Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia

Background: Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.

Objectives: We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. 

Methods: A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10⁴ colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. 

Results: Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p<0.001). The area under the receiver operator characteristic curve for IL-1β was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1β and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%). 

Conclusions: Low BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

Accuracy of LightCycler SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review and meta-analysis

Purpose: There is an urgent need to develop diagnostic tests to improve the detection of pathogens causing life-threatening infection (sepsis). SeptiFast is a CE-marked multi-pathogen real-time PCR system capable of detecting DNA sequences of bacteria and fungi present in blood samples within a few hours. We report here a systematic review and meta-analysis of diagnostic accuracy studies of SeptiFast in the setting of suspected sepsis.

Methods: A comprehensive search strategy was developed to identify studies that compared SeptiFast with blood culture in suspected sepsis. Methodological quality was assessed using QUADAS. Heterogeneity of studies was investigated using a coupled forest plot of sensitivity and specificity and a scatter plot in receiver operator characteristic space. Bivariate model method was used to estimate summary sensitivity and specificity.

Results: From 41 phase III diagnostic accuracy studies, summary sensitivity and specificity for SeptiFast compared with blood culture were 0.68 (95 % CI 0.63–0.73) and 0.86 (95 % CI 0.84–0.89) respectively. Study quality was judged to be variable with important deficiencies overall in design and reporting that could impact on derived diagnostic accuracy metrics.

Conclusions: SeptiFast appears to have higher specificity than sensitivity, but deficiencies in study quality are likely to render this body of work unreliable. Based on the evidence presented here, it remains difficult to make firm recommendations about the likely clinical utility of SeptiFast in the setting of suspected sepsis.

Optimizing geometric accuracy of four dimensional CT scans acquired using the wall and couch mounted Varian Real-Time Position Management camera systems

Objective:

The aim of this study was to identify sources of anatomical misrepresentation due to the location of camera mounting, tumour motion velocity and image processing artefacts in order to optimise the 4DCT scan protocol and improve geometrical-temporal accuracy.

A phantom with an imaging insert was driven with a sinusoidal superior-inferior motion of varying amplitude and period for 4DCT scanning. The length of a high density cube within the insert was measured using treatment planning software to determine the accuracy of its spatial representation. Scan parameters were varied including the tube rotation period and the cine time between reconstructed images. A CT image quality phantom was used to measure various image quality signatures under the scan parameters tested.

No significant difference in spatial accuracy was found for 4DCT scans carried out using the wall mounted or couch mounted camera for sinusoidal target motion. Greater spatial accuracy was found for 4DCT scans carried out using a tube rotation speed of 0.5s rather than 1.0s. The reduction in image quality when using a faster rotation speed was not enough to require an increase in patient dose.

4DCT accuracy may be increased by optimising scan parameters, including choosing faster tube rotation speeds. Peak misidentification in the recorded breathing trace leads to spatial artefacts and this risk can be reduced by using a couch mounted infrared camera.

This study explicitly shows that 4DCT scan accuracy is improved by scanning with a faster CT tube rotation speed.

Diagnostic accuracy of loop-mediated isothermal amplification as a near-patient test for meningococcal disease in children: An observational cohort study

Background: Diagnosis of meningococcal disease relies on recognition of clinical signs and symptoms that are notoriously non-specific, variable, and often absent in the early stages of the disease. Loop-mediated isothermal amplification (LAMP) has previously been shown to be fast and effective for the molecular detection of meningococcal DNA in clinical specimens. We aimed to assess the diagnostic accuracy of meningococcal LAMP as a near-patient test in the emergency department.

Methods: For this observational cohort study of diagnostic accuracy, children aged 0-13 years presenting to the emergency department of the Royal Belfast Hospital for Sick Children (Belfast, UK) with suspected meningococcal disease were eligible for inclusion. Patients underwent a standard meningococcal pack of investigations testing for meningococcal disease. Respiratory (nasopharyngeal swab) and blood specimens were collected from patients and tested with near-patient meningococcal LAMP and the results were compared with those obtained by reference laboratory tests (culture and PCR of blood and cerebrospinal fluid).

