Breathlessness with Pleural Effusion: What Do We Know?

Breathlessness is the most common symptom in individuals with pleural effusion and is often disabling. The pathophysiology of breathlessness associated with pleural effusion is complex. The severity of breathlessness correlates weakly with the size of the effusion. Improvements in ventilatory capacity following pleural drainage are small and correlate poorly with the volume of fluid drained and improvements in breathlessness. Impaired hemidiaphragm function and a compensatory increase in respiratory drive to maintain ventilation appear to be an important mechanism of breathlessness associated with pleural effusion. Thoracocentesis reduces diaphragm distortion and improves its movement; these changes appear to reduce respiratory drive and associated breathlessness by improving the neuromechanical efficiency of the diaphragm.

Indwelling Pleural Catheter: Management of Complications.

Multiple randomized clinical trials have established the advantages of indwelling pleural catheter (IPC) in the management of malignant pleural effusions, resulting in its widespread adoption in clinical practice. Complications can occur with IPC use and must be recognized and managed effectively. This review provides a comprehensive overview of IPC complications and their best care. Pain postinsertion or during drainage of IPC is easily manageable and must be distinguished from tumor-related chest wall pain. IPC-related infections require systemic antibiotics and often intrapleural fibrinolytic/deoxyribonuclease therapy. The removal of IPC for infection is usually unnecessary. Symptomatic loculation usually responds to fibrinolytics but may recur. Catheter tract metastases are common in mesothelioma patients and usually respond to radiotherapy without inducing damages to the IPC. Less common complications include dislodgement, irreversible blockage, and fractures (upon removal) of the catheter. Recommendations on the management of IPC complications by recent consensus statement/guideline are discussed. Expert opinions on management approaches are included in areas where evidence is lacking to guide care.

Device assessed activity behaviours in patients with indwelling pleural catheter: A sub-study of the Australasian Malignant PLeural Effusion (AMPLE)-2 randomized trial.

BACKGROUND AND OBJECTIVE: Device-assessed activity behaviours are a novel measure for comparing intervention outcomes in patients with malignant pleural effusion (MPE). Australasian Malignant PLeural Effusion (AMPLE)-2 was a multi-centre clinical trial where participants with MPE treated with an indwelling pleural catheter were randomized to daily (DD) or symptom-guided (SGD) drainage for 60-days. Our aim was to describe activity behaviour patterns in MPE patients, explore the impact of drainage regimen on activity behaviours and examine associations between activity behaviours and quality of life (QoL). METHODS: Following randomization to DD or SGD, participants enrolled at the lead site (Perth) completed accelerometry assessment. This was repeated monthly for 5-months. Activity behaviour outcomes were calculated as percent of daily waking-wear time and compared between groups (Mann-Whitney U test; Median [IQR]). Correlations between activity behaviour outcomes and QoL were examined. RESULTS: Forty-one (91%) participants provided ≥1 valid accelerometry assessment (DDn = 20, SGD n = 21). Participants spent a large proportion of waking hours sedentary (72%-74% across timepoints), and very little time in moderate-to-vigorous physical activity (<1% across timepoints). Compared to SGD group, DD group had a more favourable sedentary-to-light ratio in the week following randomization (2.4 [2.0-3.4] vs. 3.2 [2.4-6.1]; p = 0.047) and at 60-days (2.0 [1.9-2.9] vs. 2.9 [2.8-6.0]; p = 0.016). Sedentary-to-light ratio was correlated with multiple QoL domains at multiple timepoints. CONCLUSION: Patients with MPE are largely sedentary. Preliminary results suggest that even modest differences in activity behaviours favouring the DD group could be meaningful for this clinical population. Accelerometry reflects QoL and is a useful outcome measure in MPE populations.

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).

Missed diagnosis or misdiagnosis: how often do hospitalised patients with a diagnosis of chronic obstructive pulmonary disease have spirometry that supports the diagnosis?

