Severe asthma assessment, management and the organisation of care in Australia and New Zealand: expert forum roundtable meetings.

Severe asthma imposes a significant burden on individuals, families and the healthcare system. Treatment is complex, due to disease heterogeneity, comorbidities and complexity in care pathways. New approaches and treatments improve health outcomes for people with severe asthma. However, emerging multidimensional and targeted treatment strategies require a reorganisation of asthma care. Consensus is required on how reorganisation should occur and what areas require further research. The Centre of Excellence in Severe Asthma convened three forums between 2015 and 2018, hosting experts from Australia, New Zealand and the UK. The forums were complemented by a survey of clinicians involved in the management of people with severe asthma. We sought to: (i) identify areas of consensus among experts; (ii) define activities and resources required for the implementation of findings into practice; and (iii) identify specific priority areas for future research. Discussions identified areas of unmet need including assessment and diagnosis of severe asthma, models of care and treatment pathways, add-on treatment approaches and patient perspectives. We recommend development of education and training activities, clinical resources and standards of care documents, increased stakeholder engagement and public awareness campaigns and improved access to infrastructure and funding. Further, we propose specific future research to inform clinical decision-making and develop novel therapies. A concerted effort is required from all stakeholders (including patients, healthcare professionals and organisations and government) to integrate new evidence-based practices into clinical care and to advance research to resolve questions relevant to improving outcomes for people with severe asthma.

Treatable traits can be identified in a severe asthma registry and predict future exacerbations.

BACKGROUND AND OBJECTIVE: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk. METHODS: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months. RESULTS: In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea. CONCLUSION: Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.

AAPM-RSS Medical Physics Practice Guideline 9.a. for SRS-SBRT.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances. Approved by AAPM Professional Council 3-31-2017 and Executive Committee 4-4-2017.

The Impact of Patient Preference on Attendance and Completion Rates at Centre-Based and mHealth Pulmonary Rehabilitation: A Non-Inferiority Pragmatic Clinical Trial.

Purpose: Pulmonary rehabilitation (PR) is vital in the management of chronic respiratory disorders (CRDs) although uptake, attendance and completion are poor. Differing models of delivering PR are emerging in an attempt to increase the uptake and completion of this intervention. This study aimed to evaluate participant rate of attendance and completion of PR when given a preference regarding model of delivery (centre-based and mPR). Secondary aims were to evaluate the factors affecting patient preference for model of delivery and determine whether mPR is non-inferior to centre-based PR in health outcomes. Methods: A multi-centre non-inferiority preference based clinical trial in Auckland, New Zealand. Participants with a CRD referred for PR were offered the choice of centre-based or mHealth PR (mPR). The primary outcome was completion rate of chosen intervention. Results: A total of 105 participants were recruited to the study with 67 (64%) preferring centre-based and 38 (36%) mPR. The odds of completing the PR programme were higher in the centre-based group compared to mPR (odds ratio 1.90 95% CI [0.83-4.35]). Participants opting for mPR were significantly younger (p = 0.002) and significantly more likely to be working (p = 0.0001). Results showed that mPR was not inferior to centre-based regarding changes in symptom scores (CAT) or time spent in sedentary behaviour (SBQ). When services were forced to transition to telehealth services during COVID-19 restrictions, the attendance and completion rates were higher with telephone calls and video conferencing compared to mPR - suggesting that synchronous interpersonal interactions with clinicians may facilitate the best attendance and completion rates. Conclusion: When offered the choice of PR delivery method, the majority of participants preferred centre-based PR and this facilitated the best completion rates. mPR was the preferred choice for younger, working participants suggesting that mPR may offer a viable alternative to centre-based PR for some participants, especially younger, employed participants.

Randomised controlled trial for emphysema with a selective agonist of the γ-type retinoic acid receptor.

