Methodology for the development of the NHF-McMaster Guideline on Care Models for Haemophilia Management.

BACKGROUND: Rigorous and transparent methods are necessary to develop clinically relevant and evidence-based practice guidelines. We describe the development of the National Hemophilia Foundation-McMaster Guideline on Care Models for Haemophilia Management, which addresses best practices in haemophilia care delivery. METHODS: We assembled a Panel of persons with haemophilia (PWH), parents of PWH, clinical experts and guideline methodologists. Conflicts of interest were disclosed and managed throughout. Panel members and key stakeholders were surveyed to develop the guideline questions and identify patient-important outcomes. Systematic reviews of the literature were conducted for all factors important in decision-making: benefits and harms; patient values and preferences; resource implications; acceptability; equity; and feasibility. We used the GRADE approach to create evidence profiles to evaluate the evidence and present key results. Evidence to Decision frameworks were created to guide the Panel in making evidence-based recommendations. When evidence was very low quality or not available, evidence from other chronic disease populations was presented to the Panel to inform the recommendations. Additionally, we systematically pooled observations from experts, and conducted qualitative interviews exploring key stakeholder experiences and perspectives. The Panel made recommendations for each guideline question and elaborated on research priorities, implementation considerations, and monitoring. Final recommendations were circulated for public and peer review. CONCLUSIONS: Despite the paucity of high-quality evidence typical of a rare condition such as haemophilia, we successfully applied a rigorous and transparent methodology based on GRADE to develop an evidence-based clinical practice guideline.

Understanding stakeholder important outcomes and perceptions of equity, acceptability and feasibility of a care model for haemophilia management in the US: a qualitative study.

INTRODUCTION: Care for persons with haemophilia (PWH) is most commonly delivered through the integrated care model used by Hemophilia Treatment Centers (HTCs). Although this model is widely accepted as the gold standard for the management of haemophilia; there is little evidence comparing different care models. AIM: We performed a qualitative study to gain insight into issues related to outcomes, acceptability, equity and feasibility of different care models operating in the US. METHODS: We used a qualitative descriptive approach with semi-structured interviews. Purposive sampling was used to recruit individuals with experience providing or receiving care for haemophilia in the US through either an integrated care centre, a specialty pharmacy or homecare company, or by a specialist in a non-specialized centre. Persons with haemophilia, parents of PWH aged ≤18, healthcare providers, insurance company representatives and policy developers were invited to participate. RESULTS AND CONCLUSIONS: Twenty-nine interviews were conducted with participants representing 18 US states. Participants in the study sample had experience receiving or providing care predominantly within an HTC setting. Integrated care at HTCs was highly acceptable to participants, who appreciated the value of specialized, expert care in a multidisciplinary team setting. Equity and feasibility issues were primarily related to health insurance and funding limitations. Additional research is required to document the impact of care on health and psychosocial outcomes and identify effective ways to facilitate equitable access to haemophilia treatment and care.

NHF-McMaster Guideline on Care Models for Haemophilia Management.

This guideline was developed to identify evidence-based best practices in haemophilia care delivery, and discuss the range of care providers and services that are most important to optimize outcomes for persons with haemophilia (PWH) across the United States. The guideline was developed following specific methods described in detail in this supplement and based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation approach). Direct evidence from published literature and the haemophilia community, as well as indirect evidence from other chronic diseases, were reviewed, synthesized and applied to create evidence-based recommendations. The Guideline panel suggests that the integrated care model be used over non-integrated care models for PWH (conditional recommendation, moderate certainty in the evidence). For PWH with inhibitors and those at high risk for inhibitor development, the same recommendation was graded as strong, with moderate certainty in the evidence. The panel suggests that a haematologist, a specialized haemophilia nurse, a physical therapist, a social worker and round-the-clock access to a specialized coagulation laboratory be part of the integrated care team, over an integrated care team that does not include all of these components (conditional recommendation, very low certainty in the evidence). Based on available evidence, the integrated model of care in its current structure, is suggested for optimal care of PWH. There is a need for further appropriately designed studies that address unanswered questions about specific outcomes and the optimal structure of the integrated care delivery model in haemophilia.

