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IntroductionWe present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis.Methods12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis.ResultsThe commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2 months (range 0.8–32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63versus0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18versus0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27versus0.09, p=0.09).DiscussionThis is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP.

The purpose of this study is to understand the educational assessment standards in Indonesia based on Minister of Education and Culture Regulation No. 21 of 2022. The research method used is literature review. The type of data used is data generated from the literature review, specifically related to Minister of Education and Culture Regulation No. 21 of 2022. The descriptive analysis method is employed. Minister of Education and Culture Regulation No. 21 of 2022 encompasses the assessment standards for students and the aspects developed in the learning process. The assessment of students' learning outcomes is conducted in accordance with fair, objective, and educative assessment objectives. In performing assessments, teachers must first determine the assessment criteria before making decisions, which should be adjusted to the classroom conditions. The structured and systematic assessment procedure consists of formulating assessment objectives, selecting and developing assessment instruments, processing assessment results, and reporting assessment outcomes. Assessments are carried out by educators considering the characteristics and needs of the students, based on an assessment plan that aligns with the learning plan.

PHOSP-COVID is a national UK multi-centre cohort study of patients who were hospitalised for COVID-19 and subsequently discharged.PHOSP-COVID was established to investigate the medium- and long-term sequelae of severe COVID-19 requiring hospitalisation, understand the underlying mechanisms of these sequelae, evaluate the medium- and long-term effects of COVID-19 treatments, and to serve as a platform to enable future studies, including clinical trials.Data collected covered a wide range of physical measures, biological samples, and Patient Reported Outcome Measures (PROMs).Participants could join the cohort either in Tier 1 only with remote data collection using hospital records, a PROMs app and postal saliva sample for DNA, or in Tier 2 where they were invited to attend two specific research visits for further data collection and biological research sampling. These research visits occurred at five (range 2-7) months and 12 (range 10-14) months post-discharge. Participants could also participate in specific nested studies (Tier 3) at selected sites.All participants were asked to consent to further follow-up for 25 years via linkage to their electronic healthcare records and to be re-contacted for further research.In total, 7935 participants were recruited from 83 UK sites: 5238 to Tier 1 and 2697 to Tier 2, between August 2020 and March 2022.Cohort data are held in a Trusted Research Environment and samples stored in a central biobank. Data and samples can be accessed upon request and subject to approvals.

Hepatic hydrothorax can be present in 5% to 15% of patients with underlying cirrhosis and portal hypertension, often reflecting advanced liver disease. Its impact can be variable, because patients may have small pleural effusions and minimal pulmonary symptoms or massive pleural effusions and respiratory failure. Management of hepatic hydrothorax can be difficult because these patients often have a number of comorbidities and potential for complications. Minimal high-quality data are available for guidance specifically related to hepatic hydrothorax, potentially resulting in pulmonary or critical care physician struggling for best management options. We therefore provide a Case-based presentation with management options based on currently available data and opinion. We discuss the role of pleural interventions, including thoracentesis, tube thoracostomy, indwelling tunneled pleural catheter, pleurodesis, and surgical interventions. In general, we recommend that management be conducted within a multidisciplinary team including pulmonology, hepatology, and transplant surgery. Patients with refractory hepatic hydrothorax that are not transplant candidates should be managed with palliative intent; we suggest indwelling tunneled pleural catheter placement unless otherwise contraindicated. For patients with unclear or incomplete hepatology treatment plans or those unable to undergo more definitive procedures, we recommend serial thoracentesis. In patients who are transplant candidates, we often consider serial thoracentesis as a standard treatment, while also evaluating the role indwelling tunneled pleural catheter placement may play within the course of disease and transplant evaluation.

