Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Eradication of post-lobectomy mucormycosis and bacterial empyema with intrapleural antimicrobial therapy in a patient with surgically resected Mycobacterium xenopi (non-tuberculous Mycobacteria) pulmonary infection.

Empyema thoracis is a collection of pus in the pleural space associated with pleural fibrin deposition. Treatment involves systemic antimicrobials, pleural drainage, intrapleural enzymes and sometimes decortication. Our case is a 57-year-old gentleman who developed chronic mucormycosis (Cunninghamella sp.) and bacterial (Enterococcus sp.) empyema in a high-risk post-lobectomy space in the setting of a non-expandable lung following non-tuberculous mycobacterial (NTM) infection. The patient did not tolerate antimicrobial therapy for progressive pulmonary NTM infection, and required lobectomy, complicated by polymicrobial empyema. He did not respond to systemic treatment and long-term intercostal catheter drainage and therefore intrapleural taurolidine-citrate, and enzyme therapy was used to help eradicate infection. Intrapleural antifungals and taurolidine-citrate in combination with long-term antifungal therapy may help eradicate infection in patients with fungal empyemas. Further studies investigating the safety of taurolidine-citrate in pleural catheters are needed.

Australasian Malignant PLeural Effusion (AMPLE)-3 trial: study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion.

INTRODUCTION: Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. METHODS AND ANALYSIS: A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. DISCUSSION: Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12618001013257 . Registered on 18 June 2018. PROTOCOL VERSION: Version 3.00/4.02.19.

Steroid Therapy and Outcome of Parapneumonic Pleural Effusions (STOPPE): A Pilot Randomized Clinical Trial.

Rationale: Pleural effusion commonly complicates community-acquired pneumonia and is associated with intense pleural inflammation. Whether antiinflammatory treatment with corticosteroids improves outcomes is unknown. Objectives: To assess the effects of corticosteroids in an adult population with pneumonia-related pleural effusion. Methods: The STOPPE (Steroid Therapy and Outcome of Parapneumonic Pleural Effusions) trial was a pilot, multicenter, double-blinded, placebo-controlled, randomized trial involving six Australian centers. Patients with community-acquired pneumonia and pleural effusion were randomized (2:1) to intravenous dexamethasone (4 mg twice daily for 48 h) or placebo and followed for 30 days. Given the diverse effects of corticosteroids, a comprehensive range of clinical, serological, and imaging outcomes were assessed in this pilot trial (ACTRN12618000947202). Measurements and Main Results: Eighty patients were randomized (one withdrawn before treatment) and received dexamethasone (n = 51) or placebo (n = 28). This pilot trial found no preliminary evidence of benefits of dexamethasone in improving time to sustained (>12 h) normalization of vital signs (temperature, oxygen saturations, blood pressure, heart, and respiratory rates): median, 41.0 (95% confidence interval, 32.3-54.5) versus 27.8 (15.4-49.5) hours in the placebo arm (hazard ratio, 0.729 [95% confidence interval, 0.453-1.173]; P = 0.193). Similarly, no differences in C-reactive protein or leukocyte counts were observed, except for a higher leukocyte count in the dexamethasone group at Day 3. Pleural drainage procedures were performed in 49.0% of dexamethasone-treated and 42.9% of placebo-treated patients (P = 0.60). Radiographic pleural opacification decreased over time with no consistent intergroup differences. Mean duration of antibiotic therapy (22.4 [SD, 15.4] vs. 20.4 [SD, 13.8] d) and median hospitalization (6.0 [interquartile range, 5.0-10.0] vs. 5.5 [interquartile range, 5.0-8.0] d) were similar between the dexamethasone and placebo groups. Serious adverse events occurred in 25.5% of dexamethasone-treated and 21.4% of placebo-treated patients. Transient hyperglycemia more commonly affected the dexamethasone group (15.6% vs. 7.1%). Conclusions: Systemic corticosteroids showed no preliminary benefits in adults with parapneumonic effusions. Clinical trial registered with www.anzctr.org.au (ACTRN12618000947202).

