Cardiac Troponin T and NT-proBNP for Prediction of 30-Day Readmission or Death in Patients with Acute Dyspnea: Data from the Akershus Cardiac Examination 2 Study.

INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) measurements are recommended in patients with acute dyspnea. We aimed to assess the prognostic merit of cTnT compared to NT-proBNP for 30-day readmission or death in patients hospitalized with acute dyspnea. METHODS: We measured cTnT and NT-proBNP within 24 h in 314 patients hospitalized with acute dyspnea and adjudicated the cause of the index admission. Time to first event of readmission or death ≤30 days after hospital discharge was recorded, and cTnT and NT-proBNP measurements were compared head-to-head. RESULTS: Patients who died (12/314) or were readmitted (71/314) within 30 days had higher cTnT concentrations (median: 32.6, Q1-Q3: 18.4-74.2 ng/L vs. median: 19.4, Q1-Q3: 8.4-36.1 ng/L; p for comparison <0.001) and NT-proBNP concentrations (median: 1,753.6, Q1-Q3: 464.2-6,862.0 ng/L vs. median 984, Q1-Q3 201-3,600 ng/L; for comparison p = 0.027) compared to patients who survived and were not readmitted. cTnT concentrations were associated with readmission or death within 30 days after discharge both in the total cohort (adjusted hazard ratio [aHR]: 1.64, 95% confidence interval [CI]: 1.30-2.05) and in patients with heart failure (HF) (aHR: 1.58, 95% CI: 1.14-2.18). In contrast, NT-proBNP concentrations were not associated with short-term events, neither in the total cohort (aHR: 1.10, 95% CI: 0.94-1.30) nor in patients with adjudicated HF (aHR: 1.06, 95% CI: 0.80-1.40). CONCLUSION: cTnT concentrations are associated with 30-day readmission or death in patients hospitalized with acute dyspnea, as well as in patients adjudicated HF.

Additional Up-Front Thoracic Ultrasound in the Workup of Patients with Unilateral Pleural Effusion: A Prospective Observational Pilot Study.

BACKGROUND: In patients with pleural effusion, specific ultrasound characteristics are associated with pleural malignancy. OBJECTIVES: This study aimed to evaluate the added value of an additional, up-front, systematic thoracic ultrasound (TUS) to standard imaging in patients with unilateral pleural effusion of unknown cause in a clinical setting. METHODS: In a prospective observational pilot study, patients referred for workup and thoracentesis of a unilateral pleural effusion received up-front TUS following a set protocol in addition to available imaging and US guiding the thoracentesis or diagnostic puncture. The primary outcome was the proportion of cases where systematic TUS changed the planned diagnostic workup. Follow-up took place 26 weeks after inclusion. RESULTS: From February to December 2020, 55 patients were included. Thirty-six (65%) patients had other chest imaging available before TUS. Twenty-one (38%) were diagnosed with malignant pleural effusion. Three patients (5%) had clinically relevant changes in the diagnostic workup after additional systematic TUS. CONCLUSIONS: Additional up-front, systematic TUS had limited clinically relevant effect on the planned diagnostic workup in patients with unilateral pleural effusion in a setting where chest CT scans often are available at referral.

Prediction of Time to Next Therapeutic Thoracentesis and Identification of Risk Factors of Rapid Pleural Fluid Recurrence: A Prospective Observational Study.

