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21 result(s) for "de Mol, Mark"
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The association of depressive symptoms, personality traits, and sociodemographic factors with health-related quality of life and quality of life in patients with advanced-stage lung cancer: an observational multi-center cohort study
Background Identification of patient-related factors associated with Health-Related Quality of Life (HRQoL) and Quality of Life (QoL) at the start of treatment may identify patients who are prone to a decrease in HRQoL and/or QoL resulting from chemotherapy. Identification of these factors may offer opportunities to enhance patient care during treatment by adapting communication strategies and directing medical and psychological interventions. The aim was to examine the association of sociodemographic factors, personality traits, and depressive symptoms with HRQoL and QoL in patients with advanced-stage lung cancer at the start of chemotherapy. Methods Patients ( n  = 151) completed the State-Trait Anxiety Inventory (trait anxiety subscale), the Neuroticism-Extraversion-Openness-Five Factor Inventory (NEO-FFI), the Center for Epidemiologic Studies Depression (CES-D), the World Health Organization Quality of Life-BREF (WHOQOL-BREF), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Simple linear regression analyses were performed to select HRQoL and QoL associated factors (a P  ≤ 0.10 was used to prevent non-identification of important factors) followed by multiple linear regression analyses ( P  ≤ 0.05). Results In the multiple regression analyses, CES-D score (β = − 0.63 to − 0.53; P -values < 0.001) was most often associated with the WHOQOL-BREF domains and general facet, whereas CES-D score (β = − 0.67 to − 0.40; P -values < 0.001) and Eastern Cooperative Oncology Group (ECOG) performance status (β = − 0.30 to − 0.30; P -values < 0.001) were most often associated with the scales of the EORTC QLQ-C30. Personality traits were not related with HRQoL or QoL except for trait anxiety (Role functioning: β = 0.30; P  = 0.02, Environment: β = − 0.39; P  = 0.007) and conscientiousness (Physical health: β = 0.20; P -value < 0.04). Conclusions Higher scores on depressive symptoms and ECOG performance status were related to lower HRQoL and QoL in patients with advanced-stage non-small cell lung cancer. Supportive care interventions aimed at improvement of depressive symptoms and performance score may facilitate an increase of HRQoL and/or QoL during treatment.
Satisfactory results of a psychometric analysis and calculation of minimal clinically important differences of the World Health Organization quality of life-BREF questionnaire in an observational cohort study with lung cancer and mesothelioma patients
Background To determine the psychometric properties and minimal clinically important differences (MCIDs) of the World Health Organization Quality of Life-BREF (WHOQOL-BREF) in advanced stage lung cancer patients. Methods Patients ( n  = 153) completed the WHOQOL-BREF and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Confirmatory factor analysis (CFA) was performed and reliability and construct validity determined. MCIDs were estimated with two distribution-based methods (0.5 standard deviation (SD) and 1 standard error of measurement (1 SEM)). Results CFA confirmed WHOQOL-BREF domain structure. All domains demonstrated good internal consistency (α > 0.70), except Social Relationships (α = 0.57). Nineteen of the 24 WHOQOL-BREF items had correlations of ≥ 0.40 with their intended domain. Four items had higher correlations with a domain other than their intended domain. Moderate to strong correlations were observed for corresponding domains of the two questionnaires, except for the social domains ( r  = 0.07). For 0.5 SD, MCIDs ranged from 0.88 to 1.55, and for 1 SEM MCIDs ranged from 1.76 to 2.72. Conclusions The WHOQOL-BREF has satisfactory psychometric properties in patients with advanced stage lung cancer, whereas the observed MCIDs provide a method for interpretation of scores.
