areas, which is worthy of clinical application. Randomized controlled trials are still needed, however, to fully confirm the effects of mindfulness decompression therapy.


Assuntos
Esgotamento Profissional , COVID-19 , Humanos , Estudos Retrospectivos , Pandemias , Saúde Mental , COVID-19/terapia , Esgotamento Profissional/epidemiologia , Esgotamento Psicológico , SARS-CoV-2 , Descompressão
8.
Risk Manag Healthc Policy ; 15: 2257-2268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36475274

RESUMO

Purpose: The present study aims to evaluate the current situation of knowledge, attitude and practice of clinical nurses in catheter-related thrombosis, analyze its influencing factors, enhance the attention of nursing managers and clinical nurses about catheter-related thrombosis, and provide a basis for formulating catheter-related thrombosis training plan. Patients and Methods: The research was conducted from January 1 to February 31, 2022, we recruited 549 nurses from two hospitals in Hunan province in this cross-sectional study using a two-stage random sampling method. We used a self-designed questionnaire with good reliability and validity to measure clinical nurses' knowledge, attitudes, and practice toward catheter-related thrombosis. We used χ 2 test, Welch t-test, and multiple linear regression analysis to analyze the data. Results: The knowledge of clinical nurses about catheter-related thrombosis was insufficient (55.00%), while the attitude was positive (88.49%) and the practice was inadequate (68.62%). Knowledge of clinical nurses was significantly associated with job title (ß: 1.069, P<0.001), educational level (ß: 0.094, P<0.05), and training times (ß: 0.085, P<0.05), which were positive factors while whether they are specialized nurses in intravenous therapy (ß: -0.126, P<0.05), and hospital level (ß: -0.101, P<0.05) were negative factors. Training times (ß: 0.166, P<0.001), job title (ß: 0.099, P<0.019), and hospital level (ß: 0.090, P<0.05) were associated factors of attitude. Moreover, training times (ß: 0.255, P<0.001) was the only factor associated with the practice. Conclusion: Although clinical nurses hold a positive attitude towards catheter-related thrombosis, their knowledge level was unsatisfactory and their practice was affected by many factors, suggesting that nursing managers should strengthen the training and skill assessment of catheter-related thrombosis. At the same time, the hospital can formulate relevant rules, regulations, and guidelines to reduce the incidence of catheter-related thrombosis.

9.
Risk Manag Healthc Policy ; 15: 1395-1405, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911086

RESUMO

Purpose: The present study aimed to investigate nurses' willingness and demand for Internet +home care services in different levels of hospitals in China and analyze the influencing factors. Participants and Methods: From October 1 to December 31, 2021, 5714 nurses from 15 hospitals in five regions of China were recruited in this cross-sectional study using a two-stage random sampling method. A self-designed questionnaire with good reliability and validity was used to measure nurses' willingness and demand for Internet +home care services. χ 2 test, Welch t-test, and multiple linear regression analyses were used to analyze the data. Results: Nurses were highly willing to provide Internet +home care services. Statistical differences were found in the willingness to provide Internet +home care services and the preference for service distance, service platform, and single service fee between nurses in different levels of hospitals (both P<0.05). The willingness to provide "catheter maintenance service" and "rehabilitation nursing service" of nurses in different levels of hospitals were statistically significant (both P<0.05). Nurses' demand for Internet +home care services increased with the level of their hospital. Multiple linear regression showed that professional title, educational level, monthly family income, and mortgage or car loan influence nurses' demand for Internet +home care services. Conclusion: Nurses' willingness and demand for Internet +home care services vary with the level of their hospitals. It is recommended that government and hospitals regulate the service items, the service distance, single service fee, and other contents according to nurses' willingness and demand and establish relevant laws and regulations to ensure the steady and orderly development of the Internet +home care services.

