A comparison of diagnostic performance between two quantitative rapid fecal calprotectin assays in detecting active inflammatory bowel disease.

BACKGROUND: Fecal calprotectin (FC) is widely used for the diagnosis and monitoring disease activity of inflammatory bowel disease (IBD). Quantitative rapid assays can be a reliable alternative to the time-consuming assay. This study aimed to evaluate and compare the diagnostic performance of two quantitative rapid FC assays (Ichroma calprotectin, and Buhlmann Quantum blue). METHODS: A total of 192 patients were included in this study; 84 patients with IBD (67 ulcerative colitis and 17 Crohn's disease) and 108 patients with non-IBD. We compared quantitative FC levels in different disease statuses and evaluated the correlation between the FC results of the two FC kits. Diagnostic performances in predicting active IBD were evaluated in reference to different cut-off levels. RESULTS: The FC levels in 45 patients with active IBD as defined by endoscopic score were significantly higher compared to the inactive IBD and other diseases (P<0.05). Although the two assays' results correlated (r = 0.642, P < 0.001), a significant deviation was observed (y (Buhlmannn) = -45.2 +8.9X (Ichroma)). The Diagnostic performances in predicting active IBD were comparable as area under the curve (AUC), 0.812, cut-off, 50, sensitivity, 64.4%, and specificity, 85.0% for iChroma assay and AUC, 0.826, cut-off, 100, sensitivity, 84.4%, and specificity 61.9% for Buhlmann Quantum Blue assay. FC levels using a cut-off of > 250 µg/g confirmed 85.7% (iChroma) and 64.1% (Buhlmann) of active IBD patients. CONCLUSION: The results of the two rapid FC assays iChroma and Buhlmann showed a significant correlation, but the two test results were not interchangeable. With optimized cut-off values, rapid FC tests could be helpful in the diagnosis of IBD and differentiating active IBD from inactive or organic bowel disease.

Comparative performance evaluation of Wako ß-glucan test and Fungitell assay for the diagnosis of invasive fungal diseases.

The Fungitell assay (FA) and the Wako ß-glucan test (GT) are employed to measure the serum/plasma 1,3-ß-D-glucan (BDG), a well-known invasive fungal disease biomarker. Data to convincingly and/or sufficiently support the GT as a valuable alternative to the FA are yet limited. In this study, we evaluated the FA and the GT to diagnose invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis jirovecii pneumonia (PJP). The FA and GT performances were compared in sera of patients with IA (n = 40), IC (n = 78), and PJP (n = 17) with respect to sera of control patients (n = 187). Using the manufacturer's cutoff values of 80 pg/mL and 11 pg/mL, the sensitivity and specificity for IA diagnosis were 92.5% and 99.5% for the FA and 60.0% and 99.5% for the GT, respectively; for IC diagnosis were 100.0% and 97.3% for the FA and 91.0% and 99.5% for the GT, respectively; for PJP diagnosis were 100.0% and 97.3% for the FA and 88.2% and 99.5% for the GT, respectively. When an optimized cutoff value of 7.0 pg/mL for the GT was used, the sensitivity and specificity were 80.0% and 97.3% for IA diagnosis, 98.7% and 97.3% for IC diagnosis, and 94.1% and 97.3% for PJP diagnosis, respectively. At the 7.0-pg/mL GT cutoff, the agreement between the assays remained and/or became excellent for IA (95.1%), IC (97.3%), and PJP (96.5%), respectively. In conclusion, we show that the GT performed as well as the FA only with a lowered cutoff value for positivity. Further studies are expected to establish the equivalence of the two BDG assays.

A comparison study between wide-range and high-sensitivity C-reactive protein assays (Roche Cobas c702) for low C-reactive protein concentration in patients with cardiovascular risk.

BACKGROUND: Low concentration C-reactive protein (CRP) has favorable prognostic significance in patients with cardiovascular risks. METHODS: We compared the wr-CRP method with the hs-CRP method both on Roche Cobas c702 analyzer for the determination of low CRP concentration (<20 mg/L) including 200 patients treated in Cardiology Department in Beijing Tsinghua Changgung Hospital (Beijing, China) from December 2018 to March 2019. RESULTS: The two methods were highly correlated (Spearman's rho = 0.995). Deming regression was used to fit the regression analysis model, giving a slope of 1.058 with an intercept of 0.008. The median method difference (wr-CRP - hr-CRP) was 0.120 mg/L (95% CI, 0.086-0.200 mg/L), and the median percent differences were 7.34% (95% CI, 4.27%-8.47%). The percent bias between both methods at the given cutoff CRP values of 1, 3, and 10 mg/L evaluated by Deming regression was 6.60%, 6.07%, and 5.88%, respectively, all of which were less than the acceptable standard (12.50%). The percentage of sample results concordant by both methods for the risk stratification was 96.0% (kappa = 0.937, P < 0.001). CONCLUSIONS: Roche wr-CRP and hs-CRP assays are highly concordant in determining low concentration CRP. Wr-CRP may be used as an alternative to hs-CRP assay on Roche Cobas c702 analyzer to assess the cardiovascular risk, considering its convenience and lower costs.