Frequency of low-grade adverse events and quality of life during chemotherapy determine patients’ judgement about treatment in advanced-stage thoracic cancer
PurposeIn lung cancer, the preservation of well-being is warranted given the limited prognosis. Chemotherapy may negatively influence health-related quality of life (HRQoL) due to adverse events. However, patients’ judgement about this negative impact is not well understood. We examined the relationship between expectations, feelings about side effects, and satisfaction with therapy and (HR)QoL in advanced-stage thoracic cancer and investigated which of these factors has the highest impact on (HR)QoL.MethodsSixty-nine patients completed the Cancer Therapy Satisfaction Questionnaire (CTSQ), the World Health Organization Quality of Life-BREF (WHOQOL-BREF), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Multiple regression analyses were performed to investigate the relation of the CTSQ domains (i.e., expectations of therapy, feelings about side effects, satisfaction with therapy) with (HR)QoL and simple regression analyses to identify the factors of the CTSQ domain that was most often associated with (HR)QoL.ResultsFeelings about side effects were associated with the (HR)QoL domain/scale scores (i.e., WHOQOL-BREF domains: β = 0.36 to 0.58; EORTC QLQ-C30 scales: β = 0.33 to 0.61) except social relationships of the WHOQOL-BREF. Low-grade adverse events were related to feelings about side effects (β = − 0.326; P = 0.007).ConclusionsPatients experiencing negative feelings about side effects have worse (HR)QoL. Additional care should be provided to prevent low-grade adverse events.
Stereotactic Ablative Radiotherapy Induces Peripheral T-Cell Activation in Patients with Early-Stage Lung Cancer
Figure 2A shows that in PD-11 CD4 and CD8 T cells, the fractions of IFN-g-producing cells were larger than in the PD-12 T cell populations (P < 0.001 for both CD4 and CD8 T cells), indicating that the PD-11 cells are more functionally active than the PD-12 T cells. [...]in four of nine SABR-treated patients (one patient had a nonevaluable sample at baseline), PD-11 proportions increased at least more than 4%. [...]combinations of surgery and radiotherapy treatment are sometimes administered in the context of postsurgical adjuvant radiotherapy (10). [...]a phase 2 clinical trial is currently recruiting to evaluate this hypothesis (11). [...]SABR induces systemic T-cell activation, characterized by PD1 expression in a subset of patients, whereas surgery does not.
Cathether-based interventional strategies for cor triatriatum in the adult – feasibility study through a hybrid approach
Background Cor triatriatum is a rare congenital cardiac abnormality, consisting of an obstructing membrane between the pulmonary veins and the mitral valve in varying patterns. The entitiy can mimick the pathophysiology of mitral stenosis, necessitating surgical resection. Occasionally, percutaneous balloon dilatation of the membrane has been successfully performed. Case presentation We report two cases with cor triatriatum where intraoperative balloon dilatation of the membrane was attempted followed by surgical resection, to explore the feasibility of cathether-based interventional strategies for cor triatriatum. Conclusions Various anatomical variations exist of cor triatriatum, depending on the drainage of the pulmonary veins and the drainage of the proximal chamber in the right or left atrium. Only isolated forms of cor triatriatum where all pulmonary veins ultimately drain into the left atrium can be recommended for percutaneous strategies. In addition, several anatomical characteristics should be considered to predict technical success of cathether-based interventional strategies, such as the location of the membrane, the degree of pulmonary vein stenosis, the extent of calcification, and the presence of other (congenital) cardiovascular abnormalities. Furthermore, long-term efficacy of these strategies remains to be confirmed. As such, surgical treatment of cor triatriatum remains the mainstay of treatment in adult patients, especially when other cardiovascular anomalies are present which require surgical correction.
Genetic Components of Root Architecture Remodeling in Response to Salt Stress
Salinity of the soil is highly detrimental to plant growth. Plants respond by a redistribution of root mass between main and lateral roots, yet the genetic machinery underlying this process is still largely unknown. Here, we describe the natural variation among 347 Arabidopsis thaliana accessions in root system architecture (RSA) and identify the traits with highest natural variation in their response to salt. Salt-induced changes in RSA were associated with 100 genetic loci using genome-wide association studies. Two candidate loci associated with lateral root development were validated and further investigated. Changes in CYP79B2 expression in salt stress positively correlated with lateral root development in accessions, and cyp79b2 cyp79b3 double mutants developed fewer and shorter lateral roots under salt stress, but not in control conditions. By contrast, high HKT1 expression in the root repressed lateral root development, which could be partially rescued by addition of potassium. The collected data and multivariate analysis of multiple RSA traits, available through the Salt_NV_Root App, capture root responses to salinity. Together, our results provide a better understanding of effective RSA remodeling responses, and the genetic components involved, for plant performance in stress conditions.
