John P. Corcoran

Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion: The TIME1 Randomized Clinical Trial.

IMPORTANCE For treatment of malignant pleural effusion, nonsteroidal anti-inflammatory drugs (NSAIDs) are avoided because they may reduce pleurodesis efficacy. Smaller chest tubes may be less painful than larger tubes, but efficacy in pleurodesis has not been proven. OBJECTIVE To assess the effect of chest tube size and analgesia (NSAIDs vs opiates) on pain and clinical efficacy related to pleurodesis in patients with malignant pleural effusion. DESIGN, SETTING, AND PARTICIPANTS A 2×2 factorial phase 3 randomized clinical trial among 320 patients requiring pleurodesis in 16 UK hospitals from 2007 to 2013. INTERVENTIONS Patients undergoing thoracoscopy (n = 206; clinical decision if biopsy was required) received a 24F chest tube and were randomized to receive opiates (n = 103) vs NSAIDs (n = 103), and those not undergoing thoracoscopy (n = 114) were randomized to 1 of 4 groups (24F chest tube and opioids [n = 28]; 24F chest tube and NSAIDs [n = 29]; 12F chest tube and opioids [n = 29]; or 12F chest tube and NSAIDs [n = 28]). MAIN OUTCOMES AND MEASURES Pain while chest tube was in place (0- to 100-mm visual analog scale [VAS] 4 times/d; superiority comparison) and pleurodesis efficacy at 3 months (failure defined as need for further pleural intervention; noninferiority comparison; margin, 15%). RESULTS Pain scores in the opiate group (n = 150) vs the NSAID group (n = 144) were not significantly different (mean VAS score, 23.8 mm vs 22.1 mm; adjusted difference, -1.5 mm; 95% CI, -5.0 to 2.0 mm; P = .40), but the NSAID group required more rescue analgesia (26.3% vs 38.1%; rate ratio, 2.1; 95% CI, 1.3-3.4; P = .003). Pleurodesis failure occurred in 30 patients (20%) in the opiate group and 33 (23%) in the NSAID group, meeting criteria for noninferiority (difference, -3%; 1-sided 95% CI, -10% to ∞; P = .004 for noninferiority). Pain scores were lower among patients in the 12F chest tube group (n = 54) vs the 24F group (n = 56) (mean VAS score, 22.0 mm vs 26.8 mm; adjusted difference, -6.0 mm; 95% CI, -11.7 to -0.2 mm; P = .04) and 12F chest tubes vs 24F chest tubes were associated with higher pleurodesis failure (30% vs 24%), failing to meet noninferiority criteria (difference, -6%; 1-sided 95% CI, -20% to ∞; P = .14 for noninferiority). Complications during chest tube insertion occurred more commonly with 12F tubes (14% vs 24%; odds ratio, 1.91; P = .20). CONCLUSIONS AND RELEVANCE Use of NSAIDs vs opiates resulted in no significant difference in pain scores but was associated with more rescue medication. NSAID use resulted in noninferior rates of pleurodesis efficacy at 3 months. Placement of 12F chest tubes vs 24F chest tubes was associated with a statistically significant but clinically modest reduction in pain but failed to meet noninferiority criteria for pleurodesis efficacy. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN33288337.

Indwelling pleural catheters for non-malignant effusions: a multicentre review of practice

Indwelling pleural catheters (IPCs) are commonly used in the management of malignant pleural effusion (MPE). There is little data on their use in non-malignant conditions. All IPC insertions for non-malignant cases from five large UK centres were found using prospectively maintained databases. Data were collected on 57 IPC insertions. The commonest indications were hepatic hydrothorax (33%) and inflammatory pleuritis (26%). The mean weekly fluid output was 2.8 L (SD 2.52). 48/57 (84%) patients had no complications. Suspected pleural infection was documented in 2 (3.5%) cases. 33% (19/57) of patients underwent ‘spontaneous’ pleurodesis at a median time of 71 days. Patients with hepatic disease achieved pleurodesis significantly less often than those with non-hepatic disease (p=0.03). These data support the use of IPCs in select cases of non-malignant disease when maximal medical therapy has failed.

