The interrelationship between multiple long-term conditions (MLTC) and delirium: a scoping review.

INTRODUCTION: Delirium and multiple long-term conditions (MLTC) share numerous risk factors and have been shown individually to be associated with adverse outcomes following hospitalisation. However, the extent to which these common ageing syndromes have been studied together is unknown. This scoping review aims to summarise our knowledge to date on the interrelationship between MLTC and delirium. METHODS: Searches including terms for delirium and MLTC in adult human participants were performed in PubMed, EMBASE, Medline, Psycinfo and CINAHL. Descriptive analysis was used to summarise findings, structured according to Synthesis Without Meta-analysis reporting guidelines. RESULTS: After removing duplicates, 5256 abstracts were screened for eligibility, with 313 full-texts sought along with 17 additional full-texts from references in review articles. In total, 140 met inclusion criteria and were included in the final review. Much of the literature explored MLTC as a risk factor for delirium (n = 125). Fewer studies explored the impact of MLTC on delirium presentation (n = 5), duration (n = 3) or outcomes (n = 6) and no studies explored how MLTC impacts the treatment of delirium or whether having delirium increases risk of developing MLTC. The most frequently used measures of MLTC and delirium were the Charlson Comorbidity Index (n = 98/140) and Confusion Assessment Method (n = 81/140), respectively. CONCLUSION: Existing literature largely evaluates MLTC as a risk factor for delirium. Major knowledge gaps identified include the impact of MLTC on delirium treatment and the effect of delirium on MLTC trajectories. Current research in this field is limited by significant heterogeneity in defining both MLTC and delirium.

Chest x-ray has low sensitivity to detect silicosis in artificial stone benchtop industry workers.

BACKGROUND AND OBJECTIVE: Chest x-ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. METHODS: Paired CXR and high-resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. RESULTS: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29-68) and specificity 97% (90-100). CONCLUSION: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry.

Deep Learning-based Outcome Prediction in Progressive Fibrotic Lung Disease Using High-Resolution Computed Tomography.

Rationale: Reliable outcome prediction in patients with fibrotic lung disease using baseline high-resolution computed tomography (HRCT) data remains challenging. Objectives: To evaluate the prognostic accuracy of a deep learning algorithm (SOFIA [Systematic Objective Fibrotic Imaging Analysis Algorithm]), trained and validated in the identification of usual interstitial pneumonia (UIP)-like features on HRCT (UIP probability), in a large cohort of well-characterized patients with progressive fibrotic lung disease drawn from a national registry. Methods: SOFIA and radiologist UIP probabilities were converted to Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED)-based UIP probability categories (UIP not included in the differential, 0-4%; low probability of UIP, 5-29%; intermediate probability of UIP, 30-69%; high probability of UIP, 70-94%; and pathognomonic for UIP, 95-100%), and their prognostic utility was assessed using Cox proportional hazards modeling. Measurements and Main Results: In multivariable analysis adjusting for age, sex, guideline-based radiologic diagnosis, anddisease severity (using total interstitial lung disease [ILD] extent on HRCT, percent predicted FVC, DlCO, or the composite physiologic index), only SOFIA UIP probability PIOPED categories predicted survival. SOFIA-PIOPED UIP probability categories remained prognostically significant in patients considered indeterminate (n = 83) by expert radiologist consensus (hazard ratio, 1.73; P < 0.0001; 95% confidence interval, 1.40-2.14). In patients undergoing surgical lung biopsy (n = 86), after adjusting for guideline-based histologic pattern and total ILD extent on HRCT, only SOFIA-PIOPED probabilities were predictive of mortality (hazard ratio, 1.75; P < 0.0001; 95% confidence interval, 1.37-2.25). Conclusions: Deep learning-based UIP probability on HRCT provides enhanced outcome prediction in patients with progressive fibrotic lung disease when compared with expert radiologist evaluation or guideline-based histologic pattern. In principle, this tool may be useful in multidisciplinary characterization of fibrotic lung disease. The utility of this technology as a decision support system when ILD expertise is unavailable requires further investigation.

