Prevalence, Diagnostic Utility and Associated Characteristics of Bronchodilator Responsiveness.

Rationale: The prevalence and diagnostic utility of bronchodilator responsiveness (BDR) in a real-life setting is unclear. Objective: To explore this uncertainty in patients aged ⩾12 years with physician-assigned diagnoses of asthma, asthma and chronic obstructive pulmonary disease (COPD), or COPD in NOVELTY, a prospective cohort study in primary and secondary care in 18 countries. Methods: The proportion of patients with a positive BDR test in each diagnostic category was calculated using 2005 (ΔFEV1 or ΔFVC ⩾12% and ⩾200 ml) and 2021 (ΔFEV1 or ΔFVC >10% predicted) European Respiratory Society/American Thoracic Society criteria. Measurements and Main Results: We studied 3,519 patients with a physician-assigned diagnosis of asthma, 833 with a diagnosis of asthma + COPD, and 2,436 with a diagnosis of COPD. The prevalence of BDR was 19.7% (asthma), 29.6% (asthma + COPD), and 24.7% (COPD) using 2005 criteria and 18.1%, 23.3%, and 18.0%, respectively, using 2021 criteria. Using 2021 criteria in patients diagnosed with asthma, BDR was associated with higher fractional exhaled nitric oxide; lower lung function; higher symptom burden; more frequent hospital admissions; and greater use of triple therapy, oral corticosteroids, or biologics. In patients diagnosed with COPD, BDR (2021) was associated with lower lung function and higher symptom burden. Conclusions: BDR prevalence in patients with chronic airway diseases receiving treatment ranges from 18% to 30%, being modestly lower with the 2021 than with the 2005 European Respiratory Society/American Thoracic Society criteria, and it is associated with lower lung function and greater symptom burden. These observations question the validity of BDR as a key diagnostic tool for asthma managed in clinical practice or as a standard inclusion criterion for clinical trials of asthma and instead suggest that BDR be considered a treatable trait for chronic airway disease.

A Bispecific Monoclonal Antibody Targeting Psl and PcrV Enhances Neutrophil-Mediated Killing of Pseudomonas aeruginosa in Patients with Bronchiectasis.

RATIONALE AND OBJECTIVES: Pseudomonas aeruginosa infection is associated with worse outcomes in bronchiectasis. Impaired neutrophil antimicrobial responses contribute to bacterial persistence. Gremubamab is a bivalent, bispecific monoclonal antibody targeting Psl exopolysaccharide and the type 3 secretion system component PcrV. This study evaluated the efficacy of gremubamab to enhance killing of P.aeruginosa by neutrophils from bronchiectasis patients and to prevent P.aeruginosa-associated cytotoxicity. METHODS: P.aeruginosa isolates from a global bronchiectasis cohort (n=100) underwent whole-genome sequencing to determine target prevalence. Functional activity of gremubamab against selected isolates was tested in-vitro and in-vivo. Patients with bronchiectasis (n=11) and controls (n=10) were enrolled and the effect of gremubamab in peripheral-blood neutrophil opsonophagocytic killing (OPK) assays against P.aeruginosa was evaluated. Serum antibody titers to Psl and PcrV were determined (n=30; 19: chronic P.aeruginosa infection, 11: no-known P.aeruginosa infection), as was the effect of gremubamab treatment in OPK and anti-cytotoxic activity assays. MEASUREMENTS AND RESULTS: Psl and PcrV were conserved in isolates from chronically-infected bronchiectasis patients. 73/100 isolates had a full psl locus and 99/100 contained the pcrV gene, with 20 distinct full-length PcrV protein subtypes identified. PcrV subtypes were successfully bound by gremubamab and the mAb mediated potent protective activity against tested isolates. Gremubamab increased bronchiectasis patient neutrophil-mediated OPK (+34.6±8.1%) and phagocytosis (+70.0±48.8%), similar to effects observed in neutrophils from controls (OPK:+30.1±7.6%). No evidence of competition between gremubamab and endogenous antibodies was found, with protection against P.aeruginosa-induced cytotoxicity and enhanced OPK demonstrated with and without addition of patient serum. CONCLUSION: Gremubamab enhanced bronchiectasis patient neutrophil phagocytosis and killing of P.aeruginosa and reduced virulence.