BACKGROUND: The value of pre-booked repeated thoracentesis in patients with recurrent pleural effusion is reliant on the estimation of time to next drainage. Identifying factors associated with rapid pleural fluid recurrence could be supportive. OBJECTIVE: We aimed to evaluate the ability of the patient and physician to predict the time to next therapeutic thoracentesis and to identify characteristics associated with rapid pleural fluid recurrence. METHOD: In a prospective, observational study, patients with recurrent unilateral pleural effusion and the physician were to predict the time to next symptom-guided therapeutic thoracentesis. Primary outcome was difference between days to actual thoracentesis and days predicted by the patient and the physician. Factors associated with pleural fluid recurrence within 60-day follow-up were assessed using Cox regression analysis. RESULTS: A total of 98 patients were included, 71% with malignant pleural effusion. Patients' and physicians' predictions numerically deviated by 6 days from the actual number of days to re-thoracentesis (IQR 2-12 and 2-13, respectively). On multivariate analyses, factors associated with increased hazard of pleural fluid recurrence included daily fluid production (HR 1.35 [1.16-1.59], p > 0.001) and large effusion size (HR 2.76 [1.23-6.19], p = 0.01). Septations were associated with decreased hazard (HR 0.48 [0.24-0.96], p = 0.04). CONCLUSION: Patients and physicians were equally unable to predict the time to next therapeutic thoracentesis. Daily fluid production and large effusion size were associated with increased risk of rapid pleural fluid recurrence, while septations were associated with a decreased risk. This may guide patients and physicians in when to expect a need for therapeutic thoracentesis.

Objective structured clinical examination in basic thoracic ultrasound: a European study of validity evidence.

BACKGROUND: Basic thoracic ultrasound is being used more frequently by clinicians in several settings due to its high diagnostic accuracy for many common causes of respiratory failure and dyspnoea. However, ultrasound examinations are operator-dependent, and sufficient competences are needed to obtain high sensitivity and specificity of examinations. Additionally, it is crucial for ultrasound operators to perceive the competence to interpret the images and integrate them into the patient history and other examinations. This study aims to explore and gather validity evidence for an objective structured clinical examination test of basic thoracic ultrasound competences and establish a pass/fail score. METHODS: An expert panel created the test which included two theoretical and five practical stations representing cases with different diagnoses that cause respiratory symptoms and which are possible to establish by basic thoracic ultrasound. Twenty-five participants with different levels of experience in basic thoracic ultrasound completed the test. Data of the test scores were used for item analysis, and exploring validity evidence was done according to Messick's framework which is recommended. The contrasting groups' standard setting method was used to establish a pass/fail score. RESULTS: The summarised internal consistency reliability was high with a Cronbach's alpha of 0.87. The novice group (n = 4) had a mean test score of 42 ± 10.1 points, the intermediate group (n = 8) scored 79.1 ± 8.1 points, and the experienced group (n = 13) 89.0 ± 6.2 points (one-way ANOVA, p < 0.001). A pass/fail score of 71 points was thus derived (maximum test score = 105 points). CONCLUSION: We developed a test for the assessment of clinical competences in basic thoracic ultrasound with solid validity evidence, and a pass/fail standard with no false positives or false negatives.

Randomised trial of indwelling pleural catheters for refractory transudative pleural effusions.

OBJECTIVE: Refractory symptomatic transudative pleural effusions are an indication for pleural drainage. There has been supportive observational evidence for the use of indwelling pleural catheters (IPCs) for transudative effusions, but no randomised trials. We aimed to investigate the effect of IPCs on breathlessness in patients with transudative pleural effusions when compared with standard care. METHODS: A multicentre randomised controlled trial, in which patients with transudative pleural effusions were randomly assigned to either an IPC (intervention) or therapeutic thoracentesis (TT; standard care). The primary outcome was mean daily breathlessness score over 12 weeks from randomisation. RESULTS: 220 patients were screened from April 2015 to August 2019 across 13 centres, with 33 randomised to intervention (IPC) and 35 to standard care (TT). Underlying aetiology was heart failure in 46 patients, liver failure in 16 and renal failure in six. In primary outcome analysis, the mean±sd breathlessness score over the 12-week study period was 39.7±29.4 mm in the IPC group and 45.0±26.1 mm in the TT group (p=0.67). Secondary outcomes analysis demonstrated that mean±sd drainage was 17 412±17 936 mL and 2901±2416 mL in the IPC and TT groups, respectively. A greater proportion of patients had at least one adverse event in the IPC group (p=0.04). CONCLUSION: We found no significant difference in breathlessness over 12 weeks between IPCs or TT. TT is associated with fewer complications and IPCs reduced the number of invasive pleural procedures required. Patient preference and circumstances should be considered in selecting the intervention in this cohort.

Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion.

BACKGROUND: Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. METHODS: Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through the indwelling pleural catheter on an outpatient basis. Talc or placebo was administered on a single-blind basis. Follow-up lasted for 70 days. The primary outcome was successful pleurodesis at day 35 after randomization. RESULTS: The target of 154 patients undergoing randomization was reached after 584 patients were approached. At day 35, a total of 30 of 69 patients (43%) in the talc group had successful pleurodesis, as compared with 16 of 70 (23%) in the placebo group (hazard ratio, 2.20; 95% confidence interval, 1.23 to 3.92; P=0.008). No significant between-group differences in effusion size and complexity, number of inpatient days, mortality, or number of adverse events were identified. No significant excess of blockages of the indwelling pleural catheter was noted in the talc group. CONCLUSIONS: 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 .).

European Respiratory Society statement on thoracic ultrasound.

Thoracic ultrasound is increasingly considered to be an essential tool for the pulmonologist. It is used in diverse clinical scenarios, including as an adjunct to clinical decision making for diagnosis, a real-time guide to procedures and a predictor or measurement of treatment response. The aim of this European Respiratory Society task force was to produce a statement on thoracic ultrasound for pulmonologists using thoracic ultrasound within the field of respiratory medicine. The multidisciplinary panel performed a review of the literature, addressing major areas of thoracic ultrasound practice and application. The selected major areas include equipment and technique, assessment of the chest wall, parietal pleura, pleural effusion, pneumothorax, interstitial syndrome, lung consolidation, diaphragm assessment, intervention guidance, training and the patient perspective. Despite the growing evidence supporting the use of thoracic ultrasound, the published literature still contains a paucity of data in some important fields. Key research questions for each of the major areas were identified, which serve to facilitate future multicentre collaborations and research to further consolidate an evidence-based use of thoracic ultrasound, for the benefit of the many patients being exposed to clinicians using thoracic ultrasound.

Pleural Fluid suPAR Levels Predict the Need for Invasive Management in Parapneumonic Effusions.

Rationale: Parapneumonic effusions have a wide clinical spectrum. The majority settle with conservative management but some progress to complex collections requiring intervention. For decades, physicians have relied on pleural fluid pH to determine the need for chest tube drainage despite a lack of prospective validation and no ability to predict the requirement for fibrinolytics or thoracic surgery.Objectives: To study the ability of suPAR (soluble urokinase plasminogen activator receptor), a potential biomarker of pleural fluid loculation, to predict the need for invasive management compared with conventional fluid biomarkers (pH, glucose, and lactate dehydrogenase) in parapneumonic effusions.Methods: Patients presenting with pleural effusions were prospectively recruited to an observational study with biological samples stored at presentation. Pleural fluid and serum suPAR levels were measured using the suPARnostic double-monoclonal antibody sandwich ELISA on 93 patients with parapneumonic effusions and 47 control subjects (benign and malignant effusions).Measurements and Main Results: Pleural suPAR levels were significantly higher in effusions that were loculated versus nonloculated parapneumonic effusions (median, 132 ng/ml vs. 22 ng/ml; P < 0.001). Pleural suPAR could more accurately predict the subsequent insertion of a chest tube with an area under the curve (AUC) of 0.93 (95% confidence interval, 0.89-0.98) compared with pleural pH (AUC 0.82; 95% confidence interval, 0.73-0.90). suPAR was superior to the combination of conventional pleural biomarkers (pH, glucose, and lactate dehydrogenase) when predicting the referral for intrapleural fibrinolysis or thoracic surgery (AUC 0.92 vs. 0.76).Conclusions: Raised pleural suPAR was predictive of patients receiving more invasive management of parapneumonic effusions and added value to conventional biomarkers. These results need validation in a prospective multicenter trial.

Management of malignant pleural effusions.

