Therapeutic thoracentesis symptoms and activity: a qualitative study

Introduction Malignant pleural effusions (MPEs) commonly occur in patients with advanced cancer. Drainage of fluid is used to relieve symptoms and improve quality of life. Objective To improve our understanding of how therapeutic aspiration affects symptoms and activities in patients with MPE. Methods Patients presenting to the Pleural Clinic at Norfolk and Norwich University Hospital with a confirmed or suspected MPE participated in up to three semistructured interviews during their diagnostic/therapeutic pathway. Interviews were analysed using framework analysis by two researchers independently. Results Sixteen patients participated. Symptoms reported before drainage included breathlessness, cough, chest pain, fatigue and anorexia. Symptoms affected their activities, including walking, bending over and socialisation. Patients described anxiety about the underlying diagnosis and fear of over-reliance on others. Expectations of drainage outcome varied, with some hoping for a cure and others hoping for any improvement. After drainage, breathlessness, chest pain and cough improved in some patients. They reported feeling and sleeping better, but fatigue and poor appetite remained. Participants were more active after aspiration, but the duration of improvement was a few days only. Despite this, patients still felt the procedure worthwhile. Conclusion Overall health and respiratory symptoms improved following drainage, but constitutional symptoms did not improve. This may be because constitutional symptoms are caused by the underlying cancer. This study suggests that clinicians should consider a range of symptoms, rather than just breathlessness, in planning outcomes for clinical trials. These results are important to inform patients about the potential benefits and duration of symptom improvement after therapeutic aspiration

Trial Protocol: Reaccumulation rate of pleural effusions after therapeutic aspiration: An observational cohort study to determine baseline factors associated with rate of pleural fluid reaccumulation following therapeutic aspiration in patients with malignant pleural effusion attending a pleural clinic (REPEAT) [version 1; peer review: 2 approved]

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

Assessment of patient-reported outcome measures in pleural interventions

Introduction: There is a lack of data evaluating the clinical effect on symptoms of pleural intervention procedures. This has led to the development of patient-reported outcome measures (PROMs) to define what constitutes patient benefit. The primary aim of this paper was to prospectively assess the effect of pleural procedures on PROMs and investigate the relationship between symptom change and clinical factors. Methods: We prospectively collected data as part of routine clinical care from 158 patients with pleural effusion requiring interventions. Specific questionnaires included two patient-reported scores (a seven-point Likert scale and a 100 mm visual analogue scale (VAS) to assess symptoms). Results: Excluding diagnostic aspiration, the majority of patients (108/126, 85.7%) experienced symptomatic benefit from fluid drainage (mean VAS improvement 42.6 mm, SD 24.7, 95% CI 37.9 to 47.3). There was a correlation between symptomatic benefit and volume of fluid removed post aspiration. A negative association was identified between the number of septations seen on ultrasound and improvement in dyspnoea VAS score in patients treated with intercostal chest drain. Conclusion: The results of our study highlight the effect of pleural interventions from a patient’s perspective. The outcomes defined have the potential to form the basis of a clinical useful tool to appraise the effect, compare the efficiency and identify the importance of pleural interventions to the patients

A review on development and application of plant-based bioflocculants and grafted bioflocculants

Flocculation is extensively employed for clarification through sedimentation. Application of eco-friendly plant-based bioflocculants in wastewater treatment has attracted significant attention lately with high removal capability in terms of solids, turbidity, color, and dye. However, moderate flocculating property and short shelf life restrict their development. To enhance the flocculating ability, natural polysaccharides derived from plants are chemically modified by inclusion of synthetic, nonbiodegradable monomers (e.g., acrylamide) onto their backbone to produce grafted bioflocculants. This review is aimed to provide an overview of the development and flocculating efficiencies of plant-based bioflocculants and grafted bioflocculants for the first time. Furthermore, the processing methods, flocculation mechanism, and the current challenges are discussed. All the reported studies about plant-derived bioflocculants are conducted under lab-scale conditions in wastewater treatment. Hence, the possibility to apply natural bioflocculants in food and beverage, mineral, paper and pulp, and oleo-chemical and biodiesel industries is discussed and evaluated

Randomized controlled trial of urokinase versus placebo for nondraining malignant pleural effusion