OBJECTIVE: To investigate the effect of early diagnosis and intervention in adult patients with complicated parapneumonic pleural effusion or pleural empyema and the impact on outcomes.METHODS: A systematic review based on a literature search of the PubMed database was performed.RESULTS: Eleven eligible studies were included; nine observational studies and two randomised controlled trials totalling a study population of 10,717 patients. The studies were conducted from 1992 to 2018, all in Europe and Northern America except one. Results varied between studies, but a trend towards better outcome in patients with shorter duration of symptoms and quicker initiation of treatment was found. We found that duration of symptoms before treatment may affect length of hospital stay, rate of conversion to open surgery, and frequency of complications.CONCLUSION: We found that an earlier intervention in adults suffering from complicated parapneumonic pleural effusion and pleural empyema may potentially improve the outcome of patients in terms of length of stay, conversion to open surgery, and general complications following treatment, but not regarding mortality. Further studies are required to specify the timing of each intervention, and direct comparison in early management of interventions.

Research question Pulmonary rehabilitation is the best treatment for chronic breathlessness in COPD but there remains an unmet need to improve efficacy. Pulmonary rehabilitation has strong parallels with exposure-based cognitive behavioural therapies (CBT), both clinically and in terms of brain activity patterns. The partial N-methyl-D-aspartate (NMDA)-receptor agonist D-cycloserine has shown promising results in enhancing efficacy of CBT, thus we hypothesised that it would similarly augment the effects of pulmonary rehabilitation in the brain. Positive findings would support further development in phase 3 clinical trials. Methods 72 participants with mild-to-moderate COPD were recruited to a double-blind pre-registered (ClinicalTrials.gov identifier: NCT01985750) experimental medicine study running parallel to a pulmonary rehabilitation course. Participants were randomised to 250 mg D-cycloserine or placebo, administered immediately prior to the first four sessions of pulmonary rehabilitation. Primary outcome measures were differences between D-cycloserine and placebo in brain activity in the anterior insula, posterior insula, anterior cingulate cortices, amygdala and hippocampus following completion of pulmonary rehabilitation. Secondary outcomes included the same measures at an intermediate time point and voxel-wise difference across wider brain regions. An exploratory analysis determined the interaction with breathlessness anxiety. Results No difference between D-cycloserine and placebo groups was observed across the primary or secondary outcome measures. D-cycloserine was shown instead to interact with changes in breathlessness anxiety to dampen reactivity to breathlessness cues. Questionnaire and measures of respiratory function showed no group difference. This is the first study testing brain-active drugs in pulmonary rehabilitation. Rigorous trial methodology and validated surrogate end-points maximised statistical power. Conclusion Although increasing evidence supports therapeutic modulation of NMDA pathways to treat symptoms, we conclude that a phase 3 clinical trial of D-cycloserine would not be worthwhile., ERJ Open Research, 9 (2)

Healthcare-associated infections are major causes of complications that lead to extended hospital stays and significant medical costs. The use of medical devices, including catheters, increases the risk of bacterial colonization and infection through the presence of a foreign surface. Two outcomes are observed for catheterized patients: catheter-associated asymptomatic bacteriuria and catheter-associated urinary tract infection (CAUTI). However, the relationship between these two events remains unclear. To understand this relationship, we studied a murine model of Pseudomonas aeruginosa CAUTI. In this model, we also observe two outcomes in infected animals: acute symptoms that is associated with CAUTI and chronic colonization that is associated with asymptomatic bacteriuria. The timing of the acute outcome takes place in the first week of infection, whereas chronic colonization occurs in the second week of infection. We further showed that mutants lacking genes encoding type III secretion system (T3SS), T3SS effector proteins, T3SS injection pore, or T3SS transcriptional activation all fail to cause acute symptoms of CAUTI. Nonetheless, all mutants defective for T3SS colonized the catheter and bladders at levels similar to the parental strain. In contrast, through induction of the T3SS master regulator ExsA, all infected animals showed acute phenotypes with bacteremia. Our results demonstrated that the acute symptoms, which are analogous to CAUTI, and chronic colonization, which is analogous to asymptomatic bacteriuria, are independent events that require distinct bacterial virulence factors. Experimental delineation of asymptomatic bacteriuria and CAUTI informs different strategies for the treatment and intervention of device-associated infections.

