A review of prednisolone prescribing for children with acute asthma in the UK

Abstract: Introduction: Worldwide asthma guidelines recommend short courses of oral prednisolone in children with acute exacerbations generating high prescription numbers. There is a paucity of evidence to inform the optimal dose and course duration. This has led to a variation in the recommendations for prednisolone prescribing. Our objective was to assess prednisolone prescribing practise for children with acute asthma in a representative sample of UK prescribers. Methods: We developed an online questionnaire asking prescribers the prednisolone dosage, course duration and formulation used, whether they discussed oral prednisolone side effects with the family and at what child's age they changed from prescribing soluble to non-soluble formulations. This was sent to 1006 UK prescribers including Paediatric Respiratory Consultants, doctors in training, asthma nurses and General Practitioners. Results: 200 complete responses were received (response rate 20%). The majority of surveyed prescribers follow the British National Formulary for Children recommendations on dosage rather than those included in the British Thoracic Society and the Scottish Intercollegiate Guidelines Network. Despite this, we highlighted a 4-fold variation in prednisolone dosages for acute asthma. The majority of prescribers chose 3 days as the course duration. High use of soluble formulations was highlighted. Conclusions: There is wide variation in the dose of prednisolone prescribed for children with acute asthma in the UK. This reflects a relative lack of evidence that needs addressing

Evaluation of inhaler technique and achievement and maintenance of mastery of budesonide/formoterol Spiromax® compared with budesonide/formoterol Turbuhaler® in adult patients with asthma: the Easy Low Instruction Over Time (ELIOT) study

Background: Incorrect inhaler technique is a common cause of poor asthma control. This two-phase pragmatic study evaluated inhaler technique mastery and maintenance of mastery with DuoResp® (budesonide-formoterol [BF]) Spiromax® compared with Symbicort® (BF) Turbuhaler® in patients with asthma who were receiving inhaled corticosteroids/long-acting β2-agonists. Methods: In the initial cross-sectional phase, patients were randomized to a 6-step training protocol with empty Spiromax and Turbuhaler devices. Patients initially demonstrating ≥1 error with their current device, and then achieving mastery with both Spiromax and Turbuhaler (absence of healthcare professional [HCP]-observed errors), were eligible for the longitudinal phase. In the longitudinal phase, patients were randomized to BF Spiromax or BF Turbuhaler. Co-primary endpoints were the proportions of patients achieving device mastery after three training steps and maintaining device mastery (defined as the absence of HCP-observed errors after 12 weeks of use). Secondary endpoints included device preference, handling error frequency, asthma control, and safety. Exploratory endpoints included assessment of device mastery by an independent external expert reviewing video recordings of a subset of patients. Results: Four hundred ninety-three patients participated in the cross-sectional phase, and 395 patients in the longitudinal phase. In the cross-sectional phase, more patients achieved device mastery after three training steps with Spiromax (94%) versus Turbuhaler (87%) (odds ratio [OR] 3.77 [95% confidence interval (CI) 2.05–6.95], p < 0.001). Longitudinal phase data indicated that the odds of maintaining inhaler mastery at 12 weeks were not statistically significantly different (OR 1.26 [95% CI 0.80–1.98], p = 0.316). Asthma control improved in both groups with no significant difference between groups (OR 0.11 [95% CI -0.09–0.30]). An exploratory analysis indicated that the odds of maintaining independent expert-verified device mastery were significantly higher for patients using Spiromax versus Turbuhaler (OR 2.11 [95% CI 1.25–3.54]). Conclusions: In the cross-sectional phase, a significantly greater proportion of patients using Spiromax versus Turbuhaler achieved device mastery; in the longitudinal phase, the proportion of patients maintaining device mastery with Spiromax versus Turbuhaler was similar. An exploratory independent expert-verified analysis found Spiromax was associated with higher levels of device mastery after 12 weeks. Asthma control was improved by treatment with both BF Spiromax and BF Turbuhaler

The role of coping strategies in quality of life of adolescents with asthma

This study aimed to determine which coping strategies are associated with better quality of life (QOL) in adolescents with asthma. Furthermore, because coping can mediate the effects of health stressors on QOL, this study also examined the indirect effect of asthma severity on QOL via coping. Between January and May 2003, 553 Dutch adolescents with asthma (aged 12–6 years) completed questionnaires assessing coping strategies, symptom severity, overall QOL and positive QOL domain (positive effects of asthma domain). The relations between symptom severity, coping strategies and QOL were tested with structural equation modelling (SEM). Symptom severity affected overall and positive QOL, both directly and indirectly via coping. The coping strategies restricted lifestyle and worrying about asthma were associated with poorer overall QOL. The use of the coping strategies restricted lifestyle, positive reappraisal, and information seeking was related to increased scores on the positive QOL domain, whereas hiding asthma was related to lower scores on the positive QOL domain

