Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

The impact of outpatient versus inpatient management on health-related quality of life outcomes for patients with malignant pleural effusion: the OPTIMUM randomised clinical trial.

BACKGROUND: The principal aim of malignant pleural effusion (MPE) management is to improve health-related quality of life (HRQoL) and symptoms. METHODS: In this open-label randomised controlled trial, patients with symptomatic MPE were randomly assigned to either indwelling pleural catheter (IPC) insertion with the option of talc pleurodesis or chest drain and talc pleurodesis. The primary end-point was global health status, measured with the 30-item European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) at 30 days post-intervention. 142 participants were enrolled from July 2015 to December 2019. RESULTS: Of participants randomly assigned to the IPC (n=70) and chest drain (n=72) groups, primary outcome data were available in 58 and 56 patients, respectively. Global health status improved in both groups at day 30 compared with baseline: IPC (mean difference 13.11; p=0.001) and chest drain (mean difference 10.11; p=0.001). However, there was no significant between-group difference at day 30 (mean intergroup difference in baseline-adjusted global health status 2.06, 95% CI -5.86-9.99; p=0.61), day 60 or day 90. No significant differences were identified between groups in breathlessness and chest pain scores. All chest drain arm patients were admitted (median length of stay 4 days); seven patients in the IPC arm required intervention-related hospitalisation. CONCLUSIONS: While HRQoL significantly improved in both groups, there were no differences in patient-reported global health status at 30 days. The outpatient pathway using an IPC was not superior to inpatient treatment with a chest drain.

Associations of physical activity and quality of life in parapneumonic effusion patients.

Introduction: Little is known about activity behaviours and quality of life (QoL) of patients with parapneumonic pleural effusions (PPE) after hospital discharge. This study is a secondary analysis of a randomised trial (dexamethasone versus placebo) for hospitalised patients with PPE. We: 1) described the patients' activity behaviour patterns and QoL measured at discharge and at 30 days post-discharge; and 2) examined the association between activity behaviours and QoL scores. Methods: Activity behaviour (7-day accelerometry; Actigraph GT3X+) and QoL (Medical Outcomes Study Short-Form 36) were assessed. Repeated measures analysis of covariance controlling for baseline values and a series of linear regression models were undertaken. Results: 36 out of 53 eligible participants completed accelerometry assessments. Despite modest increases in light physical activity (+7.5%) and some domains of QoL (>2 points) from discharge to 30 days post-discharge, patients had persistently high levels of sedentary behaviour (>65% of waking wear time) and poor QoL (≤50 out of 100 points) irrespective of treatment group (p=0.135-0.903). Increasing moderate-to-vigorous physical activity was associated with higher scores on most QoL domains (p=0.006-0.037). Linear regression indicates that a clinically important difference of 5 points in physical composite QoL score can be achieved by reallocating 16.1 min·day-1 of sedentary time to moderate-to-vigorous physical activity. Conclusion: Patients with PPE had low levels of physical activity and QoL at discharge and 30 days post-discharge irrespective of treatment. Moderate-to-vigorous physical activity participation was associated with higher QoL scores. Increasing moderate-to-vigorous physical activity following discharge from the hospital may be associated with improvements in QoL.

Expert Review on Nonsurgical Management of Parapneumonic Effusion: Advances, Controversies, and New Directions.

Parapneumonic effusion and empyema are rising in incidence worldwide, particularly in association with comorbidities in an aging population. Also driving this change is the widespread uptake of pneumococcal vaccines, leading to the emergence of nonvaccine-type pneumococci and other bacteria. Early treatment with systemic antibiotics is essential but should be guided by local microbial guidelines and antimicrobial resistance patterns due to significant geographical variation. Thoracic ultrasound has emerged as a leading imaging technique in parapneumonic effusion, enabling physicians to characterize effusions, assess the underlying parenchyma, and safely guide pleural procedures. Drainage decisions remain based on longstanding criteria including the size of the effusion and fluid gram stain and biochemistry results. Small-bore chest drains appear to be as effective as large bore and are adequate for the delivery of intrapleural enzyme therapy (IET), which is now supported by a large body of evidence. The IET dosing regimen used in the UK Multicenter Sepsis Trial -2 has the most evidence available but data surrounding alternative dosing, concurrent and once-daily instillations, and novel fibrinolytic agents are promising. Prognostic scores used in pneumonia (e.g., CURB-65) tend to underestimate mortality in parapneumonic effusion/empyema. Scores specifically based on pleural infection have been developed but require validation in prospective cohorts.

