Histopathology of removed indwelling pleural catheters from patients with malignant pleural diseases.

BACKGROUND AND OBJECTIVE: Indwelling pleural catheters (IPC), used for management of malignant pleural effusions, are often left in situ for a long duration. This study reports for the first time the histological findings of IPCs removed from patients with underlying pleural malignancy. METHODS: Forty-one IPCs (in situ for median 126 days, interquartile range 43-226) that were removed over a 54-month period from a single centre were examined. RESULTS: Mesothelioma (n = 18) was the predominant underlying malignancy followed by breast, tubo-ovarian and lung carcinomas. The catheter tubing was fully intact macroscopically in all IPCs. There was no evidence of direct tumour invasion or cancer cell growth on the catheter surfaces in none of the 29 IPCs that were histologically examined. Malignant cells were seen within organizing fibrinous tissues in the lumen of 11 IPCs (27%). A foreign body giant cell reaction was present at the cuff site in all the 29 IPC in which the subcutaneous cuff was examined. Acute (n = 10) and/or chronic inflammatory changes were seen in the luminal contents in all 41 IPCs. CONCLUSION: Our study provides reassuring evidence that the IPC material does not support direct tumour growth or invasion even in the setting of high mesothelioma prevalence. See Editorial, page 787.

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

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

Pleural infection: what we need to know but don't.

PURPOSE OF REVIEW: Pleural infection remains a common and difficult problem to manage in the 21st century. Despite advances in modern healthcare, the rising incidence and mortality of empyema highlights a need for better understanding of the disease and more effective strategies in its diagnosis and treatment. RECENT FINDINGS: Recent studies have progressed our knowledge and understanding of the bacteriology and pathophysiology of pleural infection. However, rather than providing firm conclusions, examination of current literature provokes several unanswered questions on most aspects of the disease. SUMMARY: This review aims to challenge traditional current concepts and approaches to clinical practice in pleural infection, to stimulate debate and research into potential novel future therapies.

Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial.

BACKGROUND: Indwelling pleural catheters are an established management option for malignant pleural effusion and have advantages over talc slurry pleurodesis. The optimal regimen of drainage after indwelling pleural catheter insertion is debated and ranges from aggressive (daily) drainage to drainage only when symptomatic. METHODS: AMPLE-2 was an open-label randomised trial involving 11 centres in Australia, New Zealand, Hong Kong, and Malaysia. Patients with symptomatic malignant pleural effusions were randomly assigned (1:1) to the aggressive (daily) or symptom-guided drainage groups for 60 days and minimised by cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group [ECOG] score 0-1 vs ≥2), presence of trapped lung, and prior pleurodesis. Patients were followed up for 6 months. The primary outcome was mean daily breathlessness score, measured by use of a 100 mm visual analogue scale during the first 60 days. Secondary outcomes included rates of spontaneous pleurodesis and self-reported quality-of-life measures. Results were analysed by an intention-to-treat approach. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12615000963527. FINDINGS: Between July 20, 2015, and Jan 26, 2017, 87 patients were recruited and randomly assigned to the aggressive (n=43) or symptom-guided (n=44) drainage groups. The mean daily breathlessness scores did not differ significantly between the aggressive and symptom-guided drainage groups (geometric means 13·1 mm [95% CI 9·8-17·4] vs 17·3 mm [13·0-22·0]; ratio of geometric means 1·32 [95% CI 0·88-1·97]; p=0·18). More patients in the aggressive group developed spontaneous pleurodesis than in the symptom-guided group in the first 60 days (16 [37·2%] of 43 vs five [11·4%] of 44, p=0·0049) and at 6 months (19 [44·2%] vs seven [15·9%], p=0·004; hazard ratio 3·287 [95% CI 1·396-7·740]; p=0·0065). Patient-reported quality-of-life measures, assessed with EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L), were better in the aggressive group than in the symptom-guided group (estimated means 0·713 [95% CI 0·647-0·779] vs 0·601 [0·536-0·667]). The estimated difference in means was 0·112 (95% CI 0·0198-0·204; p=0·0174). Pain scores, total days spent in hospital, and mortality did not differ significantly between groups. Serious adverse events occurred in 11 (25·6%) of 43 patients in the aggressive drainage group and in 12 (27·3%) of 44 patients in the symptom-guided drainage group, including 11 episodes of pleural infection in nine patients (five in the aggressive group and six in the symptom-guided drainage group). INTERPRETATION: We found no differences between the aggressive (daily) and the symptom-guided drainage regimens for indwelling pleural catheters in providing breathlessness control. These data indicate that daily indwelling pleural catheter drainage is more effective in promoting spontaneous pleurodesis and might improve quality of life. FUNDING: Cancer Council of Western Australia and the Sir Charles Gairdner Research Advisory Group.

Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters.