Palliative Subcutaneous Terbutaline Infusion in Severe Asthma.

Continuous subcutaneous infusion of terbutaline (CSIT) has been shown to improve asthma control. As an adjunct to standard asthma pharmacotherapy, 3-12mg/day of CSIT can stabilise asthmatic symptoms, reduce hospitalisations and reduce corticosteroid need1,2. Asthmatics who demonstrate a wide diurnal variability in their peak-flows (>40%), termed brittle asthmatics tend to benefit the most from this therapy3. CSIT can have adverse effects and should only be used in specialist respiratory centres.

The Value of the Combined Assessment of COPD in Accurate Characterization of Stable COPD.

There is evidence showing a tendency to upgrade COPD severity previously staged with spirometric-based GOLD (GOLD 1234) when using the new GOLD combined disease assessment (GOLD ABCD). The aim of our study was to compare the GOLD 1234 classification in a population of stable COPD patients with the GOLD ABCD classification to determine whether stable COPD was upgraded when using this new classification. After an observational study of a stable COPD cohort (n = 112), 61 patients (54.5%) had an increase in their COPD severity when moving from the old GOLD 1234 classification to the current GOLD ABCD assessment (p < 0.01). 42 patients (37.5%) had no change in severity of COPD. 9 patients COPD were assessed to be better on using GOLD ABCD. This study highlights previously missed high-risk patients when reviewing stable COPD. Continued incorporation of GOLD ABCD will translate into better evidence-based management.

The Efficacy of Bronchial Thermoplasty for Severe Persistent Asthma: The First National Experience.

There is an unmet need for new therapies in severe persistent asthma. Bronchial thermoplasty is a bronchoscopic procedure which employs radiofrequency energy to reduce airway smooth muscle and has been demonstrated to improve symptomatic control in severe persistent asthma in other populations. Seven patients have completed bronchial thermoplasty at a tertiary referral centre in Ireland. Asthma Control Test scores and data on hospitalisations, exacerbations, maintenance corticosteroid requirements, rescue bronchodilator use and peak expiratory flow rate (PEFR) were compared one year before and one year post treatment. Significant improvements were demonstrated in mean Asthma Control Test scores, from 8.9 to 14.7 (p = 0.036). Trends towards improvement were seen in mean hospitalisations (respective values for total in 12 month period 5.0, 0.9; p = 0.059) and PEFR (181.4 l/min, 280 l/min respectively; p = 0.059). These data support the use of bronchial thermoplasty in severe persistent asthma in the Irish population.

Treatment decision-making among Canadian youth with severe haemophilia: a qualitative approach.

The first generation of young men using primary prophylaxis is coming of age. Important questions regarding the management of severe haemophilia with prophylaxis persist: Can prophylaxis be stopped? At what age? To what effect? Can the regimen be individualized? The reasons why some individuals discontinue or poorly comply with prophylaxis are not well understood. These issues have been explored using predominantly quantitative research approaches, yielding little insight into treatment decision-making from the perspectives of persons with haemophilia (PWH). Positioning the PWH as a source of expertise about their condition and its management, we undertook a qualitative study: (i) to explore and understand the lived experience of young men with severe haemophilia A or B and (ii) to identify the factors and inter-relationships between factors that affect young men's treatment decision-making. This manuscript reports primarily on the second objective. A modified Straussian, grounded theory methodology was used for data collection (interviews) and preliminary analysis. The study sample, youth aged 15-29, with severe haemophilia A or B, was chosen selectively and recruited through three Canadian Haemophilia Treatment Centres. We found treatment decision-making to be multi-factorial and used the Framework method to analyze the inter-relationships between factors. A typology of four distinct approaches to treatment was identified: lifestyle routine prophylaxis, situational prophylaxis, strict routine prophylaxis and no prophylaxis. Standardized treatment definitions (i.e.: 'primary' and 'secondary', 'prophylaxis') do not adequately describe the ways participants treat. Naming the variation of approaches documented in this study can improve PWH/provider communication, treatment planning and education.