Device assessed activity behaviours in patients with indwelling pleural catheter: A sub-study of the Australasian Malignant PLeural Effusion (AMPLE)-2 randomized trial.

BACKGROUND AND OBJECTIVE: Device-assessed activity behaviours are a novel measure for comparing intervention outcomes in patients with malignant pleural effusion (MPE). Australasian Malignant PLeural Effusion (AMPLE)-2 was a multi-centre clinical trial where participants with MPE treated with an indwelling pleural catheter were randomized to daily (DD) or symptom-guided (SGD) drainage for 60-days. Our aim was to describe activity behaviour patterns in MPE patients, explore the impact of drainage regimen on activity behaviours and examine associations between activity behaviours and quality of life (QoL). METHODS: Following randomization to DD or SGD, participants enrolled at the lead site (Perth) completed accelerometry assessment. This was repeated monthly for 5-months. Activity behaviour outcomes were calculated as percent of daily waking-wear time and compared between groups (Mann-Whitney U test; Median [IQR]). Correlations between activity behaviour outcomes and QoL were examined. RESULTS: Forty-one (91%) participants provided ≥1 valid accelerometry assessment (DDn = 20, SGD n = 21). Participants spent a large proportion of waking hours sedentary (72%-74% across timepoints), and very little time in moderate-to-vigorous physical activity (<1% across timepoints). Compared to SGD group, DD group had a more favourable sedentary-to-light ratio in the week following randomization (2.4 [2.0-3.4] vs. 3.2 [2.4-6.1]; p = 0.047) and at 60-days (2.0 [1.9-2.9] vs. 2.9 [2.8-6.0]; p = 0.016). Sedentary-to-light ratio was correlated with multiple QoL domains at multiple timepoints. CONCLUSION: Patients with MPE are largely sedentary. Preliminary results suggest that even modest differences in activity behaviours favouring the DD group could be meaningful for this clinical population. Accelerometry reflects QoL and is a useful outcome measure in MPE populations.

Malignant pleural disease.

Malignant pleural disease represents a growing healthcare burden. Malignant pleural effusion affects approximately 1 million people globally per year, causes disabling breathlessness and indicates a shortened life expectancy. Timely diagnosis is imperative to relieve symptoms and optimise quality of life, and should give consideration to individual patient factors. This review aims to provide an overview of epidemiology, pathogenesis and suggested diagnostic pathways in malignant pleural disease, to outline management options for malignant pleural effusion and malignant pleural mesothelioma, highlighting the need for a holistic approach, and to discuss potential challenges including non-expandable lung and septated effusions.

Ipsilateral and contralateral hemidiaphragm dynamics in symptomatic pleural effusion: The 2nd PLeural Effusion And Symptom Evaluation (PLEASE-2) Study.

BACKGROUND AND OBJECTIVE: The pathophysiology of breathlessness in pleural effusion is unclear. In the PLEASE-1 study, abnormal ipsilateral hemidiaphragm shape and movement, assessed qualitatively, were independently associated with breathlessness relief after pleural drainage. Effects of pleural effusion on contralateral hemidiaphragm function are unknown. PLEASE-2, a prospective exploratory pilot study, assessed the effects of unilateral effusion and drainage on both hemidiaphragms using advanced quantitative bedside ultrasonography. METHODS: Individuals with symptomatic unilateral pleural effusion undergoing therapeutic drainage were included. Measurements pre- and post-drainage included severity of breathlessness (visual analogue scale) and ultrasound measurements of diaphragm excursion and thickness, in addition to shape and movement. Diaphragm measurements were compared to published reference values. RESULTS: Twenty participants were recruited (mean age 68.9 [SD 12.8] years, 12 females). During tidal breathing, contralateral hemidiaphragm excursion exceeded ipsilateral excursion and reference values (all p ≤ 0.001). Contralateral excursion was greatest in participants with abnormal ipsilateral hemidiaphragm movement and was inversely correlated with ipsilateral tidal excursion (r = -0.676, p = 0.001). Following drainage (mean volume 2121 [SD = 1206] ml), abnormal shape (n = 12) and paradoxical movement (n = 9) of the ipsilateral hemidiaphragm resolved in all participants, and tidal excursion of the contralateral hemidiaphragm normalized. Relief of breathlessness post-drainage correlated with improvement in ipsilateral hemidiaphragm excursion (r = 0.556, p = 0.031). CONCLUSION: This pilot study suggests, for the first time, that unilateral pleural effusion not only impairs ipsilateral hemidiaphragm function but also causes compensatory hyperactivity of the contralateral hemidiaphragm, which resolves post-drainage. These findings provide a basis for detailed studies of diaphragmatic function and ventilatory drive in patients with symptomatic pleural effusion.