INTRODUCTION: Malignant pleural effusions (MPEs) can complicate most cancers, causing dyspnoea and impairing quality of life (QoL). Indwelling pleural catheters (IPCs) are a novel management approach allowing ambulatory fluid drainage and are increasingly used as an alternative to pleurodesis. IPC drainage approaches vary greatly between centres. Some advocate aggressive (usually daily) removal of fluid to provide best symptom control and chance of spontaneous pleurodesis. Daily drainages however demand considerably more resources and may increase risks of complications. Others believe that MPE care is palliative and drainage should be performed only when patients become symptomatic (often weekly to monthly). Identifying the best drainage approach will optimise patient care and healthcare resource utilisation. METHODS AND ANALYSIS: A multicentre, open-label randomised trial. Patients with MPE will be randomised 1:1 to daily or symptom-guided drainage regimes after IPC insertion. Patient allocation to groups will be stratified for the cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group status 0-1 vs ≥2), presence of trapped lung (vs not) and prior pleurodesis (vs not). The primary outcome is the mean daily dyspnoea score, measured by a 100 mm visual analogue scale (VAS) over the first 60 days. Secondary outcomes include benefits on physical activity levels, rate of spontaneous pleurodesis, complications, hospital admission days, healthcare costs and QoL measures. Enrolment of 86 participants will detect a mean difference of VAS score of 14 mm between the treatment arms (5% significance, 90% power) assuming a common between-group SD of 18.9 mm and a 10% lost to follow-up rate. ETHICS AND DISSEMINATION: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study (number 2015-043). Results will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: ACTRN12615000963527; Pre-results.

Regulatory responses to over-the-counter codeine analgesic misuse in Australia, New Zealand and the United Kingdom.

OBJECTIVE: Analysis of the policy response by Australia's National Drugs and Poisons Schedule Committee (NDPSC) and comparison with recommendations by expert advisory committees in New Zealand and the United Kingdom. METHODS: Analysis of public policy documents of relevant regulatory authorities was conducted. Data were extracted regarding changes to over-the-counter (OTC) codeine analgesic scheduling, indications, maximum unit dose, maximum daily dose, maximum pack size, warning labels, consumer medicine information and advertising. Where available, public submissions and other issues considered by the committees and rationale for their recommendations were recorded and thematically analysed. RESULTS: Expert advisory committees in Australia, NZ and the UK defined the policy problem of OTC codeine misuse and harm as small relative to total use and responded by restricting availability. Pharmacist supervision was required at the point-of-sale and pack sizes were reduced to short-term use. CONCLUSIONS: Comparison with recommendations by expert advisory committees in NZ and the UK suggests the NDPSC's actions in response to OTC codeine misuse were appropriate given the available evidence of misuse and harm, but highlights opportunities to utilise additional regulatory levers. IMPLICATIONS: Framing policy problems as matters of public health in the context of limited evidence may support decision makers to implement cautionary incremental policy change.

Support for breaking the nexus between alcohol and community sports settings: findings from the VicHealth Community Attitudes Survey in Australia.

INTRODUCTION AND AIMS: This study describes levels and predictors of community attitudes towards alcohol, support for structural alterations to the drinking context, and intention to increase participation in community sports clubs. DESIGN AND METHODS: Cross-sectional data were obtained from the VicHealth Community Attitudes Survey on Healthy Sporting Environments, administered to a random sample of Victorian adults. Descriptive and multivariate logistic regression analysis was undertaken. RESULTS: Very high support for removing alcohol sponsorship of community sport and for a levy on alcohol advertising was found. The groups most supportive of breaking the nexus between alcohol and community sport were female, older-aged and non-English-speaking citizens and those not involved in sport clubs. If alcohol sales at community sports clubs were reduced, participation may increase among population groups currently identified as least engaged with community sport. DISCUSSION AND CONCLUSIONS: An optimal climate exists for policy reforms to make community sporting environments healthier by reducing the ties with alcohol. If implemented, these reforms may lead to an increase and diversification of participants in community sport.

Over-the-counter codeine analgesic misuse and harm: characteristics of cases in Australia and New Zealand.

AIM: To describe the characteristics of clients addicted to over-the-counter (OTC) codeine analgesics presenting to an Auckland open-access clinic, and to compare them to clients admitted to a New Zealand detoxification unit, and in the Australian community. METHOD: Cross-sectional study of clients presenting to a regional, open-access detoxification clinic covering the Greater Auckland area between 1 January and 31 March 2010. RESULTS: Fifteen clients were analysed, and compared to 77 similar clients identified in Victoria and five other Australian States, and 7 clients admitted to a New Zealand detoxification unit. Cases in each cohort were consistent with those in the published literature, and appear to be similar to each other both demographically and in terms of the high average tablets consumption (49-65 tablets per day), the serious non-steroidal anti-inflammatory drug (NSAID) adverse drug reactions identified, and the long duration of misuse. Many had a history of alcohol or other drug use and mental health disorder. CONCLUSIONS: This study has identified that controls on OTC codeine analgesics in both countries were not sufficient to limit non-medical use of these products. As a result, cases identified in these two countries escalated the number of self-administered tablets taken daily for misuse, resulting in codeine dependence and serious NSAID toxicity secondary to this dependence.

Serious morbidity associated with misuse of over-the-counter codeine-ibuprofen analgesics: a series of 27 cases.

OBJECTIVE: To investigate morbidity related to misuse of over-the-counter (OTC) codeine-ibuprofen analgesics. DESIGN AND SETTING: Prospective case series collected from Victorian hospital-based addiction medicine specialists between May 2005 and December 2008. MAIN OUTCOME MEASURES: Morbidity associated with codeine-ibuprofen misuse. RESULTS: Twenty-seven patients with serious morbidity were included, mainly with gastrointestinal haemorrhage and opioid dependence. The patients were taking mean daily doses of 435-602 mg of codeine phosphate and 6800-9400 mg ibuprofen. Most patients had no previous history of substance use disorder. The main treatment was opioid substitution treatment with buprenorphine-naloxone or methadone. CONCLUSIONS: Although codeine can be considered a relatively weak opioid analgesic, it is nevertheless addictive, and the significant morbidity and specific patient characteristics associated with overuse of codeine-ibuprofen analgesics support further awareness, investigation and monitoring of OTC codeine-ibuprofen analgesic use.