A Dual-Channel Deep Learning Approach for Lung Cavity Estimation From Hyperpolarized Gas and Proton MRI.

BACKGROUND: Hyperpolarized gas MRI can quantify regional lung ventilation via biomarkers, including the ventilation defect percentage (VDP). VDP is computed from segmentations derived from spatially co-registered functional hyperpolarized gas and structural proton (1 H)-MRI. Although acquired at similar lung inflation levels, they are frequently misaligned, requiring a lung cavity estimation (LCE). Recently, single-channel, mono-modal deep learning (DL)-based methods have shown promise for pulmonary image segmentation problems. Multichannel, multimodal approaches may outperform single-channel alternatives. PURPOSE: We hypothesized that a DL-based dual-channel approach, leveraging both 1 H-MRI and Xenon-129-MRI (129 Xe-MRI), can generate LCEs more accurately than single-channel alternatives. STUDY TYPE: Retrospective. POPULATION: A total of 480 corresponding 1 H-MRI and 129 Xe-MRI scans from 26 healthy participants (median age [range]: 11 [8-71]; 50% females) and 289 patients with pulmonary pathologies (median age [range]: 47 [6-83]; 51% females) were split into training (422 scans [88%]; 257 participants [82%]) and testing (58 scans [12%]; 58 participants [18%]) sets. FIELD STRENGTH/SEQUENCE: 1.5-T, three-dimensional (3D) spoiled gradient-recalled 1 H-MRI and 3D steady-state free-precession 129 Xe-MRI. ASSESSMENT: We developed a multimodal DL approach, integrating 129 Xe-MRI and 1 H-MRI, in a dual-channel convolutional neural network. We compared this approach to single-channel alternatives using manually edited LCEs as a benchmark. We further assessed a fully automatic DL-based framework to calculate VDPs and compared it to manually generated VDPs. STATISTICAL TESTS: Friedman tests with post hoc Bonferroni correction for multiple comparisons compared single-channel and dual-channel DL approaches using Dice similarity coefficient (DSC), average boundary Hausdorff distance (average HD), and relative error (XOR) metrics. Bland-Altman analysis and paired t-tests compared manual and DL-generated VDPs. A P value < 0.05 was considered statistically significant. RESULTS: The dual-channel approach significantly outperformed single-channel approaches, achieving a median (range) DSC, average HD, and XOR of 0.967 (0.867-0.978), 1.68 mm (37.0-0.778), and 0.066 (0.246-0.045), respectively. DL-generated VDPs were statistically indistinguishable from manually generated VDPs (P = 0.710). DATA CONCLUSION: Our dual-channel approach generated LCEs, which could be integrated with ventilated lung segmentations to produce biomarkers such as the VDP without manual intervention. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 1.

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies: incidence using different testing criteria, and case series.

OBJECTIVES: To estimate the incidence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies utilising different testing criteria, and review the clinical details of a series of patients with associated autoimmune myopathy. METHODS: The incidence of anti-HMGCR antibodies in 2019 from 3 groups, South West London, Berkshire/Surrey and Southampton, were compared in the adult population. Anti-HMGCR antibodies were measured by commercial chemiluminescent and immunodot assays. The case notes of patients with anti-HMGCR antibodies were reviewed for the case series. RESULTS: The estimated incidence of anti-HMGCR antibodies in the first 2 groups was 1.94 per million adults per year, and in the third group 10.3 per million adults per year. In the first 2 groups the test criteria restricted analysis to specific clinician request for anti-HMGCR. In the third group test criteria included cases with less specific clinical features or a cytoplasmic indirect immunofluorescence anti-nuclear antibody pattern. The latter strategy had a positive predictive value of 66.1% for anti-HMGCR associated myopathy. A case series of 27 patients with anti-HMGCR antibodies revealed 19 with myopathy, oesophageal involvement in 26% and median peak CK 8000 IU/L. Response to treatment, including intravenous immunoglobulin, was good with CK normalising after median 5.5 months. In 8 cases there was no evidence of autoimmune muscle disease, 7 not statin exposed. CONCLUSIONS: Varying criteria result in a 5-fold difference in estimated incidence of anti-HMGCR antibodies, revealing positive cases without evidence of myopathy. Patients with anti-HMGCR myopathy respond well to immune suppression, supporting wider testing for these antibodies amongst patients with myopathy.