10.
Risk Manag Healthc Policy ; 15: 1325-1341, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35855767

RESUMO

Background: With the aging of China's population, the incidence rate of chronic diseases is rising. At the same time, residents' health awareness is also increasing. Implementing Internet +home care is an inevitable trend in adapting social development. Currently, Internet +home care is in the pilot stage in China, relevant institutional measures are neither standardized nor perfect, and there is no set of quality supervision indicators (QSIs). Purpose: The construction of Internet +home care QSIs in China will provide a theoretical basis for Internet +home care quality supervision. Materials and Methods: The Service-Quality model was used as the theoretical framework, and a literature review, semi-structured interviews, focus group discussions, and Delphi consultations determined the contents of the QSIs and the weight of each indicator. Results: Internet +home care QSIs were constructed and included 5 first-level indicators, 17 secondary indicators, and 69 tertiary indicators. The effective recovery rates of the two rounds of Delphi expert consultation were 100% and 85%, the expert authority coefficients were 0.810 and 0.833, and the Kendall harmony coefficients were 0.189 and 0.125 (P<0.01). The final set of Internet +home care QSIs was as follows: tangibility (4 secondary and 16 tertiary indicators), reliability (4 secondary and 19 tertiary indicators), guarantee (5 secondary and 20 tertiary indicators), responsiveness (2 secondary and 8 tertiary indicators), and empathy (2 secondary and 6 tertiary indicators). Conclusion: The construction of Internet +home care QSIs based on the SERVQUAL model is scientifically valid, and the indicators are reliable. They provide guidance and reference values for the continuous improvement and promotion of Internet +home care. This work also provides a theoretical basis for researching and developing an Internet +home care quality supervision platform.

11.
Psychol Res Behav Manag ; 15: 533-546, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281999

RESUMO

Purpose: Investigating psychological status and job burnout of nurses working in the frontline of the novel coronavirus in Zhangjiajie city in China during the Delta variant outbreak, comparing differences and analyzing factors of these two variables between the nurses from different nucleic acid testing (NAT) sites. Patients and methods: This survey was conducted from August 1 to 31, 2021. The participants were 512 nurses, 198 nurses of whom were from temporary NAT sites in communities/towns in Zhangjiajie city, and the rest were from NAT sites inside hospitals. The psychological status and the job burnout were measured by the Symptom Checklist-90 (SCL-90) and the Maslach Burnout Inventory-General Scale (MBI-GS). Results: The prevalence of the SCL-90 positive result and job burnout were 49.4% and 61.1%, respectively. The factors influencing the psychological status of nurses included the contact with COVID-19 patients or their body fluids and specimens, working seniority and the duration of working in the frontline of the novel coronavirus. The independent risk factors of nurses' job burnout included the following four factors. Firstly, the contact with COVID-19 patients or their body fluids and specimens (OR=150.95, 95% CI=(44.87,507.77), P<0.001). Secondly, five to nine years of working seniority (OR=8.91, 95% CI=(3.59,22.14), P<0.001). Thirdly, 10 to 19 days (OR=2.63, 95% CI=(1.19,5.82), P=0.017), 20 to 29 days (OR=161.31, 95% CI=(49.48,525.9), P<0.001). Lastly, more than 30 days (OR=92.05, 95% CI=(33.88,250.14), P<0.001) of working in the frontline of the novel coronavirus. Conclusion: The prevalence of psychological problems and job burnout were at a high level among nurses working in the frontline of the novel coronavirus in different NAT sites. The nurses from NAT sites inside hospitals and temporary NAT sites in communities/towns in Zhangjiajie city had an equal risk of developing psychological problems and job burnout. Interventions need to be immediately implemented to promote psychological well-being and decrease job burnout of nurses.