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the most common clinical diagnoses among hospital inpatients. Diagnosis requires the demonstration of post-bronchodilator airflow obstruction. However, it is uncertain how often spirometry results are available at the time a diagnostic label of COPD is applied. AIMS: To identify how frequently spirometry results were available following an inpatient admission with a clinical diagnosis of COPD, and to determine how often the available spirometry results supported a clinical diagnosis of COPD. Inhaler prescription, at discharge, was also evaluated to determine one of the potential implications of diagnostic inaccuracy. METHODS: A single-centre retrospective observational study was undertaken at a 400-bed metropolitan health service between October 2016 and March 2018. RESULTS: A total of 2239 inpatient separations occurred in 1469 individuals who had a clinical diagnosis of COPD during the study. Spirometry results were not available in 43.6% (n = 641) of those with a diagnosis of COPD. A further 19.7% (n = 289) had spirometry results available at the time of admission that did not demonstrate fixed airflow obstruction. The available prescribing data (n = 443) demonstrated that inhaled medications were prescribed in a similar pattern, regardless of the availability of spirometry or whether the results supported a clinical diagnosis of COPD. CONCLUSIONS: Inpatients with a clinical diagnosis of COPD frequently did not have supportive spirometry results that confirmed the diagnosis or had results inconsistent with COPD. Misdiagnosis and inappropriate prescribing require further attention to improve the quality of care in this setting.

Early outcomes following the implementation of a specialised pleural disease service.

BACKGROUND: Pleural effusion is a common cause of hospitalisation and a poor prognostic marker that is associated with morbidity and mortality. The evaluation and management of pleural effusion may be performed more effectively by a specialised pleural disease service (SPDS). AIMS: To evaluate the impact of a SPDS established in 2017 at a 400-bed metropolitan hospital in Victoria, Australia. METHODS: A retrospective observational study was undertaken comparing outcomes of individuals with pleural effusions. People with pleural effusion were identified using administrative data. Two 12-month time periods were compared, 2016 (Period 1, before SPDS) and 2018 (Period 2, after SPDS). RESULTS: Period 1 had n = 76 and Period 2 had n = 96 individuals with pleural effusion receiving intervention. Age (69.8 ± 17.6 vs 71.8 ± 15.8), gender and Charlson Comorbidity Index (4.9 ± 2.8 vs 5.4 ± 3.0) were similar across both periods. Utilisation of point-of-care ultrasound for pleural procedures increased from Period 1 to 2, 57.3-85.7% (P < 0.001). There was a reduction in median days from admission to intervention (3.8-2.1 days, P = 0.048) and pleural-related re-intervention rate (32% vs 19%, P = 0.032). Pleural fluid testing was more consistent with recommendations (16.8% vs 43.2%, P < 0.001). Overall, there was no difference in the median length of stay (7.9 vs 6.4 days, P = 0.23), pleural-related readmissions (11% vs 16%, P = 0.69) or mortality (17.1% vs 15.6%, P = 0.79). Procedural complications were similar between the two periods. CONCLUSIONS: The introduction of a SPDS was associated with increased point-of-care ultrasound utilisation for pleural procedures, shorter delays to intervention and improved standardisation of tests on pleural fluid.

A Narrative Review-Management of Malignant Pleural Effusion Related to Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive, almost universally fatal cancer with limited therapeutic options. Despite efforts, a real breakthrough in treatment and outcomes has been elusive. Pleural effusion with significant breathlessness and pain is the most typical presentation of individuals with MPM. Although thoracentesis provides relief of breathlessness, most such pleural effusions recur rapidly, and a definitive procedure is often required to prevent a recurrence. Unfortunately, the optimal treatment modality for individuals with recurrent MPM-related effusion is unclear, and considerable variation exists in practice. In addition, non-expandable lung is common in pleural effusions due to MPM and makes effective palliation of symptoms more difficult. This review delves into the latest advances in the available management options (both surgical and non-surgical) for dealing with pleural effusion and non-expandable lung related to MPM. We discuss factors that determine the choice of definitive procedures that need to be tailored to the individual patient.