Treatable traits in the NOVELTY study.

BACKGROUND AND OBJECTIVE: Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent and complex diseases that require personalized management. Although a strategy based on treatable traits (TTs) has been proposed, the prevalence and relationship of TTs to the diagnostic label and disease severity established by the attending physician in a real-world setting are unknown. We assessed how the presence/absence of specific TTs relate to the diagnosis and severity of 'asthma', 'COPD' or 'asthma + COPD'. METHODS: The authors selected 30 frequently occurring TTs from the NOVELTY study cohort (NOVEL observational longiTudinal studY; NCT02760329), a large (n = 11,226), global study that systematically collects data in a real-world setting, both in primary care clinics and specialized centres, for patients with 'asthma' (n = 5932, 52.8%), 'COPD' (n = 3898, 34.7%) or both ('asthma + COPD'; n = 1396, 12.4%). RESULTS: The results indicate that (1) the prevalence of the 30 TTs evaluated varied widely, with a mean ± SD of 4.6 ± 2.6, 5.4 ± 2.6 and 6.4 ± 2.8 TTs/patient in those with 'asthma', 'COPD' and 'asthma + COPD', respectively (p < 0.0001); (2) there were no large global geographical variations, but the prevalence of TTs was different in primary versus specialized clinics; (3) several TTs were specific to the diagnosis and severity of disease, but many were not; and (4) both the presence and absence of TTs formed a pattern that is recognized by clinicians to establish a diagnosis and grade its severity. CONCLUSION: These results provide the largest and most granular characterization of TTs in patients with airway diseases in a real-world setting to date.

Heterogeneity within and between physician-diagnosed asthma and/or COPD: NOVELTY cohort.

BACKGROUND: Studies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort. METHODS: Patients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis. RESULTS: Of 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1 s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12 months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses. CONCLUSION: This analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications.

Reducing emergency department presentations among chronically ill patients in Western Sydney: a key role for coordinated primary care.

Coordination of health services is thought to improve health outcomes for patients with chronic and complex illness; however, there is limited quantitative evidence for the effectiveness of coordinated care programs. HealthOne Mount Druitt (HOMD) is a coordinated care program operating in a disadvantaged area of Western Sydney, Australia. It operates as a combination 'virtual' and 'hub and spoke' model, with care coordination provided by liaison nurses. We aimed to determine whether there were changes in the number of emergency department (ED) presentations, length of stay, and community health referrals in the 12 months following enrolment in HOMD, compared to the 12 months prior. A quantitative survey was also conducted to determine the perspectives of service providers on key aspects of HOMD. Enrolment in HOMD was followed by reductions in both the number of ED presentations and the amount of time spent by patients in the ED. Community health referrals were increased, and the pattern of referral to different types of community health services was altered. This study provides quantitative evidence that a coordinated care intervention improves patient health outcomes.

Role of the GP liaison nurse in a community health program to improve integration and coordination of services for the chronically ill.