Healthcare-associated infections are major causes of complications that lead to extended hospital stays and significant medical costs. The use of medical devices, including catheters, increases the risk of bacterial colonization and infection through the presence of a foreign surface. Two outcomes are observed for catheterized patients: catheter-associated asymptomatic bacteriuria and catheter-associated urinary tract infection (CAUTI). However, the relationship between these two events remains unclear. To understand this relationship, we studied a murine model of

Malignant pleural effusion (MPE) is a common condition which often causes significant symptoms to patients and costs to healthcare systems. Over the past decade, the management of MPE has progressed enormously with large scale, randomised trials answering key questions regarding optimal diagnostic strategies and effective management strategies. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. The future goals for providing improved care for patients lies in changing the treatment paradigm from a generic pathway to personalised care, based on probability of malignancy type and survival. This article reviews the current evidence base, new discoveries and future directions in the diagnosis and management of MPE.

Rationale: Sonographic septations are assumed to be important clinical predictors of outcome in pleural infection but the evidence for this is sparse. The inflammatory and fibrinolysis-associated intrapleural pathway(s) leading to septation formation have not been studied in a large cohort of pleural fluid (PF) samples with confirmed pleural infection, matched with ultrasound and clinical outcome data. Objectives: To assess the presence and severity of septations against baseline PF Plasminogen-Activator Inhibitor-1 (PAI-1) and other inflammatory and fibrinolysis-associated proteins as well as to correlate these with clinically important outcomes. Methods: We analysed 214 pleural fluid samples from the PILOT study, a prospective observational pleural infection study, for inflammatory and fibrinolysis-associated proteins using the Luminex platform. Multivariate regression analyses were utilised to assess association of pleural biological markers with septation presence and severity (on ultrasound), and clinical outcomes. Results: PF PAI-1 level was the only protein independently associated with septation presence (p=

Background: Thoracoscopy is the “gold standard” diagnostic modality for investigation of suspected pleural malignancy. It is postulated that meticulous assessment of the pleural cavity may be adequate to indicate malignancy through the macroscopic findings of nodules, pleural thickening, and lymphangitis. We attempted to critically assess this practice, by precisely defining objective macroscopic criteria which might differentiate benign from malignant pleural diseases according to intrapleural pattern and anatomical location, and thereby to explore the predilection of abnormalities to specific sites on pleural surfaces. Methods: A structured review of recorded video footage from medical thoracoscopy procedures in 96 patients was conducted by 2 independent assessors. Abnormalities were scored on agreed, objective criteria for the presence of nodules, lymphangitis and inflammation on each of the costoparietal, visceral and diaphragmatic surfaces. The costoparietal pleura was divided into 6 levels (apical, middle, and inferior surfaces of the lateral and posterior parietal pleura). The anterior surface of the costoparietal pleura was excluded from analysis after interim review as this surface was rarely seen. Results: In the benign group, inflammation was the predominant finding in 65% (n = 33; costoparietal), 44% (n = 21; visceral), and 42% (n = 15; diaphragmatic). Nodules were detected in 24% (n = 12; costoparietal), 8% (n = 4; visceral), and 8% (n = 3; diaphragmatic). The most affected surfaces with inflammation were the middle lateral (60%) and the inferior lateral (57.8%) parts of the costoparietal pleura. In the malignant group, nodules were the predominant finding according to surface in 73% (n = 33; costoparietal), 32% (n = 13; visceral) and 48% (n = 17; diaphragmatic). Inflammation was detected in 44% (n = 20; costoparietal), 25% (n = 10; visceral), and 29% (n = 10; diaphragmatic). The most affected surfaces with nodules were the middle lateral (67.4%) and inferior lateral (66.7%) costoparietal pleural surfaces. Conclusion: This is the first detailed, anatomical description of abnormalities in the pleural space during thoracoscopy. While nodules were the predominant pattern in malignant pleural effusion, they were detected in 24% of benign diagnoses. Detection of nodules in >1 area of the costoparietal pleura was in favor of a malignant diagnosis. Inflammation was the predominant pattern in benign pleural effusion. Our results suggest that macroscopic nodules in malignant diagnoses have a predilection for the middle and inferior surfaces of the lateral costoparietal pleura.

