The discussion of prophylactic therapy in haemophilia is largely focused on joint outcomes. The impact of prophylactic therapy on intracranial haemorrhage (ICH) is less known. This study aimed to analyse ICH in children with haemophilia, with a focus on different prophylaxis regimens and sequelae of ICH. We conducted a multicentre retrospective and prospective study that included 33 haemophilia centres from 20 countries. Inclusion criteria were children and adolescents born between 1993 and 2014, with severe haemophilia A or B without inhibitors. Participants were categorized by prophylaxis regimen: full, partial or none, based on dose and dose frequency of regular infusions. The cohort study included 1515 children: 29 cases of ICH over 8038 patient years were reported. The incidence of ICH in the prophylaxis group, 0·00033 cases of ICH/patient year, was significantly lower compared to the no prophylaxis group, 0·017 cases of ICH/patient year (RR 50·06; P < 0·001) and the partial prophylaxis group, 0·0050 cases of ICH/patient year (RR 14·92; P = 0·007). In the on-demand-group, 8% (2/24) children with ICH died and 33% had long-term sequelae, including intellectual and behavioural problems, paresis and epilepsy. Children on regular, frequent prophylaxis have a low risk of ICH compared to those using non-frequent or no prophylaxis.
Summary Haemorrhage is often responsible for the lethal course of acute myeloid leukaemia (AML). Previously, multiple platelet function defects were identified by flow cytometric analysis of platelet activation markers in AML. The role of flow cytometric analysis of platelet function in characterization of prognostic markers of haemorrhage in AML patients has not been well elucidated. The objective of this prospective study was to analyse platelet function in 50 AML patients at diagnosis and to compare results with clinical bleeding score, graded by common toxicity criteria. Platelet activation markers CD62P, CD42b, CD63 and PAC‐1 were analysed following in vitro activation by thrombin receptor activating peptide. The following plasma haemostasis parameters were measured: soluble P‐selectin, activated partial thromboplastin time, thrombin time, prothrombin time, d‐dimer, fibrinogen, and von Willebrand factor antigen. In a multivariate analysis, P‐selectin (CD62P) <36 molecules of equivalent soluble fluorochrome × 103 (P < 0·0015) and platelet count <40 × 109/l (P = 0·01) were significant predictors of haemorrhage at diagnosis. Haemorrhage at diagnosis predicted grade 3–4 haemorrhage in the first 28 d following diagnosis (P = 0·018). The presented results indicate that low P‐selectin is a prognostic marker of haemorrhage in AML.
Purpose Despite improved treatment and care, children and adolescents diagnosed with cancer continue to die, while many of those cured are burdened by treatment-related sequelae. The best clinical management of children and adolescents with cancer depends on healthcare professionals with various skills and expertise. Complex treatment, care and rehabilitation require collaboration between healthcare professionals. The purpose of this scoping review is to identify and evaluate existing interprofessional education in paediatric cancer. Methods We utilised the scoping review methodology and searched PubMed, Scopus and Education Resources Information Center. Inclusion criteria were postgraduate studies targeting more than one profession and evaluation of the educational intervention. We applied Kirkpatrick’s modified interprofessional education outcomes model to systematise outcomes. Results Of 418 references, nine studies fulfilled the inclusion criteria. The design, strategy and content of all the studies were heterogeneous. None of the interprofessional educations systematically evaluated knowledge, skills, attitudes or the effects on patient outcomes or quality of care. Conclusion There is a lack of well-structured, interprofessional education in paediatric cancer that has undergone evaluation. Paediatric cancer may benefit from systematic education and evaluation frameworks since interprofessional education could potentially strengthen the treatment, care and rehabilitation for children and adolescents with cancer. Electronic supplementary material The online version of this article (10.1007/s00520-019-04856-4) contains supplementary material, which is available to authorized users.
The binding between F-actin and myosin has been studied by analyzing the amount of radio-actively labelled (by means of 14C-NEM) F-actin and myosin in the formed unsoluble actomyosin pellet after centrifugation of the reaction mixture. In the absence of ATP, the amount of actin bound to myosin varies, depending on the amounts of actin and myosin present, between 0.18 mg actin/mg myosin (2 actin units per 1 myosin molecule) and about 2 mg actin/mg myosin (each actin fibril only uncompletely saturated with myosin). In 0.03 ᴍ KCl ATP decreases, if at all, the affinity of actin towards myosin only slightly; but less actin is bound to myosin in the presence of MgATP and in low ionic strength, indicating that myosin is now more densily distributed over fewer actin fibrils leaving the rest of fibrils free. For precipitation of the total amount of myosin (myosin alone is soluble in MgATP) incomplete saturation of myosin with actin suffices; obviously actin promotes filament formation of myosin. The activation of myosin ATPase by actin depends in a similar manner as actin binding does on actin concentration, hence the enzymatic interaction between actin and myosin is accompanied by true actin-myosin binding. An actin-tropomyosin-troponin preparation, whose reduced viscosity is lower than that of F-actin and which consists of about 30% actin, activates myosin ATPase to the same extent as F-actin does. It competes with F-actin for the same binding sites on myosin and can in the presence of MgATP be displaced from myosin by those preparations of F-actin which have a strong tendency to become fully saturated with myosin. The activation of myosin ATPase by actin-tropomyosin-troponin is reduced after tryptic digestion of actin-tropomyosin-troponin, which affects, according to SDS gel electro phoresis, mainly two components of troponin with molecular weights of about 32 000 and 25 000, respectively
Conclusions: These observations support that leukemic blast heterogeneity detected by MFC has additional prognostic significance in de novo AML; however, the score system needs to be prospectively validated in future clinical trials before implementation. V C 2012 International Clinical Cytometry Society
BackgroundComplex treatment, care and rehabilitation require continuous healthcare professional development and maintenance of competencies in collaboration with other professionals. Interprofessional education in childhood cancer involves several groups of healthcare professionals with both general and specific knowledge and skills.ObjectiveTo establish consensus on content and interprofessional learning objectives for an interprofessional education in childhood cancer.DesignA three-round Delphi survey in Scandinavian childhood cancer departments.ParticipantsHealthcare professionals appointed by their head of departments and head nurses based on their profession and their involvement in continuing professional development.Main outcome measuresA prioritised list of interprofessional learning objectives with a mean score of ≥3 on a five-point scale (1=not relevant, 5=extremely relevant).Results12 childhood cancer departments participated with 30 healthcare professionals: 11 nurses, 10 medical doctors, 5 social workers, 2 physiotherapists and 2 pedagogues. In total, 28 (93%), 25 (83%) and 22 (73%) completed the first, second and third round, respectively. In the first round, we asked open-ended questions and used directed content analysis to analyse 386 statements. We formulated 170 interprofessional learning objectives in six categories: (1) acute life-threatening situations, (2) gastrointestinal toxicities and side effects, (3) pain, (4) palliation, (5) play and activity, and (6) prescription and administration of medicine. The second round resulted in 168 interprofessional learning objectives receiving a mean score of ≥3 on a five-point scale. Final agreement in the third round resulted in a prioritised list of 168 learning objectives.ConclusionsConsensus on content and interprofessional learning objectives for an interprofessional education in childhood cancer was established across five groups of healthcare professionals in three countries. Some learning objectives are generic and can be applied in settings other than childhood cancer, where healthcare professionals collaborate to provide patients and families optimal treatment and care.
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