Online education for safer opioid prescribing in hospitals-lessons learnt from the Opioid Use Change (OUCh) project.

BACKGROUND: Opioids are often required for acute inpatient pain relief but lack of knowledge about common and less common long-term side effects can lead to inappropriate discharge prescribing. There are few validated educational tools available for junior prescribers on hospital wards. Education around opioid prescribing and deprescribing remains limited in the undergraduate curriculum and yet almost all controlled drug prescribing in hospitals is done by junior doctors. METHODS: A 5-minute video was developed with iterative feedback from medical students, junior prescribers, pain specialists, primary care educational leads, and a patient who had developed opioid addiction after hospital prescribing. It explained the need for clear stop dates on discharge summaries and the range of opioid side effects. It also highlighted the hospital admission as an opportunity to reduce inappropriate high-dose opioids. A short knowledge-based quiz before and after viewing the video was used to evaluate the impact on and change in knowledge and confidence around opioid prescribing. This tool was designed to be used entirely online to allow delivery within existing mandatory training. RESULTS: Feedback was positive and showed that knowledge of side effects significantly increased but also contacts with ward pharmacists and the acute pain team increased. Junior doctors highlighted that the undergraduate curriculum did little to prepare them for prescription addiction and that pharmacy and senior support was needed to support any changes in longer-term, high-dose opioids. CONCLUSIONS: This short educational video improved knowledge of safe opioid prescribing and could be incorporated within wider opioid education in UK healthcare.

A 4-tier Protocolized Radiological Classification System for Leaks Following Sleeve Gastrectomy.

OBJECTIVES: To develop and validate a classification of sleeve gastrectomy leaks able to reliably predict outcomes, from protocolized computed tomography (CT) findings and readily available variables. SUMMARY OF BACKGROUND DATA: Leaks post sleeve gastrectomy remain morbid and resource-consuming. Incidence, treatments, and outcomes are variable, representing heterogeneity of the problem. A predictive tool available at presentation would aid management and predict outcomes. METHODS: From a prospective database (2009-2018) we reviewed patients with staple line leaks. A Delphi process was undertaken on candidate variables (80-20). Correlations were performed to stratify 4 groupings based on outcomes (salvage resection, length of stay, and complications) and predictor variables. Training and validation cohorts were established by block randomization. RESULTS: A 4-tiered classification was developed based on CT appearance and duration postsurgery. Interobserver agreement was high (κ = 0.85, P < 0.001). There were 59 patients, (training: 30, validation: 29). Age 42.5 ± 10.8 versus 38.9 ± 10.0 years (P = 0.187); female 65.5% versus 80.0% (P = 0.211), weight 127.4 ± 31.3 versus 141.0 ± 47.9 kg, (P = 0.203). In the training group, there was a trend toward longer hospital stays as grading increased (I = 10.5 d; II = 24 d; III = 66.5 d; IV = 72 d; P = 0.005). Risk of salvage resection increased (risk ratio grade 4 = 9; P = 0.043) as did complication severity (P = 0.027).Findings were reproduced in the validation group: risk of salvage resection (P = 0.007), hospital stay (P = 0.001), complications (P = 0.016). CONCLUSION: We have developed and validated a classification system, based on protocolized CT imaging that predicts a step-wise increased risk of salvage resection, complication severity, and increased hospital stay. The system should aid patient management and facilitate comparisons of outcomes and efficacy of interventions.

Biomarker signatures for progressive idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers have the potential for guiding management in clinical practice. We assessed the prognostic role of serum biomarkers in three independent IPF cohorts: Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE). METHODS: In the AIPFR cohort, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. LASSO (least absolute shrinkage and selection operator) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at 1 year in the AIPFR cohort, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in the PROFILE cohort. Four significantly replicating biomarkers were aggregated into a progression index model based on tertiles of circulating concentrations. RESULTS: 189 participants were included in the AIPFR cohort, 205 participants from the TLF cohort and 122 participants from the PROFILE cohort. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at 1 year. Proteomic data did not replicate. The progression index in the AIPFR, TLF and PROFILE cohorts predicted risk of progression, mortality and progression-free survival. A statistical model incorporating the progression index demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP (gender, age and physiology) score model alone in all cohorts, and significantly so within the incidence-based TLF and PROFILE cohorts. CONCLUSION: A panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.

