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

A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: A proof of principle pilot study

© 2015 Clive et al. Introduction: Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. Methods: We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Results: Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. Conclusions: This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. Trial Registration: UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Supporting Transitions with Creative Software Engineering

In this paper we explore the use of creative software engineering design methods, particularly for rebuilding experiences in new contexts. We present results from a comparative evaluation of three approaches (scenarios with personas, TAPT, and no formal method): these suggest that techniques such as brainstorming are helpful, while structure and formality can distract from the creative process. Scenarios’ user-focus was noted as positive, as were TAPT’s analytical output and abstraction of experiences away from their original contexts. The best approach to design may be to apply multiple methods in a complementary fashion

Creative Software Engineering

Software engineering is traditionally seen as very structured and methodical. However, it often involves creative steps: consider requirements analysis, architecture engineering and GUI design. This poster describes three existing software engineering methods which include creative steps, alongside a method called 'experience deconstruction'. Deconstruction, which also includes a creative step, is used to help understand user experiences and re-provide these experiences in new contexts