12.
Sci Signal ; 15(722): eabj3554, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35192416

RESUMO

The pseudokinase scaffolds PEAK1 and PEAK2 are implicated in cancer cell migration and metastasis. We characterized the regulation and role of the third family member PEAK3 in cell signaling. Similar to PEAK1 and PEAK2, PEAK3 formed both homotypic and heterotypic complexes. In addition, like PEAK1, it bound to the adaptors Grb2 and CrkII. However, unlike PEAK1 and PEAK2, homodimerized PEAK3 also interacted with the ARF GTPase-activating protein ASAP1, the E3 ubiquitin ligase Cbl, and the kinase PYK2. Dimerization and subsequent phosphorylation on Tyr24, likely by a Src family kinase, were required for the binding of PEAK3 to Grb2 and ASAP1. Interactions with Grb2, CrkII, ASAP1, Cbl, and PYK2 exhibited contrasting dynamics upon cell stimulation with epidermal growth factor (EGF), in part due to PEAK3 dephosphorylation mediated by the phosphatase PTPN12. Overexpressing PEAK3 in mesenchymal-like MDA-MB-231 breast cancer cells enhanced cell elongation in a manner dependent on PEAK3 dimerization, and manipulation of PEAK3 expression demonstrated a positive role for this scaffold in regulating cell migration. Overexpressing PEAK3 in PEAK1/2 double-knockout MCF-10A breast epithelial cells enhanced acinar growth, impaired basement membrane integrity, and promoted invasion in three-dimensional cultures, with the latter two effects dependent on the binding of PEAK3 to Grb2 and ASAP1. PEAK1 and PEAK2 quantitatively and temporally influenced PEAK3 function. These findings characterize PEAK3 as an integral, signal-diversifying member of the PEAK family with scaffolding roles that promote cell proliferation, migration, and invasion.


Assuntos
Proteínas Tirosina Quinases , Transdução de Sinais , Movimento Celular , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Quinases da Família src/metabolismo
13.
Risk Manag Healthc Policy ; 14: 4931-4938, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34924775

RESUMO

BACKGROUND AND AIM: Drug extravasation is one of the most common complications of intravenous therapy, which can lead to severe tissue injury if inappropriately treated. This study analyzes the current situation of extravasation and the risk factors affecting the severity of extravasation to provide a theoretical basis for carrying out prospective research, reducing the severity of drug extravasation, and strengthening the management of drug extravasation. MATERIALS AND METHODS: We retrieved the data on extravasation from January 2016 to December 2020 from the hospital's safe infusion management system. We used nonparametric tests to assess the differences in the severity of drug extravasation among each variable and performed a multivariate analysis using multivariate ordered logistic regression. RESULTS: Extravasation occurred in 0.038% (263/694,043) of patients, including 203 cases of mild extravasation (77.2%), 57 cases of moderate extravasation (21.7%), and 3 cases of severe extravasation (1.1%). The main diseases of the patients with extravasation were cancer (24.7%), neurological-related diseases (19.4%), circulatory-related diseases (14.8%), and digestive-related diseases (14.1%); the main extravasated drugs were hypotonic or hypertonic drugs (31.9%) and contrast media (27.8%); the infusion tools of extravasation were indwelling needles (92.0%) and steel needles (8.0%). The multi-factor analysis showed that close to joints, patients' age ≤6 or age >65, cancer, neurological-related diseases, circulatory-related diseases, antineoplastic agents, hypotonic or hypertonic drugs and strong acid or alkali drugs were independent risk factors for more severe extravasation. The nurses' age and first identified by nurse were nurse-related factors that influenced the severity of drug extravasation. CONCLUSION: To prevent the occurrence of drug extravasation and reduce its severity, the nurses should strengthen the learning of emergency plans related drug extravasation, strengthen inspections of high-risk patients. Besides, the managers should strengthen the risk warning management of high-risk extravasated drugs.

