215 research outputs found

    Paul RicƓur’s Search for a Just Community. The Phenomenological Presupposition of a Life “with and for others”

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    The aim of this article is to examine how RicƓur’s critique of Husserl’s and Levinas’s notions of intersubjectivity informs his own alternative conceptualization of the intra- and interpersonal as a complex intertwining of moral selfhood and a just community. My first assumption is that law, as a prescriptive intervention in the social structure of our communal life, presupposes a phenomenology of our “being with others”. My second assumption is that RicƓur’s entire philosophical anthropology, and specifically his ideas on ethics, legality and justice, can be read as a prolonged response to Husserl’s solipsistic deadlock in the famous Fifth Cartesian Meditation. Taken together these two assumptions connect RicƓur’s early analysis of phenomenology with his complex reconceptualization of moral selfhood in Oneself as Another, culminating in the ethical maxim of “a good life with and for others in just institutions.

    Reduced number and impaired function of circulating progenitor cells in patients with systemic lupus erythematosus

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    Systemic lupus erythematosus (SLE) is associated with premature and accelerated atherosclerosis. Circulating progenitor cells (CPCs) are circulating bone-marrow derived cells that play an important role in the repair of vascular damage that underlies the development of atherosclerosis. The objective of this study was to determine the number and functionality of CPCs in patients with SLE. The study included 44 female SLE patients in an inactive stage of disease and 35 age-matched female controls. CPC numbers in the circulation were determined by FACS with monoclonals against CD14, CD34 and CD133. Peripheral blood-derived mononuclear cell (PBMNC) fractions were cultured in angiogenic medium. The endothelial-like phenotype was confirmed and the colony forming unit (CFU) capacity, migratory capacity and the potential to form clusters on Matrigel were determined. Expression of apoptosis inhibiting caspase 8L was analyzed in PBMNCs and CPCs by gene transcript and protein expression assays. The number of CD34–CD133 double-positive cells (P < 0.001) as well as the CFU capacity (P = 0.048) was reduced in SLE patients. Migratory activity on tumor necrosis factor-α tended to be reduced in patient CPCs (P = 0.08). Migration on vascular endothelial growth factor showed no significant differences, nor were differences observed in the potential to form clusters on Matrigel. The expression of caspase 8L was reduced at the transcriptional level (P = 0.049) and strongly increased at the protein level after culture (P = 0.003). We conclude that CPC numbers are reduced in SLE patients and functionality is partly impaired. We suggest these findings reflect increased susceptibility to apoptosis of CPCs from SLE patients

    Small artery elasticity is decreased in patients with systemic lupus erythematosus without increased intima media thickness

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    Introduction: The objectives of this study were to determine small arterial elasticity (SAE) in systemic lupus erythematosus (SLE) and to investigate its relationship with intima media thickness (IMT), accumulation of advanced glycation end products (AGEs), endothelial activation and inflammation. Methods: Thirty SLE patients with inactive disease and 30 age- and sex-matched healthy controls were included. Twenty patients with essential hypertension (EH) served as positive control. SAE was assessed by pulse-wave analysis using tonometric recordings of the radial artery. IMT of the carotid arteries was measured by ultrasound. AGE accumulation was assessed with an AGE-reader. Endothelial activation markers and C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assay (ELISA). Results: SAE was decreased in SLE (P = 0.01) and further decreased in EH (P <0.01) compared to healthy controls. IMT was increased in EH (P <0.05), but not in SLE. AGE accumulation was increased in SLE (P <0.05) and further increased in EH (P <0.01) compared to healthy controls. Endothelial activation markers and CRP were increased in SLE but not in EH. SAE related to AGE accumulation (r = -0.370, P <0.05), CRP (r = -0.429, P <0.05) and creatinine clearance (r = 0.440, P <0.05), but not to IMT and endothelial activation markers. In multivariate analysis SLE was an independent predictor of SAE. Conclusions: SAE is decreased in SLE patients without increased IMT, independently of traditional cardiovascular risk factors. Longitudinal studies are needed to investigate whether SAE, endothelial activation and AGE accumulation are early markers for cardiovascular disease in SLE

    Long-Term Health-Related Quality of Life after Four Common Surgical Treatment Options for Breast Cancer and the Effect of Complications: A Retrospective Patient-Reported Survey among 1871 Patients

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    Background: Differences in quality-of-life outcomes after different surgical breast cancer treatment options, including breast reconstruction, are relevant for counseling individual patients in clinical decision-making, and for (societal) evaluations such as cost-effectiveness analyses. However, current literature shows contradictory results, because of use of different patient-reported outcome measures and study designs with limited patient numbers. The authors set out to improve this evidence using patient-reported outcome measures in a large, cross-sectional study for different surgical breast cancer treatment options. Methods: Quality of life was assessed through the EQ-5D-5L, European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BR23, and the BREAST-Q. Patients with different treatments were compared after propensity-weighted adjustment of pretreatment differences. The EQ-5D was used to value the effect of surgical complications. Results: A total of 1871 breast cancer patients participated (breast-conserving surgery, n = 615; mastectomy, n = 507; autologous reconstruction, n = 330; and implant-based reconstruction, n = 419). Mastectomy patients reported the lowest EQ-5D score (mastectomy, 0.805, breast-conserving surgery, 0.844; autologous reconstruction, 0.849; and implant-based reconstruction, 0.850) and functioning scores of the C30 questionnaire. On the BREAST-Q, autologous reconstruction patients had higher mean Satisfaction with Outcome, Satisfaction with Breasts, and Sexual Well-being scores than implant-based reconstruction patients. Complications in autologous reconstruction patients resulted in a substantially lower quality of life than in implant-based reconstruction patients. Conclusions: This study shows the added value of breast conservation and reconstruction compared with mastectomy; however, differences among breastconserving surgery, implant-based reconstruction, and autologous breast reconstruction were subtle. Complications resulted in poorer health-related quality of life. (Plast. Reconstr. Surg. 146: 1, 2020.