Background Patients with malignant pleural effusions (MPEs) experience breathlessness and poor survival. Breathlessness is associated with poor survival in other conditions. Research Question Is breathlessness, measured using a visual analog scale for dyspnea (VASD), associated with survival in patients with MPE? Study Design and Methods Individual patient data from five randomized controlled trials of 553 patients undergoing interventions for MPE were analyzed. VASD was recorded at baseline and daily after intervention. Patients were followed up until death or end of trial. Univariate and multivariable Cox regression were used to identify factors associated with survival. Results Baseline VASD was significantly associated with worse survival, with a hazard ratio of 1.10 (95% CI, 1.06-1.15) for a 10-mm increase in VASD. On multivariable regression, it remained a significant predictor of survival. Mean 7-day VASD and mean total VASD were also predictors of survival (mean 7-day VASD: hazard ratio [HR], 1.26 [95% CI, 1.19-1.34]; total VASD: HR, 1.25 [95% CI, 1.15-1.37]). Other predictors of survival were serum C-reactive protein level and tumor type. Previous treatment with chemotherapy, performance status, pleural fluid lactate dehydrogenase, serum albumin, hemoglobin, serum neutrophil:lymphocyte ratio, and size of effusion were associated with survival on univariate but not multivariable analysis. Interpretation Breathlessness, measured using VASD at baseline and postprocedure, is a predictor of survival in patients with MPE.

To determine the prevalence of pleural abnormalities and describe the computed tomography (CT) features observed in a well-characterised population of patients with pleural infection.A retrospective study of a subgroup of patients from the Second Multi-centre Intra-pleural Sepsis Trial (MIST 2) trial was carried out. Patients were diagnosed with pleural infection on robust clinical criteria. CT examinations were assessed by three observers independently for the presence of predefined features. Planned subgroup comparisons of patients with and without evidence of parenchymal infection were performed.Eighty-one patients were included. Parietal pleural thickening and enhancement were seen in 98.7% of patients. Visceral pleural changes were observed in most, including several previously undescribed features. Consolidation was observed in 61.7% of patients and there was a significant association of parenchymal consolidation with CT evidence of small airways infection (p0.001) and visceral pleural thickening and enhancement (p0.05). Features of parenchymal infection were absent in one third of patients.This study provides a comprehensive account of the parietal pleural, visceral pleural, and parenchymal changes of pleural infection on CT. Parenchymal infection is absent in a significant proportion of patients with pleural infection, suggesting that a pneumonic process may not be necessary for the development of pleural infection.

Pleural biopsy findings offer greater diagnostic sensitivity in malignant pleural effusions compared with pleural fluid. The adequacy of pleural biopsy techniques in achieving molecular marker status has not been studied, and such information (termed "actionable" histology) is critical in providing a rational, efficient, and evidence-based approach to diagnostic investigation.What is the adequacy of various pleural biopsy techniques at providing adequate molecular diagnostic information to guide treatment in malignant pleural effusions?This study analyzed anonymized data on 183 patients from four sites across three countries in whom pleural biopsy results had confirmed a malignant diagnosis and molecular profiling was relevant for the diagnosed cancer type. The primary outcome measure was adequacy of pleural biopsy for achieving molecular marker status. Secondary outcomes included clinical factors predictive of achieving a molecular diagnosis.The median age of patients was 71 years (interquartile range, 63-78 years), with 92 of 183 (50%) male. Of the 183 procedures, 105 (57%) were local anesthetic thoracoscopies (LAT), 12 (7%) were CT scan guided, and 66 (36%) were ultrasound guided. Successful molecular marker analysis was associated with mode of biopsy, with LAT having the highst yield and ultrasound-guided biopsy the lowest (LAT vs CT scan guided vs ultrasound guided: LAT yield, 95%; CT scan guided, 86%; and ultrasound guided, 77% [P = .004]). Biopsy technique and size of biopsy sample were independently associated with successful molecular marker analysis. LAT had an adjusted OR for successful diagnosis of 30.16 (95% CI, 3.15-288.56; P = .003) and biopsy sample size an OR of 1.18 (95% CI, 1.02-1.37) per millimeter increase in tissue sample size (P .03).Although previous studies have shown comparable overall diagnostic yields, in the modern era of targeted therapies, this study found that LAT offers far superior results to image-guided techniques at achieving molecular profiling and remains the optimal diagnostic tool.