Rationale: Patients with malignant pleural effusion experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage. Objectives: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion. Methods: We conducted a prospective, double-blind, randomized trial. Patients with nondraining effusion were randomly allocated in a 1:1 ratio to intrapleural urokinase (100,000 IU, three doses, 12-hourly) or matched placebo. Measurements and Main Results: Co–primary outcome measures were dyspnea (average daily 100-mm visual analog scale scores over 28 d) and time to pleurodesis failure to 12 months. Secondary outcomes were survival, hospital length of stay, and radiographic change. A total of 71 subjects were randomized (36 received urokinase, 35 placebo) from 12 U.K. centers. The baseline characteristics were similar between the groups. There was no difference in mean dyspnea between groups (mean difference, 3.8 mm; 95% confidence interval [CI], −12 to 4.4 mm; P = 0.36). Pleurodesis failure rates were similar (urokinase, 13 of 35 [37%]; placebo, 11 of 34 [32%]; adjusted hazard ratio, 1.2; P = 0.65). Urokinase was associated with decreased effusion size visualized by chest radiography (adjusted relative improvement, −19%; 95% CI, −28 to −11%; P < 0.001), reduced hospital stay (1.6 d; 95% CI, 1.0 to 2.6; P = 0.049), and improved survival (69 vs. 48 d; P = 0.026). Conclusions: Use of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo and cannot be recommended as an adjunct to pleurodesis. Other palliative treatments should be used. Improvements in hospital stay, radiographic appearance, and survival associated with urokinase require further evaluation. Clinical trial registered with ISRCTN (12852177) and EudraCT (2008-000586-26)

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

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

Evaluation of a standardised Vi poly-l-lysine ELISA for serology of Vi capsular polysaccharide antibodies

Typhoid vaccines based on protein-conjugated capsular Vi polysaccharide (TCVs) prevent typhoid in infants and young children. Analysis of the serum anti-Vi IgG response following immunisation against typhoid confirms the immunogenicity of TCVs and forms an important part of the pathway to licensing. Comparative studies could expedite the licencing process, and the availability of a standardised ELISA method alongside the 1st International Standard (IS) 16/138 for anti-typhoid capsular Vi polysaccharide IgG (human) will facilitate this process. To this end, a non-commercial ELISA based on a coat of Vi and poly-l-lysine (Vi-PLL ELISA) was evaluated by 10 laboratories. Eight serum samples, including IS 16/138, were tested in the standardised Vi-PLL ELISA (n = 10), a commercial Vi ELISA (n = 3) and a biotinylated Vi ELISA (n = 1). Valid estimates of potencies relative to IS 16/138 were obtained for all samples in the Vi-PLL ELISA and the commercial ELISA, with good repeatability and reproducibility evident from the study results and concordant estimates obtained by the two ELISA methods. The study demonstrates that the Vi-PLL ELISA can be used in clinical trial studies to determine the immunogenicity of TCVs

Climate risk management and rural poverty reduction

Climate variability is a major source of risk to smallholder farmers and pastoralists, particularly in dryland regions. A growing body of evidence links climate-related risk to the extent and the persistence of rural poverty in these environments. Stochastic shocks erode smallholder farmers’ long-term livelihood potential through loss of productive assets. The resulting uncertainty impedes progress out of poverty by acting as a disincentive to investment in agriculture – by farmers, rural financial services, value chain institutions and governments. We assess evidence published in the last ten years that a set of production technologies and institutional options for managing risk can stabilize production and incomes, protect assets in the face of shocks, enhance uptake of improved technologies and practices, improve farmer welfare, and contribute to poverty reduction in risk-prone smallholder agricultural systems. Production technologies and practices such as stress-adapted crop germplasm, conservation agriculture, and diversified production systems stabilize agricultural production and incomes and, hence, reduce the adverse impacts of climate-related risk under some circumstances. Institutional interventions such as index-based insurance, adaptive safety nets and climate services play a complementary role in enabling farmers to manage risk, overcome risk-related barriers to adoption of improved technologies and practices, and protect their assets against the impacts of extreme climatic events. While some research documents improvements in household welfare indicators, there is limited evidence that the risk-reduction benefits of the interventions reviewed have benefited significant numbers of chronically poor farmers. We discuss the roles that climate-risk management interventions can play in efforts to reduce rural poverty, and the need for further research on identifying and targeting environments and farming populations where improved climate risk management could accelerate efforts to reduce rural poverty

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$  < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust