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Background Spatial differences in conduction velocity (CV) are critical for cardiac arrhythmias induction. We propose a method for an automated CV calculation to identify areas of slower conduction during cardiac arrhythmias and sinus rhythm. Methods Color-coded representations of the isochronal activation map using data coming from the RHYTHMIA™ Mapping System were reproduced by applying a temporal isochronal window at 20 ms. Geodesic distances of the 3D mesh were calculated using an algorithm selecting the minimum distance pathway (MDP). The CV estimation was performed considering points on the boundary of two spatially and temporally adjacent isochrones. For each of the boundary points of a given isochrone, the nearest boundary point of the consecutive isochrone was chosen, the MDP was evaluated, and a map of CV was created. The proposed method has been applied to a population of 29 patients. Results In all cases of perimitral atrial flutter (16 pts out of 29 (55%)), areas with significantly low CV ( Conclusions The proposed software for automated CV estimation allows the identification of low CV areas, potentially helping electrophysiologists to plan the ablation strategy.

Recepção crítica de Basílio da Gama do século XX.

BACKGROUND Low-dose computed tomography (LDCT) screening can reduce lung cancer deaths in high-risk individuals, yet current Australian guidelines do not recommend screening. Little is known about current screening practices in Australia. AIM To evaluate the proportion of general practitioners who report ordering lung cancer screening for their patients, identify factors associated with ordering lung cancer screening and assess general practitioners (GP) rationale for recommending screening and preference of composition of any future national targeted screening programme. METHODS A survey was distributed to a nationally representative sample of 4000 Australian GP. The questionnaire included respondent demographics, self-reported screening practices, knowledge of screening recommendations, recent screening education, preference for recruitment methodologies for potential screening programmes and potential factors influencing the screening practices of GP. Two logistic regression models identified factors associated with self-reported chest X-ray (CXR) and LDCT screening within the past 12 months. RESULTS A total of 323 GP completed the survey (participation rate 8.1%). Participants were mostly females (50.6%), from collective/group (79.1%) and metropolitan-based practices (73.5%). Despite the majority of responders understanding that screening is not recommended by Australian professional societies (71.2%), a substantial proportion of participants requested a CXR or LDCT screening (46.4% and 20.8% respectively). A variety of shared (GP reassurance, affordability of screening, believing screening is funded) and unique practice, educational and cognitive factors were associated with self-reported LDCT and CXR screening, with the strongest association being recent education about screening from radiology practices (odds ratio (aOR) for LDCT screening 10.4, P

The experiment MEGLIO follows the seminal work of Marra et al. (2018) where the authors demonstrate the possibility to observe seismic waves on fiber optic cables over large distances. The measure was based on an interferometric technique using an ultra stable laser. In theory, this active measurement technique is compatible with a commercial operation on a fiber, i.e. the fiber does not need to be dark. In 2019, Open Fiber, the largest optic fiber infrastructure provider in Italy, has decided to test this new technology on its own commercial network on land.A team of experts in the different fields has been gathered to achieve this goal : besides Open Fiber, Metallurgica Bresciana; INRiM, which initially developed the technique, for their expertise on laser and sensors; Bain & Company for the analysis and the processing of the data; INGV for the expertise in the seismology field and for the validation of the observations.The first year has been dedicated to developing the sensors. In the meantime, a buried optic cable has been chosen in function of its length and the seismicity nearby. The best candidate was the fiber connecting the towns of Ascoli Piceno (Marche, Italy) and Teramo (Abruzzo, Italy) for a length of around 30 km. Although this technique allows using cable lengths larger than 5.000 km, for this first test we have decided to keep the length short. Actually the cable is mainly buried underneath a road with medium traffic, passes across different bridges and viaducts, starts in the middle of a town and loops in the middle of another town. Thus we expected a strong anthropic noise on the data.The measurement on the field started in mid June 2020 and the system was operational in early July. We also installed a seismic station at one end of the cable. During these first six months, we have compared the observations on the fiber with the Italian national seismic catalog and the worldwide catalog for the major events. We consider the first results a success. We have detected so far nearly all the seismic activity with magnitude larger than 2.5 for epicentral distance lesser than 50 km. Moreover, we have recorded large events in Mediterranean region and teleseisms. Finally we have recorded new and interesting noise signals. Collecting additional events will be helpful for a better characterization of the technique, its performances and for a statistical analysis.