Morbidity and mortality associated with GBS begin with colonization of the female reproductive tract (FRT). To date, our understanding of the factors required for GBS persistence in this environment remain limited.

Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined.What is the bleeding complication risk associated with IET use in pleural infection?This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria.Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of 100 × 10IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

Trypanosoma cruzi has three biochemically and morphologically distinct developmental stages that are programmed to rapidly respond to environmental changes the parasite faces during its life cycle. Unlike other eukaryotes, Trypanosomatid genomes contain protein coding genes that are transcribed into polycistronic pre-mRNAs and have their expression controlled by post-transcriptional mechanisms. Transcriptome analyses comparing three stages of the T. cruzi life cycle revealed changes in gene expression that reflect the parasite adaptation to distinct environments. Several genes encoding RNA binding proteins (RBPs), known to act as key post-transcriptional regulatory factors, were also differentially expressed. We characterized one T. cruzi RBP, named TcZH3H12, which contains a zinc finger domain and is up-regulated in epimastigotes compared to trypomastigotes and amastigotes. TcZC3H12 knockout (KO) epimastigotes showed decreased growth rates and increased capacity to differentiate into metacyclic trypomastigotes. Transcriptome analyses comparing wild type and TcZC3H12 KOs revealed a TcZC3H12-dependent expression of epimastigote-specific genes such as genes encoding amino acid transporters and proteins associated with differentiation (PADs). RNA immunoprecipitation assays showed that transcripts from the PAD family interact with TcZC3H12. Taken together, these findings suggest that TcZC3H12 positively regulates the expression of genes involved in epimastigote proliferation and also acts as a negative regulator of metacyclogenesis.

Background The management of recurrent pleural effusions remains a challenging issue for clinicians. Advances in management have led to increased use of indwelling tunneled pleural catheters (IPC) because of their effectiveness and ease of outpatient placement. However, with the increase in IPC placement there have also been increasing reports of complications, including infections. Currently there is minimal guidance in IPC-related management issues after placement. Research Question Our objective was to formulate clinical consensus statements related to perioperative and long-term IPC catheter management based on a modified Delphi process from experts in pleural disease management. Study Design and Methods Expert panel members used a modified Delphi process to reach consensus on common perioperative and long-term management options related to IPC use. Members were identified from multiple countries, specialties, and practice settings. A series of meetings and anonymous online surveys were completed. Responses were used to formulate consensus statements among panel experts, using a modified Delphi process. Consensus was defined a priori as greater than 80% agreement among panel constituents. Results A total of 25 physicians participated in this project. The following topics were addressed during the process: definition of an IPC infection, management of IPC-related infectious complications, interventions to prevent IPC infections, IPC-related obstruction/malfunction management, assessment of IPC removal, and instructions regarding IPC management by patients and caregivers. Strong consensus was obtained on 36 statements. No consensus was obtained on 29 statements. Interpretation The management of recurrent pleural disease with IPC remains complex and challenging. This statement offers statements for care in numerous areas related to IPC management based on expert consensus and identifies areas that lack consensus. Further studies related to long-term management of IPC are warranted.

Background: While the efficacy of Indwelling pleural catheters for palliation of malignant pleural effusions is supported by relatively robust evidence, there is less clarity surrounding the postinsertion management. Methods: The Trustworthy Consensus-Based Statement approach was utilized to develop unbiased, scientifically valid guidance for the management of patients with malignant effusions treated with indwelling pleural catheters. A comprehensive electronic database search of PubMed was performed based on a priori crafted PICO questions (Population/Intervention/Comparator/Outcomes paradigm). Manual searches of the literature were performed to identify additional relevant literature. Dual screenings at the title, abstract, and full-text levels were performed. Identified studies were then assessed for quality based on a combination of validated tools. Appropriateness for data pooling and formation of evidence-based recommendations was assessed using predetermined criteria. All panel members participated in development of the final recommendations utilizing the modified Delphi technique. Results: A total of 7 studies were identified for formal quality assessment, all of which were deemed to have a high risk of bias. There was insufficient evidence to allow for data pooling and formation of any evidence-based recommendations. Panel consensus resulted in 11 ungraded consensus-based recommendations. Conclusion: This manuscript was developed to provide clinicians with guidance on the management of patients with indwelling pleural catheters placed for palliation of malignant pleural effusions. Through a systematic and rigorous process, management suggestions were developed based on the best available evidence with augmentation by expert opinion when necessary. In addition, these guidelines highlight important gaps in knowledge which require further study.