PURPOSE OF REVIEW: Malignant pleural effusion (MPE) is a common cause of breathlessness indicative of advanced disease. Treatment approaches focus on relief of breathlessness and optimizing quality of life. A number of recent, high-impact publications give further insight into the advantages of different treatment options. This article provides a summary of the most up-to-date evidence in this area. RECENT FINDINGS: Recent publications have demonstrated comparable pleurodesis outcomes of talc slurry to talc poudrage and explore strategies to combine the advantages of indwelling pleural catheters (IPCs) with a chemical pleurodesis. A daily IPC drainage regime improves the chances of pleurodesis success and early IPC removal in patients without significant trapped lung. SUMMARY: MPE is a diverse condition, with no one strategy representing the 'best' approach for all. Management decisions should be made in conjunction with the patient, taking their views and preferences into consideration.

Interventions for the management of malignant pleural effusions: a network meta-analysis.

BACKGROUND: Malignant pleural effusion (MPE) is a common problem for people with cancer and usually associated with considerable breathlessness. A number of treatment options are available to manage the uncontrolled accumulation of pleural fluid, including administration of a pleurodesis agent (via a chest tube or thoracoscopy) or placement of an indwelling pleural catheter (IPC). This is an update of a review published in Issue 5, 2016, which replaced the original, published in 2004. OBJECTIVES: To ascertain the optimal management strategy for adults with malignant pleural effusion in terms of pleurodesis success and to quantify differences in patient-reported outcomes and adverse effects between interventions. SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and three other databases to June 2019. We screened reference lists from other relevant publications and searched trial registries. SELECTION CRITERIA: We included randomised controlled trials of intrapleural interventions for adults with symptomatic MPE, comparing types of sclerosant, mode of administration and IPC use. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on study design, characteristics, outcome measures, potential effect modifiers and risk of bias. The primary outcome was pleurodesis failure rate. Secondary outcomes were adverse events, patient-reported breathlessness control, quality of life, cost, mortality, survival, duration of inpatient stay and patient acceptability. We performed network meta-analyses of primary outcome data and secondary outcomes with enough data. We also performed pair-wise meta-analyses of direct comparison data. If we deemed interventions not jointly randomisable, or we found insufficient available data, we reported results by narrative synthesis. For the primary outcome, we performed sensitivity analyses to explore potential causes of heterogeneity and to evaluate pleurodesis agents administered via a chest tube only. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified 80 randomised trials (18 new), including 5507 participants. We found all except three studies at high or unclear risk of bias for at least one domain. Due to the nature of the interventions, most studies were unblinded. Pleurodesis failure rate We included 55 studies of 21 interventions in the primary network meta-analysis. We estimated the rank of each intervention's effectiveness. Talc slurry (ranked 6, 95% credible interval (Cr-I) 3 to 10)  is an effective pleurodesis agent (moderate certainty for comparison with placebo) and may result in fewer pleurodesis failures than bleomycin and doxycycline (bleomycin versus talc slurry: odds ratio (OR) 2.24, 95% Cr-I 1.10 to 4.68; low certainty; ranked 11, 95% Cr-I 7 to 15; doxycycline versus talc slurry: OR 2.51, 95% Cr-I 