Among patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an indwelling catheter alone, with no deleterious effects. (Funded by Becton Dickinson; EudraCT number, 2012-000599-40 .).

IMPORTANCE Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. OBJECTIVE To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. INTERVENTIONS Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. MAIN OUTCOMES AND MEASURES The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. RESULTS Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference,-1.8% [95% CI,-10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. CONCLUSIONS AND RELEVANCE Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences.

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A pfADA level <30 IU/l makes a diagnosis of TB highly unlikely in the South London population. Its high sensitivity and negative predictive values make pfADA a valuable screening test for excluding suspected pleural TB.

IntroductionThe development of malignant pleural effusion (MPE) results in disabling breathlessness, pain and reduced physical capability with treatment a palliative strategy. Ambulatory management of MPE has the potential to improve quality of life (QoL). The OPTIMUM trial is designed to determine whether full outpatient management of MPE with an indwelling pleural catheter (IPC) and pleurodesis improves QoL compared with traditional inpatient care with a chest drain and talc pleurodesis. OPTIMUM is currently open for any centres interested in collaborating in this study.Methods and analysisOPTIMUM is a multicentre non-blinded randomised controlled trial. Patients with a diagnosis of MPE will be identified and screened for eligibility. Consenting participants will be randomised 1:1 either to an outpatient ambulatory pathway using IPCs and talc pleurodesis or standard inpatient treatment with chest drain and talc pleurodesis as per British Thoracic Society guidelines. The primary outcome measure is global health-related QoL at 30 days measured using the EORTC QLQ-C30 questionnaire. Secondary outcome measures include breathlessness and pain measured using a 100 mm Visual Analogue Scale and health-related QoL at 60 and 90 days. A sample size of 142 patients is needed to demonstrate a clinically significant difference of 8 points in global health status at 30 days, for an 80% power and a 5% significance level.Ethics and disseminationThe study has been approved by the NRES Committee South East Coast—Brighton and Sussex (reference 15/LO/1018). The trial results will be published in peer-reviewed journals and presented at scientific conferences.Trial registration numbersUKCRN19615 and ISRCTN15503522; Pre-results.

Background and objective: Intrapleural tissue plasminogen activator/ deoxyribonuclease (tPA/DNase) therapy is increasingly used in pleural infection. Bleeding risks and costs associated with tPA remain the clinical concerns. Our dose de-escalation series aims to establish the lowest effective dosing regimen for tPA/DNase. This study assesses the intrapleural use of 2.5 mg tPA/5 mg DNase for pleural infection. Methods: Consecutive patients with pleural infection treated with a starting regime of 2.5 mg tPA/5 mg DNase were included from two centres in Australia and UK. Escalation of tPA dose was permitted if clinical response was inadequate. Results: Sixty-nine patients (mean age 61.0 years) received intrapleural 2.5 mg tPA/5 mg DNase. Most (88.4%) were treated successfully and discharged from hospital without surgery by 90 days. Patients received a median of 5 [interquartile range [IQR] = 3-6] doses of tPA/DNase. Total amount of tPA used per patient was 12.5 mg [median, IQR = 7.5-15.0]. Seventeen patients required dose escalation of tPA; most (n = 12) for attempted drainage of distant non-communicating locule(s). Treatment success was corroborated by clearance of pleural opacities on radiographs (from median 27.0% [IQR = 17.1-44.5] to 11.0% [IQR = 6.4-23.3] of hemithorax, p < 0.0001), increased pleural fluid drainage (1.98 L [median, IQR = 1.38-2.68] over 72 h following commencement of tPA/DNase) and reduction of serum C-reactive protein level (by 45.0% [IQR = 39.3-77.0] from baseline at day 5, p < 0.0001). Two patients required surgery. Six patients with significant comorbidities (e.g., advanced cancer) had ongoing infection when palliated and died. Two patients experienced selflimiting pleural bleeding and received blood transfusion. Conclusion: A starting intrapleural regime of 2.5 mg tPA/5 mg DNase, with uptitration if needed, can be effective and deserves further exploration.

Physicians face considerable challenges in ensuring safe and effective care for patients admitted to hospital with pleural disease. While subspecialty development has driven up standards of care, this has been tempered by the resulting loss of procedural experience in general medical teams tasked with managing acute pleural disease. This review aims to define a framework though which a minimum standard of care might be implemented. This review has been written by pleural clinicians from across the UK representing all types of secondary care hospital. Its content has been formed on the basis of literature review, national guidelines, National Health Service England policy and consensus opinion following a round table discussion. Recommendations have been provided in the broad themes of procedural training, out-of-hours management and pleural service specification. Procedural competences have been defined into descriptive categories: emergency, basic, intermediate and advanced. Provision of emergency level operators at all times in all trusts is the cornerstone of out-of-hours recommendations, alongside readily available escalation pathways. A proposal for minimum standards to ensure the safe delivery of pleural medicine have been described with the aim of driving local conversations and providing a framework for service development, review and risk assessment.

<b><i>Background:</i></b> Indwelling pleural catheters (IPC) are increasingly used for management of recurrent (especially malignant) effusions. Pleural infection associated with IPC use remains a concern. Intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) significantly reduces surgical referrals in non-IPC pleural infection, but data on its use in IPC-related pleural infection are scarce. <b><i>Objective:</i></b> To assess the safety and efficacy of intrapleural tPA and DNase in IPC-related pleural infection. <b><i>Methods:</i></b> Patients with IPC-related pleural infection who received intrapleural tPA/DNase in five Australian and UK centers were identified from prospective databases. Outcomes on <i>feasibility</i> of intrapleural tPA/DNase delivery, its <i>efficacy</i> and <i>safety</i> were recorded. <b><i>Results:</i></b> Thirty-nine IPC-related pleural infections (predominantly <i>Staphylococcus aureus</i> and gram-negative organisms) were treated in 38 patients; 87% had malignant effusions. In total, 195 doses (median 6 [IQR = 3–6]/patient) of tPA (2.5 mg–10 mg) and DNase (5 mg) were instilled. Most (94%) doses were delivered via IPCs using local protocols for non-IPC pleural infections. The mean volume of pleural fluid drained during the first 72 h of treatment was 3,073 (SD = 1,685) mL. Most (82%) patients were successfully treated and survived to hospital discharge without surgery; 7 required additional chest tubes or therapeutic aspiration. Three patients required thoracoscopic surgery. Pleurodesis developed post-infection in 23/32 of successfully treated patients. No major morbidity/mortality was associated with tPA/DNase. Four patients received blood transfusions; none had systemic or significant pleural bleeding. <b><i>Conclusion:</i></b> Treatment of IPC-related pleural infection with intrapleural tPA/DNase instillations via the IPC appears feasible and safe, usually without additional drainage procedures or surgery. Pleurodesis post-infection is common.