High Pretest Probability Research Articles

Comprehensive Proteomics Profiling Identifies Patients With Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in the Hypertrophic Cardiomyopathy Population.

IntroductionIn hypertrophic cardiomyopathy (HCM), late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) represents myocardial fibrosis and is associated with sudden cardiac death. However, CMR requires particular expertise and is expensive and time-consuming. Therefore, it is important to specify patients with a high pre-test probability of having LGE as the utility of CMR is higher in such cases. The objective was to determine whether plasma proteomics profiling can distinguish patients with and without LGE on CMR in the HCM population.Materials and MethodsWe performed a multicenter case-control (LGE vs. no LGE) study of 147 patients with HCM. We performed plasma proteomics profiling of 4,979 proteins. Using the 17 most discriminant proteins, we performed logistic regression analysis with elastic net regularization to develop a discrimination model with data from one institution (the training set; n = 111) and tested the discriminative ability in independent samples from the other institution (the test set; n = 36). We calculated the area under the receiver-operating-characteristic curve (AUC), sensitivity, and specificity.ResultsOverall, 82 of the 147 patients (56%) had LGE on CMR. The AUC of the 17-protein model was 0.83 (95% confidence interval [CI], 0.75–0.90) in the training set and 0.71 in the independent test set for validation (95% CI, 0.54–0.88). The sensitivity of the training model was 0.72 (95% CI, 0.61–0.83) and the specificity was 0.78 (95% CI, 0.66–0.90). The sensitivity was 0.71 (95% CI, 0.49–0.92) and the specificity was 0.74 (95% CI, 0.54–0.93) in the test set. Based on the discrimination model derived from the training set, patients in the test set who had high probability of having LGE had a significantly higher odds of having LGE compared to those who had low probability (odds ratio 29.6; 95% CI, 1.6–948.5; p = 0.03).ConclusionsIn this multi-center case-control study of patients with HCM, comprehensive proteomics profiling of 4,979 proteins demonstrated a high discriminative ability to distinguish patients with and without LGE. By identifying patients with a high pretest probability of having LGE, the present study serves as the first step to establishing a panel of circulating protein biomarkers to better inform clinical decisions regarding CMR utilization.

Allergy evaluation of messenger RNA vaccine reactions is crucial, with a specific role for polyethylene glycol testing

Allergy evaluation of messenger RNA vaccine reactions is crucial, with a specific role for polyethylene glycol testing

Surgeons' Recommendations for Neurodiagnostic Testing With High Pretest Probability of Idiopathic Median Neuropathy at the Carpal Tunnel

The utility of electrodiagnostic tests (EDx) for patients with a high pretest probability of idiopathic median neuropathy at the carpal tunnel (IMNCT) based on characteristic symptoms and signs is debated. Decision-making and care strategies could be informed by a better understanding of factors associated with surgeon recommendations for electrodiagnostic testing. Ninety-one upper-extremity surgeons participated in an online, survey-based experiment. Participants viewed 7 vignettes of patients with carpal tunnel syndrome, with the following factors randomized in each vignette: patient age, gender, magnitude of incapability, symptom intensity and the presence of nocturnal symptoms, palmar abduction weakness, and positive provocative tests results. We sought patient and surgeon factors associated with ordering EDx and surgeon-rated comfort with performing carpal tunnel release (CTR) without EDx. Surgeons recommended EDx for over half of the patient vignettes, with notable variation (median, 57%; interquartile range, 14-100), and felt relatively neutral, on average, offering CTR without EDx. Twenty-six (29%) out of 91 surgeons ordered EDx for all patient scenarios, and 18 surgeons (20%) did not order testing for any scenario. A lower likelihood of EDx was associated with older age and positive provocative tests results. Greater surgeon comfort offering CTR without EDx was associated with older patients, the presence of nocturnal symptoms, palmar abduction weakness, and positive provocative tests results. Upper-extremity surgeons are neutral regarding diagnosing IMNCT based on electrodiagnostic evidence of pathology and are relatively more comfortable offering surgery without EDx in older patients that present with key aspects of carpal tunnel syndrome. There is notable variation in care, with half of all surgeons always or never ordering EDx. Future studies can investigate whether a treatment strategy offering surgery to patients with a high pretest probability of IMNCT and only using EDx in intermediate probability scenarios can limit use of testing without affecting patient health.