X chromosome inactivation skewing is common in advanced carotid atherosclerotic lesions in females and predicts secondary peripheral artery events
Background and aim Sex differences in atherosclerosis have been described with female plaques being mostly perceived as stable and fibrous. Sex-specific mechanisms such as mosaic loss of the Y chromosome in men have been linked to cardiovascular health. In women, X-linked mechanisms such as X chromosome inactivation (XCI) skewing is common in several tissues. Yet, information on the role of XCI in female atherosclerotic plaques is lacking. Here, we investigated the presence of XCI skewing in advanced atherosclerotic lesions and its association with cardiovascular risk factors, histological plaque data, and clinical data. Methods XCI skewing was quantified in 154 atherosclerotic plaque and 55 blood DNA samples of women included in the Athero-Express study. The skewing status was determined performing the HUMARA assay. Then, we studied the relationship of XCI skewing in female plaque and cardiovascular risk factors using regression models. In addition, we studied if plaque XCI predicted plaque composition, and adverse events during 3-years follow-up using Cox proportional hazard models. Results XCI skewing was detected in 76 of 154 (49.4%) plaques and in 27 of 55 (67%) blood samples. None of the clinical risk factors were associated with plaque skewing. Plaque skewing was more often detected in plaques with a plaque hemorrhage (OR [95% CI]: 1.44 [1.06–1.98], P = 0.02). Moreover, skewed plaques were not associated with a higher incidence of composite and major events but were specifically associated with peripheral artery events during a 3-year follow-up period in a multivariate model (HR [95%CI]: 1.46 [1.09–1.97]; P = 0.007). Conclusions XCI skewing is common in carotid plaques of females and is predictive for the occurrence of peripheral artery events within 3 years after carotid endarterectomy. Plain language summary Sex-differences have been observed in the development of atherosclerosis between men and women. Women tend to have more stable and fibrous plaques compared to men. Sex-specific mechanisms such as mosaic loss of the Y chromosome in men, were associated with cardiovascular health. In women, despite X-linked mechanisms like X chromosome inactivation (XCI) skewing was identified in various tissues. However, its relationship with atherosclerosis has not yet been investigated. In our study, we explored if prevalence of XCI skewing in advanced atherosclerotic lesions related to cardiovascular risk factors, histological plaque data, and clinical information. We found that XCI skewing was present in approximately 50% of human plaques, particularly those with plaque hemorrhage. Interestingly, we did not find any notable relationship between plaque skewing and clinical risk factors. However, we found that XCI was more present in women with peripheral artery events during the 3 years period following carotid endarterectomy. In summary, our findings indicate that XCI skewing is commonly observed in carotid plaques among females and may serve as a predictive factor for the occurrence of peripheral artery events within 3 years after carotid endarterectomy. Highlights XCI skewing is common in half of the carotid plaques of females and mostly in those plaques with a plaque hemorrhage. None of the clinical risk factors were associated with plaque skewing. Skewed plaques were specifically associated with peripheral artery events during a 3-year follow-up period after carotid endarterectomy.
Unexpected species diversity in electric eels with a description of the strongest living bioelectricity generator
Is there only one electric eel species? For two and a half centuries since its description by Linnaeus, Electrophorus electricus has captivated humankind by its capacity to generate strong electric discharges. Despite the importance of Electrophorus in multiple fields of science, the possibility of additional species-level diversity in the genus, which could also reveal a hidden variety of substances and bioelectrogenic functions, has hitherto not been explored. Here, based on overwhelming patterns of genetic, morphological, and ecological data, we reject the hypothesis of a single species broadly distributed throughout Greater Amazonia. Our analyses readily identify three major lineages that diverged during the Miocene and Pliocene—two of which warrant recognition as new species. For one of the new species, we recorded a discharge of 860 V, well above 650 V previously cited for Electrophorus , making it the strongest living bioelectricity generator. A single species of electric eel, Electrophorus electricus , has been described. Here, de Santana et al. show that there are three major lineages of Electrophorus distributed across Greater Amazonia and describe two new species, one with a much stronger electric discharge than was previously known.
A variant in FTO shows association with melanoma risk not due to BMI
We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model
Background Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care. Methods A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration. Results Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of −0.11, 95% CI −0.13 to −0.08). Conclusions The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.