Palovarotene is an oral γ-selective retinoid agonist. In animal emphysema models, palovarotene reduced inflammation, promoted structural repair and functional improvement. REPAIR (Retinoid treatment of Emphysema in Patients on the α(1)-antitrypsin International Registry), was an investigator-initiated, double-blind, placebo-controlled randomised study to assess the safety and efficacy of 5 mg·day(-1) palovarotene given for 1 year to 262 patients with severe α(1)-antitrypsin deficiency and emphysema confirmed by computed tomography. Change in volume-adjusted 15th percentile point lung density from baseline in 1 year was the primary end-point; functional end-points were also regularly assessed. We randomly assigned 133 and 129 patients to placebo or palovarotene, respectively. Both groups were well matched for all baseline characteristics, including respiratory medications. 88% and 85% of patients completed 1 year of treatment with placebo and palovarotene, respectively. Palovarotene was generally well tolerated. In the study completers population, the placebo-corrected difference of lung density was -0.45 HU at week 28 (p=0.64) and -0.25 HU at week 52 (p=0.94). A nonsignificant treatment difference in most functional parameters of the lung in favour of the drug was observed over time suggesting potential pharmacological effects of palovarotene. Palovarotene 5 mg·day(-1) over 1 yr failed to show a significant benefit on lung density in moderate-to-severe emphysema secondary to severe α(1)-antitrypsin deficiency.

Hospital Cost Savings for Sequential COPD Patients Receiving Domiciliary Nasal High Flow Therapy.

Purpose: To estimate the 5-year budget impact to Aotearoa New Zealand (NZ) hospitals of domiciliary nasal high flow (NHF) therapy to patients with chronic obstructive pulmonary disease (COPD) who require long term oxygen therapy. Methods: Hospital admission counts along with length of stay were obtained from hospital records of 200 COPD patients enrolled in a 12-month randomized clinical trial of NHF in Denmark, both over a 12-month baseline and then in the study period while on randomized treatment (control or NHF). NZ costings from similar COPD patients were estimated using data from Middlemore Hospital, Auckland and were applied to the Danish trial. The budget impact of NHF was estimated over the predicted 5-year lifetime of the device when used by patients sequentially. Results: Fifty-five of 100 patients in the NHF group and 44 of 100 patients in the control group were admitted to hospital with a respiratory diagnosis during the baseline year. They had 108 admissions in the treatment group vs 89 in the control group, with 632 vs 438 days in hospital, and modeled annual costs of $9443 vs $6512 per patient, respectively. During the study period there were 38 vs 44 patients with 67 vs 80 admissions and 302 vs 526 days in hospital, at a modeled annual cost of $6961 vs $9565 per patient respectively. Taking into account capital expenditure and running costs, this resulted in cost savings of $5535 per patient-year (95% CI, -$36 to -$11,034). With 90% usage over the estimated five-year lifetime of the NHF device, amortized capital costs of $594 per year and annual running costs of $662, we estimate a 5-year undiscounted cost saving per NHF device of $18,626 ($16,934 when discounted to net present value at 5% per annum). There would still be annual cost savings over a wide range of assumptions. Conclusion: Domiciliary NHF therapy for patients with severe COPD has the potential to provide substantial hospital cost savings over the five-year lifetime of the NHF device.

Report of AAPM TG 135: quality assurance for robotic radiosurgery.

The task group (TG) for quality assurance for robotic radiosurgery was formed by the American Association of Physicists in Medicine's Science Council under the direction of the Radiation Therapy Committee and the Quality Assurance (QA) Subcommittee. The task group (TG-135) had three main charges: (1) To make recommendations on a code of practice for Robotic Radiosurgery QA; (2) To make recommendations on quality assurance and dosimetric verification techniques, especially in regard to real-time respiratory motion tracking software; (3) To make recommendations on issues which require further research and development. This report provides a general functional overview of the only clinically implemented robotic radiosurgery device, the CyberKnife. This report includes sections on device components and their individual component QA recommendations, followed by a section on the QA requirements for integrated systems. Examples of checklists for daily, monthly, annual, and upgrade QA are given as guidance for medical physicists. Areas in which QA procedures are still under development are discussed.

The role of high-flow nasal therapy in bronchiectasis: a post hoc analysis.

High-flow nasal therapy significantly reduces exacerbation rates and improves quality of life in patients with stable bronchiectasis. High-flow nasal therapy is therefore a potential treatment option for patients with bronchiectasis. https://bit.ly/2JFXuQc.

Endoscopic lung volume reduction effectively treats acute respiratory failure secondary to bullous emphysema.

Emphysema often affects the lungs in a heterogeneous fashion, and collapse or removal of severely hyperinflated portions of lung can improve overall lung function and symptoms. The role of lung volume reduction (LVR) surgery in selected patients is well established, but that of non-surgical LVR is still being defined. In particular, use of endobronchial LVR is still under development. This case report describes a 48-year-old non-smoker with severe bullous emphysema complicated by acute hypercapnic respiratory failure, who was successfully treated by endobronchial valve placement while intubated in an intensive care unit.