Ipsilateral and contralateral hemidiaphragm dynamics in symptomatic pleural effusion: The 2nd PLeural Effusion And Symptom Evaluation (PLEASE-2) Study.

BACKGROUND AND OBJECTIVE: The pathophysiology of breathlessness in pleural effusion is unclear. In the PLEASE-1 study, abnormal ipsilateral hemidiaphragm shape and movement, assessed qualitatively, were independently associated with breathlessness relief after pleural drainage. Effects of pleural effusion on contralateral hemidiaphragm function are unknown. PLEASE-2, a prospective exploratory pilot study, assessed the effects of unilateral effusion and drainage on both hemidiaphragms using advanced quantitative bedside ultrasonography. METHODS: Individuals with symptomatic unilateral pleural effusion undergoing therapeutic drainage were included. Measurements pre- and post-drainage included severity of breathlessness (visual analogue scale) and ultrasound measurements of diaphragm excursion and thickness, in addition to shape and movement. Diaphragm measurements were compared to published reference values. RESULTS: Twenty participants were recruited (mean age 68.9 [SD 12.8] years, 12 females). During tidal breathing, contralateral hemidiaphragm excursion exceeded ipsilateral excursion and reference values (all p ≤ 0.001). Contralateral excursion was greatest in participants with abnormal ipsilateral hemidiaphragm movement and was inversely correlated with ipsilateral tidal excursion (r = -0.676, p = 0.001). Following drainage (mean volume 2121 [SD = 1206] ml), abnormal shape (n = 12) and paradoxical movement (n = 9) of the ipsilateral hemidiaphragm resolved in all participants, and tidal excursion of the contralateral hemidiaphragm normalized. Relief of breathlessness post-drainage correlated with improvement in ipsilateral hemidiaphragm excursion (r = 0.556, p = 0.031). CONCLUSION: This pilot study suggests, for the first time, that unilateral pleural effusion not only impairs ipsilateral hemidiaphragm function but also causes compensatory hyperactivity of the contralateral hemidiaphragm, which resolves post-drainage. These findings provide a basis for detailed studies of diaphragmatic function and ventilatory drive in patients with symptomatic pleural effusion.

Diaphragm dysfunction: a comprehensive review from diagnosis to management.

Although the diaphragm represents a critical component of the respiratory pump, the clinical presentations of diaphragm dysfunction are often non-specific and can be mistaken for other more common causes of dyspnoea. While acute bilateral diaphragm dysfunction typically presents dramatically, progressive diaphragm dysfunction associated with neuromuscular disorders and unilateral hemidiaphragm dysfunction may be identified incidentally or by recognising subtle associated symptoms. Diaphragm dysfunction should be considered in individuals with unexplained dyspnoea, restrictive respiratory function tests or abnormal diaphragm position on plain chest imaging. A higher index of suspicion should occur for individuals with profound orthopnoea, those who have undergone procedures in proximity to the phrenic nerve(s) or those with co-morbid conditions that are associated with diaphragm dysfunction, particularly neuromuscular disorders. A systematic approach to the evaluation of diaphragm function using non-invasive diagnostic techniques such as respiratory function testing and diaphragm imaging can often confirm a diagnosis. Neurophysiological assessment may confirm diaphragm dysfunction and assist in identifying an underlying cause. Identifying those with or at risk of respiratory failure can allow institution of respiratory support, while specific cases may also benefit from surgical plication or phrenic nerve pacing techniques.

Intrapleural Fibrinolytics and Deoxyribonuclease for Treatment of Indwelling Pleural Catheter-Related Pleural Infection: A Multi-Center Observational Study.

BACKGROUND: 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. OBJECTIVE: To assess the safety and efficacy of intrapleural tPA and DNase in IPC-related pleural infection. METHODS: Patients with IPC-related pleural infection who received intrapleural tPA/DNase in five Australian and UK centers were identified from prospective databases. Outcomes on feasibility of intrapleural tPA/DNase delivery, its efficacy and safety were recorded. RESULTS: Thirty-nine IPC-related pleural infections (predominantly Staphylococcus aureus 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. CONCLUSION: 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.

