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Testing the association between the enabling and enacting factors of patient safety culture and patient safety: structural equation modelling
Get PDFBackground: Despite evidence linking a safety culture with patient safety, the processes by which aspect of safety culture influences patient safety are not yet well understood. Thus, this study aimed to test a theoretical model of the relationships between three enabling factors (supervisor/clinical leader support for patient safety, hospital management support for patient safety, and psychological safety), and four enacting factors of patient safety culture (handoffs and information exchange, teamwork, error reporting intention, and withholding voice) with nurse assessments of patient safety.
Methods: A cross-sectional, descriptive correlational study design was used. Between May and June 2020, 526 nurses who provided direct care to patients in medical surgical units in three Korean hospitals completed an online survey that included four standardized scales or subscales. Structural equation modelling was used to test the hypothesized model.
Results: Among the three enabling factors, psychological safety was associated with all four enacting factors, and all enacting factors were associated with overall patient safety. Hospital management support was associated with all enacting factors except teamwork, but supervisor/clinical leader support was associated with only handoffs and information exchange, and withholding voice. Thus, teamwork was influenced only by psychological safety. Findings demonstrate overall support for the theoretical model of safety culture wherein enabling factors influence enacting factors which, in turn, lead to patient safety outcomes, but emphasize the critical nature of psychological safety among nursing staff.
Conclusion: This study provides further insight into the importance of support from hospital management and unit supervisors/clinical leaders for patient safety to motivate and enable hospital nurses to enact behaviours necessary for patient safety. However, such support must also take the form of enhancing psychological safety for nursing staff.ope
Atezolizumab plus bevacizumab in patients with child–Pugh B advanced hepatocellular carcinoma
Get PDFBackground:Atezolizumab plus bevacizumab (Ate/Bev) demonstrated promising efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III IMbrave150 trial. However, patients with Child–Pugh B HCC were excluded in the abovementioned prospective trial. Therefore, we aimed to investigate the efficacy and safety of Ate/Bev in patients with Child–Pugh B HCC.
Methods:This multicenter retrospective study included 36 patients with Child–Pugh B advanced HCC who received Ate/Bev at four cancer referral centers between May 2020 and August 2021. Comparative analyses were performed with an independent cohort of patients with Child–Pugh A HCC from the same registry (n = 133).
Results:All patients received Ate/Bev as first-line systemic treatment for advanced HCC. The objective response and disease control rates of patients in the Child–Pugh groups B and A were 11.1% and 58.3% and 34.6% and 76.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.0 months [95% confidence interval (CI), 1.7–4.3) and 7.7 months (95% CI, 4.8–10.6) in the Child–Pugh B group, whereas the median PFS and OS were 9.6 months (95% CI, 5.1–14.2) and not reached (95% CI, not available) in the Child–Pugh A group, respectively. Compared to the Child–Pugh A group, grade 3–4 adverse events (AEs) were more common in the Child–Pugh B group (44.4% versus 15.8, p < 0.001), with the most frequent grade 3–4 AEs being gastrointestinal bleeding (n = 6, 16.7%), neutropenia (n = 5, 13.9%), and thrombocytopenia (n = 4, 11.1%).