14.
J Vasc Access ; 22(4): 613-622, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32928030

RESUMO

BACKGROUND: Most studies focused on the application of intracavitary electrocardiogram (IC-ECG) location in superior vena cava access catheterization, this study aimed to explore the effect of IC-ECG for tip location of femoral vein catheters in chemotherapy patients with superior vena cava obstruction (SVCO). METHODS: A total of 158 patients placed catheters through superficial femoral vein from July 2016 to May 2019 were enrolled in the randomized controlled study. The patients were divided into two groups by envelope lottery method: X-ray location was used in the control group (n = 79); IC-ECG location was used in the observation group (n = 79). The catheters should be located at or near the inferior vena cava (IVC)-right atrium (RA) junction (above the level of diaphragm within the IVC). The general information of patients, clinical catheterization effects and catheter-related complications were compared between the groups. RESULTS: No significant differences in general information, catheter obstruction, catheter-related thrombosis, catheter exit-site bleeding and infection were found between the groups. The rate of successful insertion at the first attempt and patient satisfaction in the observation group were significantly higher than that in the control group (p < 0.05). The time and cost of location and the incidence of catheter-related complications in the control group were 32.57 min and 140.51 Yuan and 21.5%, which were significantly higher than 6.94 min and 13.59 Yuan and 7.6% in the observation group (p < 0.05). CONCLUSION: IC-ECG accurately located the tip of femoral vein catheters, reduced the incidence of catheter-related complications and the time and cost of location, improved patient satisfaction.


Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Síndrome da Veia Cava Superior , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Eletrocardiografia , Veia Femoral/diagnóstico por imagem , Humanos , Síndrome da Veia Cava Superior/diagnóstico por imagem , Síndrome da Veia Cava Superior/etiologia , Síndrome da Veia Cava Superior/terapia , Veia Cava Superior
15.
Risk Manag Healthc Policy ; 13: 903-913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801965

RESUMO

BACKGROUND AND AIM: The promotion of peripherally inserted central catheter (PICC) maintenance in primary hospitals can benefit discharged patients with PICCs living in remote areas a lot. Yet, no primary hospitals had introduced PICC maintenance technology in Hunan province, China. The present study aimed to evaluate nurses' attitudes and knowledge of PICC maintenance in primary hospitals in Hunan province, China. MATERIALS AND METHODS: From November 2018 to January 2019, a total of 560 nurses from 28 community hospitals and 28 township hospitals in 14 cities across Hunan were recruited in the present study. All nurses were registered nurses engaged in clinical work related to intravenous infusion, and their attitudes and knowledge of PICC maintenance were measured by a self-designed questionnaire that was based on literature review and expert consultation. RESULTS: The response rate was 93.6% (560 of 598). Almost all participants could realize the importance and necessity of PICC maintenance. More than 90% of the participants expressed interest in PICC maintenance and showed strong demands for relevant training. However, the nurses' correct response rate of most knowledge items was at a low level (7.14-57.68%), with only three items exhibiting the correct response rate of 90% or higher. The factors influencing the nurses' PICC maintenance knowledge included their nursing experience, professional title, work setting, and department. CONCLUSION: Although nurses in primary hospitals had a positive attitude toward PICC maintenance, their knowledge level was unsatisfactory, which might be a barrier to the promotion of PICC maintenance technology in primary hospitals in Hunan province, China. Multiple parties should get involved and take measures to improve the nurses' PICC maintenance knowledge, including the government, nursing associations, large-scale hospitals, and primary hospitals themselves. Besides, new training models and dynamic assessment methods should be explored to improve training effectiveness in the future.

16.
Med Sci Monit ; 26: e923909, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32634134

RESUMO

BACKGROUND Chlamydia trachomatis is an obligate intracellular pathogen that can cause severe reproductive tract complications while ascending infection occurs. When spreading from cell to cell in a host, C. trachomatis utilizes various survival strategies to offset host defense mechanisms. One such strategy is to degrade host antimicrobial defense proteins before they can attack the invading C. trachomatis cells. MATERIAL AND METHODS We expressed and purified recombinant chlamydia high temperature requirement protein A (cHtrA) including 2 cHtrA mutants (MT-H143A and MT-S247A), and also extracted endogenous cHtrA. Proteins were identified and their purity evaluated by SDS-PAGE and Western blot. The anti-chlamydial activity and degradation of 5 antimicrobial peptides (cathelicidin LL-37, alpha-defensin-1 and -3, and ß-defensin-2 and -4) by cHtrA and 2 cHtrA mutants (MT-H143A and MT-S247A) were tested by immunoassay and Western blot. RESULTS Of the 5 antimicrobial peptides (cathelicidin LL-37, alpha-defensin-1 and -3, and ß-defensin-2 and -4) tested, cathelicidin LL-37 showed the strongest anti-chlamydial activity. Interestingly, cHtrA effectively and specifically degraded LL-37, suppressing its anti-chlamydial activity. The 2 cHtrA mutants (MT-H143A and MT-S247A) were unable to degrade LL-37. Comparison of cHtrA activity from C. trachomatis D, L2, and MoPn strains on LL-37 showed similar responses. CONCLUSIONS cHtrA may contribute to C. trachomatis pathogenicity by clearing the passage of invasion by specific LL-37 degradation.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia , Serina Peptidase 1 de Requerimento de Alta Temperatura A/metabolismo , Anti-Infecciosos , Chlamydia trachomatis/patogenicidade , Endopeptidases , Células Epiteliais , Células HeLa , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Humanos , Fatores Imunológicos , Peptídeo Hidrolases , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Serina Proteases/metabolismo , Proteína Estafilocócica A , Temperatura , Catelicidinas
17.
BMJ Open ; 10(5): e033804, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32444430