Understanding End-User Perspectives of Mobile Pulmonary Rehabilitation (mPR): Cross-Sectional Survey and Interviews.

BACKGROUND: Pulmonary rehabilitation (PR) is an effective intervention for the management of people with chronic respiratory diseases, but the uptake of and adherence to PR programs is low. There is potential for mobile health (mHealth) to provide an alternative modality for the delivery of PR, overcoming many of the barriers contributing to poor attendance to current services. OBJECTIVE: The objective of this study was to understand the needs, preferences, and priorities of end users for the development of an adaptive mobile PR (mPR) support program. METHODS: A mixed methods (qualitative and quantitative) approach was used to assess the needs, preferences, and priorities of the end users (ie, patients with chronic respiratory disorders) and key stakeholders (ie, clinicians working with patients with chronic respiratory disorders and running PR). The formative studies included the following: (1) a survey to understand the preferences and priorities of patients for PR and how mobile technology could be used to provide PR support, (2) ethnographic semistructured interviews with patients with chronic respiratory disorders to gain perspectives on their understanding of their health and potential features that could be included in an mPR program, and (3) key informant interviews with health care providers to understand the needs, preferences, and priorities for the development of an mPR support program. RESULTS: Across all formative studies (patient survey, n=30; patient interviews, n=8; and key stakeholder interviews, n=8), the participants were positive about the idea of an mPR program but raised concerns related to digital literacy and confidence in using technology, access to technology, and loss of social support currently gained from traditional programs. Key stakeholders highlighted the need for patient safety to be maintained and ensuring appropriate programs for different groups within the population. Finding a balance between ensuring safety and maximizing access was seen to be essential in the success of an mPR program. CONCLUSIONS: These formative studies found high interest in mHealth-based PR intervention and detailed the potential for an mPR program to overcome current barriers to accessing traditional PR programs. Key considerations and features were identified, including the importance of technology access and digital literacy being considered in utilizing technology with this population.

The use of keratin biomaterials derived from human hair for the promotion of rapid regeneration of peripheral nerves.

The management of trauma-associated nerve defects is difficult because of the absence of autologous donor motor or sensory nerves. Pre-clinical development and clinical experience has shown that damaged nerves can be surgically repaired using a tubular conduit interposed across the defect. Acceptable patient outcomes are achieved so long as the gap distance does not exceed a few centimeters. Although research in animals has demonstrated that nerve repair can be facilitated across slightly larger gaps by introducing a biomaterial filler into the conduit lumen, these biomaterials are not typically "neuroinductive" (i.e. capable of acting directly on regenerative cells to enhance nerve tissue formation beyond clinical limits). Moreover, their use does not often result in functional recovery equivalent to nerve autograft, the clinical gold standard. Here we show that a biomaterial gel made from the proteins found in human hair can mediate a robust nerve regeneration response, in part through activation of Schwann cells. In vitro, keratins extracted from human hair enhance the activity of Schwann cells by a chemotactic mechanism, increase their attachment and proliferation, and up-regulate expression of important genes. Moreover, these characteristics translate to improved functional nerve recovery in an animal model. These results suggest that a biomaterial derived from human hair keratins is neuroinductive and can facilitate an outcome comparable to autograft in a nerve injury model.

Peripheral nerve regeneration using a keratin-based scaffold: long-term functional and histological outcomes in a mouse model.

PURPOSE: The management of peripheral nerve injuries with segmental defects is a challenge to both patient and surgeon. Repairs under tension have a poor prognosis; sensory nerve allografts have donor site morbidity and suboptimal motor recovery, but remain the gold standard. The development of conduit-based repair strategies has evolved and these are promising for sensory nerves and short defects; however, no conduit filler is clinically available that improves motor recovery equivalent to sensory autografts. In this study, motor recovery using keratin-based hydrogel filler was compared with that for sensory nerve autografts and empty conduits. METHODS: Fifty-four mice were randomized into 3 treatment groups: empty conduit, sural nerve autograft, and keratin hydrogel-filled conduit. Animals were followed for 6 weeks, 3 months, and 6 months. Outcomes included compound motor action potential (CMAP), nerve area, myelinated axon number and density, and myelinated axon diameter. RESULTS: Neuromuscular recovery with keratin was greater than with empty conduits in most outcome measures. Nerves that regenerated through the keratin hydrogel had lower conduction delays, greater amplitudes, more myelinated axons, and larger axons than nerves that regenerated through empty conduits. Sensory nerve autografts and keratin hydrogel were statistically equivalent in CMAP measurements at 6 months. Moreover, keratin-filled conduits demonstrated greater axon density and larger average axon diameter than both empty conduits and autograft at 6 months. CONCLUSIONS: In a mouse tibial nerve model, keratin hydrogels significantly improved electrophysiological recovery, compared with empty conduits and sensory nerve autografts, at an early time point of regeneration. Keratin hydrogels also produce long-term electrical and histological results superior to empty conduits and equivalent to sensory nerve autografts.