Australasian Malignant PLeural Effusion (AMPLE)-3 trial: study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion.

INTRODUCTION: Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. METHODS AND ANALYSIS: A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. DISCUSSION: Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12618001013257 . Registered on 18 June 2018. PROTOCOL VERSION: Version 3.00/4.02.19.

Changes in body composition in patients with malignant pleural mesothelioma and the relationship with activity levels and dietary intake.

BACKGROUND: Skeletal muscle loss is common in advanced cancer and is associated with negative outcomes. In malignant pleural mesothelioma (MPM), no study has reported body composition changes or factors associated with these changes. This study aimed to describe changes in body composition over time and its relationship with activity levels, dietary intake and survival. METHODS: The study was a secondary analysis of data collected from a longitudinal observational study of patients with MPM. Participants completed 3-month assessments for up to 18 months. Participants with two dual-energy x-ray absorptiometry (DXA) scans were included. Changes in appendicular skeletal muscle mass (ASM) and total fat mass were used to categorise participants into phenotypes. Activity levels were measured with an ActiGraph GT3X+ accelerometer and energy and protein intake was measured with a 3-day food record and 24-h recall. RESULTS: Eighteen participants were included (89% men, mean age 68.9 ± 7.1 years). Median time between DXA was 91 [IQR 84-118] days. Compared to participants with ASM maintenance (n = 9), fewer participants with ASM loss (n = 9) survived ≥12 months from follow-up (p = 0.002). Participants with ASM loss increased sedentary time (p = 0.028) and decreased light activity (p = 0.028) and step count (p = 0.008). Activity levels did not change in participants with ASM maintenance (p > 0.05). Energy and protein intake did not change in either group (p > 0.05). CONCLUSIONS: Muscle loss was associated with poorer survival and decreased activity levels. Interventions that improve physical activity or muscle mass could benefit patients with MPM.

Steroid Therapy and Outcome of Parapneumonic Pleural Effusions (STOPPE): A Pilot Randomized Clinical Trial.

Rationale: Pleural effusion commonly complicates community-acquired pneumonia and is associated with intense pleural inflammation. Whether antiinflammatory treatment with corticosteroids improves outcomes is unknown. Objectives: To assess the effects of corticosteroids in an adult population with pneumonia-related pleural effusion. Methods: The STOPPE (Steroid Therapy and Outcome of Parapneumonic Pleural Effusions) trial was a pilot, multicenter, double-blinded, placebo-controlled, randomized trial involving six Australian centers. Patients with community-acquired pneumonia and pleural effusion were randomized (2:1) to intravenous dexamethasone (4 mg twice daily for 48 h) or placebo and followed for 30 days. Given the diverse effects of corticosteroids, a comprehensive range of clinical, serological, and imaging outcomes were assessed in this pilot trial (ACTRN12618000947202). Measurements and Main Results: Eighty patients were randomized (one withdrawn before treatment) and received dexamethasone (n = 51) or placebo (n = 28). This pilot trial found no preliminary evidence of benefits of dexamethasone in improving time to sustained (>12 h) normalization of vital signs (temperature, oxygen saturations, blood pressure, heart, and respiratory rates): median, 41.0 (95% confidence interval, 32.3-54.5) versus 27.8 (15.4-49.5) hours in the placebo arm (hazard ratio, 0.729 [95% confidence interval, 0.453-1.173]; P = 0.193). Similarly, no differences in C-reactive protein or leukocyte counts were observed, except for a higher leukocyte count in the dexamethasone group at Day 3. Pleural drainage procedures were performed in 49.0% of dexamethasone-treated and 42.9% of placebo-treated patients (P = 0.60). Radiographic pleural opacification decreased over time with no consistent intergroup differences. Mean duration of antibiotic therapy (22.4 [SD, 15.4] vs. 20.4 [SD, 13.8] d) and median hospitalization (6.0 [interquartile range, 5.0-10.0] vs. 5.5 [interquartile range, 5.0-8.0] d) were similar between the dexamethasone and placebo groups. Serious adverse events occurred in 25.5% of dexamethasone-treated and 21.4% of placebo-treated patients. Transient hyperglycemia more commonly affected the dexamethasone group (15.6% vs. 7.1%). Conclusions: Systemic corticosteroids showed no preliminary benefits in adults with parapneumonic effusions. Clinical trial registered with www.anzctr.org.au (ACTRN12618000947202).