This paper explores the role of the General Practitioner Liaison Nurse (GPLN) in improving integration and coordination of services within Primary Health Care. This position can play a major role in care coordination and cultural change. The GPLN within HealthOne Mt Druitt (HOMD) identifies patients' needs and facilitates communication, case conferencing and care coordination between health and other providers. The priority areas of children and their families at risk or with significant unmet needs, and chronic aged and complex care, were identified as target areas. This paper focuses on the GPLN within the chronic aged and complex care service model. The GPLN within HOMD was able to improve coordination and integration of services for patients of the facility. Activities included organising multidisciplinary services and addressing psychosocial issues. Patients and community health staff identified the importance of the role for improving coordination and integration of services. Decision and policy makers saw the position as vital to the implementation, operation and sustainability of HOMD.

The many faces of COPD in real life: a longitudinal analysis of the NOVELTY cohort.

Background: The diagnosis of COPD requires the demonstration of non-fully reversible airflow limitation by spirometry in the appropriate clinical context. Yet, there are patients with symptoms and relevant exposures suggestive of COPD with either normal spirometry (pre-COPD) or preserved ratio but impaired spirometry (PRISm). Their prevalence, clinical characteristics and associated outcomes in a real-life setting are unclear. Methods: To investigate them, we studied 3183 patients diagnosed with COPD by their attending physician included in the NOVELTY study (clinicaltrials.gov identifier NCT02760329), a global, 3-year, observational, real-life cohort that included patients recruited from both primary and specialist care clinics in 18 countries. Results: We found that 1) approximately a quarter of patients diagnosed with (and treated for) COPD in real life did not fulfil the spirometric diagnostic criteria recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), and could be instead categorised as pre-COPD (13%) or PRISm (14%); 2) disease burden (symptoms and exacerbations) was highest in GOLD 3-4 patients (exacerbations per person-year (PPY) 0.82) and lower but similar in those in GOLD 1-2, pre-COPD and PRISm (exacerbations range 0.27-0.43 PPY); 3) lung function decline was highest in pre-COPD and GOLD 1-2, and much less pronounced in PRISm and GOLD 3-4; 4) PRISm and pre-COPD were not stable diagnostic categories and change substantially over time; and 5) all-cause mortality was highest in GOLD 3-4, lowest in pre-COPD, and intermediate and similar in GOLD 1-2 and PRISm. Conclusions: Patients diagnosed COPD in a real-life clinical setting present great diversity in symptom burden, progression and survival, warranting medical attention.

Relationships between symptoms and lung function in asthma and/or chronic obstructive pulmonary disease in a real-life setting: the NOVEL observational longiTudinal studY.

BACKGROUND: The relationships between spirometric assessment of lung function and symptoms (including exacerbations) in patients with asthma and/or chronic obstructive pulmonary disease (COPD) in a real-life setting are uncertain. OBJECTIVES: To assess the relationships between baseline post-bronchodilator (post-BD) spirometry measures of lung function and symptoms and exacerbations in patients with a physician-assigned diagnosis of asthma and/or COPD. DESIGN: The NOVEL observational longiTudinal studY (NOVELTY) is a global, prospective, 3-year observational study. METHODS: Logistic regression analysis was used to evaluate relationships. Spirometry measures were assessed as percent predicted (%pred). Symptoms were assessed at baseline, and exacerbations were assessed at baseline and Year 1. RESULTS: A total of 11,181 patients in NOVELTY had spirometry data (asthma, n = 5903; COPD, n = 3881; asthma + COPD, n = 1397). A 10% lower post-BD %pred forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) - adjusted for age and sex - were significantly associated with dyspnea (modified Medical Research Council ⩾ grade 2), frequent breathlessness [St George's Respiratory Questionnaire (SGRQ)], frequent wheeze attacks (SGRQ), nocturnal awakening (Respiratory Symptoms Questionnaire; ⩾1 night/week), and frequent productive cough (SGRQ). Lower post-BD %pred FEV1 and, to a lesser extent, lower post-BD %pred FVC were significantly associated with ⩾1 physician-reported exacerbation at baseline or Year 1. This association was stronger in patients with COPD than in those with asthma. CONCLUSION: In a real-life setting, reduced lung function is consistently associated with symptoms in patients with asthma, COPD, or asthma + COPD. The relationship with exacerbations is stronger in COPD only than in asthma. TRAIL REGISTRATION: clinicaltrials.gov identifier: NCT02760329 (www.clinicaltrials.gov).