Chronic haemothorax: an important cause of pleural effusion.

We describe a case of chronic exudative pleural effusion in a patient initially referred with anorexia, weight loss, and past history of breast cancer, following multiple presentations with chest pain and dyspnoea. Detailed history included past blunt thoracic trauma with pleural effusion drainage and anticoagulation for atrial fibrillation (AF). This case highlights several learning points for physicians around the management of thoracic trauma, anticoagulation for AF, and chronic haemothorax as an uncommon but important cause of exudative pleural effusion.

Airway pressure release ventilation in mechanically ventilated patients with COVID-19: a multicenter observational study.

BACKGROUND: Evidence prior to the coronavirus disease 2019 (COVID-19) pandemic suggested that, compared with conventional ventilation strategies, airway pressure release ventilation (APRV) can improve oxygenation and reduce mortality in patients with acute respiratory distress syndrome. We aimed to assess the association between APRV use and clinical outcomes among adult patients receiving mechanical ventilation for COVID-19 and hypothesized that APRV use would be associated with improved survival compared with conventional ventilation. METHODS: A total of 25 patients with COVID-19 pneumonitis was admitted to intensive care units (ICUs) for invasive ventilation in Perth, Western Australia, between February and May 2020. Eleven of these patients received APRV. The primary outcome was survival to day 90. Secondary outcomes were ventilation-free survival days to day 90, mechanical complications from ventilation, and number of days ventilated. RESULTS: Patients who received APRV had a lower probability of survival than did those on other forms of ventilation (hazard ratio, 0.17; 95% confidence interval, 0.03-0.89; P=0.036). This finding was independent of indices of severity of illness to predict the use of APRV. Patients who received APRV also had fewer ventilator-free survival days up to 90 days after initiation of ventilation compared to patients who did not receive APRV, and survivors who received APRV had fewer ventilator-free days than survivors who received other forms of ventilation. There were no differences in mechanical complications according to mode of ventilation. CONCLUSIONS: Based on the findings of this study, we urge caution with the use of APRV in COVID-19.

Nivolumab-associated myositis myocarditis and myasthenia and anti-striated muscle antibodies.

An 82-year-old man was treated with neo-adjuvant nivolumab (programmed cell death protein 1 or PD-1 inhibitor) for local recurrence of melanoma developed myositis, myocarditis and a myasthenic-like syndrome with a fatal outcome. The occurrence of these three conditions may constitute a new immune checkpoint-induced syndrome. The relevance of the clinical features and the immunology is discussed. This case highlights the special role of anti-striated muscle antibodies as a predictor of mortality.

Management of Indwelling Tunneled Pleural Catheters: A Modified Delphi Consensus Statement.

BACKGROUND: The management of recurrent pleural effusions remains a challenging issue for clinicians. Advances in management have led to increased use of indwelling tunneled pleural catheters (IPC) because of their effectiveness and ease of outpatient placement. However, with the increase in IPC placement there have also been increasing reports of complications, including infections. Currently there is minimal guidance in IPC-related management issues after placement. RESEARCH QUESTION: Our objective was to formulate clinical consensus statements related to perioperative and long-term IPC catheter management based on a modified Delphi process from experts in pleural disease management. STUDY DESIGN AND METHODS: Expert panel members used a modified Delphi process to reach consensus on common perioperative and long-term management options related to IPC use. Members were identified from multiple countries, specialties, and practice settings. A series of meetings and anonymous online surveys were completed. Responses were used to formulate consensus statements among panel experts, using a modified Delphi process. Consensus was defined a priori as greater than 80% agreement among panel constituents. RESULTS: A total of 25 physicians participated in this project. The following topics were addressed during the process: definition of an IPC infection, management of IPC-related infectious complications, interventions to prevent IPC infections, IPC-related obstruction/malfunction management, assessment of IPC removal, and instructions regarding IPC management by patients and caregivers. Strong consensus was obtained on 36 statements. No consensus was obtained on 29 statements. INTERPRETATION: The management of recurrent pleural disease with IPC remains complex and challenging. This statement offers statements for care in numerous areas related to IPC management based on expert consensus and identifies areas that lack consensus. Further studies related to long-term management of IPC are warranted.