Atrial activation during typical atrioventricular nodal reentrant tachycardia (AVNRT) exhibits anatomic variability and spatially heterogeneous propagation inside the Koch’s triangle (KT). The mechanism of the reentrant circuit has not been elucidated yet. Aim of this study is to describe the distribution of Jackman and Haissaguerre potentials within the KT and to explore the activation mode of the KT, in sinus rhythm and during the slow-fast AVNRT. Forty-five consecutive cases of successful slow pathway (SP) ablation of typical slow-fast AVNRT from the CHARISMA registry were included. The KT geometry was obtained on the basis of the electroanatomic information using the Rhythmia mapping system (Boston Scientific) (mean number of points acquired inside the KT = 277 ± 47, mean mapping time = 11.9 ± 4 min). The postero-septal regions bounded anteriorly by the tricuspid annulus and posteriorly by the lateral wall toward the crista terminalis showed a higher prevalence of Jackman potentials than mid-postero-septal regions along the tendon of Todaro and coronary sinus (CS) (98% vs. 16%, p

Lung cancer screening is effective at reducing lung cancer deaths when individuals at greatest risk are screened. Recruitment initiatives target all current and former smokers, of whom only some are eligible for screening, potentially leading to discordance between screening preference and eligibility in ineligible individuals. The objective of the present study was to identify factors associated with preference for screening among ever-smokers. Ever-smokers aged 55–80 years attending outpatient clinics at three Australian hospitals were invited. The survey recorded: 1) demographics; 2) objective lung cancer risk and screening eligibility using the Prostate Lung Colon Ovarian 2012 risk model; and 3) perceived lung cancer risk, worry about and seriousness of lung cancer using a validated questionnaire. Multivariable ordinal logistic regression identified predictors of screening preference. The survey was completed by 283 individuals (response rate 27%). Preference for screening was high (72%) with no significant difference between low-dose computed tomography screening-eligible and -ineligible individuals (77% versus 68%, p=0.11). Worry about lung cancer (adjusted-proportional odds ratio (adj-OR) 1.31, 95% CI 1.08–1.58; p=0.007) and perceived seriousness of lung cancer (adj-OR 1.31, 95% CI 1.05–1.64; p=0.02) were associated with higher preference for lung cancer screening while screening eligibility was not. The concept of “early detection” was the most important driver to have screening while practical obstacles like difficulty travelling to the scan or taking time off work were the least important barriers to screening. Most current or former smokers prefer to undergo screening. Worry about lung cancer and perceived seriousness of the diagnosis are more important drivers for screening preference than eligibility status., Preference for lung cancer screening is high among Australian current and former smokers. Worry about lung cancer and perceived seriousness of the disease are associated with screening preference, while eligibility based on lung cancer risk is not. http://bit.ly/36PZlYA

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

In this paper we studied the effect of engineering expertise in providing directional judgments. We asked two groups of people, engineers and non-engineers, to observe and memorize five maps, each including a four-point path, for 30 sec. The path was then removed and the participants had to provide two directional judgments: aligned (the imagined perspective on the task was the same as the one just learned), and counter-aligned (the imagined perspective on the task was rotated by 180°). Our results showed that engineers are equally able to perform aligned and counter-aligned directional judgments. The alignment effect due to the distance from the learning perspective was, in fact, shown only by non-engineers. Results are discussed considering engineering both learning expertise and specific predisposition.

