High Pretest Probability Research Articles

Comparison of the Wells score and the revised Geneva score as a tool to predict pulmonary embolism in outpatients over age 65

TitleComparison of the Wells score and the revised Geneva score as a tool to predict pulmonary embolism in outpatients over 65 years of age. IntroductionThe incidence and mortality of pulmonary embolism (PE) is high in the elderly. The Wells score (SW) and the revised Geneva score (RGS) have been validated in patient populations with a large age range. The aim of this study was to compare the predictive accuracy of these two scores in diagnosis of PE in patients over 65 years of age. MethodA prospective multicentre study (nine French and three Belgian centres) was conducted at the same time as the PERCEPIC study. A total of 1757 patients admitted with suspected PE were included and divided into two groups according to age (≥65 years or <65 years). The pre-test probability of PE was assessed prospectively for the RGS. The SW was calculated retrospectively. The predictive accuracy of the two scores was compared by the area under the curve (AUC) of the ROC curves. ResultsThe overall prevalence of PE was 11.3%. The prevalence among patients aged ≥65 in the low, moderate and high pre-test probability groups, evaluated using the WS and was respectively 13.5% (CI 95%: CI 9.9–17.3), 28.2% (CI 22.1–34.3), 50% (CI 26–74) and 8.1% (CI 3.2–12.9), 22.3% (CI 18.2–26.3), 43.7% (CI 25.6–61.9) using the RGS. The AUC for the WS and RGS for patients aged ≥65 was 0.632 (CI 0.574–0.691) and 0.610 (CI 0.555–0.666). The difference between the AUCs was not statistically significant (p = .441). ConclusionIn the population for this study, the WS and RGS have the same PE diagnostic accuracy in patients over age 65. This result should be validated in a prospective study that directly compares these scores.

Accuracy of a Novel Urine Test, Fujifilm SILVAMP Tuberculosis Lipoarabinomannan, for the Diagnosis of Pulmonary Tuberculosis in Children.

An accurate point-of-care test for tuberculosis (TB) in children remains an elusive goal. Recent evaluation of a novel point-of-care urinary lipoarabinomannan test, Fujifilm SILVAMP Tuberculosis Lipoarabinomannan (FujiLAM), in adults living with human immunodeficiency virus (HIV) showed significantly superior sensitivity than the current Alere Determine Tuberculosis Lipoarabinomannan test (AlereLAM). We therefore compared the accuracy of FujiLAM and AlereLAM in children with suspected TB. Children hospitalized with suspected TB in Cape Town, South Africa, were enrolled (consecutive admissions plus enrichment for a group of children living with HIV and with TB), their urine was collected and biobanked, and their sputum was tested with mycobacterial culture and Xpert MTB/RIF or Xpert MTB/RIF Ultra. Biobanked urine was subsequently batch tested with FujiLAM and AlereLAM. Children were categorized as having microbiologically confirmed TB, unconfirmed TB (clinically diagnosed), or unlikely TB. A total of 204 children were enrolled and had valid results from both index tests, as well as sputum microbiological testing. Compared to a microbiological reference standard, the sensitivity of FujiLAM and AlereLAM was similar (42% and 50%, respectively), but lower than that of Xpert MTB/RIF of sputum (74%). The sensitivity of FujiLAM was higher in children living with HIV (60%) and malnourished children (62%). The specificity of FujiLAM was substantially higher than that of AlereLAM (92% vs 66%, respectively). The specificity of both tests was higher in children 2 years or older (FujiLAM, 96%; AlereLAM, 72%). The high specificity of FujiLAM suggests utility as a "rule-in" test for children with a high pretest probability of TB, including hospitalized children living with HIV or with malnutrition.

Baseline use of angiotensin-converting enzyme inhibitor/AT1 blocker and outcomes in hospitalized coronavirus disease 2019 African-American patients.