    Recurrence risk of venous thromboembolism associated with systemic lupus erythematosus:A retrospective cohort study

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    BACKGROUND: Recurrence risk of systemic lupus erythematosus (SLE)‐associated venous thromboembolism (VTE) is unclear. AIM: To determine the recurrence risk of SLE‐associated VTE overall and by presence of provoking factors and SLE flares. METHODS: A multicenter, retrospective cohort study was conducted among patients with first SLE‐associated VTE who discontinued anticoagulation. SLE flares were defined as Systemic Lupus Erythematosus Disease Activity Index 2000 greater than 4. The primary outcome was recurrent VTE. Incidence rates and cumulative incidences were calculated by presence of provoking factors and antiphospholipid syndrome (APS) at index VTE. The hazard ratio (HR) for recurrence after SLE flare–associated index VTE was estimated with Cox regression, adjusted for provoking factor presence and APS. RESULTS: Eighty patients were included with 21 recurrent VTEs in median 8 years. For provoked index VTE, the recurrence rate in patients without APS was 1.1 per 100 person‐years (PY; 95% confidence interval [CI], 0.1–3.1) and in the presence of APS 3.5 per 100 PY (95% CI, 0.9–8.9), yielding cumulative incidences of 7.5% (95% CI, 1.2%–21.7%) and 31.4% (95% CI, 6.3%–61.6%) respectively. For unprovoked index VTE, these analogous rates were 3.8 per 100 PY (95% CI, 1.2–9.0) and 16.7 per 100 PY (95% CI, 4.5–42.7), with cumulative incidences of 33.7% (95% CI, 10.7%–58.9%) and 54.2% (95% CI, 10.7%–84.5%), respectively. Forty‐six index VTEs were flare associated, and the adjusted HR for recurrence was 0.4 (95% CI, 0.1–1.8) compared to those without flares at their index VTE. CONCLUSION: Antiphospholipid syndrome is the main determinant for recurrence risk of SLE‐associated VTE irrespective of presence of a provoking factor. Future research should attempt to confirm that flare‐associated VTE has a lower recurrence risk

    The Development of Practice Recommendations for Drug-Disease Interactions by Literature Review and Expert Opinion

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    Background Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion. Methods The development of recommendations for drug-disease interactions will follow a six-step plan involving a multidisciplinary expert panel (1). The scope of the drug-disease interaction will be specified by defining the disease and by describing relevant effects of this drug-disease interaction. Drugs possibly involved in this drug-disease interaction are selected by checking the official product information, literature, and expert opinion (2). Evidence will be collected from the official product information, guidelines, handbooks, and primary literature (3). Study characteristics and outcomes will be evaluated and presented in standardized reports, including preliminary conclusions on the clinical relevance and practice recommendations (4). The multidisciplinary expert panel will discuss the reports and will either adopt or adjust the conclusions (5). Practice recommendations will be integrated in clinical decision support systems and published (6). The results of the evaluated drug-disease interactions will remain up-to-date by screening new risk information, periodic literature review, and (re)assessments initiated by health care providers. Actionable Recommendations The practice recommendations will result in advices for specific DDSI. The content and considerations of these DDSIs will be published and implemented in all Clinical Decision Support Systems in the Netherlands. Discussion The recommendations result in professional guidance in the context of individual patient care. The professional will be supported in the decision making in concerning pharmacotherapy for the treatment of a medical problem, and the clinical risks of the proposed medication in combination with specific diseases

    The Development of Practice Recommendations for Drug-Disease Interactions by Literature Review and Expert Opinion

    Get PDF
    Background: Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion. Methods: The development of recommendations for drug-disease interactions will follow a six-step plan involving a multidisciplinary expert panel (1). The scope of the drug-disease interaction will be specified by defining the disease and by describing relevant effects of this drug-disease interaction. Drugs possibly involved in this drug-disease interaction are selected by checking the official product information, literature, and expert opinion (2). Evidence will be collected from the official product information, guidelines, handbooks, and primary literature (3). Study characteristics and outcomes will be evaluated and presented in standardized reports, including preliminary conclusions on the clinical relevance and practice recommendations (4). The multidisciplinary expert panel will discuss the reports and will either adopt or adjust the conclusions (5). Practice recommendations will be integrated in clinical decision support systems and published (6). The results of the evaluated drug-disease interactions will remain up-to-date by screening new risk information, periodic literature review, and (re)assessments initiated by health care providers. Actionable Recommendations: The practice recommendations will result in advices for specific DDSI. The content and considerations of these DDSIs will be published and implemented in all Clinical Decision Support Systems in the Netherlands. Discussion: The recommendations result in professional guidance in the context of individual patient care. The professional will be supported in the decision making in concerning pharmacotherapy for the treatment of a medical problem, and the clinical risks of the proposed medication in combination with specific diseases
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