Lung cancer screening of high-risk individuals with computed tomography is a promising intervention to reduce lung cancer mortality. Patient Decision Aids (PtDAs) may assist eligible individuals assess the risks and benefits associated with screening. Screening preference is high among lower-risk, screening-ineligible individuals and strategies are needed to reduce screening demand among this group. We developed and evaluated a resource comprising a recruitment pamphlet combined with either a PtDA for screening-eligible individuals or an education pamphlet for screening-ineligible individuals. Quasi-experimental pre-post pamphlet exposure design. Ever-smokers aged 55–80 years attending hospital outpatient clinics were invited. Among screening-eligible participants, the assessed outcome was change in score on the Decisional Conflict Scale (DCS). Among screening-ineligible participants, the assessed outcomes were change in screening preference. In the study 51% (55/107) of invited individuals participated, with mean ± standard deviation age 66.9 ± 6.4 years, 53% (29/55) male, and 65% (36/55) eligible for screening. Median (interquartile range) DCS among screening-eligible participants reduced from 28.9 (22.7–45.3) pre-PtDA to 25 (1.6–29.7) post-PtDA (p < .001), but there was no significant change in the proportion that reached the accepted threshold for decisional certainty (DCS < 25, 10/36 [28%] pre-exposure vs. 14/36 [39%] post-exposure, p = .1). Screening preference among screening-ineligible individuals reduced after viewing the screening-ineligible brochure (pre-exposure median of “Prefer” to post-exposure median of “Unsure,” p = .001). Our consumer information pamphlets about lung cancer screening may reduce decisional conflict and improve alignment of screening preference with eligibility.

Atrial activation during typical atrioventricular nodal reentrant tachycardia (AVNRT) exhibits anatomic variability and spatially heterogeneous propagation inside the Koch's triangle (KT). The mechanism of the reentrant circuit has not been elucidated yet. Aim of this study is to describe the distribution of Jackman and Haïssaguerre potentials within the KT and to explore the activation mode of the KT, in sinus rhythm and during the slow-fast AVNRT.Forty-five consecutive cases of successful slow pathway (SP) ablation of typical slow-fast AVNRT from the CHARISMA registry were included.The KT geometry was obtained on the basis of the electroanatomic information using the Rhythmia mapping system (Boston Scientific) (mean number of points acquired inside the KT = 277 ± 47, mean mapping time = 11.9 ± 4 min). The postero-septal regions bounded anteriorly by the tricuspid annulus and posteriorly by the lateral wall toward the crista terminalis showed a higher prevalence of Jackman potentials than mid-postero-septal regions along the tendon of Todaro and coronary sinus (CS) (98% vs. 16%, p 0.0001). Haïssaguerre potentials seemed to have a converse distribution across the KT (0% vs. 84%, p 0.0001). Fast pathway insertion, as located during AVNRT, was mostly recorded in an antero-septal position (n = 36, 80%), rather than in a mid-septal (n = 6, 13.3%) or even postero-septal (n = 3, 7%) location. During typical slow-fast AVNRT, two types of propagation around the CS were discernible: anterior and posterior, n = 31 (69%), or only anterior, n = 14 (31%). During the first procedure, the SP was eliminated, and acute procedural success was achieved (median of 4 [3-5] RF ablations).High-density mapping of KT in AVNRT patients both during sinus rhythm and during tachycardia provides new electrophysiological insights. A better understanding and a more precise definition of the arrhythmogenic substrate in AVNRT patients may have prognostic value, especially in high-risk cases.Catheter Ablation of Arrhythmias With High Density Mapping System in the Real World Practice (CHARISMA) URL: http://clinicaltrials.gov/ Identifier: NCT03793998.

Following publication of the original article [1], the authors flagged that the article had gone to publishing with errors in Tables 1-3.

Use of non-invasive ventilation (NIV) in patients with hypercapnic respiratory failure has clear benefits over invasive ventilation. Existing risk prediction models are complex and difficult to apply in the acute setting. We developed the Midland NIV score comprising only five parameters for use to predict NIV failure (in-hospital death or intubation) at initiation. Individuals with Midland NIV score of ≤11 (average 13% NIV failure) may be suitable for general ward care, compared to intensive care for those with Midland NIV score ≥12 (average 66% NIV failure rate). Prospective external validation is required.