The primary objective of this study is to determine the effect of baseline use of angiotensin-converting enzyme inhibitor (ACE-i)/AT1 blocker (ARB) on mortality in hospitalized coronavirus disease 2019 (Covid-19) African-American patients. The secondary objectives are, to determine the effect of baseline use of ACE-i/ARB on the need for mechanical ventilation, new dialysis, ICU care, and on composite of above-mentioned outcomes in the same cohort. In this retrospective study, we analyzed data using electronic medical records from all hospitalized Covid-19 African-American patients, who either died in the hospital or survived to discharge between 2 March and 22 May 2020. Patients were divided into two groups, those on ACE-i/ARB at baseline and those not on them. We used Pearson chi-square test for categorical variables, and Student's t test for continuous variables. We performed multiple logistic regression to test the primary and secondary objectives using SAS 9.4. Out of 531 patients included in the analysis, 207 (39%) were on ACE-i/ARB at baseline. Patients in ACE-i/ARB group were older (64 vs. 57 years, P < 0.001), and had higher prevalence of hypertension (96.6 vs. 69.4%, P < 0.001) and diabetes mellitus (55.6 vs. 34.9%, P < 0.001). There was no difference in sex, BMI, other comorbidities, and presenting illness severity among the groups. After adjustment of multiple covariates, there was no difference in outcomes between the two groups including mortality, need for mechanical ventilation, new dialysis, ICU care, as well as composite outcomes. Baseline use of ACE-i/ARB does not worsen outcomes in hospitalized Covid-19 African-American patients.

Chest CT accuracy in diagnosing COVID-19 during the peak of the Italian epidemic: A retrospective correlation with RT-PCR testing and analysis of discordant cases

ObjectivesThe goal of this study was to assess chest computed tomography (CT) diagnostic accuracy in clinical practice using RT-PCR as standard of reference. MethodsFrom March 4th to April 9th 2020, during the peak of the Italian COVID-19 epidemic, we enrolled a series of 773 patients that performed both non-contrast chest CT and RT-PCR with a time interval no longer than a week due to suspected SARS-CoV-2 infection. The diagnostic performance of CT was evaluated according to sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy, considering RT-PCR as the reference standard. An analysis on the patients with discrepant CT scan and RT-PCR result and on the patient with both negative tests was performed. ResultsRT-PCR testing showed an overall positive rate of 59.8 %. CT sensitivity, specificity, PPV, NPV, and accuracy for SARS-CoV-2 infection were 90.7 % [95 % IC, 87.7%–93.2%], 78.8 % [95 % IC, 73.8−83.2%], 86.4 % [95 % IC, 76.1 %–88.9 %], 85.1 % [95 % IC, 81.0 %–88.4] and 85.9 % [95 % IC 83.2−88.3%], respectively. Twenty-five/66 (37.6 %) patients with positive CT and negative RT-PCR results and 12/245 (4.9 %) patients with both negative tests were nevertheless judged as positive cases by the clinicians based on clinical and epidemiological criteria and consequently treated. ConclusionsIn our experience, in a context of high pre-test probability, CT scan shows good sensitivity and a consistently higher specificity for the diagnosis of COVID-19 pneumonia than what reported by previous studies, especially when clinical and epidemiological features are taken into account.

Radiographic and chest CT imaging presentation and follow-up of COVID-19 pneumonia: a multicenter experience from an endemic area.

COVID-19 has infected more than 2 million people in the world in less than 5 months outbreak. Chest imaging is recommended for triage of suspected cases of COVID-19 with moderate-severe clinical features and high pre-test probability of disease, and may help for patient follow-up and to identify patients at higher risk of disease worsening. This pictorial essay illustrates typical and uncommon imaging findings of COVID-19 pneumonia and the role of imaging for patient management.

Distinguish Obstructive and Central Sleep Apnea by Portable Peripheral Arterial Tonometry.

Sleep apnea has a very high prevalence in the general population. Sleep apnea can be the cause for cardiovascular disorders. An increased risk for suffering from hypertension, stroke, and myocardial infarction had been shown in large studies, like the Sleep Heart Health Study. Sleep related breathing disorders and sleep apnea had been diagnosed in sleep laboratories with polysomnography in the past. Today in view of the high prevalence of sleep disordered breathing, home sleep apnea testing (HSAT) has become the accepted test for the diagnosis of sleep apnea, if there are no other comorbidities, and if a high pretest probability was confirmed by a sleep physician. For home sleep apnea testing, the number of sensors needed should be reduced. Some methods use indirect means to derive features to detect sleep apnea and hypopnea events. A very well developed method is peripheral arterial tonometry (PAT). This method records the pulse wave on a finger and derives sleep and sleep apnea feature. The PAT method has been tested under many conditions. As an indirect method, it was long seen as a limitation that obstructive and central sleep apnea events could not be distinguished. A new multicenter trial was set up to develop algorithms, which could distinguish central and obstructive apnea events with sufficient accuracy.