CLIA-waived molecular influenza testing in the emergency department and outpatient settings.

Respiratory tract infections are a common cause of visits to emergency departments and outpatient settings. Infections with influenza viruses A and B in particular, are responsible for significant morbidity and mortality in both pediatric and adult populations worldwide. A significant number of influenza diagnoses occur in the emergency departments with many being performed using rapid influenza diagnostic tests (RIDT) which have sensitivities as low as 30% depending on the specific RIDT and patient population. More recently, rapid molecular tests for the detection of influenza viruses A and B have become commercially available as point-of-care platforms. In the United States, several of these new tests are approved by the Food and Drug Administration as CLIA-waived tests. In this report, we review the data on the analytical and clinical performance of RIDTs and CLIA-waived molecular tests, present and discuss potential key challenges and opportunities for implementation of CLIA-waived molecular tests at or near point of care in the emergency departments and outpatient settings.

The normal range: it is not normal and it is not a range.

The NHS 'Choose Wisely' campaign places greater emphasis on the clinician-patient dialogue. Patients are often in receipt of their laboratory data and want to know whether they are normal. But what is meant by normal? Comparator data, to a measured value, are colloquially known as the 'normal range'. It is often assumed that a result outside this limit signals disease and a result within health. However, this range is correctly termed the 'reference interval'. The clinical risk from a measured value is continuous, not binary. The reference interval provides a point of reference against which to interpret an individual's results-rather than defining normality itself. This article discusses the theory of normality-and describes that it is relative and situational. The concept of normality being not an absolute state influenced the development of the reference interval. We conclude with suggestions to optimise the use and interpretation of the reference interval, thereby facilitating greater patient understanding.

Network meta-analysis of diagnostic test accuracy studies identifies and ranks the optimal diagnostic tests and thresholds for health care policy and decision-making.

OBJECTIVES: Network meta-analyses (NMA) have extensively been used to compare the effectiveness of multiple interventions for health care policy and decision-making. However, methods for evaluating the performance of multiple diagnostic tests are less established. In a decision-making context, we are often interested in comparing and ranking the performance of multiple diagnostic tests, at varying levels of test thresholds, in one simultaneous analysis. STUDY DESIGN AND SETTING: Motivated by an example of cognitive impairment diagnosis following stroke, we synthesized data from 13 studies assessing the efficiency of two diagnostic tests: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), at two test thresholds: MMSE <25/30 and <27/30, and MoCA <22/30 and <26/30. Using Markov chain Monte Carlo (MCMC) methods, we fitted a bivariate network meta-analysis model incorporating constraints on increasing test threshold, and accounting for the correlations between multiple test accuracy measures from the same study. RESULTS: We developed and successfully fitted a model comparing multiple tests/threshold combinations while imposing threshold constraints. Using this model, we found that MoCA at threshold <26/30 appeared to have the best true positive rate, whereas MMSE at threshold <25/30 appeared to have the best true negative rate. CONCLUSION: The combined analysis of multiple tests at multiple thresholds allowed for more rigorous comparisons between competing diagnostics tests for decision making.

Elevated Liver Enzymes: Emergency Department-Focused Management.

BACKGROUND: Liver function test (LFT) abnormalities are a common problem faced by emergency physicians. This has become more common with the introduction of laboratory panels and automated routine laboratory testing. Fortunately, not all patients with irregularities in liver enzymes possess underlying pathology. This emergency medicine focused review provides a discussion of the various biochemical tests, their underlying biological basis, and an algorithmic approach to the interpretation of abnormalities. OBJECTIVE: Our aim was to provide emergency physicians with an overview of the evaluation and management of patients with elevated LFTs. DISCUSSION: The liver is a complex organ with multiple roles. The key biochemical markers of hepatic function can be organized into the groupings of hepatocellular, cholestatic, or functioning liver, based on underlying enzymatic roles. Pathologic alterations to these markers can be algorithmically assessed by separating disease processes of these groupings, followed by assessment of the magnitude of enzymatic elevation. This review conducts an in-depth evaluation of the differential diagnosis and emergency department-centered clinical response of elevated LFTs based on subcategories of mild, moderate, and severe transaminase elevation. CONCLUSIONS: By understanding the biochemical basis of each LFT, it is possible to correlate laboratory findings to a patient's clinical presentation. An algorithmic approach can be taken to help narrow the spectrum of a differential diagnosis. This may assist providers in ensuring appropriate management and evaluation of the patient with elevated LFTs.