Clinically Significant Pleural Effusion in Intensive Care: A Prospective Multicenter Cohort Study.

OBJECTIVES: The prevalence and optimal management of clinically significant pleural effusion, confirmed by thoracic ultrasound, in the critically ill is unknown. This study aimed to determine: 1) the prevalence, characteristics, and outcomes of patients treated in intensive care with clinically significant effusion and 2) the comparative efficacy and safety of pleural drainage or expectant medical management. DESIGN: A prospective multicenter cohort study. SETTING: ICUs in four teaching hospitals in Western Australia. PATIENTS: Consecutive patients with clinically significant pleural effusions (depth ≥ 2 cm on thoracic ultrasound with clinician-determined adverse effects on patient progress). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was the change in Pao2:Fio2 (mm Hg) ratio from baseline to 24 hours. Changes in diagnosis and treatment based on pleural fluid analysis and pleural effusion related serious adverse events between those who underwent either drainage within 24 hours or expectant management were compared. Of the 7,342 patients screened, 226 patients (3.1%) with 300 pleural effusions were enrolled. Early drainage of pleural effusion occurred in 76 patients (34%) and significantly improved oxygenation (Pao2:Fio2 ratio 203 at baseline vs 263 at 24 hr, +29.6% increment; p < 0.01). This was not observed in the other 150 patients who had expectant management (Pao2:Fio2 ratio 250 at baseline vs 268 at 24 hr, +7.2% increment; p = 0.44). The improvement in oxygenation after early drainage remained unchanged after adjustment for a propensity score on the decision to initiate early drainage. Pleural effusion related serious adverse events were not different between the two groups (early drainage 10.5% vs no early drainage 16.0%; p = 0.32). Improvements in diagnosis were noted in 91 initial (nonrepetitive) drainages (76.5% out of 119); treatment strategy was optimized after 80 drainage episodes (59.7% out of 134). CONCLUSIONS: Early drainage of clinically significant pleural effusion was associated with improved oxygenation and diagnostic accuracy without increased complications.

Use of indwelling pleural/peritoneal catheter in the management of malignant ascites: a retrospective study of 48 patients.

BACKGROUND: Patients suffering from malignant ascites usually require repeated large volume paracentesis (LVP) for symptomatic relief. This often requires hospital admission and has inherent risks. AIMS: To report the first Australian experience of placing tunnelled indwelling peritoneal catheters (IPeC) for management of recurrent malignant ascites. METHODS: A retrospective study was conducted of tunnelled IPeC use in patients with symptomatic malignant ascites in four hospitals in Western Australia (from 2010 to 2018). Procedure data, success rate and safety profile were collected from a database. RESULTS: Forty-eight patients (median age 65 years; female 56%) underwent 51 peritoneal catheter insertion procedures that were performed mostly by pleural specialists. The majority of patients (96%) had prior LVP (median two drainages, interquartile range (IQR) 1-4) before IPeC insertion. The IPeC was inserted successfully under ultrasound guidance in all patients. The median length of hospital stay for IPeC insertion and initial ascites drainage was 2 days (IQR 2-3 days) and most patients (96%) did not require further paracentesis after IPeC placement. The majority (96%) of patients experienced relief from ascites symptoms after catheter insertion. Most IPeC-related adverse events were self-limiting, including pain (in 25% cases), transient hypotension after initial fluid drainage (10%), peritoneal fluid leakage (10%), bacterial peritonitis (8%), fluid loculation (2%) and catheter dislodgement (2%). Six (12%) patients had IPeC removed. All patients with bacterial peritonitis responded to antibiotics and one required catheter removal. CONCLUSIONS: Use of tunnelled IPeC improves symptoms and can minimise further invasive drainage procedures in patients with symptomatic malignant ascites. Placement of IPeC was associated with a low rate of adverse events, most of which could be managed conservatively.