Reassessing the Evidence Hierarchy in Asthma: Evaluating Comparative Effectiveness

Classical randomized controlled trials are the gold standard in medical evidence because of their high internal validity. However, their necessarily strict design can limit their external validity and the ability to extrapolate these data to real world patients. Therefore, alternatively designed studies may play a complementary role in evaluating the comparative effectiveness of therapies in nonidealized patients in more naturalistic, real world settings. Observational studies have high external validity and can evaluate real world outcomes. Their strength lies in hypothesis generation and testing and in identifying areas in which further clinical trials may be required. Pragmatic trials are designed to maximize applicability of trial results to usual care settings by relying on clinically important outcomes and enrolling a wide range of participants. A combination of these approaches is preferable and necessary

A Glutathione Peroxidase, Intracellular Peptidases and the TOR Complexes Regulate Peptide Transporter PEPT-1 in C. elegans

The intestinal peptide transporter PEPT-1 in Caenorhabditis elegans is a rheogenic H+-dependent carrier responsible for the absorption of di- and tripeptides. Transporter-deficient pept-1(lg601) worms are characterized by impairments in growth, development and reproduction and develop a severe obesity like phenotype. The transport function of PEPT-1 as well as the influx of free fatty acids was shown to be dependent on the membrane potential and on the intracellular pH homeostasis, both of which are regulated by the sodium-proton exchanger NHX-2. Since many membrane proteins commonly function as complexes, there could be proteins that possibly modulate PEPT-1 expression and function. A systematic RNAi screening of 162 genes that are exclusively expressed in the intestine combined with a functional transport assay revealed four genes with homologues existing in mammals as predicted PEPT-1 modulators. While silencing of a glutathione peroxidase surprisingly caused an increase in PEPT-1 transport function, silencing of the ER to Golgi cargo transport protein and of two cytosolic peptidases reduced PEPT-1 transport activity and this even corresponded with lower PEPT-1 protein levels. These modifications of PEPT-1 function by gene silencing of homologous genes were also found to be conserved in the human epithelial cell line Caco-2/TC7 cells. Peptidase inhibition, amino acid supplementation and RNAi silencing of targets of rapamycin (TOR) components in C. elegans supports evidence that intracellular peptide hydrolysis and amino acid concentration are a part of a sensing system that controls PEPT-1 expression and function and that involves the TOR complexes TORC1 and TORC2

Projection of participant recruitment to primary care research: a qualitative study.

BACKGROUND: Recruitment to clinical trials remains a challenge, particularly in primary care settings. Initial projections of participant recruitment need to be as accurate as possible in order to avoid the financial, clinical and ethical costs of trial extensions or failures. However, estimation of recruitment rates is challenging and often poorly executed, if attempted at all. We used qualitative methods to explore the experiences and views of researchers on the planning of recruitment in this setting. METHODS: Participants had registered accrual to a UK-based primary care research study between April 2009 and March 2012. We conducted nine interviews with chief investigators or study managers, using a semi-structured topic guide. Analysis was conducted using the framework approach. RESULTS: Three themes are presented: 1) the factors affecting recruitment rates, 2) the use of planning techniques, and 3) influences on poor estimation. 1) A large number of factors affecting recruitment rates were discussed, including those relating to the study protocol, the clinical setting and the research setting. Use of targeted mail-outs to invite apparently eligible individuals to participate was preferred in order to eliminate some of the uncertainty in the recruitment rate associated with opportunistic clinician referrals. 2) The importance of pilot work was stressed. We identified significant uncertainty as to how best to schedule trial timelines to maximise efficiency. 3) Several potential sources of bias involved in the estimation of recruitment rates were explored and framed as technological, psychological or political factors. CONCLUSIONS: We found a large number of factors that interviewees felt impact recruitment rates to primary care research and highlighted the complexity of realistic estimation. Suitable early planning of the recruitment process is essential, and there may be potential to improve the projection of trial timelines by reducing biases involved in the process. Further research is needed to develop formal approaches that would be suitable for use in this setting