Adherence to prophylaxis in adolescents and young adults with severe haemophilia, A qualitative study with patients

© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Abstract Introduction: Reported levels of adherence to prophylaxis among young people with haemophilia (YPH) vary widely and are predominately based on estimations made by healthcare professionals and parents. Reasons for (non)adherence among YPH in particular have not been evidenced. Aim: to examine experiences in relation to prophylaxis with YPH themselves, and barriers and facilitators to their adherence. Methods: 11 Participants were recruited in five haemophilia centres across England and Wales. All patients who met the inclusion criteria (aged 12-25, diagnosed with haemophilia, on prophylaxis) were approached during a routine check-up appointment, and all participants who agreed to take part were interviewed. Interviews were audio recorded, transcribed and analysed using Interpretative Phenomenological Analysis. Results: Self-reported adherence to prophylaxis was good. Few participants admitted to intentionally skipping injections although they reported sometimes forgetting. However, due to the increasingly personalised and flexible approach to prophylaxis, adherence is not straightforward to define. Barriers to adherence included a busy lifestyle, dislike of the intravenous injection, venous access issues, anxiety or stress and being out of one’s normal routine. Support was an important facilitator to adherence, including support from health professionals at the haemophilia centre as well as friends. Parents appear to be very involved with their sons’ haemophilia management, even after their sons leave home. Conclusion: What this study adds is that the increasingly flexible and personalized approach to managing prophylaxis in haemophilia may sometimes lead to confusion around treatment frequency and dosing. This may lead to accidental non-adherence, which is distinct from both skipping and forgetting. Advice from haemophilia teams may not always be consistent, and is likely to be interpreted differently by different individuals. Some additional training and education of patients and their families to increase their knowledge and skills around prophylaxis may reduce this confusion and therefore is likely to improve adherence further.Peer reviewedFinal Published versio

Use of reactance with synchronous converters: An insurance to continuity of service and a protection to apparatus

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Psychometric properties of the Vertigo symptom scale – Short form

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to examine the psychometric properties of the Vertigo symptom scale – short form (VSS-SF), a condition-specific measure of dizziness, following translation of the scale into Norwegian.</p> <p>Methods</p> <p>A cross-sectional survey design was used to examine the factor structure, internal consistency and discriminative ability (sample I, n = 503). A cross-sectional pre-intervention design was used to examine the construct validity (sample II, n = 36) of the measure and a test-retest design was used to examine reliability (sub-sample of sample II, n = 28).</p> <p>Results</p> <p>The scree plot indicated a two factor structure accounting respectively for 41% and 12% of the variance prior to rotation. The factors were related to vertigo-balance (VSS-V) and autonomic-anxiety (VSS-A). Twelve of the items loaded clearly on either of the two dimensions, while three items cross-loaded. Internal consistency of the VSS-SF was high (alpha = 0.90). Construct validity was indicated by correlation between path length registered by platform posturography and the VSS-V (r = 0.52), but not with the VSS-A. The ability to discriminate between dizzy and not dizzy patients was excellent for the VSS-SF and sub-dimension VSS-V (area under the curve 0.87 and 0.91, respectively), and acceptable for the sub-dimension VSS-A (area under the curve 0.77). High test-retest reliability was demonstrated (ICC VSS-SF: 0.88, VSS-V: 0.90, VSS-A: 0.90) and no systematic change was observed in the scores from test to retest after 2 days.</p> <p>Conclusion</p> <p>Using a Norwegian translated version of the VSS-SF, this is the first study to provide evidence of the construct validity of this instrument demonstrating a stable two factor structure of the scale, and the identified sub-dimensions of dizziness were related to vertigo-balance and autonomic-anxiety, respectively. Evidence regarding a physical construct underlying the vertigo-balance sub-scale was provided. Satisfactory internal consistency was indicated, and the discriminative ability of the instruments was demonstrated. The instrument showed satisfactory test-retest reliability.</p

Dexrazoxane significantly impairs the induction of doxorubicin resistance in the human leukaemia line, K562