Steroid therapy and outcome of parapneumonic pleural effusions (STOPPE): Study protocol for a multicenter, double-blinded, placebo-controlled randomized clinical trial.

BACKGROUND: Community-acquired pneumonia (CAP) is a major global disease. Parapneumonic effusions often complicate CAP and range from uninfected (simple) to infected (complicated) parapneumonic effusions and empyema (pus). CAP patients who have a pleural effusion at presentation are more likely to require hospitalization, have a longer length of stay and higher mortality than those without an effusion. Conventional management of pleural infection, with antibiotics and chest tube drainage, fails in about 30% of cases. Several randomized controlled trials (RCT) have evaluated the use of corticosteroids in CAP and demonstrated some potential benefits. Importantly, steroid use in pneumonia has an acceptable safety profile with no adverse impact on mortality. A RCT focused on pediatric patients with pneumonia and a parapneumonic effusion demonstrated shorter time to recovery. The effects of corticosteroid use on clinical outcomes in adults with parapneumonic effusions have not been tested. We hypothesize that parapneumonic effusions develop from an exaggerated pleural inflammatory response. Treatment with systemic steroids may dampen the inflammation and lead to improved clinical outcomes. The steroid therapy and outcome of parapneumonic pleural effusions (STOPPE) trial will assess the efficacy and safety of systemic corticosteroid as an adjunct therapy in adult patients with CAP and pleural effusions. METHODS: STOPPE is a pilot multicenter, double-blinded, placebo-controlled RCT that will randomize 80 patients with parapneumonic effusions (2:1) to intravenous dexamethasone or placebo, administered twice daily for 48 hours. This exploratory study will capture a wide range of clinically relevant endpoints which have been used in clinical trials of pneumonia and/or pleural infection; including, but not limited to: time to clinical stability, inflammatory markers, quality of life, length of hospital stay, proportion of patients requiring escalation of care (thoracostomy or thoracoscopy), and mortality. Safety will be assessed by monitoring for the incidence of adverse events during the study. DISCUSSION: STOPPE is the first trial to assess the efficacy and safety profile of systemic corticosteroids in adults with CAP and pleural effusions. This will inform future studies on feasibility and appropriate trial endpoints. TRIAL REGISTRATION: ACTRN12618000947202 PROTOCOL VERSION:: version 3.00/26.07.18.

Air in the Pleural Cavity Enhances Detection of Pleural Abnormalities by CT Scan.

Detection of pleural abnormalities on CT scan is critical in diagnosis of pleural disease. CT scan detects minute parenchymal lung nodules, but often fails to detect similar-sized pleural nodularity. This is likely because the density of the visceral/parietal pleura and pleural fluid is similar. We hypothesize that an air-pleural interface enhances detection of pleural abnormalities. We describe six patients with pleural abnormalities that were not (or barely) detected on initial CT scan. However, pneumothorax (either ex vacuo or from a genuine air leak) after pleural fluid drainage permitted the visualization of small pleural abnormalities on CT scan, which would be amenable to imaging-guided biopsies. This case series provides proof-of-principle evidence that the sensitivity of CT scan detection of pleural abnormalities is dependent on adjacent tissue density and can be enhanced by intrapleural air. Future studies of the potential for artificial pneumothorax to improve the diagnosis of pleural disease are warranted.

Effect of an Indwelling Pleural Catheter vs Talc Pleurodesis on Hospitalization Days in Patients With Malignant Pleural Effusion: The AMPLE Randomized Clinical Trial.