Conclusions:In the Child–Pugh B subgroup of patients with advanced HCC, Ate/Bev treatment showed modest clinical activity. However, due to the increased frequency of serious AEs, careful evaluation of treatment response and AE management is required in this subgroup of patients.ope
DRP1 Inhibition Enhances Venetoclax-Induced Mitochondrial Apoptosis in TP53-Mutated Acute Myeloid Leukemia Cells through BAX/BAK Activation
Get PDFAlthough TP53 mutations in acute myeloid leukemia (AML) are associated with poor response to venetoclax, the underlying resistance mechanism remains unclear. Herein, we investigated the functional role of dynamin-related protein 1 (DRP1) in venetoclax sensitivity in AML cells with respect to TP53 mutation status. Effects of DRP1 inhibition on venetoclax-induced cell death were compared in TP53-mutated (THP-1 and Kasumi-1) and TP53 wild-type leukemia cell lines (MOLM-13 and MV4-11), as well as in primary AML cells obtained from patients. Venetoclax induced apoptosis in TP53 wild-type AML cells but had limited effects in TP53-mutated AML cells. DRP1 expression was downregulated in MOLM-13 cells after venetoclax treatment but was unaffected in THP-1 cells. Cotreatment of THP-1 cells with venetoclax and a TP53 activator NSC59984 downregulated DRP1 expression and increased apoptosis. Combination treatment with the DRP1 inhibitor Mdivi-1 and venetoclax significantly increased mitochondria-mediated apoptosis in TP53-mutated AML cells. The combination of Mdivi-1 and venetoclax resulted in noticeable downregulation of MCL-1 and BCL-xL, accompanied by the upregulation of NOXA, PUMA, BAK, and BAX. These findings suggest that DRP1 is functionally associated with venetoclax sensitivity in TP53-mutated AML cells. Targeting DRP1 may represent an effective therapeutic strategy for overcoming venetoclax resistance in TP53-mutated AML.ope
Validity and Reliability of a Non-Radiographic Postural Analysis Device Based on an RGB-Depth Camera Comparing EOS 3D Imaging: A Prospective Observational Study
Get PDFThe posture-analyzing and virtual reconstructing device (PAViR) used a Red Green Blue-Depth camera as a sensor and skeleton reconstruction images were produced. This PAViR quickly analyzed the whole posture from multiple repetitive shots without radiation exposure in clothes and provided a virtual skeleton within seconds. This study aims to evaluate the reliability when shooting repeatedly and to assess the validity compared to parameters of full-body, low-dose X-rays (EOSs) when applied as diagnostic imaging. As a prospective and observational study, 100 patients with musculoskeletal pain underwent an EOS to obtain whole body coronal and sagittal images. The outcome measures were human posture parameters, which were divided by the standing plane in both EOSs and PAViRs as follows: (1) a coronal view (asymmetric clavicle height, pelvic oblique, bilateral Q angles of the knee, and center of seventh cervical vertebra-central sacral line (C7-CSL)) and (2) a sagittal view (forward head posture). A validation of the PAViR compared to the EOSs revealed that C7-CSL showed a moderate positive correlation with that of the EOS (r = 0.42, p < 0.01). The forward head posture (r = 0.39, p < 0.01), asymmetric clavicle height (r = 0.37, p < 0.01), and pelvic oblique (r = 0.32, p < 0.01) compared to those of the EOS had slightly positive correlations. The PAViR has excellent intra-rater reliability in people with somatic dysfunction. Except for both Q angles, the PAViR has fair-to-moderate validation when compared to EOS diagnostic imaging in the parameter representing coronal and sagittal imbalance. Although the PAViR system is not yet available in the medical field, it has the potential to become a radiation-free, accessible, and cost-effective postural analysis diagnostic tool after the EOS era.ope
The effectiveness of non-pharmacological interventions using information and communication technologies for behavioral and psychological symptoms of dementia: A systematic review and meta-analysis
Get PDFBackground: Although behavioral and psychological symptoms of dementia are a global public health challenge, non-pharmacological interventions using information and communication technologies can be an affordable, cost-effective, and innovative solution.
Objectives: This study aimed to examine the effectiveness of non-pharmacological interventions using information and communication technologies on the behavioral and psychological symptoms of dementia and identify potential moderators of intervention effects.
Design: Systematic review and meta-analysis of randomized controlled trials.
Methods: A systematic literature review was conducted using PubMed, CINAHL, PsycINFO, Embase, and the Cochrane Library from May 2022. Randomized controlled trials that examined the effects of non-pharmacological interventions using information and communication technologies on the behavioral and psychological symptoms of dementia were included. A meta-analysis using a random-effects model was performed to calculate the pooled standardized mean differences between overall symptoms and each type of symptom. For moderator analyses, subgroup and meta-regression analyses were performed.
Results: Sixteen trials (15 articles) met the eligibility criteria. The interventions were grouped into activity engagement interventions using digital health that provided music and reminiscence therapy, physical exercise, social interaction interventions using social robots, and telehealth-based care aid interventions that provided coaching or counseling programs. Pooled evidence demonstrated that non-pharmacological interventions using information and communication technologies exerted a large effect on depression (SMD = -1.088, 95% CI -1.983 to -0.193, p = 0.017), a moderate effect on overall behavioral and psychological symptoms of dementia (SMD = -0.664, 95% CI -0.990 to -0.338, p < 0.001), and agitation (SMD = -0.586, 95% CI -1.130 to -0.042, p = 0.035). No effects on neuropsychiatric symptoms (SMD = -0.251, 95% CI -0.579 to 0.077, p = 0.133), anxiety (SMD = -0.541, 95% CI -1.270 to 0.188, p = 0.146), and apathy (SMD = -0.830, 95% CI -1.835 to 0.176, p = 0.106) were reported. Moderator analyses identified the mean age of the participants as a potential moderator of intervention effects.