Awake Rhinology Surgery in Response to the COVID-19 Pandemic in Europe.

BACKGROUND: European health-care systems are faced with a backlog of surgical procedures following the suspension of routine surgery during the COVID-19 crisis. Routine rhinology surgery under general anaesthetic (GA) is now faced with significant challenges which include limited theatre capacity, the negative ramifications of surgical prioritization, reduced patient throughput in secondary care, and additional personal protective equipment requirements. Delayed surgery in rhinology, particularly with regards to chronic rhinosinusitis, has previously been shown to have poorer surgical outcomes, a detrimental effect on quality of life and long-term negative health socio-economic effects. Awake rhinology surgery under local anaesthetic (LA) provides an ideal alternative to GA. It provides a means of operating on patients in a setting alternative to currently oversubscribed main theatres, by utilizing satellite facilities, while ensuring identical surgical outcomes for patients who may otherwise have been forced to wait a long time for their procedure. It also confers additional benefits in terms of shorter recovery time and hospital stay for patients. OBJECTIVES: We have developed a set of recommendations that are intended to help support clinicians and managers to better adopt LA rhinology protocols and minimize the risk to the patient and health-care professionals involved. METHODOLOGY: International roundtable forums were conducted and supplemented by individual interviews. The international board consisted of 12 rhinologists experienced in awake rhinology surgery. Feedback was analysed and shared to develop a consensus of best practice. RECOMMENDATIONS: Local and national guidelines need to be adhered to with specific focus on patient and clinician safety. When performing awake rhinology procedures in the COVID-19 recovery process, consider implementing specific safety measures and workflow practices to safeguard patients and staff and minimize the risk of infection. CONCLUSION: Awake surgery potentially provides quicker access to routine rhinology surgery in the post-COVID-19 recovery phase, ensuring patients are treated in a timely matter, thereby avoiding higher downstream costs, and improving outcomes.

Intrapleural Fibrinolytics and Deoxyribonuclease for Treatment of Indwelling Pleural Catheter-Related Pleural Infection: A Multi-Center Observational Study.

BACKGROUND: Indwelling pleural catheters (IPC) are increasingly used for management of recurrent (especially malignant) effusions. Pleural infection associated with IPC use remains a concern. Intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) significantly reduces surgical referrals in non-IPC pleural infection, but data on its use in IPC-related pleural infection are scarce. OBJECTIVE: To assess the safety and efficacy of intrapleural tPA and DNase in IPC-related pleural infection. METHODS: Patients with IPC-related pleural infection who received intrapleural tPA/DNase in five Australian and UK centers were identified from prospective databases. Outcomes on feasibility of intrapleural tPA/DNase delivery, its efficacy and safety were recorded. RESULTS: Thirty-nine IPC-related pleural infections (predominantly Staphylococcus aureus and gram-negative organisms) were treated in 38 patients; 87% had malignant effusions. In total, 195 doses (median 6 [IQR = 3-6]/patient) of tPA (2.5 mg-10 mg) and DNase (5 mg) were instilled. Most (94%) doses were delivered via IPCs using local protocols for non-IPC pleural infections. The mean volume of pleural fluid drained during the first 72 h of treatment was 3,073 (SD = 1,685) mL. Most (82%) patients were successfully treated and survived to hospital discharge without surgery; 7 required additional chest tubes or therapeutic aspiration. Three patients required thoracoscopic surgery. Pleurodesis developed post-infection in 23/32 of successfully treated patients. No major morbidity/mortality was associated with tPA/DNase. Four patients received blood transfusions; none had systemic or significant pleural bleeding. CONCLUSION: Treatment of IPC-related pleural infection with intrapleural tPA/DNase instillations via the IPC appears feasible and safe, usually without additional drainage procedures or surgery. Pleurodesis post-infection is common.