Findings: Between Nov 1, 2009, and Jan 31, 2012, 161 eligible children presenting at the hospital underwent the meningococcal pack of investigations and were tested for meningococcal disease, of whom 148 consented and were enrolled in the study. Combined testing of respiratory and blood specimens with use of LAMP was accurate (sensitivity 89% [95% CI 72-96], specificity 100% [97-100], positive predictive value 100% [85-100]; negative predictive value 98% [93-99]) and diagnostically useful (positive likelihood ratio 213 [95% CI 13-infinity] and negative likelihood ratio 0·11 [0·04-0·32]). The median time required for near-patient testing from sample to result was 1 h 26 min (IQR 1 h 20 min-1 h 32 min).

Interpretation: Meningococcal LAMP is straightforward enough for use in any hospital with basic laboratory facilities, and near-patient testing with this method is both feasible and effective. By contrast with existing UK National Institute of Health and Care Excellence guidelines, we showed that molecular testing of non-invasive respiratory specimens from children is diagnostically accurate and clinically useful.

Validation of the completeness and accuracy of the Northern Ireland Cancer Registry

Background: It has been suggested that inaccuracies in cancer registries are distorting UK survival statistics. This study compared the Northern Ireland Cancer Registry (NICR) database of living patients, with independent data held by Northern Ireland's General Practitioners (GPs) to compare and validate the recorded diagnoses and dates held by the registry. 

Methods: All 387 GP practice managers were invited to participate. 100 practices (25.84%) responded. Comparisons were made for 17,102 patients, equivalent to 29.08% of the living patients (58,798) extracted from the NICR between 1993 and 2010. 

Results: There were no significant differences (p > 0.05) between the responding and nonresponding GP patient profiles for age, marital status or deprivation score. However, the responding GPs included more female patients (p = 0.02). NICR data accuracy was high, 0.08% of GP cancer patients (n = 15) were not included in registry records and 0.02% (n = 2) had a diagnosis date which varied more than 2 weeks from GP records (3 weeks and 5 months). The NICR had recorded two different tumour types and three different tumour statuses (benign vs. malignant) to the GPs. 

Conclusion: This comparison demonstrates a high level of accuracy within the NICR and that the survival statistics based on this data can be relied upon.

Accuracy of medical subject heading indexing of dental survival analyses

PURPOSE: To assess the Medical Subject Headings (MeSH) indexing of articles that employed time-to-event analyses to report outcomes of dental treatment in patients.

MATERIALS AND METHODS: Articles published in 2008 in 50 dental journals with the highest impact factors were hand searched to identify articles reporting dental treatment outcomes over time in human subjects with time-to-event statistics (included, n = 95), without time-to-event statistics (active controls, n = 91), and all other articles (passive controls, n = 6,769). The search was systematic (kappa 0.92 for screening, 0.86 for eligibility). Outcome-, statistic- and time-related MeSH were identified, and differences in allocation between groups were analyzed with chi-square and Fischer exact statistics.

RESULTS: The most frequently allocated MeSH for included and active control articles were "dental restoration failure" (77% and 52%, respectively) and "treatment outcome" (54% and 48%, respectively). Outcome MeSH was similar between these groups (86% and 77%, respectively) and significantly greater than passive controls (10%, P < .001). Significantly more statistical MeSH were allocated to the included articles than to the active or passive controls (67%, 15%, and 1%, respectively, P < .001). Sixty-nine included articles specifically used Kaplan-Meier or life table analyses, but only 42% (n = 29) were indexed as such. Significantly more time-related MeSH were allocated to the included than the active controls (92% and 79%, respectively, P = .02), or to the passive controls (22%, P < .001).

CONCLUSIONS: MeSH allocation within MEDLINE to time-to-event dental articles was inaccurate and inconsistent. Statistical MeSH were omitted from 30% of the included articles and incorrectly allocated to 15% of active controls. Such errors adversely impact search accuracy.

Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores

Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R(2) increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase.

Accuracy of rural refractionists in western China

Purpose. We assessed the prevalence and predictors of inaccurate refractive error among rural refractionists in western China. Methods. A subset of primary school children with visual acuity (VA) ≤6/12 in ≥1 eye, undergoing subjective refinement by local refractionists after cycloplegic autorefraction in an ongoing population-based study, received repeat refraction by university optometrists for quality control. Results. Among 502 children (mean age 10.5 years, 53.2% girls), independent predictors of poor (inaccurate by ≥1.0 diopter [D]) refraction by 21 rural practitioners (66.7% with high school or lower education) included hyperopia (odds ratio [OR], 4.2; 95% confidence interval [CI], 2.4-7.3, P < 0.001), astigmatism (OR = 3.8; 95% CI, 2.5-5.6; P < 0.001) and VA uncorrectable to >6/12 by the rural refractionist (OR = 4.7; 95% CI, 3.1-7.3; P = < 0.001). Among 201 children whose vision was uncorrectable in ≥1 eye by the rural refractionists, vision could be improved to >6/12 by the university optometrist in 110 (54.7%). We estimate vision could be so improved in 9.1% of all children refracted by these rural refractionists. A reason for inaccuracy in this setting is the erroneous tendency of rural refractionists to adjust instrument values for accommodation, even under cycloplegia. Conclusions. Rural refractionists in western China have little formal training and frequently fail to optimize VA among children, even when autorefractors are used. Training is needed emphasizing better use of automated refraction, particularly in children with astigmatism and hyperopia. © 2014 The Association for Research in Vision and Ophthalmology, Inc.