RESUMO

OBJECTIVES: The present study aimed to assess the level of knowledge on peripherally inserted central catheter (PICC) maintenance among nurses in China and to analyse the related factors influencing this variable. DESIGN: A cross-sectional survey. SETTING: Ninety-one hospitals at three different levels in Hunan Province, China: county hospitals, municipal hospitals and provincial hospitals. PARTICIPANTS: A total of 4110 registered nurses engaged in clinical work related to intravenous infusion. PRIMARY AND SECONDARY OUTCOME MEASURES: Nurses' knowledge of PICC maintenance was measured by the score of an anonymous, self-reported questionnaire. RESULTS: The mean score of PICC maintenance among 4110 nurses was 72.86±14.86. 83.5% of the participants exhibited a score of 60 or above, and 34.1% of them exhibited a good grade with a score of 80 or above. The difference in the correct rate among different dimensions was statistically significant (H=17.721, p<0.01). The generalised linear model indicated that the factors influencing the nurses' PICC maintenance knowledge included gender, age, professional title, work setting and previous history of PICC maintenance training. CONCLUSIONS: In conclusion, the knowledge of PICC maintenance was at a medium level among nurses in Hunan province, China. Multiple steps should be taken to improve the nurses' PICC maintenance knowledge, including disseminating PICC maintenance knowledge in multiple ways, such as courses, lectures, seminars and new media. Particular attention should be given to populations who responded poorly in this survey, and targeted education for nurses should be distributed based on their performance on specific dimensions, such as the replacement of dressing and needle-free connectors. In addition, the quality of the nurses' practical performance could be measured in the future.


Assuntos
Cateterismo Venoso Central , Cateterismo Periférico , Competência Clínica , Enfermeiras e Enfermeiros , Catéteres , China , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e Questionários
18.
Oncologist ; 25(1): 19-e10, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31439812

RESUMO

LESSONS LEARNED: Pharmacokinetics characteristics of niraparib in Chinese patients were similar to those in white patients. Niraparib could be well tolerated by Chinese patients, and adverse events were manageable in this study. Population pharmacokinetics analysis indicated that baseline body weight had a modest impact on pharmacokinetics parameters of niraparib; however, it was not considered clinically important. BACKGROUND: This randomized, open-label, single-arm, phase I study was designed to investigate the pharmacokinetics (PK) and safety of niraparib in Chinese patients with epithelial ovarian cancer. METHODS: Eligible patients were randomized in a 1:1:1 ratio to receive 100, 200, or 300 mg of niraparib once daily. PK parameters were analyzed after single and multiple dose administrations. RESULTS: Thirty-six Chinese patients were enrolled in total. Niraparib was rapidly absorbed after administration, and median time-to-peak (Tmax ) was 3 hours. The long terminal elimination half-life (T1/2 ∼ 35 hours) supports once-daily dosing regimen. The exposure to niraparib showed linear and dose-proportional pharmacokinetics, whereas other PK parameters such as Tmax , T1/2 , and accumulation ratio were dose independent. Population PK analysis indicated that there was no effect of race on niraparib PK parameters, whereas baseline body weight had a modest impact on niraparib exposure. Grade 3/4 treatment-emergent adverse events (TEAEs; reported in ≥10% of patients) included platelet count decreased (a total of five patients who were all from the 300-mg group) and neutrophil count decreased. The TEAEs were manageable after dose modification. CONCLUSION: The PK profile of niraparib in Chinese patients is consistent with that in white patients. Niraparib is safe and well tolerated in Chinese patients with ovarian cancer.