Hyaluronic acid in viscous malignant mesothelioma pleural effusion.

Malignant pleural effusion (MPE) is common with mesothelioma. We report two cases of extraordinarily viscous MPEs associated with mesothelioma. The viscosity prohibited spontaneous gravity-dependent drainage via indwelling pleural catheters. Our ex vivo experiments found very high hyaluronic acid (HA) content within the fluid. Treatment of the fluid with hyaluronidase, but not with deoxyribonucleases, significantly reduced fluid viscosity. The results provide proof that HA can contribute to high viscosity of pleural fluid in mesothelioma. Research into strategies of counteracting HA properties in the management of MPEs may provide further insight.

Organisational interventions for preventing and minimising aggression directed towards healthcare workers by patients and patient advocates.

BACKGROUND: Workplace aggression is becoming increasingly prevalent in health care, with serious consequences for both individuals and organisations. Research and development of organisational interventions to prevent and minimise workplace aggression has also increased. However, it is not known if interventions prevent or reduce occupational violence directed towards healthcare workers. OBJECTIVES: To assess the effectiveness of organisational interventions that aim to prevent and minimise workplace aggression directed towards healthcare workers by patients and patient advocates. SEARCH METHODS: We searched the following electronic databases from inception to 25 May 2019: Cochrane Central Register of Controlled Trials (CENTRAL) (Wiley Online Library); MEDLINE (PubMed); CINAHL (EBSCO); Embase (embase.com); PsycINFO (ProQuest); NIOSHTIC (OSH-UPDATE); NIOSHTIC-2 (OSH-UPDATE); HSELINE (OSH-UPDATE); and CISDOC (OSH-UPDATE). We also searched the ClinicalTrials.gov (www.ClinicalTrials.gov) and the World Health Organization (WHO) trials portals (www.who.int/ictrp/en). SELECTION CRITERIA: We included randomised controlled trials (RCTs) or controlled before-and-after studies (CBAs) of any organisational intervention to prevent and minimise verbal or physical aggression directed towards healthcare workers and their peers in their workplace by patients or their advocates. The primary outcome measure was episodes of aggression resulting in no harm, psychological, or physical harm. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for data collection and analysis. This included independent data extraction and 'Risk of bias' assessment by at least two review authors per included study. We used the Haddon Matrix to categorise interventions aimed at the victim, the vector or the environment of the aggression and whether the intervention was applied before, during or after the event of aggression. We used the random-effects model for the meta-analysis and GRADE to assess the quality of the evidence. MAIN RESULTS: We included seven studies. Four studies were conducted in nursing home settings, two studies were conducted in psychiatric wards and one study was conducted in an emergency department. Interventions in two studies focused on prevention of aggression by the vector in the pre-event phase, being 398 nursing home residents and 597 psychiatric patients. The humour therapy in one study in a nursing home setting did not have clear evidence of a reduction of overall aggression (mean difference (MD) 0.17, 95% confidence interval (CI) 0.00 to 0.34; very low-quality evidence). A short-term risk assessment in the other study showed a decreased incidence of aggression (risk ratio (RR) 0.36, 95% CI 0.16 to 0.78; very low-quality evidence) compared to practice as usual. Two studies compared interventions to minimise aggression by the vector in the event phase to practice as usual. In both studies the event was aggression during bathing of nursing home patients. In one study, involving 18 residents, music was played during the bathing period and in the other study, involving 69 residents, either a personalised shower or a towel bath was used. The studies provided low-quality evidence that the interventions may result in a medium-sized reduction of overall aggression (standardised mean difference (SMD -0.49, 95% CI -0.93 to -0.05; 2 studies), and physical aggression (SMD -0.85, 95% CI -1.46 to -0.24; 1 study; very low-quality evidence), but not in verbal aggression (SMD -0.31, 95% CI; -0.89 to 0.27; 1 study; very low-quality evidence). One intervention focused on the vector, the pre-event phase and the event phase. The study compared a two-year culture change programme in a nursing home to practice as usual and involved 101 residents. This study provided very low-quality evidence that the intervention may result in a medium-sized reduction of physical aggression (MD 0.51, 95% CI 0.11 to 0.91), but there was no clear evidence that it reduced verbal aggression (MD 0.76, 95% CI -0.02 to 1.54). Two studies evaluated a multicomponent intervention that focused on the vector (psychiatry patients and emergency department patients), the victim (nursing staff), and the environment during the pre-event and the event phase. The studies included 564 psychiatric staff and 209 emergency department staff. Both studies involved a comprehensive package of actions aimed at preventing violence, managing violence and environmental changes. There was no clear evidence that the psychiatry intervention may result in a reduction of overall aggression (odds ratio (OR) 0.85, 95% CI 0.63 to 1.15; low-quality evidence), compared to the control condition. The emergency department study did not result in a reduction of aggression (MD = 0) but provided insufficient data to test this. AUTHORS' CONCLUSIONS: We found very low to low-quality evidence that interventions focused on the vector during the pre-event phase, the event phase or both, may result in a reduction of overall aggression, compared to practice as usual, and we found inconsistent low-quality evidence for multi-component interventions. None of the interventions included the post-event stage. To improve the evidence base, we need more RCT studies, that include the workers as participants and that collect information on the impact of violence on the worker in a range of healthcare settings, but especially in emergency care settings. Consensus on standardised outcomes is urgently needed.