Quantitative computed tomography predicts outcomes in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Prediction of disease course in patients with progressive pulmonary fibrosis remains challenging. The purpose of this study was to assess the prognostic value of lung fibrosis extent quantified at computed tomography (CT) using data-driven texture analysis (DTA) in a large cohort of well-characterized patients with idiopathic pulmonary fibrosis (IPF) enrolled in a national registry. METHODS: This retrospective analysis included participants in the Australian IPF Registry with available CT between 2007 and 2016. CT scans were analysed using the DTA method to quantify the extent of lung fibrosis. Demographics, longitudinal pulmonary function and quantitative CT metrics were compared using descriptive statistics. Linear mixed models, and Cox analyses adjusted for age, gender, BMI, smoking history and treatment with anti-fibrotics were performed to assess the relationships between baseline DTA, pulmonary function metrics and outcomes. RESULTS: CT scans of 393 participants were analysed, 221 of which had available pulmonary function testing obtained within 90 days of CT. Linear mixed-effect modelling showed that baseline DTA score was significantly associated with annual rate of decline in forced vital capacity and diffusing capacity of carbon monoxide. In multivariable Cox proportional hazard models, greater extent of lung fibrosis was associated with poorer transplant-free survival (hazard ratio [HR] 1.20, p < 0.0001) and progression-free survival (HR 1.14, p < 0.0001). CONCLUSION: In a multi-centre observational registry of patients with IPF, the extent of fibrotic abnormality on baseline CT quantified using DTA is associated with outcomes independent of pulmonary function.

Cytomegalovirus infection reduced CD70 expression, signaling and expansion of viral specific memory CD8+ T cells in healthy human adults.

BACKGROUND: Cytomegalovirus (CMV) infection leads to effector memory CD8+ T cell expansion and is associated with immune dysfunction in older adults. However, the molecular alterations of CMV-specific CD8+ T cells in CMV infected healthy young and middle-aged adults has not been fully characterized. RESULTS: We compared CD8+ T cells specific for a CMV epitope (pp65495-503, NLV) and an influenza A virus (IAV) epitope (M158-66, GIL) from the same young and middle-aged healthy adults with serum positive for anti-CMV IgG. Compared to the IAV-specific CD8+ T cells, CMV-specific CD8+ T cells contained more differentiated effector memory (TEM and TEMRA) cells. Isolated CMV-specific central memory (TCM) but not naïve (TN) cells had a significant reduced activation-induced expansion in vitro compared to their IAV-specific counterparts. Furthermore, we found that CD70 expression was reduced in CMV-specific CD28+CD8+ TCM and that CD70+ TCM had better expansion in vitro than did CD70- TCM. Mechanistically, we showed that CD70 directly enhanced MAPK phosphorylation and CMV-specific CD8+ TCM cells had a reduced MAPK signaling upon activation. Lastly, we showed that age did not exacerbate reduced CD70 expression in CMV- specific CD8+ TCM cells. CONCLUSION: Our findings showed that CMV infection causes mild expansion of CMV-NLV-specific CD8+ T cells, reduced CD70 expression and signaling, and proliferation of CMV-NLV-specific CD8+ TCM cells in young and middle-aged healthy adults and revealed an age-independent and CMV infection-specific impact on CD8+ memory T cells.

Dermatologic toxicities to immune checkpoint inhibitor therapy: A review of histopathologic features.

Antineoplastic agents that use the immune system have revolutionized cancer treatment. Specifically, implementation of immune checkpoint inhibitors, monoclonal antibodies that block cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein 1, or programmed cell death ligand 1 show improved and sustained responses in patients with cancer. However, these agents are associated with a plethora of adverse events, many manifesting in the skin. As the clinical application of cancer immunotherapies expands, understanding the clinical and histopathologic features of associated cutaneous toxicities becomes increasingly important to dermatologists, oncologists, and pathologists to ensure timely diagnosis and appropriate care. This review discusses cutaneous reactions to immune checkpoint inhibitors, focusing on histopathologic features.