Increased interdigitation zone visibility on optical coherence tomography following systemic fibroblast growth factor receptor 1-3 tyrosine kinase inhibitor anticancer therapy.

BACKGROUND: To describe ocular adverse events and retinal changes during fibroblast growth factor receptor (FGFR) inhibitor (AZD4547) anticancer therapy. METHODS: This is a sub-study examining ocular adverse effects from AZD4547 therapy (single-centre, open-label, single arm phase II clinical trial). Comprehensive ocular examinations were performed 3 weekly in 24 patients. Macular optical coherence tomography (OCT) scan (300 × 250 ) was obtained at each visit and OCT parameters [central 1 mm retinal thickness (CRT) and total macular volume in central 6 mm] extracted. OCT scans were subdivided into outer (ELM to RPE) and inner (ELM to ILM) layers to compare outer and inner retinal changes. RESULTS: In 24 patients, AZD4547 was associated with eyelash elongation (n = 5, 21%) and punctate corneal erosion (n = 2, 8%). One patient developed clinically significant posterior capsular opacification during the study. OCT data were available in 23 patients, retinal changes ranged from an asymptomatic increased visibility of the interdigitation zone (IDZ) (n = 10, 43%) to multilobular subretinal fluid pockets (n = 5, 22%), which was associated with mild visual acuity loss. In a subset of patients (n = 9) with pre-AZD4547 dosing OCT baseline, CRT increased by mean (SD) of 9 (4) µm in those with IDZ change only compared with 64 (38) µm in those with other retinal changes. Retinal changes tended to be bilateral, self-limiting and improved over time without medical intervention. CONCLUSIONS: The ocular signs and symptoms did not result in dose cessation. Posteriorly, FGFR inhibition leads to outer retinal changes ranging from increased visibility of IDZ to distinct, multiple fluid pockets.

The Pleural Effusion And Symptom Evaluation (PLEASE) study of breathlessness in patients with a symptomatic pleural effusion.

INTRODUCTION: Pathophysiology changes associated with pleural effusion, its drainage and factors governing symptom response are poorly understood. Our objective was to determine: 1) the effect of pleural effusion (and its drainage) on cardiorespiratory, functional and diaphragmatic parameters; and 2) the proportion as well as characteristics of patients with breathlessness relief post-drainage. METHODS: Prospectively enrolled patients with symptomatic pleural effusions were assessed at both pre-therapeutic drainage and at 24-36 h post-therapeutic drainage. RESULTS: 145 participants completed pre-drainage and post-drainage tests; 93% had effusions ≥25% of hemithorax. The median volume drained was 1.68 L. Breathlessness scores improved post-drainage (mean visual analogue scale (VAS) score by 28.0±24 mm; dyspnoea-12 (D12) score by 10.5±8.8; resting Borg score before 6-min walk test (6-MWT) by 0.6±1.7; all p<0.0001). The 6-min walk distance (6-MWD) increased by 29.7±73.5 m, p<0.0001. Improvements in vital signs and spirometry were modest (forced expiratory volume in 1 s (FEV1) by 0.22 L, 95% CI 0.18-0.27; forced vital capacity (FVC) by 0.30 L, 95% CI 0.24-0.37). The ipsilateral hemi-diaphragm was flattened/everted in 50% of participants pre-drainage and 48% of participants exhibited paradoxical or no diaphragmatic movement. Post-drainage, hemi-diaphragm shape and movement were normal in 94% and 73% of participants, respectively. Drainage provided meaningful breathlessness relief (VAS score improved ≥14 mm) in 73% of participants irrespective of whether the lung expanded (mean difference 0.14, 95% CI 10.02-0.29; p=0.13). Multivariate analyses found that breathlessness relief was associated with significant breathlessness pre-drainage (odds ratio (OR) 5.83 per standard deviation (sd) decrease), baseline abnormal/paralyzed/paradoxical diaphragm movement (OR 4.37), benign aetiology (OR 3.39), higher pleural pH (OR per sd increase 1.92) and higher serum albumin level (OR per sd increase 1.73). CONCLUSIONS: Breathlessness and exercise tolerance improved in most patients with only a small mean improvement in spirometry and no change in oxygenation. Breathlessness improvement was similar in participants with and without trapped lung. Abnormal hemi-diaphragm shape and movement were independently associated with relief of breathlessness post-drainage.