The Pleural Effusion And Symptom Evaluation (PLEASE) study of breathlessness in patients with a symptomatic pleural effusion.

INTRODUCTION: Pathophysiology changes associated with pleural effusion, its drainage and factors governing symptom response are poorly understood. Our objective was to determine: 1) the effect of pleural effusion (and its drainage) on cardiorespiratory, functional and diaphragmatic parameters; and 2) the proportion as well as characteristics of patients with breathlessness relief post-drainage. METHODS: Prospectively enrolled patients with symptomatic pleural effusions were assessed at both pre-therapeutic drainage and at 24-36 h post-therapeutic drainage. RESULTS: 145 participants completed pre-drainage and post-drainage tests; 93% had effusions ≥25% of hemithorax. The median volume drained was 1.68 L. Breathlessness scores improved post-drainage (mean visual analogue scale (VAS) score by 28.0±24 mm; dyspnoea-12 (D12) score by 10.5±8.8; resting Borg score before 6-min walk test (6-MWT) by 0.6±1.7; all p<0.0001). The 6-min walk distance (6-MWD) increased by 29.7±73.5 m, p<0.0001. Improvements in vital signs and spirometry were modest (forced expiratory volume in 1 s (FEV1) by 0.22 L, 95% CI 0.18-0.27; forced vital capacity (FVC) by 0.30 L, 95% CI 0.24-0.37). The ipsilateral hemi-diaphragm was flattened/everted in 50% of participants pre-drainage and 48% of participants exhibited paradoxical or no diaphragmatic movement. Post-drainage, hemi-diaphragm shape and movement were normal in 94% and 73% of participants, respectively. Drainage provided meaningful breathlessness relief (VAS score improved ≥14 mm) in 73% of participants irrespective of whether the lung expanded (mean difference 0.14, 95% CI 10.02-0.29; p=0.13). Multivariate analyses found that breathlessness relief was associated with significant breathlessness pre-drainage (odds ratio (OR) 5.83 per standard deviation (sd) decrease), baseline abnormal/paralyzed/paradoxical diaphragm movement (OR 4.37), benign aetiology (OR 3.39), higher pleural pH (OR per sd increase 1.92) and higher serum albumin level (OR per sd increase 1.73). CONCLUSIONS: Breathlessness and exercise tolerance improved in most patients with only a small mean improvement in spirometry and no change in oxygenation. Breathlessness improvement was similar in participants with and without trapped lung. Abnormal hemi-diaphragm shape and movement were independently associated with relief of breathlessness post-drainage.