Microvascular function is impaired in ankylosing spondylitis and improves after tumour necrosis factor a blockade

Objectives: Ankylosing spondylitis (AS) is associated with increased cardiovascular morbidity and mortality. Microvascular function has been linked to several risk factors for cardiovascular disease. Inflammation in AS may cause microvascular dysfunction. To test this, we assessed microvascular function in (a) patients with AS compared to healthy controls and (b) patients with AS before and after 1 month of anti-tumour necrosis factor (TNF)alpha treatment with etanercept. Methods: A total of 15 consecutive patients with AS, who were scheduled for etanercept treatment according to the Assessment in Ankylosing Spondylitis (ASAS) group guidelines, and 12 healthy controls matched for age and sex, were recruited. Endothelium-dependent and independent vasodilatation in skin were evaluated with laser Doppler fluxmetry after iontophoresis of acetylcholine and sodium nitroprusside, respectively. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. Results: Compared to healthy controls, patients with AS had impaired endothelium-dependent vasodilatation and capillary recruitment. Following anti-TNF alpha treatment, microvascular function improved significantly for endothelium-dependent vasodilatation (p = 0.03) and capillary recruitment (p = 0.006). A significant correlation was observed between changes in endothelium-dependent vasodilatation and changes in erythrocyte sedimentation rate (ESR) (r = -0.56; p = 0.03). Conclusion: Microvascular dysfunction is present in patients with AS with active disease, but improves as inflammation regresses after TNF alpha blockad

Matige bloeddrukregulatie bij patienten met diabetes mellitus type 2 in de eerste en tweede lijn.

OBJECTIVE: To investigate the degree to which the goals for adequate blood-pressure control in patients with type-2 diabetes mellitus (DM) are met in Dutch specialists' practice and in the primary-care setting. DESIGN: Cross sectional. METHOD: Data were collected from all consecutive patients with DM type 2 visiting the outpatient clinic of two physicians specialised in diabetes care, in Zwolle, the Netherlands, in the period 1 November 1999-30 April 2000. The target value for blood pressure was < or = 150/85 mmHg. In addition, baseline data were collected on patients in the primary-care setting who participated in a transmural project in Zwolle in the period 1 February 1997-31 January 1998. In 1998, the target blood pressure in the primary-care setting was < or = 160/90 mmHg. Patients who met the goals for adequate blood-pressure control were compared with patients who did not. RESULTS: A total of 502 patients from specialists' practice and 1084 patients from the primary-care setting were included. The prevalence of hypertension in specialists' practice was 89% (n = 377); of these patients, 140 (37%) had a good regulation of their blood pressure. The patients who had an adequate blood-pressure control and those who did not were comparable. Both groups were prescribed an average of 2.2 kinds of antihypertensive agent per patient. The prevalence of hypertension in the primary care was 69% (n = 733). The goal for adequate blood-pressure control, i.e. a blood pressure of < or = 160/90 mmHg, was achieved in 44% (n = 324). In the primary-care setting, an average of 1.1 kinds of antihypertensive agent was prescribed, 1.6 in patients who achieved the target value and 0.8 in those who did not (p < 0.05). CONCLUSION: Regulation of blood pressure in patients with type 2 DM and hypertension was far from optimal: 37% of patients in specialists' practice and 44% of those in the primary-care setting achieved the target value

Burnout, resilience and work engagement among Dutch intensivists in the aftermath of the COVID-19 crisis: A nationwide survey

Contains fulltext : 232385.pdf (Publisher’s version ) (Closed access)PURPOSE: The COVID-19 crisis put a strain on intensive care resources everywhere in the world increasing the risk of burnout. Previously, the prevalence of burnout among Dutch intensivists was found to be low. Engagement and resilience among intensivists have not previously been studied quantitatively, however, both are related to burnout and provide a possible way to mitigate burnout. Our objective was to study burnout and its association with work engagement and resilience among Dutch intensivists in the aftermath of the COVID-19 crisis. METHODS: An online questionnaire was sent to all Dutch intensivists. The questionnaire consisted of questions on personal and work-related characteristics and validated questionnaires: the Maslach Burnout Inventory, the Utrecht Work Engagement Scale, and the Resilience Evaluation Scale. RESULTS: The response rate was 27.2% with 162 evaluable responses. Thirteen respondents (8.0%) were classified as having burnout, 63 (38.9%) respondents were reporting high work engagement. Burnout was found to be negatively associated with both work engagement and resilience. CONCLUSION: In the aftermath of the 2020 COVID-19 crisis, we found a raised prevalence of burnout among intensivists, however this is still low in international comparisons. Intensivists with burnout scored low on resilience and low on work engagement

Time spent on documenting quality indicator data and associations between the perceived burden of documenting these data and joy in work among professionals in intensive care units in the Netherlands: a multicentre cross-sectional survey.