Gene expression of myogenic regulatory factors, nicotinic acetylcholine receptor subunits, and GAP-43 in skeletal muscle following denervation in a rat model.

Neuromuscular junction destabilization following nerve injury contributes to irreversible functional impairment. Myogenic Regulatory Factors (MRF's) including myoblast determination factor (MyoD), MRF-4, Myogenin, and myogenic factors-5 (myf-5), and Growth-associated protein 43 KDa (GAP43) regulate gene expression of nicotinic acetylcholine receptor (nAChR) subunits (alpha, beta, delta, gamma, and epsilon). We hypothesized that nerve injury induces altered gene expression of MRF's, nAChRs, and GAP-43 in the skeletal muscle which destabilize neuromuscular junctions. The tibial nerve was transected in 42 juvenile male Sprague-Dawley rats. Denervated and contralateral control gastrocnemius m. mRNA for nAChR subunits, MRF's, and GAP-43 were determined by real time reverse transcription polymerase chain reaction (real time RT-PCR). After transection, muscle mass decreased for 1 year with a nadir of 75% at 3 months. Alpha, gamma, and epsilon subunit genes increased by 3 and peaked at 7 days before returning to control levels (P < 0.05). Beta subunits and GAP-43 tended to increase. Delta subunits peaked at 3 days returning to control levels by 30 days. By one month, most of the nAChR subunits had returned to control levels. Alpha, beta, gamma, and delta subunit expression remained significantly lower than control up to 1 year later (P < 0.05). MRF4, Myogenin, and MyoD expression paralleled that of alpha, gamma, and epsilon nAChR subunits (P < 0.05). Gene expression of nAChR alpha, gamma, delta and epsilon subunits was biphasic in the first month after nerve injury, similar to that of MRF's. nAChR subunits and MRF's may play a critical role in neuromuscular junction stability.

Home overnight pulse oximetry in patients with COPD: more than one recording may be needed.

STUDY OBJECTIVES: Home overnight pulse oximetry (OPO) is used to assess nocturnal desaturation in patients with COPD, but the current practice of relying on one recording has not been studied. We assessed the variability of nocturnal desaturation in patients with COPD between nights, as measured by home OPO. DESIGN: Study subjects attended for clinical evaluation, spirometry, and arterial blood gas analysis. OPO was prospectively completed at home on 2 consecutive nights (study night 1 [N1] and study night 2 [N2]) and repeated at 3 weeks (study night 3 [N3]). SETTING: Respiratory Services, Green Lane Hospital, Auckland, New Zealand. PATIENTS: Twenty-six patients with clinically stable COPD (mean age, 69.3 years [SD, 6.9]; FEV(1), 28.6% predicted [SD, 10.6]; PO(2), 71.3 mm Hg [SD, 9.8]). Patients with asthma or clinical evidence of obstructive sleep apnea were excluded. MEASUREMENTS AND RESULTS: Mean nocturnal saturation (MNS) and time spent with saturation below 90% (TB90%) were calculated for N1, N2, and N3. Group mean recording length, MNS, and TB90% were similar for each night. Little variation in MNS was seen between nights (N1 and N2 mean difference, 1.31%; N2 and N3, 1.26%; N1 and N3, 1.25%). Larger variation was seen between nights for TB90% (N1 and N2 mean difference, 17.46%; N2 and N3, 9.95%; N1 and N3, 14.05%). No factors were identified that predicted increased variability of TB90%. Using the current definition of "significant nocturnal desaturation" (TB90% > or = 30% of the night), 9 of 26 patients (34.6%) changed category between "desaturator" and "nondesaturator" from N1 to N2. CONCLUSION: Nocturnal desaturation in patients with COPD exhibits considerable night-to-night variability when measured by home OPO. A single home OPO recording may be insufficient for accurate assessment of nocturnal desaturation.