Conclusions: Evidence from this systematic review and meta-analysis suggests that non-pharmacological interventions, using information and communication technologies, were an applicable approach to managing behavioral and psychological symptoms among older adults with dementia, with moderate to large effect sizes. However, evidence on anxiety and apathy is inconclusive due to the limited number of existing randomized controlled trials. Future studies with subgroup analyses are warranted to conclude the most effective types of intervention using information and communication technologies for each type of symptom.
Registration: CRD42021258498.ope
Molecular and radiopathologic spectrum between HCC and intrahepatic cholangiocarcinoma
No full textBackground and aims: Primary liver cancers (LCs), including HCC and intrahepatic cholangiocarcinoma (iCCA), are derived from a common developmental lineage, conferring a molecular spectrum between them. To elucidate the molecular spectrum, we performed an integrative analysis of transcriptome profiles associated with patients' radiopathologic features.
Approach and results: We identified four LC subtypes (LC1-LC4) from RNA-sequencing profiles, revealing intermediate subtypes between HCC and iCCA. LC1 is a typical HCC characterized by active bile acid metabolism, telomerase reverse transcriptase promoter mutations, and high uptake of gadoxetic acid in MRI. LC2 is an iCCA-like HCC characterized by expression of the progenitor cell-like trait, tumor protein p53 mutations, and rim arterial-phase hyperenhancement in MRI. LC3 is an HCC-like iCCA, mainly small duct (SD) type, associated with HCC-related etiologic factors. LC4 is further subclassified into LC4-SD and LC4-large duct iCCAs according to the pathological features, which exhibited distinct genetic variations (e.g., KRAS , isocitrate dehydrogenase 1/2 mutation, and FGF receptor 2 fusion), stromal type, and prognostic outcomes.
Conclusions: Our integrated view of the molecular spectrum of LCs can identify subtypes associated with transcriptomic, genomic, and radiopathologic features, providing mechanistic insights into heterogeneous LC progression.restrictio
Suggestions for Escaping the Dark Ages for Pediatric Diffuse Intrinsic Pontine Glioma Treated with Radiotherapy: Analysis of Prognostic Factors from the National Multicenter Study
No full textPurpose: This multicenter retrospective study aimed to investigate clinical, radiologic, and treatment-related factors affecting survival in patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) treated with radiotherapy.
Materials and methods: Patients aged <30 years who underwent radiotherapy as an initial treatment for DIPG between 2000 and 2018 were included; patients who did not undergo magnetic resonance imaging at diagnosis and those with pathologically diagnosed grade I glioma were excluded. We examined medical records of 162 patients collected from 10 participating centers in Korea. The patients' clinical, radiological, molecular, and histopathologic characteristics, and treatment responses were evaluated to identify the prognosticators for DIPG and estimate survival outcomes.
Results: The median follow-up period was 10.8 months (interquartile range, 7.5 to 18.1). The 1- and 2-year overall survival (OS) rates were 53.5% and 19.0%, respectively, with a median OS of 13.1 months. Long-term survival rate (≥ 2 years) was 16.7%, and median OS was 43.6 months. Age (< 10 years), poor performance status, treatment before 2010, and post-radiotherapy necrosis were independently associated with poor OS in multivariate analysis. In patients with increased post-radiotherapy necrosis, the median OS estimates were 13.3 months and 11.4 months with and without bevacizumab, respectively (p=0.138).