Relationships between symptoms and lung function in asthma and/or chronic obstructive pulmonary disease in a study performed in a real-life setting: the NOVELTY studyBackground: Asthma and chronic obstructive pulmonary disease (COPD) have many symptoms in common. To confirm diagnosis, doctors use spirometry, a test to measure the amount of air that can be breathed out from the lungs and how fast it can be blown out. The relationship between these measurements and symptoms in asthma and COPD is not well understood.Objectives: The aim of this research is to describe the characteristics, treatment, and impact of asthma and/or COPD in patients who are receiving their usual medical care.Methods: NOVELTY is a large study of around 12,000 patients across 19 countries. This analysis of NOVELTY looked at the relationships between two spirometry measurements and the symptoms of asthma and/or COPD experienced by patients. The spirometry measurements were: - forced expiratory volume in 1 second (FEV₁) ­ the amount of air that can be blown out of the lungs in 1 second- forced vital capacity (FVC) ­ the amount of air that can be forcibly breathed out from the lungs after taking the deepest breath possibleResults: The lower the FEV₁ and FVC, the more common the symptoms of breathlessness, wheeze attacks, night-time awakening, and coughing up of phlegm or mucus. These relationships were similar for FEV₁ and FVC. Lower FEV₁ was more strongly associated with worse symptoms in COPD than in asthma.Conclusion: These findings help to improve our understanding of the relationships between spirometry measures and symptoms in patients with asthma and/or COPD.

Functional imaging in asthma and COPD: design of the NOVELTY ADPro substudy.

The NOVEL observational longiTudinal studY (NOVELTY; ClinicalTrials.gov identifier NCT02760329) is a global, prospective, observational study of ∼12 000 patients with a diagnosis of asthma and/or COPD. Here, we describe the design of the Advanced Diagnostic Profiling (ADPro) substudy of NOVELTY being conducted in a subset of ∼180 patients recruited from two primary care sites in York, UK. ADPro is employing a combination of novel functional imaging and physiological and metabolic modalities to explore structural and functional changes in the lungs, and their association with different phenotypes and endotypes. Patients participating in the ADPro substudy will attend two visits at the University of Sheffield, UK, 12±2 months apart, at which they will undergo imaging and physiological lung function testing. The primary end-points are the distributions of whole lung functional and morphological measurements assessed with xenon-129 magnetic resonance imaging, including ventilation, gas transfer and airway microstructural indices. Physiological assessments of pulmonary function include spirometry, bronchodilator reversibility, static lung volumes via body plethysmography, transfer factor of the lung for carbon monoxide, multiple-breath nitrogen washout and airway oscillometry. Fractional exhaled nitric oxide will be measured as a marker of type-2 airways inflammation. Regional and global assessment of lung function using these techniques will enable more precise phenotyping of patients with physician-assigned asthma and/or COPD. These techniques will be assessed for their sensitivity to markers of early disease progression.

PhysVENeT: a physiologically-informed deep learning-based framework for the synthesis of 3D hyperpolarized gas MRI ventilation.

Functional lung imaging modalities such as hyperpolarized gas MRI ventilation enable visualization and quantification of regional lung ventilation; however, these techniques require specialized equipment and exogenous contrast, limiting clinical adoption. Physiologically-informed techniques to map proton (1H)-MRI ventilation have been proposed. These approaches have demonstrated moderate correlation with hyperpolarized gas MRI. Recently, deep learning (DL) has been used for image synthesis applications, including functional lung image synthesis. Here, we propose a 3D multi-channel convolutional neural network that employs physiologically-informed ventilation mapping and multi-inflation structural 1H-MRI to synthesize 3D ventilation surrogates (PhysVENeT). The dataset comprised paired inspiratory and expiratory 1H-MRI scans and corresponding hyperpolarized gas MRI scans from 170 participants with various pulmonary pathologies. We performed fivefold cross-validation on 150 of these participants and used 20 participants with a previously unseen pathology (post COVID-19) for external validation. Synthetic ventilation surrogates were evaluated using voxel-wise correlation and structural similarity metrics; the proposed PhysVENeT framework significantly outperformed conventional 1H-MRI ventilation mapping and other DL approaches which did not utilize structural imaging and ventilation mapping. PhysVENeT can accurately reflect ventilation defects and exhibits minimal overfitting on external validation data compared to DL approaches that do not integrate physiologically-informed mapping.