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.

Simplified Criteria Using Pleural Fluid Cholesterol and Lactate Dehydrogenase to Distinguish between Exudative and Transudative Pleural Effusions.

BACKGROUND: An important part of the investigation of pleural effusion is the identification of markers that help separate exudate from transudate. OBJECTIVES: The purposes of this study were to compare the accuracy of published and new sets of criteria to distinguish between exudative and transudative pleural effusions, and to determine whether serum biochemical analysis is necessary. METHODS: An externally validated cohort study was performed. Pleural effusions were determined to be transudative or exudative on the basis of an assessment of the medical record by two clinicians blinded to biochemical results. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the receiver operating characteristic curve were determined for each proposed combination of criteria. RESULTS: Pleural fluid analysis was available for 311 thoracenteses in the main cohort and for 112 thoracenteses in the validation cohort. The best sensitivity (97% [95% CI 94-99]) and negative likelihood ratio (0.04 [95% CI 0.02-0.08]) for identifying exudative effusions were observed with criteria combining pleural fluid lactate dehydrogenase greater than 0.6 the upper limit of normal serum lactate dehydrogenase and pleural fluid cholesterol greater than 1.04 mmol/L (40 mg/dL). The overall diagnostic accuracy was similar to Light's criteria. Findings were similar in the validation cohort. CONCLUSIONS: Our proposed criteria using simultaneously pleural fluid lactate dehydrogenase and pleural fluid cholesterol can identify an exudate with a sensitivity and an overall diagnostic accuracy similar to Light's criteria. It avoids simultaneous blood sampling, thus reducing patient discomfort and potential costs.

Evaluation of the implementation of a Tracheostomy Review Services (TRS): an observational cohort study.

It has been suggested that interprofessional tracheostomy teams improve safety, enhance outcomes and promote excellence. This study evaluated the effect of a Tracheostomy Review Service (TRS) on patient outcomes and staff attitudes. The TRS reviewed patients with a tracheostomy tube (TT) in situ on our wards. Data was collected via medical record audit. Two years of retrospective data (n = 39) was compared with 12 months of prospective data (n = 28) for: length of cannulation (LOC); length of ward-based cannulation (LOWBC); length of stay (LOS); ICU LOS (ICU-length of stay); the frequency and time to trial one way valve (PMV); and tracheostomy-related adverse events (AE). Staff were also surveyed regarding their knowledge and confidence in tracheostomy management. No significant difference was seen in LOC, LOWBC, LOS, ICU-LOS, and AE. A significant increase was seen in the frequency of PMV use (pre-TRS 74%; post-TRS 100%). Staff reported an improvement in knowledge and confidence in more complex areas of tracheostomy management. Limited measureable improvements in patient outcomes were seen following the implementation of a TRS. Limitations of this study include a small sample size and heterogeneous patient characteristics.

Comparison of outcomes following a cytological or histological diagnosis of malignant mesothelioma.