Recombinant Infectious Bronchitis Viruses Expressing Chimeric Spike Glycoproteins Induce Partial Protective Immunity against Homologous Challenge despite Limited Replication In Vivo.

Vaccination regimes against Infectious bronchitis virus (IBV), which are based on a single virus serotype, often induce insufficient levels of cross-protection against serotypes and two or more antigenically diverse vaccines are used in attempt to provide broader protection. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, are associated with poor cross-protection. Here, homologous vaccination trials with recombinant IBVs (rIBVs), based on the apathogenic strain, BeauR, were conducted to elucidate the role of S1 in protection. A single vaccination of specific-pathogen-free chickens with rIBV expressing S1 of virulent strains M41 or QX, BeauR-M41(S1) and BeauR-QX(S1), gave incomplete protection against homologous challenge, based on ciliary activity and clinical signs. There could be conformational issues with the spike if heterologous S1 and S2 are linked, suggesting a homologous S2 might be essential. To address this, a homologous vaccination-challenge trial incorporating rIBVs expressing full spike from M41, BeauR-M41(S), and S2 subunit from M41, BeauR-M41(S2) was conducted. All chimeric viruses grew to similar titers in vitro, induced virus-specific partial protective immunity, evident by cellular infiltrations, reductions in viral RNA load in the trachea and conjunctiva and higher serum anti-IBV titers. Collectively, these findings show that vaccination with rIBVs primed the birds for challenge but the viruses were cleared rapidly from the mucosal tissues in the head. Chimeric S1 and S2 viruses did not protect as effectively as BeauR-M41(S) based on ciliary activity and clinical signs. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection.IMPORTANCE Infectious bronchitis virus causes an acute, highly contagious respiratory disease, responsible for significant economic losses to the poultry industry. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, have been associated with poor cross-protection. Available vaccines give poor cross-protection and rationally designed live attenuated vaccines, based on apathogenic BeauR, could address these. Here, to determine the role of S1 in protection, a series of homologous vaccination trials with rIBVs were conducted. Single vaccinations with chimeric rIBVs induced virus-specific partial protective immunity, characterized by reduction in viral load and serum antibody titers. However, BeauR-M41(S) was the only vaccination to improve the level of protection against clinical signs and the loss of tracheal ciliary activity. Growth characteristics show that all of the rIBVs replicated in vitro to similar levels. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection.

Eligibility for anti-fibrotic treatment in idiopathic pulmonary fibrosis depends on the predictive equation used for pulmonary function testing.

BACKGROUND AND OBJECTIVE: Publicly funded therapy for idiopathic pulmonary fibrosis (IPF) relies on percentage predicted values from pulmonary function testing, for example Australian patients must have a forced vital capacity ≥50% (%FVC), transfer factor of the lung for carbon monoxide ≥ 30% (%TLco) and forced expiratory volume in 1 s (FEV1 )/FVC ratio > 0.7. Despite defined cut-off values, no jurisdiction prescribes a reference equation for use; multiple equations exist. We hypothesized that access to subsidized treatment varies depending on the chosen equation. The %FVC and %TLco from different commonly used reference equations across general respiratory patients, and IPF-specific patients, were compared. METHODS: FVC and TLco measurements from a large general respiratory laboratory and the Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR) database were analysed using multiple equations. Differences between %FVC and %TLco for each equation were calculated, with particular interest in classification of patients (%) at the threshold for subsidized treatment. RESULTS: A total of 20 378 general respiratory database results were analysed. The %FVC ≥ 50% increased from 86% with the Roca equation to 96% with Quanjer (European Coal and Steal Community, ECSC) and %TLco≥30% increased from 91% with Paoletti to 98% with Thompson. However, overall increase in eligibility for subsidized treatment was modest, varying from 48.2% to 49.2%. A total of 545 AIPFR database results were analysed. The %FVC ≥ 50% increased from 73% with Roca to 94% with Quanjer (ECSC) and %TLco≥30% increased from 87% with Paoletti to 96% with Miller. Overall eligibility for subsidized treatment in the AIPFR group varied from 73.6% to 82.8% between surveyed interstitial lung disease (ILD) centres based entirely on the equation used. CONCLUSION: Substantial variability exists between reference equations, impacting access to subsidized treatment. Treating clinicians should be aware of this when assessing patients around public funding thresholds.