COVID-19: Time to Rethink the Randomized Controlled Trial and Consider More Efficient and Ethical Ways of Gaining Clinical Knowledge

Many academics are advocating for the strict adherence to randomized controlled trials (RCTs) in order to find treatments for CoViD-19. The prevailing orthodoxy within the academic establishment is that we should not encourage the use of new treatments for CoViD-19 until those treatments have demonstrated statistically significant clinical benefits in an RCT. Until that point, only patients enrolled in clinical trials should have access to new treatments, no matter how promising the treatment and no matter whether the patient might otherwise be at high risk of death. However, the fundamentalist belief in the RCT fails to acknowledge the limitations of the RCT in a rapidly changing, highly complex, enormously combinatorial and evolving system in which knowledge is continually being generated by clinicians around the world; the situation during the CoViD-19 pandemic. For our patients’ sake, we need efficient and ethical means of both providing treatment and gaining knowledge during this pandemic. The RCT should not be eliminated, but it's primacy reconsidered. From an ethical perspective, discouraging or prohibiting access to off-label/compassionate-use therapies outside of the RCT creates the potential for large disequilibria of the needs of current and future patients, in addition to forsaken clinical information from wide-scale observation. Depending on the pre-test totality of all knowledge of a treatment, it is difficult to even know if the result of an RCT is a true or false result. And importantly, depending on the pre-test probability, the result of the RCT might only give marginal (or no) extra surety regarding the effect of the studied treatment. A crucial, existential concept related to knowledge acquisition is whether the cumulative observation of clinical effects without a control provides any useable information. The RCT attempts to isolate a variable using the scientific method. Yet there are systems constraints within acute clinical medicine regarding reproducibility, and this can significantly affect the fidelity of knowledge that the RCT is able to provide. In this regard, the RCT has proved to be disappointing in providing efficient clinical knowledge in acute care medicine over the decades. Even proponents of the RCT have conceded that there has been a paucity of large RCTs that have shown a clear beneficial treatment effect. A major funding body has de-prioritized the RCT. We are half a year into the lethal CoViD-19 pandemic. Yet, the RCT paradigm has seemingly contributed little and has significantly lagged behind rational treatment innovation guided by increasing understanding of the disease. One well publicized RCT demonstrated a clinical benefit for a drug that otherwise had a high pre-test probability of effect. However, many clinical units were already using this drug as part of their treatment protocols and were achieving highly competitive survival rates; saving lives through rational innovation while continuously updating knowledge of drug and disease-specific effects. Should patients be empowered with the complete accumulated knowledge of an intervention as part of informed consent, before enrolling in an RCT? To be sure, the RCT has a role. However, with it's history of being an inefficient clinical-knowledge-gaining paradigm, we should not necessarily wait for clinical trials before introducing reasoned treatment approaches for our most vulnerable CoViD-19 patients.

Molecular Markers in the Diagnosis of Thyroid Cancer in Indeterminate Thyroid Nodules.

The Bethesda System for the Reporting of Thyroid Cytology recognises six diagnostic categories of thyroid nodule cytology with an incremental risk of malignancy. Although the Bethesda system created a much-needed handhold by standardising the cytological diagnosis and management of thyroid nodules worldwide, the system does not provide a clear answer to the heterogeneous group of nodules with indeterminate cytology. Improvement in the assessment of indeterminate fine-needle aspiration (FNA) results with molecular testing allows better risk stratification and reduces the need for diagnostic thyroid surgery. The molecular markers are classified as a "rule out" test, which has a high negative predictive value and helpful in cases with a low pre-test probability of cancer to rule out thyroid cancer. The "rule in" test has a high positive predictive value and helps in confirming malignancy in those with a high pre-test probability of cancer. This review summarises the commonly used molecular studies in thyroid FNAC aspirates and their current role in clinical practice.

Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda

The Xpert MTB/RIF (Xpert) assay is used globally to rapidly diagnose tuberculosis and resistance to rifampicin. We investigated the frequency and predictors of false-positive findings of rifampicin resistance with Xpert. We did a prospective, observational study of individuals who were enrolled in a Rwandan nationwide diagnostic cohort study (DIAMA trial; NCT03303963). We included patients identified to have rifampicin resistance on initial Xpert testing. We did a repeat Xpert assay and used rpoB Sanger and deep sequencing alongside phenotypic drug susceptibility testing (pDST) to ascertain final rifampicin susceptibility status, with any (hetero)resistant result overriding. We used multivariable logistic regression to assess predictors of false rifampicin resistance on initial Xpert testing, adjusted for HIV status, tuberculosis treatment history, initial Xpert semi-quantitative bacillary load, and initial Xpert probe. Between May 4, 2017, and April 30, 2019, 175 people were identified with rifampicin resistance at initial Xpert testing, of whom 154 (88%) underwent repeat Xpert assay. 54 (35%) patients were confirmed as rifampicin resistant on repeat testing and 100 (65%) were not confirmed with resistance. After further testing and sequencing, 121 (79%) of 154 patients had a final confirmed status for rifampicin susceptibility. 57 (47%) of 121 patients were confirmed to have a false rifampicin resistance result and 64 (53%) had true rifampicin resistance. A high pretest probability of rifampicin resistance did not decrease the odds of false rifampicin resistance (adjusted odds ratio [aOR] 6·0, 95% CI 1·0-35·0, for new tuberculosis patients vs patients who needed retreatment). Ten (16%) of the 64 patients with true rifampicin resistance did not have confirmed rifampicin resistance on repeat Xpert testing, of whom four had heteroresistance. Of 63 patients with a very low bacillary load on Xpert testing, 54 (86%) were falsely diagnosed with rifampicin-resistant tuberculosis. Having a very low bacillary load on Xpert testing was strongly associated with false rifampicin resistance at the initial Xpert assay (aOR 63·6, 95% CI 9·9-410·4). The Xpert testing algorithm should include an assessment of bacillary load and retesting in case rifampicin resistance is detected on a paucibacillary sputum sample. Only when rifampicin resistance has been confirmed on repeat testing should multidrug-resistant tuberculosis treatment be started. When rifampicin resistance has not been confirmed on repeat testing, we propose that patients should be given first-line anti-tuberculosis drugs and monitored closely during treatment, including by baseline culture, pDST, and further Xpert testing. The European & Developing Countries Clinical Trials Partnership 2 programme, and Belgian Directorate General for Development Cooperation.

Combined Coronary CT-Angiography and TAVI-Planning: A Contrast-Neutral Routine Approach for Ruling-out Significant Coronary Artery Disease.

Background: Significant coronary artery disease (CAD) is a common finding in patients undergoing transcatheter aortic valve implantation (TAVI). Assessment of CAD prior to TAVI is recommended by current guidelines and is mainly performed via invasive coronary angiography (ICA). In this study we analyzed the ability of coronary CT-angiography (cCTA) to rule out significant CAD (stenosis ≥ 50%) during routine pre-TAVI evaluation in patients with high pre-test probability for CAD. Methods: In total, 460 consecutive patients undergoing pre-TAVI CT (mean age 79.6 ± 7.4 years) were included. All patients were examined with a retrospectively ECG-gated CT-scan of the heart, followed by a high-pitch-scan of the vascular access route utilizing a single intravenous bolus of 70 mL iodinated contrast medium. Images were evaluated for image quality, calcifications, and significant CAD; CT-examinations in which CAD could not be ruled out were defined as positive (CAD+). Routinely, patients received ICA (388/460; 84.3%; Group A), which was omitted if renal function was impaired and CAD was ruled out on cCTA (Group B). Following TAVI, clinical events were documented during the hospital stay. Results: cCTA was negative for CAD in 40.2% (188/460). Sensitivity, specificity, PPV, and NPV in Group A were 97.8%, 45.2%, 49.6%, and 97.4%, respectively. Median coronary artery calcium score (CAC) was higher in CAD+-patients but did not have predictive value for correct classification of patients with cCTA. There were no significant differences in clinical events between Group A and B. Conclusion: cCTA can be incorporated into pre-TAVI CT-evaluation with no need for additional contrast medium. cCTA may exclude significant CAD in a relatively high percentage of these high-risk patients. Thereby, cCTA may have the potential to reduce the need for ICA and total amount of contrast medium applied, possibly making pre-procedural evaluation for TAVI safer and faster.