A sequential classification rule based on multiple quantitative tests in the absence of a gold standard.

In many medical applications, combining information from multiple biomarkers could yield a better diagnosis than any single one on its own. When there is a lack of a gold standard, an algorithm of classifying subjects into the case and non-case status is necessary for combining multiple markers. The aim of this paper is to develop a method to construct a composite test from multiple applicable tests and derive an optimal classification rule under the absence of a gold standard. Rather than combining the tests, we treat the tests as a sequence. This sequential composite test is based on a mixture of two multivariate normal latent models for the distribution of the test results in case and non-case groups, and the optimal classification rule is derived returning the greatest sensitivity at a given specificity. This method is applied to a real-data example and simulation studies have been carried out to assess the statistical properties and predictive accuracy of the proposed composite test. This method is also attainable to implement nonparametrically.

Classification in two-stage screening.

Decision theory is applied to the problem of setting thresholds in medical screening when it is organised in two stages. In the first stage that involves a less expensive procedure that can be applied on a mass scale, an individual is classified as a negative or a likely positive. In the second stage, the likely positives are subjected to another test that classifies them as (definite) positives or negatives. The second-stage test is more accurate, but also more expensive and more involved, and so there are incentives to restrict its application. Robustness of the method with respect to the parameters, some of which have to be set by elicitation, is assessed by sensitivity analysis.

Survey of the methods and reporting practices in published meta-analyses of test performance: 1987 to 2009.

We performed a survey of meta-analyses of test performance to describe the evolution in their methods and reporting. Studies were identified through MEDLINE (1966-2009), reference lists, and relevant reviews. We extracted information on clinical topics, literature review methods, quality assessment, and statistical analyses. We reviewed 760 publications reporting meta-analyses of test performance, published between 1987 and 2009. Eligible reviews included a median of 18 primary studies that were used in quantitative analyses. Most common clinical areas were cardiovascular disease (21%) and oncology (25%); most common test categories were imaging (44%) and biomarker tests (28%). Assessment of verification and spectrum bias, blinding, prospective study design, and consecutive patient recruitment became more common over time (p < 0.001 comparing reviews published through 2004 vs 2005 onwards). These changes coincided with the increasing use of checklists to guide assessment of methodological quality. Heterogeneity tests were used in 58% of meta-analyses; subgroup or regression analyses were used in 57%. Random effects models were employed in 57% of meta-analyses (38% through 2004 vs 72% 2004-onwards; p < 0.001). Use of bivariate models of sensitivity and specificity increased in recent years (21% in 2008-2009 vs 7% in earlier years; p < 0.001). Methods employed in meta-analyses of test performance have improved with the introduction of quality assessment checklists and the development of more sophisticated statistical methods.

High altitude ataxia--its assessment and relevance.

Ataxia at altitude is reviewed in relation to acute mountain sickness (AMS). The cause of ataxia occurring at altitude is unknown but may be hypoxia affecting basal ganglia and hindbrain activity. Ataxia is an important sign of high altitude cerebral edema (HACE) but is less well-established as a clinical feature of AMS. Assessment of ataxia is part of the Environmental Systems and the Lake Louise questionnaires, together with a heel-to-toe measurement. More precise measures of ataxia include the Sharpened Romberg Test (SRT) and the use of unstable platforms. Isolated ataxia at altitude may not be related to AMS or HACE. Age affects ataxia and careful baseline measurements are essential in older subjects before results at high altitude can be interpreted. Testing for ataxia needs to be standardized with sufficient learning time. Ataxia should be distinguished from weakness or fatigue occurring at altitude. Specialized tests have not been shown to be clinically important. Our results above 5000 m showed that an abnormal SRT may be specific for AMS but with relatively poor sensitivity. Wobble board results have not correlated with AMS scores consistently. Other authors using an unstable platform in a chamber and static posturography during 3 days of exposure to 4559 m also found no relationship with AMS scores. Ataxia is a common and important clinical feature of HACE but is unhelpful in the assessment of mild or even moderate AMS in the absence of an altered mental state. The simple heel-to-toe test remains a useful part of the assessment of more severe AMS bordering on HACE.