Implications of the diagnostic criteria of idiopathic pulmonary fibrosis in clinical practice: Analysis from the Australian Idiopathic Pulmonary Fibrosis Registry.

BACKGROUND AND OBJECTIVE: Current guidelines for the diagnosis of idiopathic pulmonary fibrosis (IPF) provide specific criteria for diagnosis in the setting of multidisciplinary discussion (MDD). We evaluate the utility and reproducibility of these diagnostic guidelines, using clinical data from the Australian IPF Registry. METHODS: All patients enrolled in the registry undergo a diagnostic review whereby international IPF guidelines are applied via a registry MDD. We investigated the clinical applicability of these guidelines with regard to: (i) adherence to guidelines, (ii) Natural history of IPF diagnostic categories and (iii) Concordance for diagnostic features. RESULTS: A total of 417 participants (69% male, 70.6 ± 8.0 years) with a clinical diagnosis of IPF underwent MDD. The 23% of participants who did not meet IPF diagnostic criteria displayed identical disease behaviour to those with confirmed IPF. Honeycombing on radiology was associated with a worse prognosis and this translated into poorer prognosis in the 'definite' IPF group. While there was moderate agreement for IPF diagnostic categories, agreement for specific radiological features, other than honeycombing, was poor. CONCLUSION: In clinical practice, physicians do not always follow IPF diagnostic guidelines. We demonstrate a cohort of IPF patients who do not meet IPF diagnostic guideline criteria, based largely on their radiology and lack of lung biopsy, but who have outcomes identical to those with IPF.

Gastroesophageal reflux and antacid therapy in IPF: analysis from the Australia IPF Registry.

BACKGROUND AND OBJECTIVE: Gastroesophageal reflux disease (GORD) is highly prevalent in idiopathic pulmonary fibrosis (IPF) and may play a role in its pathogenesis. Recent IPF treatment guidelines suggest that all patients with IPF be considered for antacid therapy. However, emerging evidence suggests that antacid therapy does not improve IPF patient outcomes and may increase the risk of pulmonary infection. METHODS: Using prospectively collected data from the Australian IPF Registry including use of antacid therapy, GORD diagnosis and GORD symptoms, the relationship of these GORD variables to survival and disease progression was assessed. The severity of GORD symptoms using the frequency scale for symptoms of GORD (FSSG) and its relationships to outcomes was also assessed for the first time in an IPF cohort. RESULTS: Five hundred eighty-seven (86%) of the 684 patients in the Australian IPF Registry were eligible for inclusion. Patients were mostly male (69%), aged 71.0 ± 8.5 years with moderate disease (FVC 81.7 ± 21.5%; DLco 48.5 ± 16.4%). Most patients were taking antacids (n = 384; 65%), though fewer had a diagnosis of GORD (n = 243, 41.4%) and typical GORD symptoms were even less common (n = 171, 29.1%). The mean FSSG score was 8.39 ± 7.45 with 43% (n = 251) having a score > 8. Overall, there was no difference in survival or disease progression, regardless of antacid treatment, GORD diagnosis or GORD symptoms. CONCLUSIONS: Neither the use of antacid therapy nor the presence of GORD symptoms affects longer term outcomes in IPF patients. This contributes to the increasing evidence that antacid therapy may not be beneficial in IPF patients and that GORD directed therapy should be considered on an individual basis to treat the symptoms of reflux.