CLINICAL CHARACTERISTICS OF WOMEN REFERRED TO CARDIAC SPECT: WHEN AND WHO? DATA FROM LATVIAN CARDIAC SPECT REGISTRY

Objective: Population based cross-sectional study of cardiovascular risk (CVR) factors in Latvia from year 2009 till 2019 revealed that women in age 25 -74 are in a very high CVR group: 61% of women have dyslipidemia, more than 33% have arterial hypertension (AH) and 28% are overweight. The data indicates the necessity for focused diagnostics and early detection of cardiovascular disease. The aim of study was to define the clinical profile and risk factors for women with suspected coronary artery disease (CAD) reffered to cardiac single photon emission computed tomography (SPECT) in Latvia and to find out the correlation between nuclear test result and patient clinical presentation. Design and method: Cardiac SPECT was performed in a single centre from 2018 till 2021. The women patients were analyzed by risk factors and previous diagnosis of CAD. Exercise test was performed in all cases. Patients were divided into 2 groups: normal myocardial perfusion or true myocardial perfusion defect, defined as area of ischemia more than 10% of the left ventricle myocardium mass. Results: 726 SPECT data were analyzed. The mean age of women patients was 62.6 ± 10.6 years. More than half of the patients (n = 486,66.9%) were overweight (BMI> 25.0 kg/m2) and 33.3%(n = 242) were obese (BMI> 30.0 kg/m2). 87 (11.9%) women were current or ex-smokers. Dyslipidemia was present in in 614 (84.6%), AH in 535 (73.7%) and type 2 Diabetes mellitus (T2DM) in 60 (8.3%) patients. 104 (14.3%) patients were asymptomatic, but with intermediate to high pre-test probability for CAD. Known CAD was present in 298 (41.0%) patients. Exercise test was found positive in 306 (42.1%) patients and the test result was not always associated with ischaemia in SPECT (p = 0.063). True myocardial perfusion defect was detected in 125 patients (17.2%). Correlation was found between significant perfusion defect in SPECT and risk factors - AH (p = 0.013) and dyslipidemia (p = 0.029). Conclusions: The registry proves the high value of imaging with cardiac SPECT for diagnostics of CAD. Women patients with intermediate or high pre-test probability – even asymptomatic or with non informative exercise test should be reffered for cardiac SPECT.

Serologic biomarkers in Candida and Aspergillus infections of the central nervous system: A comparison of galactomannan, mannan and β-1,3-D-gucan testing from serum and cerebrospinal fluid.

The incidence of Aspergillus and Candida CNS infection, which are characterised by high mortality rates, is underestimated. This underdiagnosis presumably results from the limitations of available diagnostic tools and the need for invasive sampling. Little is known about the role of serologic biomarkers in the setting of CNS aspergillosis and candidiasis. Serum and cerebrospinal fluid (CSF; 10) samples of 19 patients, whose CNS specimens yielded growth of Aspergillus or Candida, were analysed for different biomarkers for fungal infection, that is galactomannan (GM), galactomannoprotein (GP), mannan, anti-mannan-antibodies and β-1,3-D-glucan (BDG). Serum and CSF specimens of time-matched patients (two each for every case of fungal CNS infection) were included as controls. Galactomannan, GP and BDG seropositivity was found in one, two and three of five cases of CNS aspergillosis. BDG and mannan/anti-mannan-antibody sensitivity in proven CNS candidiasis was 40% and 20%, respectively. Applying the serum cut-off, sensitivity in CSF testing was 100% for GM and BDG and 50% for mannans. While serum specificity for all assays ranged from 89 to 97%, specificity for CSF BDG was only 70%. No false-positive GM results from CSF were obtained. Sensitivity for diagnosing CNS aspergillosis and CNS candidiasis from serum is mediocre for all serological biomarkers. GM testing in CSF proved excellent performance. With a sensitivity of 100% but a specificity of only 70%, CSF BDG might be most useful when used in patients with a high pre-test probability.

P283 PROGRESSION OF PULMONARY ARTERIAL HYPERTENSION OR LEFT HEART DISEASE? DO EXERCISE!