Conclusion: Therapeutic strategy for DIPG has remained unchanged over time, and the associated prognosis remains poor. Our findings suggest that appropriate efforts are needed to reduce the occurrence of post-radiotherapy necrosis. Further well-designed clinical trials are recommended to improve the poor prognosis observed in DIPG patients.ope
Effect of Baicalin on Wound Healing in a Mouse Model of Pressure Ulcers
Get PDFOne of the most frequent comorbidities that develop in chronically ill or immobilized patients is pressure ulcers, also known as bed sores. Despite ischemia-reperfusion (I/R)-induced skin lesion having been identified as a primary cause of pressure ulcers, wound management efforts have so far failed to significantly improve outcomes. Baicalin, or 5,6,7-trihydroxyflavone, is a type of flavonoid which has been shown to possess a variety of biological characteristics, including antioxidative and anti-inflammatory effects and protection of I/R injury. In vitro wound scratch assay was first used to assess the function of baicalin in wound healing. We established a mouse model of advanced stage pressure ulcers with repeated cycles of I/R pressure load. In this model, topically applied baicalin (100 mg/mL) induced a significant increase in the wound healing process measured by wound area. Histological examination of the pressure ulcer mouse model showed faster granulation tissue formation and re-epithelization in the baicalin-treated group. Next, baicalin downregulated pro-inflammatory cytokines (IL-6 and IL-1β), while upregulating the anti-inflammatory IL-10. Additionally, baicalin induced an increase in several growth factors (VEGF, FGF-2, PDGF-β, and CTGF), promoting the wound healing process. Our results suggest that baicalin could serve as a promising agent for the treatment of pressures ulcers.ope
Clinical Outcomes and Prognosis of Patients with Interstitial Lung Disease Undergoing Lung Cancer Surgery: A Propensity Score Matching Study
No full textBackground: Patients with interstitial lung disease (ILD) may have a poor prognosis after lung cancer surgery because of respiratory complications and increased recurrence rates due to limited resection. Few studies have investigated prognosis after surgery by matching clinical variables between patients with and without ILD.
Patients and methods: Medical records of patients who underwent lung cancer surgery between January 2010 and August 2020 at a referral hospital in South Korea were reviewed. Patients with ILD were identified based on preoperative computed tomography findings. Through propensity score matching, the clinical outcomes and prognoses of patients with (ILD group) and without ILD (control group) were compared.
Results: Of 1629 patients, 113 (6.9%) patients with ILD were identified, of whom 104 patients were matched. Before matching, patients with ILD had higher mean age, proportion of men, and rates of sublobar resection and squamous cell carcinoma than those without ILD. After matching, there was no significant difference in postoperative mortality rates between the control and ILD groups. The 5-year survival rate was significantly lower in the ILD group (66%) than in the control group (78.8%; P= .007). The 5-year survival rate of the ILD-GAP (Gender, Age, Physiology) stage III group (12.6%) was significantly lower than that of the ILD-GAP stage I (73.5%) and II groups (72.6%; P< .0001). Multivariable Cox analysis demonstrated that idiopathic pulmonary fibrosis, higher clinical stage, and recurrence were independent prognostic factors for mortality.
Conclusion: Concomitant ILD negatively affects long-term prognosis after lung cancer surgery, and ILD subtype and physiological severity assessment help predict prognosis after surgery.restrictio
Sorafenib versus nivolumab after lenvatinib treatment failure in patients with advanced hepatocellular carcinoma
No full textBackground and aim: An optimal sequential anti-hepatocellular carcinoma (HCC) agent that can be used after failed lenvatinib treatment has not been established. Here, we compared the outcomes of sorafenib and nivolumab as second-line agents after failed lenvatinib treatment in patients with advanced HCC.
Methods: Patients with advanced HCC who had received sorafenib or nivolumab as second-line agents after failed lenvatinib treatment were recruited from two Korean tertiary institutions between November 2018 and June 2020.
Results: The median age of the 60 participants (52 treated with sorafenib and eight treated with nivolumab) at baseline was 56.8 years. The demographic, laboratory and tumor variables, as well as lenvatinib treatment duration, were similar between the two groups. The median durations of sorafenib and nivolumab treatment were 1.2 and 2.6 months, respectively ( P = 0.164). Twenty-four (40.0%) patients died during the follow-up period (median, 15.8 months). The median overall survival (OS) of the study population was 5.8 months. The median OS of patients treated with sorafenib was significantly longer than the median OS of patients treated with nivolumab (8.7 vs. 3.0 months; P = 0.046). Sorafenib treatment (vs. nivolumab) was independently associated with a lower risk of mortality (hazard ratio = 0.194; 95% confidence interval, 0.053-0.708; P = 0.013). Worse Eastern Cooperative Oncology Group performance status, larger maximal tumor size, lymph node metastases and higher total bilirubin levels were independently associated with increased mortality risk (all P < 0.05).
Conclusions: Lenvatinib-sorafenib sequential treatment resulted in significantly better survival did than lenvatinib-nivolumab sequential treatment in patients with advanced HCC. Larger studies are needed to validate our results.restrictio