INTRODUCTION: Malignant pleural effusion (MPE) is a complication of advanced cancer, associated with significant mortality and morbidity. This entity is commonly treated by respiratory physicians, oncologists, and thoracic surgeons. There have been various randomized clinical trials assessing the relative merits of chest drain pleurodesis, indwelling pleural catheters, treatment of septated MPEs, the use of thoracoscopy and pleurodesis and pleurodesis through IPCs in the past decade which have addressed some key areas in the management of MPEs, with an increasing focus on patient related outcome. AREAS COVERED: In this review, we examine and review the literature for management strategies for MPEs and discuss future directions. A detailed search of scientific literature and clinical trial registries published in the past two decades was undertaken. EXPERT OPINION: Tremendous progress has been made in management of MPE in the past decade and current strategy involves patient preference along with local expertise that is available.

Background Thoracentesis can be accomplished by active aspiration or drainage with gravity. This trial investigated whether gravity drainage could protect against negative pressure-related complications such as chest discomfort, re-expansion pulmonary edema, or pneumothorax compared with active aspiration. Methods This prospective, multicenter, single-blind, randomized controlled trial allocated patients with large free-flowing effusions estimated ≥ 500 mL 1:1 to undergo active aspiration or gravity drainage. Patients rated chest discomfort on 100-mm visual analog scales prior to, during, and following drainage. Thoracentesis was halted at complete evacuation or for persistent chest discomfort, intractable cough, or other complication. The primary outcome was overall procedural chest discomfort scored 5 min following the procedure. Secondary outcomes included measures of discomfort and breathlessness through 48 h postprocedure. Results A total of 142 patients were randomized to undergo treatment, with 140 in the final analysis. Groups did not differ for the primary outcome (mean visual analog scale score difference, 5.3 mm; 95% CI, –2.4 to 13.0; P = .17). Secondary outcomes of discomfort and dyspnea did not differ between groups. Comparable volumes were drained in both groups, but the procedure duration was significantly longer in the gravity arm (mean difference, 7.4 min; 95% CI, 10.2 to 4.6; P Conclusions Thoracentesis via active aspiration and gravity drainage are both safe and result in comparable levels of procedural comfort and dyspnea improvement. Active aspiration requires less total procedural time. Trial Registry ClinicalTrials.gov; No.: NCT03591952; URL: www.clinicaltrials.gov.

The bulk port operations are given a growing attention for their important role in the global supply chain in different industries (mining, energy ...). To guarantee their competitiveness, the efficient management of port logistics, including yard side management is crucial. In this paper, we consider a real-word storage space allocation problem at an export bulk terminal. We formulate the problem as a mixed integer linear program and we propose a heuristic method to solve large scale data sets. Both the model and the heuristic can help the yard planner to test different scenarios and provide better stock yard plan, which is a first step toward improving the management of port operation in the bulk terminal under study.

Additional file 1: Appendix A. TILT protocol.

Thoracoscopy is a technique used to visualize the pleural space and undertake diagnostic and therapeutic procedures in the presence of pleural disease. Thoracoscopy performed by physicians is usually undertaken using local anesthetic and sedation. It is commonly used to perform biopsies, mostly for the diagnosis of malignant pleural disease but can also be used for therapeutic procedures such as talc poudrage. The technique is performed by physicians in a number of centers, reducing the need for thoracic surgery, but there are some limitations to the technique where surgical intervention will still be required.

Additional file 5. PPI statement.