Cluster Analyses From the Real-World NOVELTY Study: Six Clusters Across the Asthma-COPD Spectrum.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are complex diseases, the definitions of which overlap. OBJECTIVE: To investigate clustering of clinical/physiological features and readily available biomarkers in patients with physician-assigned diagnoses of asthma and/or COPD in the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329). METHODS: Two approaches were taken to variable selection using baseline data: approach A was data-driven, hypothesis-free and used the Pearson dissimilarity matrix; approach B used an unsupervised Random Forest guided by clinical input. Cluster analyses were conducted across 100 random resamples using partitioning around medoids, followed by consensus clustering. RESULTS: Approach A included 3796 individuals (mean age, 59.5 years; 54% female); approach B included 2934 patients (mean age, 60.7 years; 53% female). Each identified 6 mathematically stable clusters, which had overlapping characteristics. Overall, 67% to 75% of patients with asthma were in 3 clusters, and approximately 90% of patients with COPD were in 3 clusters. Although traditional features such as allergies and current/ex-smoking (respectively) were higher in these clusters, there were differences between clusters and approaches in features such as sex, ethnicity, breathlessness, frequent productive cough, and blood cell counts. The strongest predictors of the approach A cluster membership were age, weight, childhood onset, prebronchodilator FEV1, duration of dust/fume exposure, and number of daily medications. CONCLUSIONS: Cluster analyses in patients from NOVELTY with asthma and/or COPD yielded identifiable clusters, with several discriminatory features that differed from conventional diagnostic characteristics. The overlap between clusters suggests that they do not reflect discrete underlying mechanisms and points to the need for identification of molecular endotypes and potential treatment targets across asthma and/or COPD.

Frequent productive cough: Symptom burden and future exacerbation risk among patients with asthma and/or COPD in the NOVELTY study.

INTRODUCTION: Persistent cough with sputum production is an important clinical trait in chronic obstructive pulmonary disease (COPD). We defined "frequent productive cough" based on 2 questions from the St George's Respiratory Questionnaire (SGRQ) and sought to determine its occurrence and associated outcomes in patients with physician-assigned asthma and/or COPD from the NOVELTY study. METHODS: Frequent productive cough was defined as cough and sputum production most or several days/week for the past 3 months (scoring ≥3 for both SGRQ questions). Relationships with baseline disease characteristics and exacerbations over 12 months' follow-up were examined using logistic regression. RESULTS: Baseline SGRQ data were available for 7125 patients, of whom 31.3% had frequent productive cough. It was more common in asthma+COPD (38.8%) and COPD (38.1%) than asthma (25.0%), increasing with physician-assessed severity, and in current versus former and never smokers. Patient-reported symptomatic worsening was more common in patients with versus without frequent productive cough. Reduced post-bronchodilator FEV1 (odds ratio [OR] per 10% decrement 1.14 [95% confidence interval 1.11-1.16]) and history of pollutant exposure at home/work (OR 1.50 [1.33-1.69]) were associated with frequent productive cough in all diagnoses. Patients with baseline frequent productive cough were more likely to have ≥1 exacerbation over the subsequent 12 months (OR 1.71 [1.52-1.93]), including exacerbations requiring hospital admission and those treated with oral corticosteroids. CONCLUSIONS: Frequent productive cough represents an important indicator of adverse clinical outcomes across asthma and/or COPD. Research into the underlying pathologic mechanisms is required to support targeted therapy development. CLINICALTRIALS: GOV: NCT02760329.