Strategies to improve the accuracy of vision measurement by teachers in rural Chinese secondary schoolchildren: Xichang Pediatric Refractive Error Study (X-PRES) report no. 6.

OBJECTIVE: To assess and improve the accuracy of lay screeners compared with vision professionals in detecting visual impairment in secondary schoolchildren in rural China. METHODS: After brief training, 32 teachers and a team of vision professionals independently measured vision in 1892 children in Xichang. The children also underwent vision measurement by health technicians in a concurrent government screening program. RESULTS: Of 32 teachers, 28 (87.5%) believed that teacher screening was worthwhile. Sensitivity (93.5%) and specificity (91.2%) of teachers detecting uncorrected presenting visual acuity of 20/40 or less were better than for presenting visual acuity (sensitivity, 85.2%; specificity, 84.8%). Failure of teachers to identify children owning but not wearing glasses and teacher bias toward better vision in children wearing glasses explain the worse results for initial vision. Wearing glasses was the student factor most strongly predictive of inaccurate teacher screening (P < .001). The sensitivity and specificity of the government screening program detecting low presenting visual acuity were 86.7% and 28.7%, respectively. CONCLUSIONS: Teacher vision screening after brief training can achieve accurate results in this setting, and there is support among teachers for screening. Screening of uncorrected rather than presenting visual acuity is recommended in settings with a high prevalence of corrected and uncorrected refractive error. Low specificity in the government program renders it ineffective.

Pupil constriction can alter the accuracy of dark room provocative test.

BACKGROUND: Primary angle-closure glaucoma (PACG) is a major cause of visual morbidity in East Asia. Dark-room provocative test (DRPT) has been used to determine which narrow angles have the risk to develop angle closure. However, the accuracy of DRPT might be altered because that after emerging from the dark room, the configuration of the angle is affected by the light of the slit-lamp and the appositionally closed angle reopens. The aim of this study was to examine the pupillary diameter in different light conditions and use it as a parameter to assess the accuracy of dark-room provocative test. METHODS: Patients with suspected primary angle-closure glaucoma undergoing DRPT were recruited. The anterior chamber angle was examined by anterior segment optical coherence tomography under the following conditions: (1) in standard room illumination; (2) after short-term dark-adaptation and (3) after DRPT. Mean values of pupil size and numbers of appositionally closed angle under different conditions were compared. RESULTS: A total of 47 eyes of 47 patients were analyzed. The pupil size after DRPT was smaller than that after short-term dark-adaptation (P < 0.001) and smaller than that in standard room illumination (P = 0.026). The numbers of appositionally closed angles after short-term dark-adaptation were significantly larger than those after DRPT (P < 0.001). There was no significant difference between the numbers of appositionally closed angles in standard room illumination and after DRPT (P = 0.157). CONCLUSIONS: Constriction of pupil size immediately after prolonged dark room provocative test may lead to change in the angle configuration, which may lead to false negative results. We suggest a modified protocol of recording intraocular pressure immediately after DRPT and performing gonioscopy following short-term dark adaptation to improve the accuracy of angle closure assessment.

Validating the accuracy of a model to predict the onset of myopia in children.