Background: The safety, effectiveness and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, in patients in the community who are multiply-vaccinated and at increased risk of morbidity and mortality from COVID-19, has not been established. We aimed to determine whether molnupiravir added to usual care reduced hospital admissions/deaths among people at higher risk from COVID-19, and here report our preliminary analyses. Methods: Participants in this UK multicentre, open-label, adaptive, multi-arm, platform, randomised controlled trial were aged ≥50, or ≥18 years with comorbidities, and unwell ≤5 days with confirmed COVID-19 in the community, and were randomised to usual care or usual care plus molnupiravir (800mg twice daily for 5 days). The primary outcome measure was all-cause hospitalisation/death within 28 days, analysed using Bayesian models. The main secondary outcome measure was time to first self-reported recovery. A sub-set of participants in each group were assessed for the virology primary outcome measure of day seven SARS-CoV-2 viral load. Trial registration: ISRCTN30448031 Findings: Between December 8, 2021 and April 27, 2022, 25783 participants were randomised to molnupiravir plus usual care (n=12821) or usual care alone (n=12962). Mean (range) age of participants was 56·6 years (18 to 99), 58·6% were female, and 99% had at least one dose of a SARS-CoV-2 vaccine. The median duration of symptoms prior to randomisation was two days (IQR 1 – 3), the median number of days from symptom onset to starting to take the medication was three days (IQR 3 – 4), 87% (11109/11997) received their medication within five days of symptom onset, and 95·4% (n=11857) of participants randomised to molnupiravir reported taking molnupiravir for five days. Primary outcome measure data were available in 25000 (97%) participants and included in this analysis. 103/12516 (0·8%) hospitalisations/deaths occurred in the molnupiravir group versus 96/12484 (0·8%) in usual care alone with a posterior probability of superiority of 0·34 (adjusted odds ratio 1·061 (95% Bayesian credible interval [BCI]) 0·80 to 1·40). Estimates were similar for all subgroups. The observed median (IQR) time-to-first-recovery from randomisation was 9 (5–23) days in molnupiravir and 15 (7–not reached) days in usual care. There was an estimated benefit of 4·2 (95% BCI: 3·8 – 4·6) days in time-to-first-recovery (TTR) giving a posterior probability of superiority of >0·999 (estimated median TTR 10·3 [10·2 – 10·6] days vs 14·5 [14·2 – 14·9] days respectively; hazard ratio [95% BCI], 1·36 [1·3–1·4] days), which met the pre-specified superiority threshold. On day 7, SARS-CoV-2 virus was below detection levels in 7/34 (21%) of the molnupiravir group, versus 1/39 (3%) in the usual care group (p=0.039), and mean viral load was lower in the molnupiravir group compared with those receiving usual care [(SD) of log10(viral load) 3·82 (1·40) in the molnupiravir group and 4.93 (1·38) in the usual care group, (P Interpretation: In this preliminary analysis, we found that molnupiravir did not reduce already low hospitalisations/deaths among higher risk, vaccinated adults with COVID-19 in the community, but resulted in faster time to recovery, and reduced viral detection and load. Funding: This project is funded by the NIHR (NIHR135366). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Additional file 2: Appendix B. Trial Specific Procedure for IMP administration.

Background: Malignant pleural effusion (MPE) is the build-up of pleural fluid in the space between the lung and chest wall due to advanced cancer. It is treated initially by large volume drainage (therapeutic aspiration). If the fluid reaccumulates, a definitive procedure is performed. There is wide variation in rate of reaccumulation. Patients with rapid reaccumulation often attend hospital as an emergency. Conversely, patients with slow reaccumulation do not need a definitive procedure and may experience cancelled or unnecessary procedures. This study aims to create and validate a multivariable prediction model to predict how quickly pleural fluid will reaccumulate in patients with MPE following therapeutic aspiration. Research question: Can we predict how quickly pleural fluid will reaccumulate in patients with MPEs? Methods: A total of 200 patients with known or suspected MPE attending for therapeutic aspiration will be recruited from 5-10 UK hospitals over 20 months. Patients will be enrolled prior to undergoing aspiration. Following this, they will undergo chest X-ray, which will be repeated one week later (treatment as usual). Rate of reaccumulation will be calculated based on change of size of the effusion seen on X-ray. Data will be collected on common clinical biomarkers e.g., size of effusion on pre-aspiration chest X-ray, volume of fluid drained. This data will be analysed to create a clinical score. A further validation cohort of 40 patients will be enrolled in parallel with creation of the score. Anticipated impact: The ability to predict rate of reaccumulation of MPE will enable patients and clinicians to make better informed treatment decisions. For patients with predicted rapid reaccumulation, a definitive procedure could be offered as first-line treatment, rather than a therapeutic aspiration. This will prevent emergency hospital admissions and decrease number of procedures. By contrast, patients whose effusions will recur slowly may avoid an unnecessary procedure.