0.81 to 8.40; low certainty; ranked 12, 95% Cr-I 5 to 18). There is little evidence of a difference between the pleurodesis failure rate of talc poudrage and talc slurry (OR 0.50, 95% Cr-I 0.21 to 1.02; moderate certainty). Evidence for any difference was further reduced when restricting analysis to studies at low risk of bias (defined as maximum one high risk domain in the risk of bias assessment) (pleurodesis failure talc poudrage versus talc slurry: OR 0.78, 95% Cr-I 0.16 to 2.08). IPCs without daily drainage are probably less effective at obtaining a definitive pleurodesis (cessation of pleural fluid drainage facilitating IPC removal) than talc slurry (OR 7.60, 95% Cr-I 2.96 to 20.47; rank = 18/21, 95% Cr-I 13 to 21; moderate certainty). Daily IPC drainage or instillation of talc slurry via IPC are likely to reduce pleurodesis failure rates. Adverse effects Adverse effects were inconsistently reported. We performed network meta-analyses for the risk of procedure-related fever and pain. The evidence for risk of developing fever was of low certainty, but suggested there may be little difference between interventions relative to talc slurry (talc poudrage: OR 0.89, 95% Cr-I 0.11 to 6.67; bleomycin: OR 2.33, 95% Cr-I 0.45 to 12.50; IPCs: OR 0.41, 95% Cr-I 0.00 to 50.00; doxycycline: OR 0.85, 95% Cr-I 0.05 to 14.29). Evidence also suggested there may be little difference between interventions in the risk of developing procedure-related pain, relative to talc slurry (talc poudrage: OR 1.26, 95% Cr-I 0.45 to 6.04; very-low certainty; bleomycin: OR 2.85, 95% Cr-I 0.78 to 11.53; low certainty; IPCs: OR 1.30, 95% Cr-I 0.29 to 5.87; low certainty; doxycycline: OR 3.35, 95% Cr-I 0.64 to 19.72; low certainty). Patient-reported control of breathlessness Pair-wise meta-analysis suggests there is likely no difference in breathlessness control, relative to talc slurry, of talc poudrage ((mean difference (MD) 4.00 mm, 95% CI -6.26 to 14.26) on a 100 mm visual analogue scale for breathlessness; studies = 1; participants = 184; moderate certainty) and IPCs without daily drainage (MD -6.12 mm, 95% CI -16.32 to 4.08; studies = 2; participants = 160; low certainty). Overall mortality There may be little difference between interventions when compared to talc slurry (bleomycin and IPC without daily drainage; low certainty) but evidence is uncertain for talc poudrage and doxycycline. Patient acceptability Pair-wise meta-analysis demonstrated that IPCs probably result in a reduced risk of requiring a repeat invasive pleural intervention (OR 0.25, 95% Cr-I 0.13 to 0.48; moderate certainty) relative to talc slurry. There is likely little difference in the risk of repeat invasive pleural intervention with talc poudrage relative to talc slurry (OR 0.96, 95% CI 0.59 to 1.56; moderate certainty). AUTHORS' CONCLUSIONS: Based on the available evidence, talc poudrage and talc slurry are effective methods for achieving a pleurodesis, with lower failure rates than a number of other commonly used interventions. IPCs provide an alternative approach; whilst associated with inferior definitive pleurodesis rates, comparable control of breathlessness can probably be achieved, with a lower risk of requiring repeat invasive pleural intervention.  Local availability, global experience of agents and adverse events (which may not be identified in randomised trials) and patient preference must be considered when selecting an intervention. Further research is required to delineate the roles of different treatments according to patient characteristics, such as presence of trapped lung. Greater attention to patient-centred outcomes, including breathlessness, quality of life and patient preference is essential to inform clinical decision-making. Careful consideration to minimise the risk of bias and standardise outcome measures is essential for future trial design.