Background Lung cancer is the leading cause of cancer mortality in Australia. Guidelines suggest that patients with suspected lung cancer on thoracic imaging be referred for urgent specialist review. However, the term “suspected” is broad and includes the common finding of lung nodules, which often require periodic surveillance rather than urgent invasive investigation. The British Thoracic Society recommends that a lung nodule with a PanCan risk > 10% be considered for invasive investigation. This study aimed to assess which factors influence general practitioners (GPs) to request urgent review for a lung nodule and if these factors concur with PanCan risk prediction model variables. Methods A discrete choice experiment was developed that produced 32 individual case vignettes. Each vignette contained eight variables, four of which form the parsimonious PanCan risk prediction model. Two additional vignettes were created that addressed haemoptysis with a normal chest computed tomography (CT) scan and isolated mediastinal lymphadenopathy. The survey was distributed to 4160 randomly selected Australian GPs and they were asked if the patients in the vignettes required urgent (less than two weeks) specialist review. Multivariate logistic regression identified factors associated with request for urgent review. Results Completed surveys were received from 3.7% of participants, providing 152 surveys (1216 case vignettes) for analysis. The factors associated with request for urgent review were nodule spiculation (adj-OR 5.57, 95% CI 3.88–7.99, p p p Conclusion Future lung cancer investigation pathways may benefit from the addition of a risk prediction m9odel to reduce variations in referral behavior for low risk lung nodules.

Prognostication tools are developed to assist clinical decision making and provide valid diagnostic and prognostic outcomes including mortality. Given significant disease and demographic heterogeneity, these tools have to be generally applicable to different patient populations. Therefore, once a model is developed it is internally and externally validated with subsequent clinical impact analyses after which its performance is evaluated and that particular model is then established., A retrospective single-centre study suggesting that patients with higher SAPS3-CNIV scores may be monitored in an ICU setting in order to reduce adverse patient events and optimal utilisation of resources http://ow.ly/F5qp30o2OT7

BackgroundOver 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter.ObjectivesTo prospectively assess a previously described risk score (the RAPID (Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) score) in adults with pleural infection.MethodsProspective observational cohort study that recruited patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment and lung function at 3 months.ResultsMortality data were available in 542 out of 546 patients recruited (99.3%). Overall mortality was 10% at 3 months (54 out of 542) and 19% at 12 months (102 out of 542). The RAPID risk category predicted mortality at 3 months. Low-risk mortality (RAPID score 0–2): five out of 222 (2.3%, 95% CI 0.9 to 5.7%); medium-risk mortality (RAPID score 3–4): 21 out of 228 (9.2%, 95% CI 6.0 to 13.7%); and high-risk mortality (RAPID score 5–7): 27 out of 92 (29.3%, 95% CI 21.0 to 39.2%). C-statistics for the scores at 3 months and 12 months were 0.78 (95% CI 0.71–0.83) and 0.77 (95% CI 0.72–0.82), respectively.ConclusionsThe RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population.

Background Reading a map requires the ability to judge one's position in a large-scale space from information presented in a small-scale representation. Individuals are more accurate and faster in making judgments when the "up" direction on the map is the same as the "forward" direction of the environment, which is when a map is aligned with the perspective of the spatial layout they have learned (alignment effect). The aim of this study was to explore whether military pilots, who have high spatial abilities, would not show the alignment effect compared with nonpilots. Methods Recruited were 20 military pilots and 20 nonpilots. Mean flight hours were 418.75. Nonpilots without flight experience were matched for age and education with pilots. Subjects were asked to learn a map and to perform directional judgments to verify whether the alignment effect was present considering absolute angular errors. Results An ANOVA for mixed designs on absolute angular errors revealed a main "group" effect: pilots performed better than nonpilots (pilots: M = 22.60 ± 5.57; nonpilots: M = 82.59 ± 5.56). A main "directional judgments" effect was also observed: aligned judgements were easier than contra-aligned judgements (aligned, M = 9.277 ± 0.938; contra-aligned, M = 11.004 ± 0.805). ANOVA showed a significant "group × directional judgments" interaction: post hoc comparison showed that contra-aligned were more difficult than aligned judgments for nonpilots. Discussion High visuo-spatial abilities preserved pilots from having alignment effect bias. They performed directional judgments equally well, being less influenced by the increased cognitive effort requested by the changing perspective.Verde P, Angelino G, Piccolo F, Carrozzo P, Bottiglieri A, Lugli L, Piccardi L, Nori R. Spatial orientation and directional judgments in pilots vs. nonpilots. Aerosp Med Hum Perform. 2018; 89(10):857-862.