Assuntos
Indazóis/farmacocinética , Indazóis/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Piperidinas/farmacocinética , Piperidinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Feminino , Humanos , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia
19.
Thromb Res ; 184: 38-43, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706066

RESUMO

OBJECTIVE: Our study aimed to scrutinize the incidence and risk factors of femoral inserted central catheter (FICC)-related thrombosis in patients with superior vena cava syndrome (SVCS) undergoing chemotherapy. METHODS: A retrospective analysis of patients with SVCS undergoing chemotherapy who received FICC catheterization at the Xiangya Hospital, Central South University, Changsha City, Hunan Province between May 2012 and February 2019 was performed. Both asymptomatic thrombosis and symptomatic thrombosis were diagnosed by color doppler ultrasound (CDUS). Univariate and multivariate logistic regression analyses were performed to identify patient-, insertion-, and catheter-related factors. RESULTS: Eight hundred and seventy-four patients with SVCS undergoing chemotherapy, with a total of 157,180 catheter days were enrolled in our study. FICC-related thrombosis was detected in 144 patients, and yielding an overall incidence of 16.47% or 0.92 events per 1000 catheter days. Of these, 19(2.17%) patients had symptomatic thrombosis. The mean time interval between FICC insertion and thrombosis onset was (10.40 ±â€¯6.32) days and the mean catheter indwelling time was (179.84 ±â€¯46.15) days. The history of deep venous thrombosis, treatment with vascular endothelial growth factor (VEGF) inhibitor (bevacizumab), puncture site (mid-thigh, groin), tip position and catheter size showed association with FICC-related thrombosis. Treatment with VEGF inhibitor [odds ratio (OR) = 2.779; 95%confidence interval (CI): 1.860-4.153; P < 0.001] and puncture site at the groin (OR = 10.843; 95%CI: 6.575-17.881; P < 0.001) were identified as independent risk factors of FICC-related thrombosis. CONCLUSION: Treatment with VEGF inhibitor and puncture site at the groin during FICC catheterization were considered as high-risk factors in FICC-related thrombosis.


Assuntos
Cateterismo Venoso Central/métodos , Veia Femoral/cirurgia , Síndrome da Veia Cava Superior/complicações , Trombose/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Síndrome da Veia Cava Superior/tratamento farmacológico , Adulto Jovem
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(6): 679-684, 2018 Jun 28.
Artigo em Chinês | MEDLINE | ID: mdl-30110012

RESUMO

OBJECTIVE: To construct a competency model for junior caregivers for the elderly and to provide a reference for the selection, evaluation and training for the junior caregivers for the elderly.
 Methods: Firstly, we drafted the primary competency model for junior caregivers for the elderly through literature review. Then, we used Delphi method to carry out 2 rounds of questionnaire survey for 20 experts to optimize the indicators for primary model. The weight of each indicator is determined by analytic hierarchy process (AHP) and expert sequencing method.
 Results: The effective recovery rates of the two-round questionnaire were 87% and 100%, respectively. The expert authority coefficient was 0.70-0.93, and the average authority coefficient was 0.80. The final version of the competency model for junior caregivers for the elderly included 4 first-grade indexes, 11 second-grade indexes and 37 third-grade indexes.
 Conclusion: The competency model for the junior caregivers for the elderly is reliable and can be used as the reference standard for the selection, evaluation and training for the junior caregivers for the elderly.


Assuntos
Competência Clínica , Serviços de Saúde para Idosos/normas , Corpo Clínico Hospitalar/normas , Idoso , Cuidadores/normas , Técnica Delphi , Humanos , Padrões de Referência , Inquéritos e Questionários
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