The burden of mild asthma: Clinical burden and healthcare resource utilisation in the NOVELTY study.

BACKGROUND: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma. METHODS: Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits. RESULTS: Overall, 2004 patients with mild asthma were included; 22.8% experienced ≥1 exacerbation in the previous 12 months, of whom 72.3% experienced ≥1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation ± 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score <20), increasing to 55.6% for those with ≥2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring ≥1 emergency department visit and 1.1% requiring ≥1 hospital admission. CONCLUSIONS: In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU.

Forensic photo-documentation in adult sexual assault- what do patients think?

Historically, some forensic practitioners and policy makers have viewed the use of photography in forensic documentation for adult victims of sexual assault as controversial. Some argue that diagrams and verbal descriptions of injury are sufficient, suggesting that sexual assault victims are so traumatised at time of examination that they are not able to provide valid consent, that the imaging process itself is humiliating, and that any decision to have photographs taken might be later regretted. Objectively, a patient capable of consenting to a forensic examination has an equal capacity to consent for forensic imaging, even when this involves sensitive areas of the body, and the process of forensic photography is not inherently problematic. Literature on forensic photography is sparse, particularly from the patient perspective. Our Forensic Medical Unit is in an excellent position to investigate this issue, as it is one of the few services in Australia that routinely offers sexual assault forensic photography, including genital, as part of its standard procedures for injury documentation. Photographs, in adult sexual assault cases, are not routinely taken of normal anatomy nor are they ever taken without patient consent. This study explores the immediate and short-term experiential impacts of forensic photography from the victims' perspective. Capacity to consent was assessed using a trauma informed, evidence-based interviewing tool at the start of their forensic assessment. Participants also completed questionnaires at the conclusion of their examination and on follow-up. Results show that victims not only have the capacity to provide informed consent but also found forensic photography, and the reasons for it, quite acceptable. A majority [80%; n = 87/108] indicated the photographic process had either been not at all or only a little embarrassing. When asked how they felt about having photographs taken, the majority 93.4% [n = 99/106) indicated that as well as having no regrets they were also happy with the way the images had been taken. 4.7% [n = 5] expressed some doubt about whether they had made the right decision. A similar pattern of responses was observed at follow-up which occurred, on average, seven weeks post examination. 72% [n = 26/36] said they did not think about the photographs at all or did so rarely. While 14% [n = 5/36] said they thought about them a fair bit or a lot of the time, most stated they had no concerns regarding the images that had been taken. Given its evidentiary salience and other benefits, such as its potential to promote greater transparency in the provision of forensic opinions and its usefulness in teaching, this study supports the case for the routine use of forensic photography in adult Sexual Assault Units more broadly.

Preparing semen slides in cases of sexual assault: Do they who smear first smear best?

When providing a forensic assessment for a victim of sexual assault, a smear is made from any swab that has been collected with the purpose of finding sperm. A smear is made to assist the laboratory identify the optimal swab for DNA testing, to aid in the selection of downstream DNA testing options, to evaluate morphology and quantity of sperm in order to provide time since intercourse assessments, and to contribute additional information to the crime scene case when trying to determine how an offender's DNA came to be at the site where it was located. In the majority of Australian states, the forensic examiner makes the smear at the time of the forensic assessment (forensic history, examination, collection of specimens, documentation of injury and prophylactic treatment for sexually transmitted infections and pregnancy). The smear could be made, however, at a later time by forensic laboratory staff. There are some jurisdictions (for example in Queensland, Australia) where this is the preferred process. This research paper compared smear preparation by the forensic examiner with that prepared, at a later time, by the laboratory scientist. 143 pairs of high vaginal smears were analysed over a two and a half year period. Smears made by the examiner contained, for the most part, higher numbers of sperm, more background material and more intact sperm than smears made at a later date by laboratory scientific staff.

The Checkpoint Program: Collaborative Care to Reduce the Reliance of Frequent Presenters on ED.