Importance: Indwelling pleural catheter and talc pleurodesis are established treatments for malignant pleural effusions among patients with poor prognosis. Objective: To determine whether indwelling pleural catheters are more effective than talc pleurodesis in reducing total hospitalization days in the remaining lifespan of patients with malignant pleural effusion. Design, Setting, and Participants: This open-label, randomized clinical trial included participants recruited from 9 centers in Australia, New Zealand, Singapore, and Hong Kong between July 2012 and October 2014; they were followed up for 12 months (study end date: October 16, 2015). Patients (n = 146) with symptomatic malignant pleural effusion who had not undergone indwelling pleural catheter or pleurodesis treatment were included. Interventions: Participants were randomized (1:1) to indwelling pleural catheter (n = 74) or talc pleurodesis (n = 72), minimized by malignancy (mesothelioma vs others) and trapped lung (vs not), and stratified by region (Australia vs Asia). Main Outcomes and Measures: The primary end point was the total number of days spent in hospital from procedure to death or to 12 months. Secondary outcomes included further pleural interventions, patient-reported breathlessness, quality-of-life measures, and adverse events. Results: Among the 146 patients who were randomized (median age, 70.5 years; 56.2% male), 2 withdrew before receiving the randomized intervention and were excluded. The indwelling pleural catheter group spent significantly fewer days in hospital than the pleurodesis group (median, 10.0 [interquartile range [IQR], 3-17] vs 12.0 [IQR, 7-21] days; P = .03; Hodges-Lehmann estimate of difference, 2.92 days; 95% CI, 0.43-5.84). The reduction was mainly in effusion-related hospitalization days (median, 1.0 [IQR, 1-3] day with the indwelling pleural catheter vs 4.0 (IQR, 3-6) days with pleurodesis; P < .001; Hodges-Lehmann estimate, 2.06 days; 95% CI, 1.53-2.58). Fewer patients randomized to indwelling pleural catheter required further ipsilateral invasive pleural drainages (4.1% vs 22.5%; difference, 18.4%; 95% CI, 7.7%-29.2%). There were no significant differences in improvements in breathlessness or quality of life offered by indwelling pleural catheter or talc pleurodesis. Adverse events were seen in 22 patients in the indwelling pleural catheter group (30 events) and 13 patients in the pleurodesis group (18 events). Conclusions and Relevance: Among patients with malignant pleural effusion, treatment with an indwelling pleural catheter vs talc pleurodesis resulted in fewer hospitalization days from treatment to death, but the magnitude of the difference is of uncertain clinical importance. These findings may help inform patient choice of management for pleural effusion. Trial Registration: anzctr.org.au Identifier: ACTRN12611000567921.

Predictors of clinical use of pleurodesis and/or indwelling pleural catheter therapy for malignant pleural effusion.

BACKGROUND: The clinical course of patients with malignant pleural effusions (MPEs) varies. The decision to undertake "definitive therapy" (pleurodesis, indwelling pleural catheter [IPC], or both) for MPEs is decided on a case-by-case basis. Identifying factors that predict definitive therapy may help guide early initiation of treatment. The aim of the study was to identify clinical, laboratory, and radiologic predictors associated with clinicians' prescription of definitive therapy for patients with MPE. METHODS: A multicenter, observational study was conducted over 55 months involving tertiary centers in Perth, Western Australia, Australia, and Lleida, Spain. Demographic, clinical, radiologic, biochemical, and histologic data and the treatments received were recorded. Logistic regression was performed to determine the variables useful for predicting definitive therapy. RESULTS: Data of 540 patients (365 from Perth and 184 from Lleida) were analyzed; 537 fulfilled the criteria of an MPE. Definitive therapy was used in 288 patients (53.6%): 199 received a pleurodesis and 89 an IPC. Univariate analysis of the combined cohort revealed that definitive therapy was more likely if the effusion has low pH, either as a continuous variable (OR, 30.30; P < .01) or with a pH cutoff of < 7.2 (OR, 2.09; P = .03); was large (> 50% of hemithorax) (OR, 2.75; P < .01); or was associated with mesothelioma (OR, 1.83; P < .01). Following multivariate analysis, low pleural pH (OR, 37.04; P < .01), large effusions (OR, 3.31; P < .01), and increasing age (OR 1.02, P = .01) were associated with the use of definitive therapy. CONCLUSIONS: Patients with MPE with an effusion of low pleural fluid pH and large size on radiographs at first presentation are more likely to be treated with pleurodesis and/or IPC.