The outcome of manipulation under general anesthesia for the management of frozen shoulder in patients with diabetes mellitus

HYPOTHESIS Frozen shoulder has a greater incidence, more severe course, and resistance to treatment in patients with diabetes mellitus compared with the general population. We hypothesized that diabetic patients with frozen shoulder undergoing treatment with manipulation under general anaesthesia (MUA) would have the same outcome as patients without diabetes. MATERIALS AND METHODS We retrospectively analyzed data collected during a 10-year period of referrals for frozen shoulder. In all cases, a standardized MUA protocol was followed once the diagnosis of frozen shoulder in the frozen phase was made; this included an early repeat MUA in individuals with recurrence. We compared outcomes for patients documented as having diabetes with a nondiabetic control group and assessed the effect of insulin dependence and frozen shoulder etiology within the diabetic group. RESULTS Of a consecutive series of 315 frozen shoulders, 36 patients (39 shoulders) were included in the diabetic group, with 256 patients (274 shoulders) as controls. There was a significant improvement in range of movement and Oxford Shoulder Score (P all <.001), with no difference between diabetic and control groups at early or late follow-up (mean, 41 months). A repeat procedure was required in 36% of diabetic patients compared with 15% of control patients. Recurrence in the diabetic group was influenced by etiology (47% of primary vs 0% of secondary frozen shoulders) and insulin requirement (39% insulin-dependent vs. 31% non-insulin-dependent). CONCLUSION We provide a strategy for the management of diabetic frozen shoulders using MUA and estimates of success and recurrence rates that may be useful when informing consent.

Role of CT in assessing pleural malignancy prior to thoracoscopy

The definitive diagnosis of pleural malignancy depends upon histological confirmation by pleural biopsy. CT is reported to have a high sensitivity and specificity for the diagnosis of malignant pleural disease, and is part of the routine diagnostic workup of these patients. The aim of this study was to assess the sensitivity and specificity of CT in detecting pleural malignancy prior to definitive histology obtained via thoracoscopy in a large cohort of patients with suspected malignant pleural disease. Retrospective review of thoracoscopies between January 2008 and January 2013 at two UK tertiary referral centres: Oxford and Preston. The histological results were compared with the CT reported diagnosis before the procedure. CT scan reports were assessed by independent respiratory physicians as to whether the radiologist concluded evidence of malignant pleural disease or benign features only. 211 (57%) of 370 patients included in the analysis had malignant disease: CT scans were reported as ‘malignant’ in 144, giving a sensitivity of 68% (95% CI 62% to 75%). Of the 159 patients with benign disease, 124 had CT scans reported as benign: specificity 78% (72% to 84%). The positive predictive value of a malignant CT report was 80% (75% to 86%), with a negative predictive value of 65% (58% to 72%). A significant proportion of patients being investigated for malignant disease will have malignancy despite a negative CT report. The use of CT alone in determining which patients should have invasive pleural biopsies should be re-evaluated, and further studies to define the diagnostic pathway are now required.

Pleural infection: past, present, and future directions.

Pleural space infections are increasing in incidence and continue to have high associated morbidity, mortality, and need for invasive treatments such as thoracic surgery. The mechanisms of progression from a non-infected, pneumonia-related effusion to a confirmed pleural infection have been well described in the scientific literature, but the route by which pathogenic organisms access the pleural space is poorly understood. Data suggests that not all pleural infections can be related to lung parenchymal infection. Studies examining the microbiological profile of pleural infection inform antibiotic choice and can help to delineate the source and pathogenesis of infection. The development of radiological methods and use of clinical indices to predict which patients with pleural infection will have a poor outcome, as well as inform patient selection for more invasive treatments, is particularly important. Randomised clinical trial and case series data have shown that the combination of an intrapleural tissue plasminogen activator and deoxyribonuclease therapy can potentially improve outcomes, but the use of this treatment as compared with surgical options has not been precisely defined, particularly in terms of when and in which patients it should be used.