INTRODUCTION: Growing pressures upon Emergency Departments [ED] call for new ways of working with frequent presenters who, although small in number, place extensive demands on services, to say nothing of the costs and consequences for the patients themselves. EDs are often poorly equipped to address the multi-dimensional nature of patient need and the complex circumstances surrounding repeated presentation. Employing a model of intensive short-term community-based case management, the Checkpoint program sought to improve care coordination for this patient group, thereby reducing their reliance on ED. METHOD: This study employed a single group interrupted time series design, evaluating patient engagement with the program and year-on-year individual differences in the number of ED visits pre and post enrolment. Associated savings were also estimated. RESULTS: Prior to intervention, there were two dominant modes in the ED presentation trends of patients. One group had a steady pattern with ≥7 presentations in each of the last four years. The other group had an increasing trend in presentations, peaking in the 12 months immediately preceding enrolment. Following the intervention, both groups demonstrated two consecutive year-on-year reductions. By the second year, and from an overall peak of 22.5 presentations per patient per annum, there was a 53% reduction in presentations. This yielded approximate savings of $7100 per patient. DISCUSSION: Efforts to improve care coordination, when combined with proactive case management in the community, can impact positively on ED re-presentation rates, provided they are concerted, sufficiently intensive and embed the principles of integration. CONCLUSION: The Checkpoint program demonstrated sufficient promise to warrant further exploration of its sustainability. However, health services have yet to determine the ideal organisational structures and funding arrangements to support such initiatives.

Validation of a diagnosis-agnostic symptom questionnaire for asthma and/or COPD.

Background: The Respiratory Symptoms Questionnaire (RSQ) is a novel, four-item patient-reported diagnosis-agnostic tool designed to assess the frequency of respiratory symptoms and their impact on activity, without specifying a particular diagnosis. Our objective was to examine its validity in patients with asthma and/or chronic obstructive pulmonary disease (COPD). Methods: Baseline data were randomly sampled from patients who completed the RSQ in the NOVELTY study (ClinicalTrials.gov: NCT02760329). The total sample (n=1530) comprised three randomly selected samples (n=510 each) from each physician-assigned diagnostic group (asthma, asthma+COPD and COPD). The internal consistency and structural validity of the RSQ were evaluated using exploratory and confirmatory factor analyses; psychometric performance was observed using Classical Test Theory and Item Response Theory analyses. Results: For the total sample, the mean±sd RSQ score was 5.6±4.3 (range 0-16). Irrespective of diagnosis, the internal consistency of items was uniformly adequate (Cronbach's α=0.76-0.80). All items had high factor loadings and structural characteristics of the measure were invariant across groups. Using the total sample, RSQ items informatively covered the θ score range of -2.0 to 2.8, with discrimination coefficients for individual items being high to very high (1.7-2.6). Strong convergent correlations were observed between the RSQ and the St George's Respiratory Questionnaire (0.77, p<0.001). Conclusions: The RSQ is a valid, brief, patient-reported tool for assessing respiratory symptoms in patients across the whole spectrum of asthma and/or COPD, rather than using different questionnaires for each diagnosis. It can be used for monitoring respiratory symptoms in clinical practice, clinical trials and real-world studies.

An unusual case of steroid responsive idiopathic ectopic calcification.

This case explores an unusual calcified lesion of the hand and its dramatic response to steroids. A 30-year-old lady presented to rheumatology with a 1-year history of swelling on the radial side of her right middle metacarpophalangeal joint. Over a 2-week period, she had developed swelling throughout her right hand. She was treated with intramuscular methylprednisolone injection and a weaning course of prednisolone. A series of photos and X-rays demonstrates the resolution of swelling and calcification after steroid treatment. This case reports a chronic calcified mass associated with an acute inflammatory episode in the hand. This is likely to represent rupture of a calcific deposit with the release of crystals into the soft tissue. While there is prior literature on treatment with bisphosphonates or surgery, a fast and complete response to modest dose steroids suggests that this would be the first treatment to try in such a case.