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Polycythaemia vera (PV) and essential thrombocythaemia (ET) are classified as Philadelphia-negative chronic myeloproliferative diseases. Both PV and ET are rare diseases, but the prevalence is high. Patients who have not been treated for the diseases are at great risk of morbidity and mortality as a result of thrombohaemorrhagic events. However, if patients have been well treated, their prognosis is good and life-expectancy approaches normal. This article provides diagnostic tools and flowcharts for treatment of PV and ET. Treatment of PV and ET should be risk-adjusted and individualised. Low-dose aspirin is recommended as an antiaggregative drug in both diseases. For PV, phlebotomy to control a haematocrit at <0.45 is the cornerstone in treatment, and treatment with hydroxycarbamide (hydroxyurea) or interferon (IFN)-alpha is added to reduce hypermetabolic symptoms or splenomegaly becoming cytoreductive. In ET, hydroxycarbamide and anagrelide are the most used drugs, and anagrelide may also be added in PV to reduce thrombocytosis. IFNalpha is the only myelosuppressive treatment available during pregnancy. Current controversies regarding treatment illustrate the need for more randomised clinical trials. Demonstration of over expression of the PV-1 gene and in particular the JAK-2 mutation will be novel diagnostic criteria and may have an impact for future therapy of both PV and ET. 相似文献
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Reply to Pajoumand A,Hassanian‐Moghaddam H,Zamani N's Letter to the Editor Regarding Our Article ‘Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication – A Systematic Review with Meta‐Analyses of Randomised Trials’
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Raffo Jennifer E. Lloyd Celeste Collier Monica Slater LaDynah Cunningham Belinda Penninga Katherine Henning Susan Coil Janis Agee Bonita Quintino-Aranda Veronica VanderMeulen Peggy Roman Lee Anne 《Maternal and child health journal》2017,21(1):93-100
Introduction Federal and state policies often require utilization of evidence-based home visiting programs. Measurement of specified interventions is important for tracking program implementation and achieving program outcomes. Thus, the Strong Beginnings program worked to define community health worker (CHW) interventions, a core service of the program to improve maternal and child health. Methods A workgroup consisting of CHWs, supervisors and other program staff was created in order to develop and define specific CHW interventions within a nurse or social worker care team. Basic interventions were first compared to the nurse or social worker care coordinator home visiting interventions by risk topic. The evaluator then grouped each CHW intervention into categories per risk domain using thematic analysis and assigned a CHW core function or role based on literature review findings. The workgroup confirmed the results. The workgroup then continued discussions to further enhance CHW interventions per risk domain once the general structure was created. Results The workgroup identified seven core functions and 28 maternal and child health risk topics to be addressed by the CHW. The process resulted in a detailed document of program interventions that the CHWs use to guide care. Conclusions The process helped CHWs feel more valued with their role in team care. The specified interventions will help others understand the CHW role within the care team, ensure consistent interventions are delivered across program partners, provide a foundation to better understand how specific CHW contributions are related to health outcomes, and support program sustainability. 相似文献
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Marjolein Heijne‐Penninga Jan B M Kuks W H Adriaan Hofman Janke Cohen‐Schotanus 《Medical education》2010,44(9):884-891
Medical Education 2010: 44 : 884–891 Objectives The ability to master discipline‐specific knowledge is one of the competencies medical students must acquire. In this context, ‘mastering’ means being able to recall and apply knowledge. A way to assess this competency is to use both open‐ and closed‐book tests. Student performance on both tests can be influenced by the way the student processes information. Deep information processing is expected to influence performance positively. The personal preferences of students in relation to how they process information in general (i.e. their level of need for cognition) may also be of importance. In this study, we examined the inter‐relatedness of deep learning, need for cognition and preparation time, and scores on open‐ and closed‐book tests. Methods This study was conducted at the University Medical Centre Groningen. Participants were Year 2 students (n = 423). They were asked to complete a questionnaire on deep information processing, a scale for need for cognition on a questionnaire on intellectualism and, additionally, to write down the time they spent on test preparation. We related these measures to the students’ scores on two tests, both consisting of open‐ and closed‐book components and used structural equation modelling to analyse the data. Results Both questionnaires were completed by 239 students (57%). The results showed that need for cognition positively influenced both open‐ and closed‐book test scores (β‐coefficients 0.05 and 0.11, respectively). Furthermore, study outcomes measured by open‐book tests predicted closed‐book test results better than the other way around (β‐coefficients 0.72 and 0.11, respectively). Conclusions Students with a high need for cognition performed better on open‐ as well as closed‐book tests. Deep learning did not influence their performance. Adding open‐book tests to the regularly used closed‐book tests seems to improve the recall of knowledge that has to be known by heart. Need for cognition may provide a valuable addition to existing theories on learning. 相似文献
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A 33-year-old woman presented with pain in the right side of the abdomen at 35 weeks of gestation. She was treated for cystitis. A few days later, her abdominal pain had disappeared; however, she had developed pain in the right thigh and fever. She delivered a healthy child, but postpartum her leg symptoms deteriorated. She was found to have a necrotizing fasciitis, which necessitated disarticulation of the hip. The source of the infection was a perforated appendix. 相似文献