BackgroundAmbulatory management of primary spontaneous pneumothorax has been shown to reduce initial hospitalisation, but at the expense of increase adverse events. As a result, questions remain about the cost-effectiveness of this option.ObjectivesA within-trial economic evaluation alongside a randomised controlled trial was performed to assess the cost-effectiveness of ambulatory care when compared with standard guideline-based management.MethodsPatients were randomly assigned to treatment with either an ambulatory device or standard guideline-based management (aspiration, standard chest tube insertion or both). Follow-up was 12 months. Outcomes included healthcare resource use and costs, quality of life, quality-adjusted life-years (QALYs) and cost-effectiveness.Results236 patients were recruited and randomly assigned to ambulatory care (n=117) and standard care (n=119). After multiple imputation for missing data, patients in the ambulatory care group had significantly lower National Health Service healthcare costs (−£788, 95% CI difference: −1527 to −50; p=0.037) than those in the standard care group. There were no differences in the number of QALYs gained (mean difference: −0.001, 95% CI difference: −0.032 to 0.030; p=0.95). When standard care was compared with ambulatory care, the incremental cost-effectiveness ratio was £799 066 per QALY gained, well above current thresholds of cost-effectiveness. As a result, the probability of ambulatory care being cost-effective was 0.93.ConclusionOutpatient ambulatory management is highly likely to be a cost-effective option in the management of primary pneumothorax.Trial registration numberISRCTN79151659.

The rising incidence and high morbidity of pleural infection remain a significant challenge to health care systems worldwide. With distinct microbiology and treatment paradigms from pneumonia, pleural infection is an area in which the evidence base has been rapidly evolving. Progress in recent years has revolved around characterizing the microbiome of pleural infection and the addition of new strategies such as intrapleural enzyme therapy to the established treatment pathway of drainage and antibiotics. The future of improving outcomes lies with personalizing treatment, establishing optimal timing of intrapleural agents and surgery, alongside wider use of risk stratification to guide treatment.

P217 Table 1A comparison of first and second wave characteristics, treatment and outcome data First wave Second wave Mean difference (95%CI) X2 (df) P value Age (years) 69.0 (52.0, 80.0) 62.0 (52.0, 71.0) -3.4 (-7.8 to +1.1) - 0.14 Sex: - Male - Female 49 (69.0%) 22 (31.0%) 180 (65.0%) 97 (35.0%) - 0.4 (1) 0.52 BMI (kg/m2) 28.5 (24.9, 33.6) 29.6 (24.8, 34.9) +0.6 (-1.7 to +2.9) - 0.63 Clinical Frailty Score: - 1 to 2 (fit) 18 (25.4%) 132 (47.7%) - 15.6 (5) 0.008 CT severity score - Moderate/severe - Severe 11 (29.7%) 23 (62.2%) 131 (52.2%) 113 (45.0%) - 16.0 (3) 0.0012 CRP prior to rHDU admission (mg/L) 180.6 (118.0, 210.0) 124.1 (78.1, 175.6) -44.1 (-66.9 to -21.3) - 0.0002 Spike gene testing - VOC B.1.1.7 variant - Wild-type - Ambiguous - - - 143 (67.1%) 57 (26.8%) 13 (6.1%) - - - Dexamethasone 3 (4.2%) 266 (96.0%) - 271.4 (1)

Rationale: Prolonged air leak (PAL) after partial lung resection can occur due to surgical complications or in the presence of residual thoracic space. The former type results in drainage-independe...