Contribution of clinical tests to the diagnosis of rotator cuff disease: a systematic literature review.

OBJECTIVE: To evaluate the diagnostic performance of clinical tests for degenerative rotator cuff disease, based on a systematic literature review. METHODS: We searched Medline, Embase, and Pascal Biomed until the first half of 2006 inclusive for articles that reported at least the sensitivity and specificity of clinical tests for rotator cuff disease. Predictive values and accuracy were recorded where available. The results were discussed and validated. RESULTS: We selected nine studies, of which three investigated tests for subacromial impingement syndrome and seven tests for rotator cuff tendinopathy. The Neer and Hawkins tests had good sensitivity but low specificity for subacromial impingement syndrome. For diagnosing tears of the supraspinatus or infraspinatus, the Jobe sign and the full can test showed similar performance characteristics to the Patte test and resisted external rotation with the elbow at the side flexed at 90 degrees . For diagnosing tendinopathies with or without tears, active unresisted external rotation for the infraspinatus and the lift off test for the subscapularis were specific but lacked sensitivity. In one study, limitation of the range of active unresisted internal rotation was sensitive and specific for subscapularis tendon disease. The palm up test performed poorly for diagnosing long head of biceps disease. CONCLUSIONS: Data on the diagnostic performance of clinical tests for rotator cuff tendon disease are fragmentary. However objective data exist to support the usefulness of some of these tests. Further studies are needed.

Assessing validity of ICD-9-CM and ICD-10 administrative data in recording clinical conditions in a unique dually coded database.

OBJECTIVE: The goal of this study was to assess the validity of the International Classification of Disease, 10th Version (ICD-10) administrative hospital discharge data and to determine whether there were improvements in the validity of coding for clinical conditions compared with ICD-9 Clinical Modification (ICD-9-CM) data. METHODS: We reviewed 4,008 randomly selected charts for patients admitted from January 1 to June 30, 2003 at four teaching hospitals in Alberta, Canada to determine the presence or absence of 32 clinical conditions and to assess the agreement between ICD-10 data and chart data. We then re-coded the same charts using ICD-9-CM and determined the agreement between the ICD-9-CM data and chart data for recording those same conditions. The accuracy of ICD-10 data relative to chart data was compared with the accuracy of ICD-9-CM data relative to chart data. RESULTS: Sensitivity values ranged from 9.3 to 83.1 percent for ICD-9-CM and from 12.7 to 80.8 percent for ICD-10 data. Positive predictive values ranged from 23.1 to 100 percent for ICD-9-CM and from 32.0 to 100 percent for ICD-10 data. Specificity and negative predictive values were consistently high for both ICD-9-CM and ICD-10 databases. Of the 32 conditions assessed, ICD-10 data had significantly higher sensitivity for one condition and lower sensitivity for seven conditions relative to ICD-9-CM data. The two databases had similar sensitivity values for the remaining 24 conditions. CONCLUSIONS: The validity of ICD-9-CM and ICD-10 administrative data in recording clinical conditions was generally similar though validity differed between coding versions for some conditions. The implementation of ICD-10 coding has not significantly improved the quality of administrative data relative to ICD-9-CM. Future assessments like this one are needed because the validity of ICD-10 data may get better as coders gain experience with the new coding system.

The carbon monoxide diffusing capacity: clinical implications, coding, and documentation.

The test for the diffusing capacity of the lung for carbon monoxide (DLCO) has been available for nearly 100 years for research and clinical purposes. The single-breath method is used almost exclusively in the United States It has been available in clinical pulmonary function laboratories for > 50 years. DLCO has great value in evaluating patients with lung diseases. Guidelines to standardize DLCO have been published by the American Thoracic Society and European Respiratory Society to reduce the interlaboratory variability that has existed. One code, 94720, should be reported for the billing for DLCO. Another code, 94725, the membrane diffusing capacity, exists for the measurement of the membrane and blood components of the DLCO. Currently, no clinical indications exist for the use of the membrane diffusing capacity. The finding that the number of tests in the Medicare population coded with 94725 has increased by > 1,000% from 2000 to 2005 is quite surprising. This rate is 14-times higher than the rate of increase in the utilization of 94720 over the same period. The possible reasons for these increases are discussed, but the most likely explanation is the financial gain derived from coding 94725. It is proposed that coding and billing of 94725 be stopped until the clinical indications for membrane diffusing capacity have been established. Those who code and bill for 94725 must be prepared to justify the use of this code to Medicare and third-party payers.