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Sotirios Michaleas Elisabeth Penninga Doris Hovgaard AnneMarie Dalseg Aldana Rosso Sinan B. Sarac Jorge Camarero Jimenez Lucia LpezAnglada Fernndez Carolina Prieto Fernndez Victor MangasSanJuan Isabel Garcia Concepcion PayaresHerrera Aranzazu SanchoLpez Harald Enzmann Marcia Sofia Sanches de Castro Lopes Silva Sílvia Duarte Francesco Pignatti 《The oncologist》2020,25(12):1067-1074
The use of daratumumab in combination with established regimens for the treatment of newly diagnosed multiple myeloma has recently been authorized by the European Medicines Agency based on results from three separate phase III randomized, active controlled, open‐label studies that have confirmed enhanced efficacy and tolerability in both transplant‐ineligible (MMY3008 and MMY3007) and transplant‐eligible (MMY3006) patients, without compromising transplant ability. Trial MMY3008 showed an improvement in progression‐free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone; the median PFS had not been reached in the daratumumab arm and was 31.9 months in the control arm (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.43–0.73; p < .0001). Trial MMY3007 showed an improvement in PFS when daratumumab was added to bortezomib, melphalan, and prednisone compared with bortezomib, melphalan, and prednisone; PFS had not been reached in the daratumumab arm and was 18.1 months in the control arm (HR, 0.5; 95% CI, 0.38–0.65; p < .0001). In trial MMY3006, daratumumab added to bortezomib, thalidomide, and dexamethasone was compared with bortezomib, thalidomide, and dexamethasone as induction and consolidation treatment prior to autologous stem cell transplant. The stringent complete response rate at day 100 after transplant in the daratumumab group was 29% compared with 20% in the control group (odds ratio, 1.60; 1.21–2.12 95% CI; p = .0010). Overall adverse events were manageable, with an increased rate of neutropenia and infections in the daratumumab arms. Regulatory assessment of efficacy and safety results from trials MMY3006, MMY3007, and MMY3008 confirmed a positive benefit‐risk ratio leading to an approval of the extensions of indication.Implications for PracticeA set of extensions of indication was recently approved for daratumumab (Darzalex) in the setting of newly diagnosed multiple myeloma in combination with established regimens. Results of the MMY3006, MMY3007, and MMY3008 trials have shown enhanced efficacy and a favorable side effect profile of several daratumumab‐based combinations in patients both ineligible and eligible for transplant, without compromising transplant ability. The combinations of daratumumab with either lenalidomide and low‐dose dexamethasone or bortezomib, melphalan, and prednisone were approved for transplant‐ineligible patients. The combination of daratumumab with bortezomib, thalidomide, and dexamethasone was approved for transplant‐eligible patients. These combinations are expected to improve the survival outlook for patients with multiple myeloma, without an unacceptable risk of increase in adverse events, and updated information on progression‐free survival and overall survival is expected from the above trials. 相似文献
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Penninga E Jensen BA Hansen PB Clausen NT Mourits-Andersen T Nielsen OJ Hasselbalch HC 《Clinical and laboratory haematology》2004,26(5):335-340
In this retrospective multi-centre study, we report our experience with anagrelide in the treatment of thrombocytosis in patients with chronic myeloproliferative diseases. Our study included 52 patients (age 20-78 years). The initial anagrelide dose was, in general, 0.5 mg once daily and mean maintenance dosage was 1.7 mg/day. The overall response rate was 79% including 75% complete remission and 4% partial remission. Forty-two patients (81%) had adverse effects and in 29% of the study population, the adverse effects necessitated cessation of anagrelide. The most common adverse effect was moderate anaemia (50%). Two patients experienced erectile dysfunction which has been described only once previously in association with anagrelide treatment. One patient progressed to acute leukaemia. However, this patient had been pre-treated with two potentially leukaemogenic drugs and had only been in short-term treatment with anagrelide. Furthermore, a total of 13 events were recorded. More than 25% of these events occurred in patients with platelet counts between 400 and 600 x 10(9)/l and almost 40% of all events occurred in patients with platelet counts above 400 x 10(9)/l. This observation supports the hypothesis that aggressive control of thrombocytosis to a platelet count <400 x 10(9)/l might reduce the number of thrombohaemorrhagic events. Anagrelide is safe and effective in reducing the platelet counts, but a high proportion of the patients discontinue treatment because of the adverse effects of the drug. 相似文献
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Ranjan A, Penninga E, Jelsig AM, Hasselbalch HC, Bjerrum OW. Inheritance of the chronic myeloproliferative neoplasms. A systematic review. This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia (CML). Sixty‐one articles were included and provided 135 families with a total of 341 participants distributed to various subtypes of MPN: 50% PV, 23% ET, 14% PMF, 10% CML and 3% non‐MPN hematological disorder. Women developed the disease earlier than men (43.1 years vs 47.3 years; p = 0.074), while the general average age of onset was 46 years, notably younger than sporadic cases. The clinical phenotype of the families showed a homogenous (67%) and a heterogeneous (33%) pattern, with the majority being PV–PV pairs (36%) and PV–PMF pairs (17%), respectively. This observation suggests that the susceptibility gene (or genes) is not restricted to one subtype supporting the hypothesis of a mutation in an early multipotent stem cell. Furthermore, a major subgroup of families provided evidence of an autosomal dominant (AD) inheritance with reduced penetrance. This study suggests that the origin of MPNs may occur in at least three different settings: (i) a sporadic, (ii) genetic heterogeneity with polygenetic and environmental impact and (iii) a familial phenotype following an AD inheritance. 相似文献