Diagnostic Stewardship Approaches to Clostridioides difficile Infection in the Era of Two-Step Testing: a Shifting Landscape

To discuss the current strategies and impact of diagnostic stewardship for Clostridioides difficile infection. The diagnosis of C. difficile infection is challenging due to complex epidemiology and the limitations of a single assay that is adequate for diagnosis. Overdiagnosis with sensitive molecular assays is common due to the prevalence of colonization with C. difficile. To overcome these challenges, multiple diagnostic stewardship strategies have been successfully deployed to optimize C. difficile testing. Diagnostic stewardship strategies should be implemented at every stage of C. difficile testing in order to limit testing to patients with a high pre-test probability, minimize the limitations of stand-alone assays, and guide clinicians to appropriate management through clear result reporting and interpretation.

The relationship between metabolic syndrome score and cardiac ischemia detected by noninvasive cardiac tests

Objective: Cardiovascular disease is the still leading cause of mortality and morbidity. Non-invasive cardiac tests are using for diagnosing CAD in symptomatic patients in clinical practice. Metabolic syndrome (MS) is a well-known risk factor for coronary artery disease (CAD). In this study we aimed to investigate the relationship between metabolic syndrome score and results of non-invasive cardiac tests. Method: The total number of 329 patients who admitted with chest pain to cardiology department were included in the study. MS score based on National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria which ranged between zero and five were calculated for each subject. After physical examination and routine laboratory tests patients with high pretest probability underwent non-invasive cardiac tests (treadmill test and myocardial perfusion scintigraphy)to rule out chest pain from non-cardiac reasons. The results of non-invasive tests evaluated with metabolic risk score of patients. Results: The study population consisted of 192 (58.4%) male, and 137 (41.6%) female subjects. The mean age was 68.3 ±9 in patients without ischemia and 69.4 ±7.2 (p=N/S) patients with ischemia. Metabolic score was 1.8±1.1 in patients without ischemia 2.67±1.3 in patients with ischemia (p=<0.01) Patients with coronary ischemia had higher metabolic syndrome score than patients without ischemia (p<0.01). Conclusions: In this study, we showed that patients with high metabolic risk score. In this study, non-invasive cardiac tests performed in patients with high metabolic risk scores showed more ischemia. Metabolic risk score should be considered in the evaluation of patients for coronary artery disease.

SUN-084 A Quantitative-PCR Based Rapid and Cost-Effective Diagnostic Method for Turner Syndrome and Its Variants

Turner’s syndrome (TS) is a common aneuploidy diagnosed by peripheral blood karyotyping in patients. Karyotyping involves manual labour, time and costs. Quantitative real-time PCR (qPCR) is a rapid molecular diagnostic test for TS that yields results of upto 48 samples within two hours at low cost with reasonable accuracy. To assess the sensitivity and specificity of qPCR in the rapid diagnosis of TS, genomic DNA was isolated and estimated from peripheral blood from 50 TS patients(45,XO-23, XO/XX mosaics - 10, Isochromosome Xq-12, XO/XY mosaics - 5), 25 normal females(46,XX) and 5 normal males(46,XY). qPCR was done using 96 well plates, fast real-time PCR. 4 primers were used - two on Xp [SHOX and ARSE] and two on Xq (VAMP7 and XIST). Autosomal gene HBB was used as housekeeping gene. The ΔΔ CT method was used for calculation of the ‘X gene dose’ with respect to the housekeeping gene and X genes from normal females. Differences of doses of the four X-chromosomal primers in different karyotypes were analysed. ROC curves were plotted to determine cut-offs to discriminate the different karyotypes of TS from normal females. qPCR could distinguish classical TS from normal females with >95% sensitivity and specificity. SHOX gene primer was the best to diagnose TS of all karyotypes combined and also classical TS(XO) from normal females. qPCR could also identify non-classical TS with >92% sensitivity and specificity,the best primer being ARSE, for detecting both mosaics and isochromosomes. The cut-offs determined from our study corroborates with past similar studies.1,2 qPCR using an appropriate panel of primers on the short and long arms of X chromosomes can be a rapid and cheaper alternative to karyotyping to diagnose TS of different karyotypes. The choice of primers should be guided by the need for a more sensitive or specific test depending on the clinical scenario. If used as a neonatal screening test, SHOX should be the best primer. For diagnostic purposes, when the pre-test probability is low, a more specific primer like SHOX would be more appropriate. However, when the pre-test probability is high, a sensitive primer for ruling out TS like VAMP7 is better. In case there is a high pre test probability of the patient having a non-classic TS rather than classic TS, ARSE should be used. This is the first study to show good sensitivity of qPCR in detecting non-classic TS of different karyotypes in addition to classic TS.