Abstract An 80–year–old man, diagnosed with idiopathic pulmonary arterial hypertension (PAH) in 2012 and treated with sildenafil, experienced his first hospitalization for heart failure in June 2019. He had several cardiovascular risk factors (overweight, hypertension, diabetes) and comorbidities (ischemic heart disease, and mild chronic obstructive pulmonary disease), whose progression was excluded. Since this event, he complained a progressive deterioration of the exertional dyspnea (NYHA III), with overt signs of fluid overload, right chambers dilation and high NTproBNP (1366 ng/L). However, the center taking care of this patient neither decided to fully re–evaluate him nor to escalate PAH–treatment due to his clinical profile (high suspicion of left heart disease, LHD). He then came to our pulmonary hypertension (PH) center where we decided to perform a cardiac catheterization, which showed the persistence of precapillary PH with high pulmonary vascular resistance, PVR (7.6 WU), low cardiac output, CO (2.2 L/min/m2), high right atrial pressure, RAP (12 mmHg). Pulmonary artery wedge pressure (PAWP) and left ventricular end–diastolic pressure (LVEDP) were at the upper limits of normal (13 mmHg and 16 mmHg, respectively) (Figure 1). Based on these “borderline” PAWP values, with an intermediate–high pre–test probability of left heart disease, we performed an exercise test with concomitant gas–exchange analysis on a cycle ergometer in the cath lab (Figure 2). Exercise induced a steep increase in pulmonary pressure (TPR 9 WU), unrelated to an exaggerate increase in PAWP or LVEDP (whose peak values reached 20 mmHg, with a PAWP/CO slope <2 mmHg/L/min), but entirely dependent on the precapillary component. Transpulmonary gradient (TPG)/CO slope was high, leading to an absent reduction in PVR (6.4 WU at peak), associated to severe increase in RAP (27 mmHg at peak, RAP/PAWP 1.4) (Figure 3). CO reserve was reduced (at peak 3.4 L/min/m2), due to both reduced increase in stroke volume and chronotropic incompetence. Accordingly, functional capacity was moderately–severely reduced (peak oxygen consumption was 8 ml/kg/min, 39% of predicted), with exercise hyperventilation. Once excluded LHD as the responsible of clinical worsening, and in consideration of the high–intermediate risk profile of this patient, we upgraded the PAH–specific therapy by adding macitentan, obtaining a subjective clinical improvement and a 3–years period of clinical stability.

Clostridioides difficile: A diagnostic intervention

Background:Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection and is associated with increased morbidity and mortality. Multiple strategies have been implemented to optimize the diagnostic accuracy of CDI testing algorithms. However, overdiagnosis of C. difficile colonization remains a challenge especially in the era of highly sensitive Nucleic acid amplification testing (NAAT). We implemented 2 interventions to reduce the rates of inappropriate C. difficile orders and tests. Methods: We performed a quasi-experimental retrospective study to examine the rates of all inpatient C. difficile test orders and results relative to 2 interventions between January 2018 and February 2021. We defined 3 periods: preintervention, after the first intervention, and after the second intervention. The first intervention, implemented May 2019, was a clinical decision support system (CDSS) tool to guide clinicians to order testing only if CDI criteria were met. The second intervention, implemented July 2020, was the requirement of mandatory antimicrobial team approval of PCR reflex testing for indeterminate toxin or antigen test results. This intervention included a discussion between clinicians and members of stewardship team prior to approval. To evaluate the impact of interventions on ordering appropriateness, chart review was conducted on a random subsample of 100 orders from each period. Hospital-onset CDI (HO-CDI) was calculated using CDC criteria. Results: In total, 3,004 C. difficile test orders were placed during the study period. The rates of reportable HO-CDI were significantly reduced by 57.1% (P = .003). We detected a significant reduction in the number of tests ordered over time from 11.6 to 7.51 per 1,000 patient days. (p Conclusions: CDSS tools target patients at high pretest probability of CDI. The restriction of PCR-reflex testing to the antimicrobial stewardship team is a novel effective measure to minimize the misdiagnosis of CDI. The incorporation of multiple strategies is necessary to improve the diagnostic accuracy of C. difficile testing.Funding: NoneDisclosures: None

An Integrated Approach on the Diagnosis of Cerebral Veins and Dural Sinuses Thrombosis (a Narrative Review).