Current controversies in the management of malignant pleural effusions.

Malignant pleural effusion (MPE) can complicate most malignancies and is a common clinical problem presenting to respiratory and cancer care physicians. Despite its frequent occurrence, current knowledge of MPE remains limited and controversy surrounds almost every aspect in its diagnosis and management. A lack of robust data has led to significant practice variations worldwide, inefficiencies in healthcare provision, and threats to patient safety. Recent studies have highlighted evolving concepts in MPE care that challenge traditional beliefs. Advancing laboratory techniques have improved the diagnostic yield from pleural fluid cytology, minimizing the need for invasive tissue biopsies, even in many cases of mesothelioma. Imaging-guided biopsy is comparable to thoracoscopy in suitable patients, if cytological examination was noncontributory. Cumulating evidence for the benefits of indwelling pleural catheters (IPCs) has led some centers to adopt this approach as first-line definitive management for MPE over conventional talc pleurodesis. The optimal technique of talc pleurodesis is still debated despite its use for many decades. Strategies combining pleurodesis and IPC are being studied. MPE consists of a heterogenous group of diseases and careful phenotyping of malignant effusion patients can provide important clinical information that will advance the field and allow better stratification of patients and planning of therapy accordingly. This review addresses the controversies in MPE diagnosis and management and exposes the deficits in knowledge of MPE that should be the focus of future research.

Protocol of the Australasian Malignant Pleural Effusion (AMPLE) trial: a multicentre randomised study comparing indwelling pleural catheter versus talc pleurodesis.

INTRODUCTION: Malignant pleural effusion can complicate most cancers. It causes breathlessness and requires hospitalisation for invasive pleural drainages. Malignant effusions often herald advanced cancers and limited prognosis. Minimising time spent in hospital is of high priority to patients and their families. Various treatment strategies exist for the management of malignant effusions, though there is no consensus governing the best choice. Talc pleurodesis is the conventional management but requires hospitalisation (and substantial healthcare resources), can cause significant side effects, and has a suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory fluid drainage without hospitalisation, and are increasingly employed for management of malignant effusions. Previous studies have only investigated the length of hospital care immediately related to IPC insertion. Whether IPC management reduces time spent in hospital in the patients' remaining lifespan is unknown. A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital, reduce costs and save healthcare resources. METHODS AND ANALYSIS: The Australasian Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial designed to compare IPC with talc pleurodesis for the management of malignant pleural effusion. This study will randomise 146 adults with malignant pleural effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end point is the total number of days spent in hospital (for any admissions) from treatment procedure to death or end of study follow-up. Secondary end points include hospital days specific to pleural effusion management, adverse events, self-reported symptom and quality-of-life scores. ETHICS AND DISSEMINATION: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals. The trial results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBERS: Australia New Zealand Clinical Trials Registry-ACTRN12611000567921; National Institutes of Health-NCT02045121.

Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score.

BACKGROUND: Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system. METHODS: Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated. RESULTS: Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228-549; n=43), 130 days (47-467; n=129) and 44 days (22-77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, p<0.01), 3 months (0.84 vs 0.75, p<0.01) and 6 months (0.85 vs 0.76, p<0.01). CONCLUSIONS: The LENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population.