Dexrazoxane combined with doxorubicin (+ 5-fluorouracil + cyclophosphamide – the FAC regime) leads to a significant decrease in doxorubicin cardiotoxicity and a significant increase in median survival time for patients with advanced breast cancer responsive to FAC. The reason for this increase in survival may be due to interference with the mechanism involved in the emergence of multidrug resistance (MDR). In order to test this hypothesis, we induced resistance to doxorubicin in the K562 cell line by growing cells in increasing concentrations of doxorubicin (10–30 nM) in the presence and absence of dexrazoxane (20 nM). The doxorubicin sensitivity of all resultant sublines was measured using the MTT assay. Flow cytometry was used to assess the MDR1 phenotype, measuring P-glycoprotein expression with MRK 16 antibody and drug accumulation in the presence and absence of PSC 833 for functional P-glycoprotein. Long-term growth in doxorubicin increased the cellular resistance (IC 50) of K562 cells in a concentration-dependent manner (r2 = 0.908). Doxorubicin resistance was not induced in the presence of dexrazoxane (P< 0.0001) for several months. In parallel, the expression of functional P-glycoprotein was delayed after concomitant addition of dexrazoxane to the selecting medium (P< 0.001). Dexrazoxane did not act as a conventional modulator of P-glycoprotein. These results suggest that dexrazoxane may delay the development of MDR1, thus allowing responders to the FAC regime to continue to respond. © 2001 Cancer Research Campaign http://www.bjcancer.co

Patients' perceptions of the potential of breathing training for asthma: a qualitative study.

Poor symptom control is common in asthma. Breathing training exercises may be an effective adjunct to medication; it is therefore important to understand facilitators and barriers to uptake of breathing training exercises

Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

AmBisome® (LAmB), a liposomal formulation of amphotericin B (AmB), is a second-line treatment for the parasitic skin disease cutaneous leishmaniasis (CL). Little is known about its tissue distribution and pharmacodynamics to inform clinical use in CL. Here, we compared the skin pharmacokinetics of LAmB with Fungizone® (DAmB), the deoxycholate form of AmB, in murine models of Leishmania major CL. Drug levels at the target site (the localized lesion) 48 hours after single intravenous (IV) dosing of the individual AmB formulations (1 mg/kg of body weight) were similar, but were 3-fold higher for LAmB than for DAmB on day 10 after multiple administrations (1 mg/kg on days 0, 2, 4, 6 and 8). After single and multiple dosing, intralesional concentrations were respectively 5- and 20-fold higher compared to those in the healthy control skin of the same infected mice. We then evaluated how drug levels in the lesion after LAmB treatment relate to therapeutic outcomes. After five administrations of the drug at 0, 6.25 or 12.5 mg/kg (IV), there was a clear correlation between dose level, intralesional AmB concentration and relative reduction in parasite load and lesion size (R2 values > 0.9). This study confirms the improved efficacy of the liposomal over the deoxycholate AmB formulation in experimental CL, which is related to higher intralesional drug accumulation

Status Update of the Parkes Pulsar Timing Array

The Parkes Pulsar Timing Array project aims to make a direct detection of a gravitational-wave background through timing of millisecond pulsars. In this article, the main requirements for that endeavour are described and recent and ongoing progress is outlined. We demonstrate that the timing properties of millisecond pulsars are adequate and that technological progress is timely to expect a successful detection of gravitational waves within a decade, or alternatively to rule out all current predictions for gravitational wave backgrounds formed by supermassive black-hole mergers.Comment: 10 pages, 3 figures, Amaldi 8 conference proceedings, accepted by Classical & Quantum Gravit

TEMPO2: A new pulsar timing package - III. Gravitational wave simulation

Analysis of pulsar timing data sets may provide the first direct detection of gravitational waves. This paper, the third in a series describing the mathematical framework implemented into the TEMPO2 pulsar timing package, reports on using TEMPO2 to simulate the timing residuals induced by gravitational waves. The TEMPO2 simulations can be used to provide upper bounds on the amplitude of an isotropic, stochastic, gravitational wave background in our Galaxy and to determine the sensitivity of a given pulsar timing experiment to individual, supermassive, binary black hole systems. © 2009 The Authors. Journal compilation © 2009 RAS