Background Indwelling pleural catheters (IPCs) are an effective option in the management of malignant pleural effusion. Up to 14% of patients with IPCs develop symptomatic pleural loculations causing ineffective fluid drainage and breathlessness. To our knowledge, this is the first study to describe intrapleural fibrinolytic therapy for IPC-related symptomatic loculations. Methods All patients who received intrapleural fibrinolytic therapy for symptomatic loculations between January 1, 2002, and June 30, 2014, in four established IPC centers were retrospectively included. Patient outcomes, treatment effectiveness, and adverse events were recorded. Results Sixty-six patients (mean age, 64.7 ± 14.2 years; 52% women) were included. Lung cancer (31.3%) and malignant pleural mesothelioma (20.3%) were the most common malignancies. Fibrinolytic instillation was performed in outpatient (61%) and inpatient settings. Tissue-plasminogen activator (n = 52), urokinase (n = 12), and streptokinase (n = 2) were used. The majority (69.7%) received only one fibrinolytic dose (range, one to six). Pleural fluid drainage increased in 93% of patients, and dyspnea improved in 83% following therapy. The median cumulative pleural fluid volume drained at 24 h posttreatment was 500 mL (interquartile range 300-1,034 mL). The area of opacity caused by pleural effusion on chest radiograph decreased from (mean, SD) 52% (14%) to 31% (21%) of the hemithorax (n = 13; P = .001). There were two cases of nonfatal pleural bleed (3%). Conclusions Intrapleural fibrinolytic therapy can improve pleural fluid drainage and symptoms in selected patients with IPC and symptomatic loculation, but it carries a small risk of pleural bleeding. There is significant heterogeneity in its use currently, and further studies are needed to determine patient selection and optimal dosing regimen and to define its safety profile.

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.

INTRODUCTION: Human navigation is a very complex ability that encompasses all four stages of human information processing (sensory input, perception/cognition, selection, and execution of an action), involving both cognitive and physical requirements. During flight, the pilot uses all of these stages and one of the most critical aspect is interference. In fact, spatial tasks competing for the same cognitive resource cause greater distraction from a concurrent task than another task that uses different resource modalities. METHODS: Here we compared and contrasted the performance of pilots and nonpilots of both genders performing increasingly complex navigational memory tasks while exposed to various forms of interference. We investigated the effects of four different sources of interference: motor, spatial motor, verbal, and spatial environment, focusing on gender differences. RESULTS: We found that flight experts perform better than controls (Pilots: 6.50 ± 1.29; Nonpilots: 5.45 ± 1.41). Furthermore, in the general population, navigational working memory is compromised only by spatial environmental interference (Nonpilots: 4.52 ± 1.50); female nonpilots were less able than male nonpilots. Also, the flight expert group showed the same interference, even if reduced (Pilots: 5.24 ± 0.92); moreover, we highlighted a complete absence of gender-related effects. DISCUSSION: Spatial environmental interference is the only interference producing a decrease in performance. Nevertheless, pilots are less affected than the general population. This is probably a consequence of the need to commit substantial cognitive resources to process spatial information during flight. Verde P, Boccia M, Colangeli S, Barbetti S, Nori R, Ferlazzo F, Piccolo F, Vitalone R, Lucertini E, Piccardi L. Domain-specific interference tests on navigational working memory in military pilots. Aerosp Med Hum Perform. 2016; 87(6):528-533. Language: en

Intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) therapy is being increasingly employed as an alternative to surgical intervention for the treatment of complicated parapneumonic effusions and empyema. Published cases are limited to one randomized control trial and few case reports. No data exist on employing sequential or repeated courses of intrapleural tPA/DNase to aid evacuation of separate collections in patients' with a multiloculated pleural infection. This is the first report of successful use of sequential delivery of separate courses of intrapleural tPA/DNase to two noncommunicating infected pleural fluid collections within the same hemithorax of a patient. Our case confirms that prior treatment with tPA/DNase therapy does not preclude subsequent effective and safe use of this intrapleural treatment.