Reducing bias from test misclassification in burden of disease studies: use of test to actual positive ratio--new test parameter.

AIM: To address the problem of estimating disease frequency identified by a diagnostic test, which may not represent the actual number of persons with disease in a community, but rather the number of persons who tested positive. Those two values may be very different, their relationship depending on the properties of the diagnostic test applied and true prevalence of the disease in a population. METHODS: We defined a new test parameter, the ratio of Test to Actual Positives (TAP), which summarizes the properties of the diagnostic test applied and true prevalence of the disease in a population, and propose that is the most useful summary measure of the potential for bias in disease frequency estimates. RESULTS: A consideration of the relationship between the sensitivity (Se) and specificity (Sp) of the diagnostic test and the true prevalence of disease in a population can inform study design by highlighting the potential for disease misclassification bias. The effects of a decrease in Sp on the TAP ratio at very low disease prevalence are dramatic, as at 80% Sp (and any Se value including 100%), the measured disease frequency will represent a 25-fold overestimate. At a disease prevalence of 0.10, the Sp needs to be 90% or greater to achieve a TAP ratio of 1.0. However, unlike at lower levels of disease prevalence, the test Se is also an important determinant of the TAP ratio. A TAP ratio of 1.0 can be achieved by a Sp of 95% and intermediate Se (40%-60%); or a Sp of 99% and very high Se (over 90%). This illustrates how a test with poor performance characteristics in a clinical setting can perform well in a disease burden study in a population. In circumstances in which the TAP ratio suggests a potential for a large bias, we suggest correction procedures that limit disease misclassification bias and which are often counter-intuitive. We also illustrate how these methods can improve the power of intervention studies, which define outcomes by use of a diagnostic test. CONCLUSIONS: Optimal screening test characteristics for use in a population-based survey are likely to be different to those when the test is used in a clinical setting. Calibrating the test a priori to bring the TAP ratio closer to unity deals with the possible large bias in disease burden estimates based on application of diagnostic (screening) test.

Suspected acute allergic reactions: analysis of admissions to the Emergency Department of the AOU Maggiore della Carità Hospital in Novara from 2003 to 2007.

OBJECTIVE OF THE STUDY: The aim of our work is to ascertain the frequency and the impact of acute allergic reactions on the routine of a highly-specialized Emergency Department collecting information on the admission, the typology of symptoms and the degree of severity calculating the incidence and the outcomes of the events. MATERIALS AND METHODS: The study started the 1 July 2006 and the records of the Emergency Department of the Maggiore della Carità Hospital in Novara were consulted retrospectively in the period between the 1 January 2003 and the 31 December 2006, and prospectively up to the 31 December 2007, using keywords that could identify admission for suspected allergic reactions. Information relating to internal medicine and/or pediatric cases were examined, excluding all surgical and/or trauma cases. The number ofadmissions per year was considered broken down by clinical signs, triage assessment upon admission and discharge outcome. RESULTS: Admissions to the Emergency Department during the period under consideration were 165,120 with 6107 suspected cases of allergic reactions. The symptoms most frequently reported both in adults (A) and children (C < or =18 years old), were: hives 37%, asthma 20.65 (A)% and 27.4% (C); drug allergy 7.5% (A) and 6.1% (C). Reactions to Hymenoptera venom were less frequent, 4.7% (A) and 1.27% (C); the frequency of angioedema, conjunctivitis and rhinitis was between 1 and 4%. The incidence of food allergies (1.4%) and anaphylaxis (0.8%) was comparable for all ages. The triage assessment showed a significant percentage of "yellow" and "red" codes, with 362 cases (5.9%) and 71 cases (1.16%) respectively. A total of 151 patients was hospitalized, no one classified as "white" code. Death occurred in 7 cases: 4 "yellow" codes and 3 "red" codes, respectively. A more detailed specialistic evaluation was recommended in only 10% of the patients. CONCLUSIONS: Admissions to the Emergency Department for suspected allergic reaction are proportional to the number of overall admissions for internal medicine cases and do not appear to be related to the general increase of allergies in the population. This led us to focus our attention on how allergic diseases impact the work of an Emergency Department and how to describe the discharge diagnosis better. A significant number of descriptive diagnoses also turned out to be inaccurate and did not allow the syndrome to be identified properly. The analysis of this information aims to be a stimulus to improve the emergency clinical approach used for allergic diseases and to plan the adequate management ofallergic patients after they have been treated in hospital.