Diagnosis and management of idiopathic pulmonary fibrosis: Thoracic Society of Australia and New Zealand and Lung Foundation Australia position statements summary.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with debilitating symptoms of dyspnoea and cough, resulting in respiratory failure, impaired quality of life and ultimately death. Diagnosing IPF can be challenging, as it often shares many features with other interstitial lung diseases. In this article, we summarise recent joint position statements on the diagnosis and management of IPF from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia, specifically tailored for physicians across Australia and New Zealand. Main suggestions: A comprehensive multidisciplinary team meeting is suggested to establish a prompt and precise IPF diagnosis. Antifibrotic therapies should be considered to slow disease progression. However, enthusiasm should be tempered by the lack of evidence in many IPF subgroups, particularly the broader disease severity spectrum. Non-pharmacological interventions including pulmonary rehabilitation, supplemental oxygen, appropriate treatment of comorbidities and disease-related symptoms remain crucial to optimal management. Despite recent advances, IPF remains a fatal disease and suitable patients should be referred for lung transplantation assessment.

Serpulanines A to C, N-Oxidized Tyrosine Derivatives Isolated from the Sri Lankan Fungus Serpula sp.: Structure Elucidation, Synthesis, and Histone Deacetylase Inhibition.

Serpulanines A (1), B (2), and C (3) have been isolated from extracts of the rare Sri Lankan macrofungus Serpula sp. The structures of 1, 2, and 3 were elucidated by a combination of spectroscopic and single-crystal X-ray diffraction analyses. Serpulanines A (1) and B (2) both contain the rare (E)-2-hydroxyimino hydroxamic acid functional group array. A proposed biogenesis for serpulanine B (2) suggests that its (E)-2-hydroxyimino hydroxamic acid moiety arises from a diketopiperazine precursor. Synthetic serpulanine A (1) inhibited class I/II histone deacetylases in murine metastatic lung carcinoma cells with an IC50 of 7 µM.

Disease progression in idiopathic pulmonary fibrosis with mild physiological impairment: analysis from the Australian IPF registry.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrosing lung disease of unknown cause. The advent of anti-fibrotic medications known to slow disease progression has revolutionised IPF management in recent years. However, little is known about the natural history of IPF patients with mild physiological impairment. We aimed to assess the natural history of these patients using data from the Australian IPF Registry (AIPFR). METHODS: Using our cohort of real-world IPF patients, we compared FVC criteria for mild physiological impairment (FVC ≥ 80%) against other proposed criteria: DLco ≥ 55%; CPI ≤40 and GAP stage 1 with regards agreement in classification and relationship with disease outcomes. Within the mild cohort (FVC ≥ 80%), we also explored markers associated with poorer prognosis at 12 months. RESULTS: Of the 416 AIPFR patients (mean age 70.4 years, 70% male), 216 (52%) were classified as 'mild' using FVC ≥ 80%. There was only modest agreement between FVC and DLco (k = 0.30), with better agreement with GAP (k = 0.50) and CPI (k = 0.48). Patients who were mild had longer survival, regardless of how mild physiologic impairment was defined. There was, however, no difference in the annual decline in FVC% predicted between mild and moderate-severe groups (for all proposed criteria). For patients with mild impairment (n = 216, FVC ≥ 80%), the strongest predictor of outcomes at 12 months was oxygen desaturation on a 6 min walk test. CONCLUSION: IPF patients with mild physiological impairment have better survival than patients with moderate-severe disease. Their overall rate of disease progression however, is comparable, suggesting that they are simply at different points in the natural history of IPF disease.

Baseline characteristics of idiopathic pulmonary fibrosis: analysis from the Australian Idiopathic Pulmonary Fibrosis Registry.

7The prevalence of idiopathic pulmonary fibrosis (IPF), a fatal and progressive lung disease, is estimated at 1.25-63 out of 100 000, making large population studies difficult. Recently, the need for large longitudinal registries to study IPF has been recognised.The Australian IPF Registry (AIPFR) is a national registry collating comprehensive longitudinal data of IPF patients across Australia. We explored the characteristics of this IPF cohort and the effect of demographic and physiological parameters and specific management on mortality.Participants in the AIPFR (n=647, mean age 70.9±8.5 years, 67.7% male, median follow up 2 years, range 6 months-4.5 years) displayed a wide range of age, disease severity and co-morbidities that is not present in clinical trial cohorts. The cumulative mortality rate in year one, two, three and four was 5%, 24%, 37% and 44% respectively. Baseline lung function (forced vital capacity, diffusing capacity of the lung for carbon monoxide, composite physiological index) and GAP (gender, age, physiology) stage (hazard ratio 4.64, 95% CI 3.33-6.47, p<0.001) were strong predictors of mortality. Patients receiving anti-fibrotic medications had better survival (hazard ratio 0.56, 95% CI 0.34-0.92, p=0.022) than those not on anti-fibrotic medications, independent of underlying disease severity.The AIPFR provides important insights into the understanding of the natural history and clinical management of IPF.

