Clinical and Cost-Effectiveness of Procalcitonin Test for Prodromal Meningococcal Disease-A Meta-Analysis

BACKGROUND: Despite vaccines and improved medical intensive care, clinicians must continue to be vigilant of possible Meningococcal Disease in children. The objective was to establish if the procalcitonin test was a cost-effective adjunct for prodromal Meningococcal Disease in children presenting at emergency department with fever without source.

METHODS AND FINDINGS: Data to evaluate procalcitonin, C-reactive protein and white cell count tests as indicators of Meningococcal Disease were collected from six independent studies identified through a systematic literature search, applying PRISMA guidelines. The data included 881 children with fever without source in developed countries.The optimal cut-off value for the procalcitonin, C-reactive protein and white cell count tests, each as an indicator of Meningococcal Disease, was determined. Summary Receiver Operator Curve analysis determined the overall diagnostic performance of each test with 95% confidence intervals. A decision analytic model was designed to reflect realistic clinical pathways for a child presenting with fever without source by comparing two diagnostic strategies: standard testing using combined C-reactive protein and white cell count tests compared to standard testing plus procalcitonin test. The costs of each of the four diagnosis groups (true positive, false negative, true negative and false positive) were assessed from a National Health Service payer perspective. The procalcitonin test was more accurate (sensitivity=0.89, 95%CI=0.76-0.96; specificity=0.74, 95%CI=0.4-0.92) for early Meningococcal Disease compared to standard testing alone (sensitivity=0.47, 95%CI=0.32-0.62; specificity=0.8, 95% CI=0.64-0.9). Decision analytic model outcomes indicated that the incremental cost effectiveness ratio for the base case was £-8,137.25 (US $ -13,371.94) per correctly treated patient.

CONCLUSIONS: Procalcitonin plus standard recommended tests, improved the discriminatory ability for fatal Meningococcal Disease and was more cost-effective; it was also a superior biomarker in infants. Further research is recommended for point-of-care procalcitonin testing and Markov modelling to incorporate cost per QALY with a life-time model.

Enhanced clinical pharmacy service targeting tools: risk-predictive algorithms

Rationale, aims and objectives: This study aimed to determine the value of using a mix of clinical pharmacy data and routine hospital admission spell data in the development of predictive algorithms. Exploration of risk factors in hospitalized patients, together with the targeting strategies devised, will enable the prioritization of clinical pharmacy services to optimize patient outcomes. 

Methods: Predictive algorithms were developed using a number of detailed steps using a 75% sample of integrated medicines management (IMM) patients, and validated using the remaining 25%. IMM patients receive targeted clinical pharmacy input throughout their hospital stay. The algorithms were applied to the validation sample, and predicted risk probability was generated for each patient from the coefficients. Risk threshold for the algorithms were determined by identifying the cut-off points of risk scores at which the algorithm would have the highest discriminative performance. Clinical pharmacy staffing levels were obtained from the pharmacy department staffing database. 

Results: Numbers of previous emergency admissions and admission medicines together with age-adjusted co-morbidity and diuretic receipt formed a 12-month post-discharge and/or readmission risk algorithm. Age-adjusted co-morbidity proved to be the best index to predict mortality. Increased numbers of clinical pharmacy staff at ward level was correlated with a reduction in risk-adjusted mortality index (RAMI). 

Conclusions: Algorithms created were valid in predicting risk of in-hospital and post-discharge mortality and risk of hospital readmission 3, 6 and 12 months post-discharge. The provision of ward-based clinical pharmacy services is a key component to reducing RAMI and enabling the full benefits of pharmacy input to patient care to be realized.

Prioritisation of citizen centric information for disaster response

In the aftermath of a disaster event, and in the absence of trained professionals, many responsibilities are taken on by uninjured citizens who are willing and able to help, such as care of the injured or search and rescue. These citizens are constrained by communications and logistics problems but are less equipped to deal with them as most often they are cut off from any coordinated assistance. The method proposed in this study would increase the survivability of those injured or trapped by a disaster event by providing a facility to allow citizens to coordinate and share information among themselves. This is facilitated by the proposed deployment and the autonomous management of an ad hoc infrastructure that liaises (OK?) directly with survivors without central control. Furthermore, as energy concerns present critical constraints to these networks, this research proposes a system of categorising information elements within the network to ensure efficient information exchange.

Galleria mellonella as a novel in vivo model for assessment of the toxicity of 1-alkyl-3-methylimidazolium chloride ionic liquids

The larval form of the Greater Wax Moth (Galleria mellonella) was evaluated as a model system for the study of the acute in vivo toxicity of 1-alkyl-3-methylimidazolium chloride ionic liquids. 24-h median lethal dose (LD50) values for nine of these ionic liquids bearing alkyl chain substituents ranging from 2 to 18 carbon atoms were determined. The in vivo toxicity of the ionic liquids was found to correlate directly with the length of the alkyl chain substituent, and the pattern of toxicity observed was in accordance with previous studies of ionic liquid toxicity in other living systems, including a characteristic toxicity ‘cut-off’ effect. However, G. mellonella appeared to be more susceptible to the toxic effects of the ionic liquids tested, possibly as a result of their high body fat content. The results obtained in this study indicate that G. mellonella represents a sensitive, reliable and robust in vivo model organism for the evaluation of ionic liquid toxicity.

A comparison of endoscopy versus pathology sizing of colorectal adenomas and potential implications for surveillance colonoscopy

Background and AimsTo compare endoscopy and pathology sizing in a large population-based series of colorectal adenomas and to evaluate the implications for patient stratification into surveillance colonoscopy.MethodsEndoscopy and pathology sizes available from intact adenomas removed at colonoscopies performed as part of the Northern Ireland Bowel Cancer Screening Programme, from 2010 to 2015, were included in this study. Chi-squared tests were applied to compare size categories in relation to clinicopathological parameters and colonoscopy surveillance strata according to current American Gastroenterology Association and British Society of Gastroenterology guidelines.ResultsA total of 2521 adenomas from 1467 individuals were included. There was a trend toward larger endoscopy than pathology sizing in 4 of the 5 study centers, but overall sizing concordance was good. Significantly greater clustering with sizing to the nearest 5 mm was evident in endoscopy versus pathology sizing (30% vs 19%, p<0.001), which may result in lower accuracy. Applying a 10-mm cut-off relevant to guidelines on risk stratification, 7.3% of all adenomas and 28.3% of those 8 to 12 mm in size had discordant endoscopy and pathology size categorization. Depending upon which guidelines are applied, 4.8% to 9.1% of individuals had differing risk stratification for surveillance recommendations, with the use of pathology sizing resulting in marginally fewer recommended surveillance colonoscopies.ConclusionsChoice of pathology or endoscopy approaches to determine adenoma size will potentially influence surveillance colonoscopy follow-up in 4.8% to 9.1% of individuals. Pathology sizing appears more accurate than endoscopy sizing, and preferential use of pathology size would result in a small, but clinically important, decreased burden on surveillance colonoscopy demand. Careful endoscopy sizing is required for adenomas removed piecemeal.