Using creative co-design to develop a decision support tool for people with malignant pleural effusion.

BACKGROUND: Malignant pleural effusion (MPE) is a common, serious problem predominantly seen in metastatic lung and breast cancer and malignant pleural mesothelioma. Recurrence of malignant pleural effusion is common, and symptoms significantly impair people's daily lives. Numerous treatment options exist, yet choosing the most suitable depends on many factors and making decisions can be challenging in pressured, time-sensitive clinical environments. Clinicians identified a need to develop a decision support tool. This paper reports the process of co-producing an initial prototype tool. METHODS: Creative co-design methods were used. Three pleural teams from three disparate clinical sites in the UK were involved. To overcome the geographical distance between sites and the ill-health of service users, novel distributed methods of creative co-design were used. Local workshops were designed and structured, including video clips of activities. These were run on each site with clinicians, patients and carers. A joint national workshop was then conducted with representatives from all stakeholder groups to consider the findings and outputs from local meetings. The design team worked with participants to develop outputs, including patient timelines and personas. These were used as the basis to develop and test prototype ideas. RESULTS: Key messages from the workshops informed prototype development. These messages were as follows. Understanding and managing the pleural effusion was the priority for patients, not their overall cancer journey. Preferred methods for receiving information were varied but visual and graphic approaches were favoured. The main influences on people's decisions about their MPE treatment were personal aspects of their lives, for example, how active they are, what support they have at home. The findings informed the development of a first prototype/service visualisation (a video representing a web-based support tool) to help people identify personal priorities and to guide shared treatment decisions. CONCLUSION: The creative design methods and distributed model used in this project overcame many of the barriers to traditional co-production methods such as power, language and time. They allowed specialist pleural teams and service users to work together to create a patient-facing decision support tool owned by those who will use it and ready for implementation and evaluation.

Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial.

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. Trial Registration: ISRCTN Identifier: ISRCTN47845793.

Outpatient talc administration via indwelling pleural catheters for malignant effusions.

PURPOSE OF REVIEW: Malignant pleural effusion is a common cause of breathlessness and signifies advanced disease. Common options for definitive pleural intervention include insertion of an indwelling pleural catheter (IPC) or talc pleurodesis. RECENT FINDINGS: Administration of graded talc through an IPC offers an increased chance of pleurodesis compared with IPC drainage alone and is not associated with a significant risk of adverse events. SUMMARY: In patients where an ambulatory treatment pathway is preferred, the increased chance of pleurodesis with talc administration via IPC can result in a faster time to device removal and may be associated with better quality of life and symptom scores.

Local Anaesthetic (Medical) Thoracoscopy Services in the UK.

BACKGROUND: Local anaesthetic thoracoscopy (LAT) is an important procedure in the management pathway of patients with pleural effusions, particularly those with suspected malignancy. The last survey evaluating the use and development of LAT services in the UK was conducted over a decade ago. OBJECTIVES: We performed a survey of LAT practices in the UK to explore procedural preferences and variations in practice. METHODS: The online survey was cascaded via regional pleural specialists to sites performing LAT. One response per site was accepted. RESULTS: Thirty-seven responses were received from England, Scotland and Wales. Most centres have regular access to a dedicated list and a designated area to perform LAT. 97% of the centres have at least 2 trained thoracoscopists. Some variation in practice is seen with patient preparation pre-procedure and medication use. Other procedures, such as insertion of indwelling pleural catheters and adhesiolysis, are not uncommon to be undertaken at the time of LAT. CONCLUSIONS: Overall, the results are comparable, excepting some minor variations in patient preparation pre-procedure. We hope that this survey functions as an information resource for centres developing a LAT service or for those considering expansion.

A Prospective Study to Evaluate a Diagnostic Algorithm for the Use of Fluid Lymphocyte Subset Analysis in Undiagnosed Unilateral Pleural Effusions.

BACKGROUND: Haematological malignancy is an important cause of pleural effusion. Pleural effusions secondary to haematological malignancy are usually lymphocyte predominant. However, several other conditions such as carcinoma, tuberculosis, and chronic heart failure also cause lymphocytic effusions. Lymphocyte subset (LS) analysis may be a useful test to identify haematological malignancy in patients with lymphocytic effusions. However, research into their utility in pleural effusion diagnostic algorithms has not yet been published. OBJECTIVES: We aimed to determine the clinical utility of pleural fluid LS analysis and whether it can be applied to a diagnostic algorithm to identify effusions secondary to haematological malignancy. The secondary aim was to evaluate the diagnostic value of pleural fluid differential cell count. METHODS: Consecutive consenting patients presenting to our pleural service between 2008 and 2013 underwent thoracentesis and differential cell count analysis. We proposed an algorithm which selected patients with lymphocytic effusions (>50%) to have further fluid sent for LS analysis. Two independent consultants agreed on the cause of the original effusion after a 12-month follow-up period. RESULTS: A total of 60 patients had samples sent for LS analysis. LS analysis had an 80% sensitivity (8/10) and a 100% specificity for the diagnosis of haematological malignancy. The positive and negative predictive values were 100 and 96.1%, respectively. Overall 344 differential cell counts were analysed; 16% of pleural effusions with a malignant aetiology were neutrophilic or eosinophilic at presentation. A higher neutrophil and eosinophil count was associated with benign diagnoses, whereas a higher lymphocyte count was associated with malignant diagnoses. CONCLUSIONS: LS analysis may identify haematological malignancy in a specific cohort of patients with undiagnosed pleural effusions. A pleural fluid differential cell count provides useful additional information to streamline patient pathway decisions.