The interstitial lung disease multidisciplinary meeting: A position statement from the Thoracic Society of Australia and New Zealand and the Lung Foundation Australia.

Interstitial lung diseases (ILD) are a diverse group of pulmonary diseases for which accurate diagnosis is critical for optimal treatment outcomes. Diagnosis of ILD can be challenging and a multidisciplinary approach is recommended in international guidelines. The purpose of this position paper is to review the evidence for the use of the multidisciplinary meeting (MDM) in ILD and suggest an approach to its governance and constitution, in an attempt to provide a standard methodology that could be applied across Australia and New Zealand. This position paper is endorsed by the Thoracic Society of Australia and New Zealand (TSANZ) and the Lung Foundation Australia (LFA).

Health-related quality of life in idiopathic pulmonary fibrosis: Data from the Australian IPF Registry.

BACKGROUND AND OBJECTIVE: Studies analysing the effect of worsening pulmonary physiological impairment in idiopathic pulmonary fibrosis (IPF) with respect to quality of life have been limited to single centres or highly selected trial populations. The aim of this study was to determine the principal determinants of baseline and longitudinal health-related quality of life (HRQoL) in a large unselected IPF population. METHODS: We used the Australian IPF Registry to examine the relationship between HRQoL, measured using the St George Respiratory Questionnaire (SGRQ), and demographic features, physiological features, co-morbidities and symptoms. Linear regression analysis was performed to identify predictors of baseline HRQoL, linear mixed model analysis to determine the effect of time and forced vital capacity (FVC) on SGRQ and Cox proportional hazards regression to examine the relationship between HRQoL and all-cause mortality. RESULTS: Baseline data from 516 patients were available (347 males; mean (SD) age: 71.3 ± 8.6 years). Univariate analysis showed significant associations between HRQoL and demographic, clinical and physiological features. However, multivariate analysis demonstrated independent associations only between SGRQ and dyspnoea (University of California San Diego Shortness of Breathlessness Questionnaire (UCSD-SOBQ); R2 = 0.71, P < 0.0001), cough severity (visual analogue scale; R2 = 0.06, P < 0.0001) and depression (Hospital Anxiety and Depression Scale; R2 = 0.04, P < 0.0001). Linear mixed-effects modelling of combined baseline and longitudinal data confirmed these associations, as well as for FVC% predicted (P = 0.005). Multivariate Cox proportionate-proportional hazards regression analysis demonstrated no association between HRQoL and risk of mortality. CONCLUSION: Cough, dyspnoea and depression are major symptomatic determinants of HRQoL in IPF. FVC decline is associated with worsening HRQoL.

A potential new form of jail diversion and reconnection to mental health services: I. Stakeholders' views on acceptability.

The most effective point of intervention to prevent unnecessary arrest/incarceration of persons with serious mental illnesses is the initial encounter with police. We piloted a new police-mental health linkage system. When officers run an enrolled participant's name/identifiers, they receive an electronic message that the person has mental health considerations and that they should call for information. The linkage specialist receives the call and assists telephonically. In this qualitative study to examine acceptability of the linkage system, we conducted nine focus groups with diverse stakeholders (e.g., enrolled patients, officers). Focus groups revealed that patients enrolled with the hope that the linkage system would prevent negative interactions with police and minimize risk of arrest. Officers reported preferring not to arrest mental health patients and were genuinely invested in helping them, and felt that the linkage system might be an additional tool during encounters. Findings revealed acceptability of the intervention, and further research is warranted.