Advanced medical interventions in pleural disease

The burden of a number of pleural diseases continues to increase internationally. Although many pleural procedures have historically been the domain of interventional radiologists or thoracic surgeons, in recent years, there has been a marked expansion in the techniques available to the pulmonologist. This has been due in part to both technological advancements and a greater recognition that pleural disease is an important subspecialty of respiratory medicine. This article summarises the important literature relating to a number of advanced pleural interventions, including medical thoracoscopy, the insertion and use of indwelling pleural catheters, pleural manometry, point-of-care thoracic ultrasound, and image-guided closed pleural biopsy. We also aim to inform the reader regarding the latest updates to more established procedures such as chemical pleurodesis, thoracentesis and the management of chest drains, drawing on contemporary data from recent randomised trials. Finally, we shall look to explore the challenges faced by those practicing pleural medicine, especially relating to training, as well as possible future directions for the use and expansion of advanced medical interventions in pleural disease. Technological advances and greater availability of techniques give a broad range of interventions for pleural disease http://ow.ly/ZNya2

Defining the minimal important difference for the visual analogue scale assessing dyspnea in patients with malignant pleural effusions.

Background The minimal important difference (MID) is essential for interpreting the results of randomised controlled trials (RCTs). Despite a number of RCTs in patients with malignant pleural effusions (MPEs) which use the visual analogue scale for dyspnea (VASD) as an outcome measure, the MID has not been established. Methods Patients with suspected MPE undergoing a pleural procedure recorded their baseline VASD and their post-procedure VASD (24 hours after the pleural drainage), and in parallel assessed their breathlessness on a 7 point Likert scale. Findings The mean decrease in VASD in patients with a MPE reporting a ‘small but just worthwhile decrease’ in their dyspnea (i.e. equivalent to the MID) was 19mm (95% CI 14-24mm). The mean drainage volume required to produce a change in VASD of 19mm was 760ml. Interpretation The mean MID for the VASD in patients with a MPE undergoing a pleural procedure is 19mm (95% CI 14-24mm). Thus choosing an improvement of 19mm in the VASD would be justifiable in the design and analysis of future MPE studies.

New therapeutic approaches to pleural infection.

Purpose of review Pleural infection is a common and serious clinical problem that because of its high morbidity and mortality imposes a significant burden on clinicians, healthcare resources and patients of all ages. Defining the optimal management strategy for pleural infection remains a cause for research and debate. This review considers the areas of interest including bacteriology and antibiotic selection, intrapleural fibrinolytics and the role of surgery. Recent findings Pleural infection is increasing in the adult and paediatric populations without clear explanation and with clinical and financial consequences. The bacteriology of pleural infection is recognized as being unique from parenchymal lung infection with implications for its treatment. Although established in paediatric management, intrapleural fibrinolytics remain of uncertain benefit in adults, though the novel combination of tissue plasminogen activator and deoxyribonuclease used in the MIST2 study offers cause for optimism. Surgery remains a key intervention in pleural infection, but its precise role is unclear with no robust evidence to show when and in whom it should be optimally utilized. Summary The high mortality in adults from pleural infection despite advances in clinical knowledge, diagnostics and therapeutics highlights the need for ongoing research. Future studies are required to focus on improving the clinical outcomes, with the identification of those patients at greatest risk of poor outcomes at presentation and most likely to benefit from more radical treatment a priority to allow the delivery of individualized care.

Pleuro-Pulmonary Complications of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease whose distinctive feature is the development of symmetrical polyarthritis. It has a prevalence of ∼1% in the general population, predominating in females and peaking between the ages of 30 and 50 years; it is found worldwide,

Ultrasound-guided pneumothorax induction prior to local anaesthetic thoracoscopy

Local anaesthetic thoracoscopy (LAT) is performed by a growing number of respiratory physicians in the context of an expanding population with pleural disease. Most LATs occur in patients with moderate to large effusions where the presence of fluid allows safe access to the pleural space. Patients with little or no fluid, but other features concerning for pleural disease, are usually investigated by surgical means. Advanced LAT practitioners can also provide this service through pneumothorax induction, although there is little published data on the safety or efficacy of this technique. We present data from a series of 77 consecutive patients in whom ultrasound-guided pneumothorax induction and LAT were attempted. 67 procedures (87.0%) were successful, with the most common histopathological diagnoses being chronic pleuritis (58.2%) and mesothelioma (16.4%). No adverse events were reported secondary to the procedure. These findings demonstrate the utility of this approach and should inform future practice and guidelines.