Safety of Grass Pollen Sublingual Immunotherapy for Allergic Rhinitis in Concomitant Asthma.

Seasonal allergic rhinitis (AR) occurs predominantly as a result of grass pollen allergy. Grass pollen sublingual immunotherapy (SLIT) has been proven effective in treating AR1. SLIT is currently licensed for use in AR with concomitant stable mild asthma. There is evidence that SLIT improves asthma control when primarily used to treat AR2. The aim was to assess the safety of SLIT in patients with severe seasonal allergic rhinitis who have co-existing stable mild asthma. The secondary aim was to determine whether asthma control improved post SLIT. There was no deterioration in asthma control after 6-36 months of SLIT. 27/30 (90%) patients' asthma control remained stable or indeed improved (p < 0.021). Of this 15 (50%) patients' asthma improved. There was no statistically significant change in their asthma pharmacotherapy after SLIT (p = 0.059). In conclusion, grass pollen SLIT is safe and can potentially treat dual allergic rhinitis- mild asthmatic patients.

The Efficacy of COPD Outreach in Reducing Length of Stay and Improving Quality of Life.

COPD exacerbations results in prolonged hospitalisation, re-admissions, reduces health-related quality of life (HRQoL) and increases mortality. The study aimed to assess the efficacy of a COPD Outreach service in reducing average length of stay (ALOS), reducing readmissions within 90 days of admission, improving HRQoL and reducing mortality among COPD patients with acute exacerbations (AECOPD). AECOPD data for a 2 year period commencing September 2011 was analysed. The COPD Assessment test (CAT) quantified HRQoL at enrolment and 6 weeks post Outreach. COPD Outreach had an ALOS of 2.47 days compared to ALOS 8.59 days and 8.5 days for all AECOPD before and during an operational COPD Outreach. Re-admission rates among patients enrolled in COPD Outreach were 36.3%. CAT improved from mean 19.3 to 13.5. Mortality was 4.9% among Outreach patients and 2.5% for overall AECOPD in 2012-2013. COPD Outreach reduced ALOS and improved HRQoL for selected patients with AECOPD. It did not reduce re-admissions or mortality.

Implementation and public acceptability: lessons from food irradiation and how they might apply to pathogen reduction in blood products.

BACKGROUND AND OBJECTIVES: The issues around food irradiation (FI) have both similarities and differences to pathogen reduction (PR) in blood products. We performed a systematic search of the FI literature to identify lessons that could help to inform the implementation of pathogen reduction technology for blood products. METHODS: A comprehensive literature search was performed in EMBASE. MEDLINE, PSYCHINFO, CINAL and Physiological Abstracts for articles related to FI that met predefined eligibility criteria. A coding scheme was developed by the investigators, and relevant information from the articles was coded using NVivo 9. Reports for each code were generated and summarized. RESULTS: One thousand two hundred and sixty-six articles were identified by the broad search, and 50 met the study eligibility criteria for inclusion. The implementation of FI was slow and has been met by significant controversy, sparked by concerns from the public and social groups about the acceptability of irradiated food. Numerous factors influenced public acceptability including: demographic factors; perceptions of safety and risk; endorsement of and trust in the FI industry and social institutions that serve as opinion leaders; knowledge and the provision of scientific information including benefits and cost; and the availability of choice. CONCLUSION: There are a number of lessons from the FI literature that may be generalizable to the implementation of PR of blood products. Based on findings from this study, six recommendations are made to facilitate public implementation of this new technology.

Pulmonary Langerhans cell histiocytosis.

We report the case of a 57 year old man who presented with increased shortness of breath together with increased pulmonary nodules in his upper lobes over a two year period. His strong smoking history and pattern of distribution makes Langerhans cell Histiocytosis a likely diagnosis that was confirmed on biopsy.

