The role of serum procalcitonin in establishing the diagnosis and prognosis of pleural infection

BACKGROUND: Bacterial pleural infection requires prompt identification to enable appropriate investigation and treatment. In contrast to commonly used biomarkers such as C-reactive protein (CRP) and white cell count (WCC), which can be raised due to non-infective inflammatory processes, procalcitonin (PCT) has been proposed as a specific biomarker of bacterial infection. The utility of PCT in this role is yet to be validated in a large prospective trial. This study aimed to identify whether serum PCT is superior to CRP and WCC in establishing the diagnosis of bacterial pleural infection. METHODS: Consecutive patients presenting to a tertiary pleural service between 2008 and 2013 were recruited to a well-established pleural disease study. Consent was obtained to store pleural fluid and relevant clinical information. Serum CRP, WCC and PCT were measured. A diagnosis was agreed upon by two independent consultants after a minimum of 12 months. The study was performed and reported according to the STARD reporting guidelines. RESULTS: 80/425 patients enrolled in the trial had a unilateral pleural effusion secondary to infection. 10/80 (12.5%) patients had positive pleural fluid microbiology. Investigations for viral causes of effusion were not performed. ROC curve analysis of 425 adult patients with unilateral undiagnosed pleural effusions showed no statistically significant difference in the diagnostic utility of PCT (AUC 0.77), WCC (AUC 0.77) or CRP (AUC 0.85) for the identification of bacterial pleural infection. Serum procalcitonin >0.085 μg/l has a sensitivity, specificity, negative predictive value and positive predictive value of 0.69, 0.80, 0.46 and 0.91 respectively for the identification of pleural infection. The diagnostic utility of procalcitonin was not affected by prior antibiotic use (p = 0.80). CONCLUSIONS: The study presents evidence that serum procalcitonin is not superior to CRP and WCC for the diagnosis of bacterial pleural infection. The study suggests routine procalcitonin testing in all patients with unilateral pleural effusion is not beneficial however further investigation may identify specific patient subsets that may benefit. TRIAL REGISTRATION: The trial was registered with the UK Clinical Research Network (UKCRN ID 8960). The trial was approved by the South West Regional Ethics Committee (Ethical approval number 08/H0102/11). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-017-0501-5) contains supplementary material, which is available to authorized users

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

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

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Implications for water quality in relocating the drinking water intake point for Västerås

Water is the most essential resource for life. In cases where drinking water is processed from surface water it is important to ensure the raw water is of good quality, and is suitable for processing through the water treatment plant. The drinking water for Västerås is sourced from Västeråsfjärden, in the western side of Lake Mälaren. The city itself is home to marinas, ports, a wastewater treatment plant, the Svartån outlet, sewage pumping stations and stormwater outlets. Because of the negative effects these activities have on surface water quality, Mälarenergi AB is interested in relocating the raw water intake point to Granfjärden, 10 km east of Västeråsfjärden. At Granfjärden the intake point would be less exposed to the activities in Västerås, and could be placed at a greater depth, resulting in better water quality. In this Master’s thesis the water quality and the pollution risks at Västeråsfjärden and Granfjärden sites are compared. Existing water quality data were compared, and pollution risks were investigated in two ways. Firstly potential risks in the catchment area were identified through compiling previously reported information and map analysis. Secondly, possible accident scenarios from shipping were identified. Following this, SMHI simulated the accident scenarios and their estimated effects on the two sites were then assessed.   This research shows that the water quality difference between sites is small but key differences exist in the levels of organic matter, color, transparency and temperature, making the Granfjärden location preferable. Potential problems associated with the low oxygen levels found during the end of summer at Granfjärden may be addressed by temporarily raising the intake point. It should be noted however that this temporary solution may increase the exposure to pollution. In conclusion, accident scenario simulations showed the potential concentration of pollutants at both sites is low, with effluents diluted at least 1000 times. Prevailing southwesterly and westerly winds occuring at both intake points generate a clockwise circulation in Västeråsfjärden.  This causes all effluents from urban activities to reach that intake point, which is the most notable risk associated with this site.  In contrast, the two largest risks for the Granfjärden site are shipping effluents and the microbiological load from individual sewage treatment systems and animal waste.Vatten är vårt viktigaste livsmedel och en förutsättning för allt liv. I de fall där råvatten för beredning av dricksvatten tas från ytvatten är det ytterst viktigt att säkerställa en bra vattenkvalitet, lämpat för dricksvattenberedning. Västerås stad tar idag sitt råvatten från Västeråsfjärden, i Mälarens västra delar, 3 km från Västerås stad. I staden finns bl.a. småbåtshamnar, oljehamn, avloppsreningsverk, Svartåns utlopp, nödbräddavlopp, avloppspumpstationer och dagvattenutsläpp. Dessa aktiviteter påverkar vattenkvaliteten i fjärden negativt och därför har Mälarenergi AB valt att undersöka möjligheterna att flytta intaget till Granfjärden, 10 km öster om Västeråsfjärden. Där skulle råvattenintaget inte vara lika utsatt för samhällets direkt negativa vattenpåverkan. Intaget kan läggas på ett större djup och där kan vattenkvaliteten vara bättre och mindre riskutsatt. I detta examensarbete har vattenkvaliteten och föroreningsriskerna jämförts mellan fjärdarna. Analysresultat från provtagningar i Granfjärden jämfördes med prover från Västeråsfjärden. Riskerna behandlades i två delar. I den första delen identifierades föroreningsrisker genom att sammanställa material från tidigare projekt samt genom att studera kartor. I den andra delen togs olycksscenarion inom sjöfarten fram. SMHI simulerade dessa scenarion och en bedömning gjordes sedan över hur riskutsatta de båda råvattenintagen är. Trots det stora avståndet från Västerås stad till Granfjärden var skillnaden i vattenkvalitet mellan fjärdarna förvånansvärt liten, men skillnader påvisades för några av de analyserade parametrarna. Granfjärdens bottenvatten hade signifikant lägre halter organiskt material, lägre färgtal och lägre temperatur än det nuvarande råvattenintaget. Däremot förekom lägre syrgashalter i slutet av sommaren än vid råvattenintaget i Västeråsfjärden. Om problem skulle uppstå i dricksvattenberedningen till följd av låga syrgashalter finns möjlighet att byta till ett grundare intag vid samma punkt. Det grundare intaget är dock mer utsatt för risker än det djupare. Samtliga utsläpp från de simulerade olyckorna späddes ut minst 1000 gånger innan de spred sig till råvattenintagen. Båda råvattenintagen är som mest utsatta vid sydvästlig och västlig vind. I Västeråsfjärden ger dessa vindriktningar en medurs strömningsbild i fjärden, vilket innebär att föroreningsutsläpp från staden förs mot råvattenintaget. De största riskerna för råvattenintaget i Granfjärden är utsläpp i farleden och den mikrobiologiska belastningen från enskilda avlopp och djurhållning. I Västeråsfjärden är den största riskfaktorn utsläpp från stadens aktiviteter och verksamheter längs den östra stranden