A 2020 review on the role of procalcitonin in different clinical settings: an update conducted with the tools of the Evidence Based Laboratory Medicine.

Biomarkers to guide antibiotic treatment decisions have been proposed as an effective way to enhancing a more appropriate use of antibiotics. As a biomarker, procalcitonin (PCT) has been found to have good specificity to distinguish bacterial from non-bacterial inflammations. Decisions regarding antibiotic use in an individual patient are complex and should be based on the pre-test probability for bacterial infection, the severity of presentation and the results of PCT serum concentration. In the context of a high pre-test probability for bacterial infections and/or a high-risk patient with sepsis, monitoring of PCT over time helps to track the resolution of infection and decisions regarding early stop of antibiotic treatment. As outlined by the Evidence Based Laboratory Medicine (EBLM), not only the pre-test probability but also the positive likelihood ratio influence the performance of a test do be really diagnostic. This aspect should be taken into account in the interpretation of the results of clinical trials evaluating the performance of PCT in guiding antibiotic therapy.

A Bayesian analysis of strategies to rule out COVID19 using reverse transcriptase-polymerase chain reaction (RT-PCR).

To the Editor.—The coronavirus disease 2019 (COVID-19) pandemic may overwhelm health care capacity in parts of the United States and United Kingdom in the coming months.1 Erroneously ruling out COVID-19 based on a false-negative diagnostic test poses a public health hazard. The probability of such an error is quantified by the false omission rate (FOR). The FOR = false negatives/(true negatives + false negatives), and this value depends on the prevalence of disease and operating characteristics of the diagnostic test. Preliminary data suggest the sensitivity of the COVID-19 reverse transcriptase–polymerase chain reaction (RT-PCR) may be 70% for nasopharyngeal (NP) and sputum samples, and 90% for bronchoalveolar lavage (BAL).2–4 We examined strategies to rule out COVID-19 by RT-PCR with an acceptably low FOR in hospitalized patients suspected of having COVID-19.We calculated the FORs of 4 strategies to rule out COVID-19 using RT-PCR across the range of prevalence rates in hospitalized patients. Strategy 1 was a single negative test result with a sensitivity of 70%, such as a single NP swab or sputum sample. Strategy 2 was a series of 2 negative tests, each with a sensitivity of 70%. Strategy 3 was a series of 2 negative tests in which the first had a sensitivity of 70% and the second a sensitivity of 90%, such as an NP swab followed by BAL. Strategy 4 was a series of 3 negative tests, each with a sensitivity of 70%. Specificity was assumed to be 99% in all calculations. We recalculated strategy 4 using a sensitivity of 50% to explore the effect lower sensitivity would have on FORs. We defined a false omission rate of ≤5% as acceptable.Results are presented in the Table and the Figure. The FORs were unacceptable at prevalence rates ≥20% for strategy 1 and at prevalence rates ≥50% for strategy 2. The FORs were acceptable at prevalence rates up to 90% for strategies 3 and 4, but reducing sensitivity to 50% in strategy 4 increased FORs 3-fold.The prevalence of COVID-19 among patients admitted with pneumonia exceeds 50% in some areas of the United States and United Kingdom, as was previously reported from Wuhan, China.3 The FORs of all diagnostic strategies rise with prevalence, and they have reached unacceptable levels for strategies 1 and 2 in many localities. Strategies 3 and 4 may retain acceptable FORs at prevalence rates &lt;90% if we have not overestimated sensitivity. Strategy 3 incorporates BAL, which has the highest reported sensitivity (3) but may aerosolize infectious particles. (The sensitivity of sputum obtained from intubated patients by deep tracheal suctioning through a closed ventilator circuit has not been reported, but it may present a practical alternative to BAL.) Sensitivity and FOR can be optimized by employing proper techniques for collecting, handling, and testing of clinical specimens,5 but clinicians who feel an individual patient has very high pretest probability might reasonably decide not to completely rule out COVID-19, even after negative results using the best diagnostic strategies we modeled.Our analysis relates to patients admitted with a clinical-radiographic syndrome consistent with pneumonia and is not generalizable to outpatients. Significant variation between patients in day-to-day viral shedding has been observed,4 and our model does not account for the possibility that COVID-19 patients with initial false-negative results may be more likely to have repeated false-negative results. Despite limitations, our modeling should help clinicians recognize that FOR increases with disease prevalence and make more objective decisions about how to interpret COVID RT-PCR test results when considering the discontinuation of infection control precautions in patients suspected of having COVID-19.

