A Mathematical Modeling Approach to the Cort-Fitness Hypothesis.

The Cort-Fitness Hypothesis has generated much interest from investigators integrating field endocrinology with evolutionary biology, ecology, and conservation. The hypothesis was developed to test the assumption that if glucocorticoid levels increase with environmental challenges and fitness decreases with environmental challenges, then there should be a negative relationship between baseline glucocorticoid levels and fitness. Indeed, studies across diverse taxa have found that the relationship between baseline glucocorticoid levels and fitness are not consistent: some studies show a positive relationship, others negative, and some show no correlation. Hence, a deeper understanding of the mechanisms underlying the relationship between baseline glucocorticoid levels, environmental challenges, and fitness is needed. We propose a mathematical model representing the links between baseline glucocorticoid levels, environmental challenges, and fitness. Our model describes how variation in the predictability and intensity of environmental challenges, reproductive strategies, and fitness metrics can all contribute to the variability observed in empirical tests of the Cort-Fitness Hypothesis. We provide qualitative results showing that much of the inconsistency in previous studies can be explained and we discuss how the model can be used to inform future Cort-Fitness studies.

Un enfoque de modelado matemático para la hipótesis de Cort-Fitness (A Mathematical Modeling Approach to The Cort-Fitness Hypothesis) La hipótesis de Cort-Fitness ha generado mucho interés por parte de los investigadores que integran la endocrinología de campo con la biología evolutiva, la ecología y la conservación. La hipótesis se desarrolló para probar el supuesto de que si los niveles de glucocorticoides aumentan con los desafíos ambientales y la aptitud física disminuye con los ambientales, entonces debería existir una relación negativa entre los niveles de glucocorticoides de referencia y la aptitud física. De hecho, los estudios en diversos taxones han encontrado que la relación entre los niveles de glucocorticoides de referencia y la aptitud no son consistentes: algunos estudios muestran una relación positiva, otros negativos y otros no muestran correlación. Por lo tanto, se necesita una comprensión más profunda de los mecanismos subyacentes en la relación entre los niveles de glucocorticoides de referencia, los desafíos ambientales y la aptitud. Proponemos un modelo matemático que representa los vínculos entre los niveles basales de glucocorticoides, los desafíos ambientales y la aptitud. Nuestro modelo describe cómo la variación en la previsibilidad e intensidad de los desafíos ambientales, las estrategias reproductivas y las métricas de aptitud pueden contribuir a la variabilidad observada en las pruebas empíricas de la hipótesis de Cort-Fitness. Proporcionamos resultados cualitativos que muestran que gran parte de la variación en estudios anteriores se puede explicar y discutimos cómo se puede usar el modelo para informar futuros estudios de Cort-Fitness. Translated to Spanish by J Heras (herasj01@gmail.com).

Uma Abordagem Matématica de Modelagem para a Hipótese Cort-Fitness (A Mathematical Modeling Approach to The Cort-Fitness Hypothesis) A hipótese de cort-fitness gerou muito interesse de pesquisadores ao integrar endocrinologia de campo com biologia evolutiva, ecologia e conservação. A hipótese foi desenvolvida para testar a suposição de que, se os níveis de glicocorticóides aumentam com os desafios ambientais e o fitness diminui, então deve haver uma relação negativa entre os níveis basais de glicocorticóides e o fitness. De fato, estudos com diversos táxons descobriram que a relação entre os níveis basais de glicocorticoides e o fitness não são consistentes: alguns mostram uma relação positiva, outros uma negativa e há ainda os que não mostram correlação alguma. Assim, é necessária uma compreensão mais profunda dos mecanismos subjacentes à relação entre os níveis basais de glicocorticóides, os desafios ambientais e o fitness. Propomos um modelo matemático que representa as ligações entre os níveis basais de glicocorticoides, os desafios ambientais e o fitness. Nosso modelo descreve como a variação na previsibilidade e intensidade dos desafios ambientais, estratégias reprodutivas e métricas de fitness podem contribuir para a variabilidade observada nos testes empíricos da hipótese cort-fitness. Nós fornecemos resultados qualitativos mostrando que grande parte da variação em estudos anteriores pode ser explicada e discutimos como o modelo pode ser usado para informar futuros estudos sobre o cort-fitness. Translated to Portuguese by G Sobral (gabisobral@).

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.

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.

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.

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.

Qualitative effects of omalizumab on concomitant IgE-mediated disease in a severe asthmatic population: a real life observational study.

INTRODUCTION: Omalizumab is a recombinant humanized monoclonal antibody (anti-IgE) licensed for use in GINA 5 asthma or for chronic idiopathic urticaria. Many patients with asthma have concomitant allergic diseases such as dermatitis and sinusitis. IgE is also implicated in allergic-bronchopulmonary disease (ABPA). In addition, extreme sensitivity to allergen can prevent the initiation of allergen immunotherapy. AIM: The aim of this study was to assess the efficacy of omalizumab on symptoms of concomitant non asthmatic IgE-mediated allergic disease in a population of severe GINA 5 in a real life observational setting. DESIGN: This study is a retrospective, observational study assessing patients reported allergic, non-asthmatic symptom response to omalizumab treatment. METHODS: Fifty-six severe asthmatics treated with omalizumab were studied. Thirty-seven patients had concomitant rhino-sinusitis, 13 had dermatitis and 4 ABPA. Subjects were asked to grade the improvement in their symptom scores on an analogue scale from 0 (no response) to 10 (excellent response). RESULTS: Mean improvement from baseline was 5 and 1.8 in patients with allergic rhino-sinusitis and dermatitis, respectively. Mean improvement from baseline in respiratory symptoms in patients with ABPA was 4.0. CONCLUSIONS: The results from our study suggest that omalizumab may have a role in allergic disease outside of its current license.

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 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.

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.