Premature Ventricular Complex is More Prevalent During Acute Exacerbated than Stable States of Chronic Obstructive Pulmonary Disease, and Is Related to Cardiac Troponin T.

During acute exacerbation of chronic obstructive pulmonary disease (AECOPD), myocardial stress may be aggravated. Sparse data exist concerning the prevalence and correlates of cardiac arrhythmias in the stable and exacerbated states of COPD. We hypothesized that AECOPD is associated with increased prevalence of cardiac arrhythmias independent of COPD-severity and co-morbidity, and explored possible mechanisms. A 24-hour Holter recording was obtained in 74 patients with stable COPD and 45 patients with AECOPD (mean age 54 years, 56% women). Any incidence of supraventricular tachycardia (SVT), frequent premature ventricular complex (PVC, >30/hour) and complex ventricular ectopy (bigeminy, trigeminy or non-sustained ventricular tachycardia) was recorded and compared between the two groups. Adjustments were made for by stable disease-related co-variates (demography, co-morbidity, COPD-severity) and by acute disease-related co-variates (heart rate, cardiac troponin T (cTnT), PO2, PCO2 and C-reactive protein (CRP)) in explorative analyses. The prevalence of SVT, frequent PVCs or complex ventricular ectopy was 40%, 27% and 33% in AECOPD, and 31%, 31% and 12% in stable COPD, respectively. Frequent PVC, but not SVT or complex ventricular ectopy, was significantly increased in AECOPD compared to stable COPD, odds ratio 3.03 (1.03-10.5, p = 0.039) when adjusted for stable disease-related co-variates. Higher heart rate, cTnT and CRP attenuated the association between AECOPD and frequent PVC to non-significant, while heart rate remained associated with frequent PVC. In conclusion, frequent PVC is more prevalent in exacerbated than in the stable states of COPD. Attenuation effects of cTnT, tachycardia and CRP suggest that cardiac stress or inflammation may be involved in mechanisms causing frequent PVC i AECOPD.

Cochrane corner: interventions for the management of malignant pleural effusions.

Optimal management of symptomatic malignant pleural effusions remains an important issue as it affects a significant number of patients each year internationally. The overall survival remains poor, necessitating an evidence based treatment strategy that provides the best outcomes for individual patients. This paper summarises the results of the recently published Cochrane review on interventions in malignant pleural effusions.

Interventions for the management of malignant pleural effusions: a network meta-analysis.