Sea level nocturnal minimal oxygen saturation can accurately detect the presence of obstructive sleep apnea in a population with high pretest probability.

To evaluate whether a predictive model based on nocturnal minimal oxygen saturation (SpO2) alone can accurately detect the presence of obstructive sleep apnea (OSA) in a population with suspected OSA. A total of 4297 participants with suspected OSA were enrolled in this study, and laboratory-based polysomnography (PSG) tests were performed at sea level in all subjects. Nocturnal minimal SpO2 was obtained automatically as part of the PSG test. Stratified sampling was used to divide the participants' data into the training set (75%) and the test set (25%). An OSA detection model based on minimal SpO2 alone was created using the training set data and its performance was evaluated using the independent test set data ("hold-out" evaluation). Gender-specific models, and models based on minimal SpO2 in combination with other predictive factors (age, body mass index, waist-to-hip ratio, snoring grade, Epworth Sleepiness Scale score, and comorbidities), were also created and compared in terms of OSA detection performance. The prevalence of OSA was 85.6% in our study population. The models including multiple predictors, and the gender-specific models, failed to outperform the model based solely on minimal SpO2, which showed good predictive performance (C statistic, 0.922) having an overall accuracy rate of 0.86, sensitivity of 0.87, specificity of 0.84, positive predictive value of 0.97, and positive likelihood ratio of 5.34. In addition, the model based on minimal SpO2 alone could also accurately predict the presence of moderate-to-severe OSA and severe OSA, with C statistics of 0.914 and 0.900, respectively. A predictive model based on nocturnal minimal SpO2 alone may be an alternative option to detect the presence of OSA in a high-risk population when standard diagnostic tests are unavailable.

Reduced myocardial blood flow reserve in kidney transplant candidates may hamper risk stratification.

Vasodilator nuclear stress testing is frequently ordered for risk stratification prior to kidney transplantation. Since 82Rb-positron emission tomography-computed tomography can measure myocardial blood flow (MBF), the response to vasodilator stress can be verified rendering the results of the scan more reliable. We reviewed the MBF response to dipyridamole infusion in 328 patients with end-stage kidney disease (ESKD) prior to transplant (188 hemodialysis-HD, 120 peritoneal dialysis-PD, and 20 pre-dialysis patients-CKD5) and in 100 controls with normal kidney function. A stress/rest MBF ratio ≥ 2 was considered an adequate response to dipyridamole. Coronary artery calcium (CAC) was measured on CT. Inadequate MBF response was seen in 36%-HD, 21%-PD, 45%-CKD5 vs. 23%-controls (p = 0.006). Univariable predictors of poor MBF response in ESKD patients were age, diabetes mellitus, and CAC (all p < 0.03) while serum hemoglobin was borderline significant (p = 0.052). Multivariable predictors of a poor MBF response were age (p = 0.002) and lower serum hemoglobin (p = 0.014). Ischemia was identified in 8% of ESKD patients and 24% of controls (p < 0.001). ESKD patients are less likely to respond appropriately to vasodilator stress compared to patients with normal renal function and had a lower incidence of ischemia despite a high pre-test probability of disease. Physicians performing vasodilator stress without MBF measurement should be aware of the high probability of a false negative response.

Optimization of serologic diagnosis of celiac disease in the pediatric setting.

The clinical presentation of celiac disease (CD) varies between children. The objective of this study was to document the pre-test probability for CD based on symptoms and routine laboratory test and to evaluate the performance of two IgA anti-tissue transglutaminase (tTG) assays. We critically reviewed the concept of using multiples of the manufacturer's upper limit of normal (ULN), as proposed in the ESPGHAN guidelines (if IgA tTG is >10 times ULN, no biopsy is needed). The retrospective study included 91 children with newly diagnosed CD and 605 controls (<16 years). All underwent upper endoscopy with small bowel biopsies. Four laboratory parameters and 16 symptoms were registered. All patients were tested for IgA anti-tTG antibodies with assays from Inova Diagnostics and Thermo Fisher Scientific. Some combinations of clinical symptoms and laboratory parameters had a high pre-test probability for CD, such as (combinations of) anorexia, failure to thrive, low ferritin level and elevated AST. The diagnostic performance of both IgA anti-tTG assays was excellent and comparable (no difference in ROC curve area under the curve). At a threshold that corresponds to a specificity of 100% (5 times ULN for Inova Diagnostics and 2 times ULN for Thermo Fisher), the sensitivity was 82% for both assays. At the 10 times ULN threshold, the sensitivity differed between the assays (77% vs. 57%), indicating that such threshold does not completely align interpretation across companies. Our study showed that some combinations of symptoms and aberrant laboratory parameters had a high pre-test probability. The use of the ESPGHAN non-biopsy approach could reduce small bowel biopsies, but thresholds for IgA-tTG levels are not aligned across assays and should be based on predefined likelihood ratios or specificity.

CORONARY CTA AND CT-DERIVED FRACTIONAL FLOW RESERVE: GATEKEEPERS TO INVASIVE ANGIOGRAPHY IN PATIENTS WITH HIGH PRE-TEST PROBABILITY OF CORONARY ARTERY DISEASE

Recently, some Radiology Benefit Managers have adopted the use of coronary CT angiography (CTA) and CT-derived fractional flow reserve (FFRCT) to determine appropriate referral for invasive coronary angiography (ICA). This study examined this approach in patients with high pre-test probability (PTP

Implementation of the FilmArray ME panel in laboratory routine using a simple sample selection strategy for diagnosis of meningitis and encephalitis

BackgroundInfectious meningitis is a serious disease and patient outcome relies on fast and reliable diagnostics. A syndromic panel testing approach like the FilmArray ME can accelerate diagnosis and therefore decrease the time to pathogen specific therapy. Yet, its clinical utility is controversial, mainly because of a remaining uncertainty in correct interpretation of results, limited data on its performance on clinical specimens and its relatively high costs. The aim of this study was to analyze clinical performance of the assay in a real life setting at a tertiary university hospital using a pragmatic and simple sample selection strategy to reduce the overall cost burden.MethodsOver a period of 18 months we received 4623 CSF samples (2338 hospitalizations, 1601 individuals). FilmArray ME analysis was restricted to CSF-samples with a high pretest probability of infectious meningitis, e.g. positive Gram-stain, samples in which leukocytes and/or bacteria were evident or urgent suspicion of infection was communicated by clinicians. N = 171 samples matched to our risk criteria and were subjected to FilmArray ME analysis. Those samples were also analyzed by reference methods: culture only (n = 45), PCR only (n = 20) or both methods (n = 106).Results56/171 (32.75%) were FilmArray ME positive. Bacterial pathogens were detected in 30/56 (53.57%), viral pathogens were detected in 27/56 (48.21%) and yeast DNA was detected in 1/56 (1.79%) of positive samples. Double detection occurred in 2/56 samples. In 52/56 (92.86%) FilmArray ME positive samples, results could be confirmed by the reference assays (sensitivity = 96.30%, specificity =96.58%).ConclusionThe FilmArray ME assay is a fast and reliable diagnostic tool for the management of infectious meningitis and can easily be implemented in routine diagnostic workflows. However, correlation of test results and underlying clinical symptoms requires experienced users and the awareness of potentially false negative or false positive results. Moreover, considering the need for antimicrobial susceptibility testing, the use of molecular tests as a stand-alone diagnostic cannot be recommended.