PURPOSE: To assess the sensitivity and specificity of models predicting myopia onset among ethnically Chinese children. METHODS: Visual acuity, height, weight, biometry (A-scan, keratometry), and refractive error were assessed at baseline and 3 years later using the same equipment and protocol in primary schools in Xiamen (China) and Singapore. A regression model predicting the onset of myopia < -0.75 diopters (D) after 3 years in either eye among Xiamen children was validated with Singapore data. RESULTS: Baseline data were collected from 236 Xiamen children (mean age, 7.82 ± 0.63 years) and from 1979 predominantly Chinese children in Singapore (7.83 ± 0.84 years). Singapore children were significantly taller and heavier, and had more myopia (31.4% vs. 6.36% < -0.75 D in either eye, P < 0.001) and longer mean axial length. Three-year follow-up was available for 80.0% of Xiamen children and 83.1% in Singapore. For Xiamen, the area under the receiver-operator curve (AUC) in a model including ocular biometry, height, weight, and presenting visual acuity was 0.974 (95% confidence interval [CI], 0.945-0.997). In Singapore, the same model achieved sensitivity, specificity, and positive predictive value of 0.844, 0.650, and 0.669, with an AUC of 0.815 (95% CI, 0.791-0.839). CONCLUSIONS: Accuracy in predicting myopia onset based on simple measurements may be sufficient to make targeted early intervention practical in settings such as Singapore with high myopia prevalence. Models based on cohorts with a greater prevalence of high myopia than that in Xiamen could be used to assess accuracy of models predicting more severe forms of myopia.

An evaluation of the accuracy of models for the determination of the weighted mean temperature of the atmosphere

The estimates of the zenith wet delay resulting from the analysis of data from space techniques, such as GPS and VLBI, have a strong potential in climate modeling and weather forecast applications. In order to be useful to meteorology, these estimates have to be converted to precipitable water vapor, a process that requires the knowledge of the weighted mean temperature of the atmosphere, which varies both in space and time. In recent years, several models have been proposed to predict this quantity. Using a database of mean temperature values obtained by ray-tracing radiosonde profiles of more than 100 stations covering the globe, and about 2.5 year’s worth of data, we have analyzed several of these models. Based on data from the European region, we have concluded that the models provide identical levels of precision, but different levels of accuracy. Our results indicate that regionally-optimized models do not provide superior performance compared to the global models.

Improvement in the Accuracy of Back Trajectories Using WRF to Identify Pollen Sources in Southern Iberian Peninsula

Airborne pollen transport at micro-, meso-gamma and meso-beta scales must be studied by atmospheric models, having special relevance in complex terrain. In these cases, the accuracy of these models is mainly determined by the spatial resolution of the underlying meteorological dataset. This work examines how meteorological datasets determine the results obtained from atmospheric transport models used to describe pollen transport in the atmosphere. We investigate the effect of the spatial resolution when computing backward trajectories with the HYSPLIT model. We have used meteorological datasets from the WRF model with 27, 9 and 3 km resolutions and from the GDAS files with 1 ° resolution. This work allows characterizing atmospheric transport of Olea pollen in a region with complex flows. The results show that the complex terrain affects the trajectories and this effect varies with the different meteorological datasets. Overall, the change from GDAS to WRF-ARW inputs improves the analyses with the HYSPLIT model, thereby increasing the understanding the pollen episode. The results indicate that a spatial resolution of at least 9 km is needed to simulate atmospheric flows that are considerable affected by the relief of the landscape. The results suggest that the appropriate meteorological files should be considered when atmospheric models are used to characterize the atmospheric transport of pollen on micro-, meso-gamma and meso-beta scales. Furthermore, at these scales, the results are believed to be generally applicable for related areas such as the description of atmospheric transport of radionuclides or in the definition of nuclear-radioactivity emergency preparedness.

Validation of the needle targeting accuracy of a MRI/TRUS- image-guided system for transperineal prostate cancer biopsy

Multi-parametric magnetic resonance imaging (mp-MRI) has become an increasingly important method for detecting and treating prostate cancer. Transrectal ultrasound (TRUS) is the most commonly used method for guiding prostate needle biopsy and remains the gold standard for diagnosis of prostate cancer. MRI-to-TRUS image reg- istration is an important technology for enabling computer-assisted targeting of the majority of prostate lesions that are visible in MRI but not independently distinguishable in TRUS images. The aim of this study was to estimate the needle placement accuracy of an image guidance system (SmartTargetÒ), developed by our research group, using a surgical training phantom.

The accuracy of the escrowed dividend model on the value of European options on a stock paying discrete dividend

This project characterizes the accuracy of the escrowed dividend model on the value of European options on a stock paying discrete dividend. A description of the escrowed dividend model is provided, and a comparison between this model and the benchmark model is realized. It is concluded that options on stocks with either low volatility, low dividend yield, low ex-dividend to maturity ratio or that are deep in or out of the money are reasonably priced with the escrowed dividend model.