BACKGROUND: Malignant pleural effusion (MPE) is a common problem for people with cancer as a result of malignant infiltration of the pleura. It is usually associated with considerable breathlessness. A number of treatment options are available to manage the uncontrolled accumulation of pleural fluid including administration of a pleurodesis agent (either via a chest tube or at thoracoscopy) or indwelling pleural catheter insertion. OBJECTIVES: To ascertain the optimal management strategy for adults with malignant pleural effusion in terms of pleurodesis success. Additionally, to quantify differences in patient-reported outcomes and adverse effects between management strategies. SEARCH METHODS: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid EMBASE; EBSCO CINAHL; SCI-EXPANDED and SSCI (ISI Web of Science) to April 2015. SELECTION CRITERIA: We included randomised controlled trials of intrapleural interventions for adults with symptomatic MPE in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on study design, study characteristics, outcome measures, potential effect modifiers and risk of bias.The primary outcome measure was pleurodesis failure rate. Secondary outcome measures were adverse effects and complications, patient-reported control of breathlessness, quality of life, cost, mortality, duration of inpatient stay and patient acceptability.We performed network meta-analysis with random effects to analyse the primary outcome data and those secondary outcomes with enough data. We also performed pair-wise random-effects meta-analyses of direct comparison data. If interventions were not deemed jointly randomisable, or insufficient data were available, we reported the results by narrative synthesis. We performed sensitivity analyses to explore heterogeneity and to evaluate only those pleurodesis agents administered via a chest tube at the bedside. MAIN RESULTS: Of the 1888 records identified, 62 randomised trials, including a total of 3428 patients, were eligible for inclusion. All studies were at high or uncertain risk of bias for at least one domain.Network meta-analysis evaluating the rate of pleurodesis failure, suggested talc poudrage to be a highly effective method (ranked second of 16 (95% credible interval (Cr-I) 1 to 5)) and provided evidence that it resulted in fewer pleurodesis failures than eight other methods. The estimated ranks of other commonly used agents were: talc slurry (fourth; 95% Cr-I 2 to 8), mepacrine (fourth; 95% Cr-I 1 to 10), iodine (fifth; 95% Cr-I 1 to 12), bleomycin (eighth; 95% Cr-I 5 to 11) and doxycyline (tenth; 95% Cr-I 4 to 15). The estimates were imprecise as evidenced by the wide credible intervals and both high statistical and clinical heterogeneity.Most of the secondary outcomes, including adverse events, were inconsistently reported by the included studies and the methods used to describe them varied widely. Hence the majority of the secondary outcomes were reported descriptively in this review. We obtained sufficient data to perform network meta-analysis for the most commonly reported adverse events: pain, fever and mortality. The fever network was imprecise and showed substantial heterogeneity, but suggested placebo caused the least fever (ranked first of 11 (95% Cr-I 1 to 7)) and mepacrine and Corynebacterium parvum (C. parvum) appeared to be associated with the most fever (ranked tenth (95% Cr-I 6 to 11) and eleventh (95% Cr-I 7 to 11) respectively). No differences between interventions were revealed by the network meta-analysis of the pain data. The only potential difference in mortality identified in the mortality network was that those receiving tetracycline appeared to have a longer survival than those receiving mitoxantrone (OR 0.16 (95% Confidence Interval (CI) 0.03 to 0.72)). Indwelling pleural catheters were examined in two randomised studies, both of which reported improved breathlessness when compared to talc slurry pleurodesis, despite lower pleurodesis success rates.The risk of bias in a number of the included studies was substantial, for example the vast majority of studies were unblinded, and the methods used for sequence generation and allocation concealment were often unclear. Overall, however, the risk of bias for all studies was moderate. We have not reported the GRADE quality of evidence for the outcomes, as the role of GRADE is not well established in the context of Network Meta-analysis (NMA). AUTHORS' CONCLUSIONS: Based on the available evidence, talc poudrage is a more effective pleurodesis method in MPE than a number of other frequently used methods, including tetracycline and bleomycin. However further data are required to definitively confirm whether it is more effective than certain other commonly used interventions such as talc slurry and doxycycline, particularly in view of the high statistical and clinical heterogeneity within the network and the high risk of bias of many of the included studies. Based on the strength of the evidence from both direct and indirect comparisons of randomised data of sclerosants administered at the bedside, there is no evidence to suggest large differences between the other highly effective methods (talc slurry, mepacrine, iodine and C. parvum). However, local availability, global experience of these agents and their adverse events, which may not be identified in randomised trials, must also be considered when selecting a sclerosant. Further research is required to delineate the roles of different treatments according to patient characteristics (e.g. according to their prognosis or presence of trapped lung) and to explore patient-centred outcomes, such as breathlessness and quality of life, in more detail. Careful consideration to minimise the risk of bias and standardise outcome measures is essential for future trial design.