OBJECTIVES: The number of indicators used to monitor and improve the quality of care is debatable and may influence professionals' joy in work. We aimed to assess intensive care unit (ICU) professionals' perceived burden of documenting quality indicator data and its association with joy in work. DESIGN: Cross-sectional survey. SETTING: ICUs of eight hospitals in the Netherlands. PARTICIPANTS: Health professionals (ie, medical specialists, residents and nurses) working in the ICU. MEASUREMENTS: The survey included reported time spent on documenting quality indicator data and validated measures for documentation burden (ie, such documentation being unreasonable and unnecessary) and elements of joy in work (ie, intrinsic and extrinsic motivation, autonomy, relatedness and competence). Multivariable regression analysis was performed for each element of joy in work as a separate outcome. RESULTS: In total, 448 ICU professionals responded to the survey (65% response rate). The overall median time spent on documenting quality data per working day is 60 min (IQR 30-90). Nurses spend more time documenting these data than physicians (medians of 60 min vs 35 min, p<0.01). Most professionals (n=259, 66%) often perceive such documentation tasks as unnecessary and a minority (n=71, 18%) perceive them as unreasonable. No associations between documentation burden and measures of joy in work were found, except for the negative association between unnecessary documentations and sense of autonomy (β=-0.11, 95% CI -0.21 to -0.01, p=0.03). CONCLUSIONS: Dutch ICU professionals spend substantial time on documenting quality indicator data they often regard as unnecessary. Despite the lacking necessity, documentation burden had limited impact on joy in work. Future research should focus on which aspects of work are affected by documentation burden and whether diminishing the burden improves joy in work

Bone morphogenetic protein 7 inhibits tumor growth of human uveal melanoma in vivo.

Item does not contain fulltextPURPOSE: Bone morphogenetic protein-7 (BMP7), a member of the TGF-beta superfamily, is essential for early ocular morphogenesis, and lack of BMP7 causes epithelial development disturbances in the eye. In the present study, the association of tumorigenicity and malignant behavior of human uveal melanoma with BMP7 expression and the possibility that overexpression of BMP7 in uveal melanoma affects intraocular tumor growth in vivo were investigated. METHODS: To establish the role of BMP7 in uveal melanoma progression, the human OCM-1 cell line was stably transfected to overexpress BMP7 (OCM-1 FRT/BMP7) using targeted homologous recombination. RESULTS: Transcriptional profiling revealed low or no detectable expression of BMP7 in primary tumor tissue of patients with uveal melanoma. In line with these clinical observations, BMP7 mRNA levels were low or not detectable in cultured human uveal melanoma cell lines, when compared with normal cultured melanocytes. Inoculation of OCM-1 FRT/BMP7 cells into the anterior chamber of the eye of nude mice inhibited tumor progression significantly, compared with progression in the control cell line (no BMP7 expression). CONCLUSIONS: Collectively, the data provide novel evidence that decreased BMP7 expression contributes to progression of uveal melanoma. Furthermore, BMP7 may represent a novel therapeutic molecule for repression of tumor growth in uveal melanoma

Whole-body bioluminescent imaging of human uveal melanoma in a new mouse model of local tumor growth and metastasis.

Item does not contain fulltextPURPOSE: Human uveal melanoma develops in one of the most capillary-rich tissues of the body and has a pure hematogenous dissemination. Radiodiagnostic examinations, such as ultrasonic diagnostic resonance imaging and chest radiographs plus liver enzyme studies in blood, are methods used to detect liver and other distant metastases in patients. Nevertheless, the mortality rate is high, because of the frequent occurrence of metastases and the lack of systemic therapy. Therefore, the development of novel anticancer strategies is urgent, and more sensitive and less invasive methods of detecting and monitoring in vivo tumor growth and metastatic disease in cancer models are needed. METHODS: A luciferase (Luc)-positive human uveal melanoma cell line (OCM-1 FRT/luc) was established. Tumor cells were inoculated into the anterior chamber of murine eyes for induction of orthotopic growth or into the left heart ventricle to mimic hematogenous micrometastatic spread. Development of metastases and tumor growth was monitored weekly by whole-body bioluminescent reporter imaging (BLI). RESULTS: Injection of cancer cells into the anterior chamber of the eye of mice closely mimicked orthotopic tumor growth of uveal melanoma. Tumor progression could be quantitatively monitored 3 weeks after inoculation of 10(5) OCM-1 FRT/luc cells. Of the mice injected, 83% exhibited a detectable tumor within 5 weeks. Intracardiac injection of tumor cells resulted in metastatic growth, especially in bone. Mice had bone (maxillofacial region and femora) and visceral (lung and mediastinum) metastases after 4 to 6 weeks. OCM-1 FRT/luc cells may also have a propensity to colonize the eye after intracardiac inoculation. CONCLUSIONS: BLI enables continuous quantitative monitoring in the same animal of growth kinetics for each tumor and its metastases. This model will accelerate the understanding of the pathogenesis and treatment of uveal melanoma and metastasis