Value of 3-D CT in classifying acetabular fractures during orthopedic residency training.

The complex anatomy of the pelvis and acetabulum have historically made classification and interpretation of acetabular fractures difficult for orthopedic trainees. The addition of 3-dimensional (3-D) computed tomography (CT) scan has gained popularity in preoperative planning, identification, and education of acetabular fractures given their complexity. Therefore, the authors examined the value of 3-D CT compared with conventional radiography in classifying acetabular fractures at different levels of orthopedic training. Their hypothesis was that 3-D CT would improve correct identification of acetabular fractures compared with conventional radiography.The classic Letournel fracture pattern classification system was presented in quiz format to 57 orthopedic residents and 20 fellowship-trained orthopedic traumatologists. A case consisted of (1) plain radiographs and 2-dimensional axial CT scans or (2) 3-D CT scans. All levels of training showed significant improvement in classifying acetabular fractures with 3-D vs 2-D CT, with the greatest benefit from 3-D CT found in junior residents (postgraduate years 1-3).Three-dimensional CT scans can be an effective educational tool for understanding the complex spatial anatomy of the pelvis, learning acetabular fracture patterns, and correctly applying a widely accepted fracture classification system.

Dose- and volume dependent-response to intramuscular injection of botulinum neurotoxin-A optimizes muscle force decrement in mice.

Botulinum neurotoxin-A (BoNTA) is a potent neurotoxin used to alter muscle tone to manage spasticity and to provide tendon bioprotection; however, the appropriate dose and injection volume to administer is not defined. Male mice (n = 120) received BoNTA injections into one gastrocnemius with either a constant volume (10 µl) with a variable dose (1, 3, 6 U/kg) or a constant dose (3 U/kg) in a variable volume (2.5, 5, 10, 20, 30 µl). Electromyographic (EMG) examination, muscle force generation (MFG), and wet muscle mass were measured in the ipsilateral and contralateral limbs at 1, 2, 4, or 12 weeks post-injection. MFG and EMG responses decreased to approximately 40% of contralateral after a 1 U/kg injection and 0% of contralateral by 3 and 6 U/kg injection at 1 week after injection. Neuromuscular blockade was greatest with a 10 µl injection volume. MFG, EMG examination, and wet muscle mass reached contralateral values 12 weeks after injection for all injection doses and volumes tested. Effective injection doses and volumes were identified for producing full and partial neuromuscular blockade in the mouse gastrocnemius. These findings have important clinical implications in the intramuscular administration of BoNTA to manage muscle tone.

The clinical utility of long-term humidification therapy in chronic airway disease.

AIM: Persistent airway inflammation with mucus retention in patients with chronic airway disorders such as COPD and bronchiectasis may lead to frequent exacerbations, reduced lung function and poor quality of life. This study investigates if long-term humidification therapy with high flow fully humidified air at 37 degrees C through nasal cannulae can improve these clinical outcomes in this group of patients. METHOD: 108 patients diagnosed with COPD or bronchiectasis were randomised to daily humidification therapy or usual care for 12 months over which exacerbations were recorded. Lung function, quality of life, exercise capacity, and measures of airway inflammation were also recorded at baseline, 3 and 12 months. RESULTS: Patients on long-term humidification therapy had significantly fewer exacerbation days (18.2 versus 33.5 days; p = 0.045), increased time to first exacerbation (median 52 versus 27 days; p = 0.0495) and reduced exacerbation frequency (2.97/patient/year versus 3.63/patient/year; p = 0.067) compared with usual care. Quality of life scores and lung function improved significantly with humidification therapy compared with usual care at 3 and 12 months. CONCLUSION: Long-term humidification therapy significantly reduced exacerbation days, increased time to first exacerbation, improved lung function and quality of life in patients with COPD and bronchiectasis. Clinical trial registered with www.actr.org.au; Number ACTRN2605000623695.

Partial cardiac denervation and sinus node modification for inappropriate sinus tachycardia.

We describe a case of inappropriate sinus tachycardia refractory to medical therapy and catheter sinus node ablation, which was successfully treated by surgery with approaches on both the sinus node and cardiac autonomic ganglia.