Sleep apnoea and its relationship with cardiovascular, pulmonary, metabolic and other morbidities.

Sleep apnoea (OSAS) is a multisystem disorder. There is a high prevalence of cardiovascular and metabolic morbidities in patients investigated for sleep apnoea. We aim to evaluate any association between cardiovascular, metabolic and pulmonary co morbidities in patients investigated for OSAS and whether clinical findings based on Epworth sleep score (ESS) and snoring helps in diagnosing sleep apnoea. 258 consecutive patients who were electively admitted for sleep assessment in Peamount Hospital, Dublin from Sept 2009 to Aug 2011 were retrospectively reviewed. 139/258 were diagnosed as OSAS. Cardiovascular, metabolic and pulmonary co morbidities were 46.12%, 37.2% and 29% respectively. There is no correlation found between ESS, Snoring with Apnoea Hypopnoea Index in OSAS group. Screening for OSAS should be considered in patients with certain cardiovascular and metabolic disorders. PSG is so far considered the gold standard investigation to diagnose OSAS and better clinical evaluating tools need to be formulated.

Exercise induced fatigue: unfit or unwell?

This case report outlines the diagnoses of a rare myophosphorylase deficiency (McArdle Syndrome) in a unique way. A set of characteristic values from a Cardiopulmonary Exercise Test (CPET) combined with a typical patient history pointed to a failure of the glycolytic pathway in the skeletal muscle. McArdle Syndrome was confirmed with a skeletal muscle biopsy. There is no evidence of such a diagnostic method in the literature.

An unusual cause of spontaneous pneumothorax: the Mounier-Kuhn syndrome.

We present the case of a 54-year old woman referred to our service with an unusual presentation of an under-diagnosed condition. A life-long non-smoker, she was referred to respiratory services by our emergency department with a left sided pneumothorax, progressive dyspnoea on exertion, and recurrent chest infections. Subsequent investigation yielded findings consistent with Mounier-Kuhn syndrome (Tracheobronchomegaly), a condition characterised by marked dilatation of the proximal airways, recurrent chest infection, and consequent emphysema and bronchiectasis. Although rarely diagnosed, some degree of Mounier-Kuhn syndrome may occur in up to 1 in 500 adults.

Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma.

Glucocorticosteroids are a very effective treatment for asthma and other chronic inflammatory diseases. However, a small proportion of patients is resistant to the therapeutic effects of glucocorticoids. Pharmacokinetic and ligand binding studies suggest that the molecular abnormality in steroid resistance lies distal to nuclear translocation. We have previously reported that there is a decreased ability of glucocorticoid receptors (GR) to bind to the DNA-binding site in peripheral blood mononuclear cells (PBMC) after dexamethasone treatment. This reduced DNA binding was due to a decrease in the number of receptors available rather than an alteration in affinity for DNA. To study this reduced DNA binding, we examined the ability of the nuclear translocated transcription factors activator protein 1 (AP-1), nuclear factor kappa B (NF-kappa B) and cyclic AMP response element-binding protein (CREB) to bind to their DNA-binding sites and to interact with GR in PBMC from patients with steroid-sensitive and steroid-resistant asthma. There was a significant reduction in the interaction between GR and AP-1 in these steroid-resistant patients, although interaction with other transcription factors activated in inflammation (NF-kappa B and CREB) was unaffected. An increase in the basal levels of AP-1 DNA binding was also detected in the nuclei from steroid-resistant asthmatic patients. There were no differences in the amount of messenger RNA detected for the components of AP-1, c-Fos and c-Jun, nor in the sequences of these messenger RNAs. These results suggest either that the ability of the GR to bind to glucocorticoid response elements and AP-1 is altered in steroid-resistant patients or that increased levels of AP-1 prevent GR DNA binding, and that this may be the molecular basis of resistance to the antiinflammatory effect of steroids in these cells.