Oxaliplatin-induced lung disease is an increasingly recognised phenomenon. We describe here three cases of presumed oxaliplatin-induced interstitial lung disease. With increasing use of oxaliplatin for colorectal cancer, awareness of this complication and the need for early diagnosis and treatment of respiratory symptoms can lead to early cessation of chemotherapy, rapid exclusion of alternative diagnoses and initiation of treatment with corticosteroids.

Indwelling pleural catheters (IPCs) are an effective option in the management of malignant pleural effusion. Up to 14% of patients with IPCs develop symptomatic pleural loculations causing ineffective fluid drainage and breathlessness. To our knowledge, this is the first study to describe intrapleural fibrinolytic therapy for IPC-related symptomatic loculations.All patients who received intrapleural fibrinolytic therapy for symptomatic loculations between January 1, 2002, and June 30, 2014, in four established IPC centers were retrospectively included. Patient outcomes, treatment effectiveness, and adverse events were recorded.Sixty-six patients (mean age, 64.7 ± 14.2 years; 52% women) were included. Lung cancer (31.3%) and malignant pleural mesothelioma (20.3%) were the most common malignancies. Fibrinolytic instillation was performed in outpatient (61%) and inpatient settings. Tissue-plasminogen activator (n = 52), urokinase (n = 12), and streptokinase (n = 2) were used. The majority (69.7%) received only one fibrinolytic dose (range, one to six). Pleural fluid drainage increased in 93% of patients, and dyspnea improved in 83% following therapy. The median cumulative pleural fluid volume drained at 24 h posttreatment was 500 mL (interquartile range 300-1,034 mL). The area of opacity caused by pleural effusion on chest radiograph decreased from (mean, SD) 52% (14%) to 31% (21%) of the hemithorax (n = 13; P = .001). There were two cases of nonfatal pleural bleed (3%).Intrapleural fibrinolytic therapy can improve pleural fluid drainage and symptoms in selected patients with IPC and symptomatic loculation, but it carries a small risk of pleural bleeding. There is significant heterogeneity in its use currently, and further studies are needed to determine patient selection and optimal dosing regimen and to define its safety profile.

Indwelling pleural catheter and talc pleurodesis are established treatments for malignant pleural effusions among patients with poor prognosis.To determine whether indwelling pleural catheters are more effective than talc pleurodesis in reducing total hospitalization days in the remaining lifespan of patients with malignant pleural effusion.This open-label, randomized clinical trial included participants recruited from 9 centers in Australia, New Zealand, Singapore, and Hong Kong between July 2012 and October 2014; they were followed up for 12 months (study end date: October 16, 2015). Patients (n = 146) with symptomatic malignant pleural effusion who had not undergone indwelling pleural catheter or pleurodesis treatment were included.Participants were randomized (1:1) to indwelling pleural catheter (n = 74) or talc pleurodesis (n = 72), minimized by malignancy (mesothelioma vs others) and trapped lung (vs not), and stratified by region (Australia vs Asia).The primary end point was the total number of days spent in hospital from procedure to death or to 12 months. Secondary outcomes included further pleural interventions, patient-reported breathlessness, quality-of-life measures, and adverse events.Among the 146 patients who were randomized (median age, 70.5 years; 56.2% male), 2 withdrew before receiving the randomized intervention and were excluded. The indwelling pleural catheter group spent significantly fewer days in hospital than the pleurodesis group (median, 10.0 [interquartile range [IQR], 3-17] vs 12.0 [IQR, 7-21] days; P = .03; Hodges-Lehmann estimate of difference, 2.92 days; 95% CI, 0.43-5.84). The reduction was mainly in effusion-related hospitalization days (median, 1.0 [IQR, 1-3] day with the indwelling pleural catheter vs 4.0 (IQR, 3-6) days with pleurodesis; P .001; Hodges-Lehmann estimate, 2.06 days; 95% CI, 1.53-2.58). Fewer patients randomized to indwelling pleural catheter required further ipsilateral invasive pleural drainages (4.1% vs 22.5%; difference, 18.4%; 95% CI, 7.7%-29.2%). There were no significant differences in improvements in breathlessness or quality of life offered by indwelling pleural catheter or talc pleurodesis. Adverse events were seen in 22 patients in the indwelling pleural catheter group (30 events) and 13 patients in the pleurodesis group (18 events).Among patients with malignant pleural effusion, treatment with an indwelling pleural catheter vs talc pleurodesis resulted in fewer hospitalization days from treatment to death, but the magnitude of the difference is of uncertain clinical importance. These findings may help inform patient choice of management for pleural effusion.anzctr.org.au Identifier: ACTRN12611000567921.

Intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) therapy for pleural infection given at the time of diagnosis has been shown to significantly improve radiological outcomes. Published cases are limited to only a single randomized controlled trial and a few case reports.Multinational observation series to evaluate the pragmatic "real-life" application of tPA/DNase treatment for pleural infection in a large cohort of unselected patients.All patients from eight centers who received intrapleural tPA/DNase for pleural infection between January 2010 and September 2013 were included. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity and inflammatory markers, need for surgery, and adverse events.Of 107 patients treated, the majority (92.3%) were successfully managed without the need for surgical intervention. No patients died as a result of pleural infection. Most patients (84%) received tPA/DNase more than 24 hours after failing to respond to initial conservative management with antibiotics and thoracostomy. tPA/DNase increased fluid drained from a median of 250 ml (interquartile range [IQR], 100-654) in the 24 hours preceding commencement of intrapleural therapy to 2,475 ml (IQR 1,800-3,585) in the 72 hours following treatment initiation (P 0.05). We observed a corresponding clearance of pleural opacity on chest radiographs from a median of 35% (IQR 25-31) to 14% (7-28) of the hemithorax (P 0.001), as well as significant reduction in C-reactive protein (P 0.05). Pain necessitating escalation of analgesia occurred in 19.6% patients, and nonfatal bleeding occurred in 1.8%.This large series of patients who received intrapleural tPA/DNase therapy provides important evidence that the treatment is effective and safe, especially as a "rescue therapy" in patients who do not initially respond to antibiotics and thoracostomy drainage.

INTRODUCTION: Malignant pleural effusion can complicate most cancers. It causes breathlessness and requires hospitalisation for invasive pleural drainages. Malignant effusions often herald advanced cancers and limited prognosis. Minimising time spent in hospital is of high priority to patients and their families. Various treatment strategies exist for the management of malignant effusions, though there is no consensus governing the best choice. Talc pleurodesis is the conventional management but requires hospitalisation (and substantial healthcare resources), can cause significant side effects, and has a suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory fluid drainage without hospitalisation, and are increasingly employed for management of malignant effusions. Previous studies have only investigated the length of hospital care immediately related to IPC insertion. Whether IPC management reduces time spent in hospital in the patients' remaining lifespan is unknown. A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital, reduce costs and save healthcare resources. METHODS AND ANALYSIS: The Australasian Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial designed to compare IPC with talc pleurodesis for the management of malignant pleural effusion. This study will randomise 146 adults with malignant pleural effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end point is the total number of days spent in hospital (for any admissions) from treatment procedure to death or end of study follow-up. Secondary end points include hospital days specific to pleural effusion management, adverse events, self-reported symptom and quality-of-life scores. ETHICS AND DISSEMINATION: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals. The trial results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBERS: Australia New Zealand Clinical Trials Registry-ACTRN12611000567921; National Institutes of Health-NCT02045121., published_or_final_version

Adults with cystic fibrosis (CF) have significant rates of asymptomatic Clostridium difficile carriage and are frequently exposed to risk factors for C. difficile infection (CDI). Despite this, the rate of reported CDI in CF is low. We describe three cases of near fatal CDI in adults with CF and review the literature regarding presentation, management, and recurrence prevention. Early recognition is important as the clinical presentation may be atypical and the illness can be severe and even life-threatening. Management can be complicated by respiratory and nutritional failure. CF-related gastrointestinal dysfunction may alter the typical host-pathogen interaction between patient and C. difficile, potentially explaining the low rates of CDI and atypical presentation.