BACKGROUND: Survival with the epithelioid subtype of malignant mesothelioma (MM) is longer than the biphasic or sarcomatoid subtypes. There is concern that cytology-diagnosed epithelioid MM may underdiagnose the biphasic subtype. This study examines survival differences between patients with epithelioid MM diagnosed by cytology only and other subtypes diagnosed by histology. METHODS: Demographics, diagnosis method, MM subtype and survival were extracted from the Western Australia (WA) Mesothelioma Registry, which records details of all MM cases occurring in WA. RESULTS: A total of 2024 MM cases were identified over 42 years. One thousand seven hundred forty-four (86.2%) were male, median (IQR) age was 68.6 (60.4-77.0) years. A total of 1212 (59.9%) cases were identified as epithelioid subtype of which 499 (41.2%) were diagnosed using fluid cytology only. Those with a cytology-only diagnosis were older than the histology group (median 70.2 vs 67.6 years, P<0.001), but median survival was similar (cytology 10.6 (5.5-19.2) vs histology 11.1 (4.8-19.8) months, P=0.727) and Cox regression modelling adjusting for age, sex, site and time since first exposure showed no difference in survival between the different diagnostic approaches. CONCLUSIONS: Survival of cytologically and histologically diagnosed epithelioid MM cases does not differ. A diagnostic tap should be considered adequate to diagnose epithelioid MM without need for further invasive testing.

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.

A narrative review on pain control interventions for non-surgical pleural procedures.

Pleural diseases are common and frequently result in disabling symptoms, impaired health-related quality of life and hospitalisation. Both diagnosis and management often require pleural procedures and despite a variety of pain control strategies available for clinicians to employ, many procedures are still complicated by pain and discomfort. This can interfere with procedure success and can limit patient satisfaction. This review examines the evidence for pain control strategies for people undergoing non-surgical pleural procedures. A systematic literature search was undertaken to identify published studies examining different pain control strategies including pharmacological (sedatives, paravertebral blocks, erector spinae blocks, intrapleural anaesthesia, epidural anaesthesia, local anaesthetic, methoxyflurane, non-steroidal anti-inflammatory drugs [NSAIDs], opioids) and non-pharmacological measures (transcutaneous electric nerve stimulation [TENS], cold application and changes to the intervention or technique). Current literature is limited by heterogeneous study design, small participant numbers and use of different endpoints. Strategies that were more effective than placebo or standard care at improving pain included intrapleural local anaesthesia, paravertebral blocks, NSAIDs, small-bore intercostal catheters (ICC), cold application and TENS. Inhaled methoxyflurane, thoracic epidural anaesthesia and erector spinae blocks may also be useful approaches but require further evaluation to determine their roles in routine non-surgical pleural procedures. Future research should utilise reliable and repeatable study designs and reach consensus in endpoints to allow comparability between findings and thus provide the evidence-base to achieve standardisation of pain management approaches.

Associations of physical activity and quality of life in parapneumonic effusion patients.

Introduction: Little is known about activity behaviours and quality of life (QoL) of patients with parapneumonic pleural effusions (PPE) after hospital discharge. This study is a secondary analysis of a randomised trial (dexamethasone versus placebo) for hospitalised patients with PPE. We: 1) described the patients' activity behaviour patterns and QoL measured at discharge and at 30 days post-discharge; and 2) examined the association between activity behaviours and QoL scores. Methods: Activity behaviour (7-day accelerometry; Actigraph GT3X+) and QoL (Medical Outcomes Study Short-Form 36) were assessed. Repeated measures analysis of covariance controlling for baseline values and a series of linear regression models were undertaken. Results: 36 out of 53 eligible participants completed accelerometry assessments. Despite modest increases in light physical activity (+7.5%) and some domains of QoL (>2 points) from discharge to 30 days post-discharge, patients had persistently high levels of sedentary behaviour (>65% of waking wear time) and poor QoL (≤50 out of 100 points) irrespective of treatment group (p=0.135-0.903). Increasing moderate-to-vigorous physical activity was associated with higher scores on most QoL domains (p=0.006-0.037). Linear regression indicates that a clinically important difference of 5 points in physical composite QoL score can be achieved by reallocating 16.1 min·day-1 of sedentary time to moderate-to-vigorous physical activity. Conclusion: Patients with PPE had low levels of physical activity and QoL at discharge and 30 days post-discharge irrespective of treatment. Moderate-to-vigorous physical activity participation was associated with higher QoL scores. Increasing moderate-to-vigorous physical activity following discharge from the hospital may be associated with improvements in QoL.