(1) Objective: This review paper aims to discuss multiple aspects of cerebral venous thrombosis (CVT), including epidemiology, etiology, pathophysiology, and clinical presentation. Different neuroimaging methods for diagnosis of CVT, such as computer tomography CT/CT Venography (CTV), and Magnetic Resonance Imaging (MRI)/MR Venography (MRV) will be presented. (2) Methods: A literature analysis using PubMed and the MEDLINE sub-engine was done using the terms: cerebral venous thrombosis, thrombophilia, and imaging. Different studies concerning risk factors, clinical picture, and imaging signs of patients with CVT were examined. (3) Results: At least one risk factor can be identified in 85% of CVT cases. Searching for a thrombophilic state should be realized for patients with CVT who present a high pretest probability of severe thrombophilia. Two pathophysiological mechanisms contribute to their highly variable clinical presentation: augmentation of venular and capillary pressure, and diminution of cerebrospinal fluid absorption. The clinical spectrum of CVT is frequently non-specific and presents a high level of clinical suspicion. Four major syndromes have been described: isolated intracranial hypertension, seizures, focal neurological abnormalities, and encephalopathy. Cavernous sinus thrombosis is the single CVT that presents a characteristic clinical syndrome. Non-enhanced CT (NECT) of the Head is the most frequently performed imaging study in the emergency department. Features of CVT on NECT can be divided into direct signs (demonstration of dense venous clot within a cerebral vein or a cerebral venous sinus), and more frequently indirect signs (such as cerebral edema, or cerebral venous infarct). CVT diagnosis is confirmed with CTV, directly detecting the venous clot as a filling defect, or MRI/MRV, which also realizes a better description of parenchymal abnormalities. (4) Conclusions: CVT is a relatively rare disorder in the general population and is frequently misdiagnosed upon initial examination. The knowledge of wide clinical aspects and imaging signs will be essential in providing a timely diagnosis.

Diagnosis, Management of, and Return to Play Guidance for Venous Thromboembolism in Athletes.

Venous thromboembolism (VTE) is not rare and is becoming more recognized in our athletic population. This diagnosis can be elusive. A provider must have a high clinical suspicion and use pretest probabilities to order the appropriate studies and accurately diagnose a VTE. Treatment using direct oral anticoagulants for 3 months is recommended in most cases. Gradual return to play can be achieved after treatment is complete. Some athletes, however, may require lifelong anticoagulation. Return to collision sports may be possible using a timed dose strategy if long-term anticoagulation is needed. The management of an athlete with a VTE should include an individualized treatment plan and involve shared decision making with the athlete, team physicians, and hematologic specialists.

Cost-effectiveness in diagnosis of stable angina patients: a decision-analytical modelling approach

ObjectiveGiven recent data on published diagnostic accuracies, this study sought to determine the most cost-effective diagnostic strategy for detection of significant coronary artery disease (CAD) in stable angina patients using...

Results of penicillin skin testing in patients with suspected penicillin allergy - the Qatar experience.

Background: Unverified penicillin allergy has been linked to adverse patient events and increased healthcare expenditure owing to the usage of broad-spectrum, expensive antibiotics. Penicillin allergy test is the gold standard to diagnose penicillin allergy; and in this study, we present data from Qatar which have not been published before.Methods: Patients with a history of penicillin allergy who underwent penicillin allergy testing between January 2015 and December 2020 at the Allergy Division of the Hamad General Hospital were retrospectively reviewed from the division registry. Benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM) kit DAP-penicillin (0.04 mg +0.5 mg)/vial) (penicillin G, amoxicillin (20 mg/vial), and lately clavulanic acid (20 mg/vial) (DAP, Diater, Madrid, Spain) were used for skin and intradermal testing according to published guidelines. Patients with negative skin tests were administered direct oral challenge with amoxicillin/clavulanate (500/125 mg) and observed for 2 hours.Results: Of the 189 charts reviewed, 183 patients had a complete data set for analysis. Patients were predominantly women (n = 132, 72%) with an average age of 42 years. Of these patients, 149 (81.4%) had a history of an immediate allergic reaction to penicillin, 10 had a history of delayed reactions, and 24 had other or undefined reactions. A total of 39 (21.3%) patients were diagnosed with penicillin allergy (30 patients with positive skin test results and 9 using a direct oral challenge).Of the 30 patients with positive skin testing, 5 reacted to PPL, 8 to MDM, 13 to amoxicillin, and 4 to clavulanic acid.Conclusion: Previous studies indicate that 90% patients with a history of penicillin allergy were able to tolerate the drug (10% were truly allergic). Our data showed that 21% were truly allergic to penicillin. This high positive rate can be attributed to the high pretest probability based on the detailed history obtained before the test, which led to the exclusion of patients with symptoms incompatible with penicillin allergy from the test.

PoCUS: Just because we can doesn't mean we should.

PoCUS: Just because we can doesn't mean we should.

Outcomes of pregnancies at high-risk for placenta accreta spectrum following negative diagnostic imaging.

To assess the pretest and negative post-test probability for placenta accreta spectrum (PAS) in a group of patients with high-risk clinical factors. We included patients with suspected and/or confirmed PAS at our institution over 8 years. Sonography performed by maternal-fetal medicine specialists, and selected patients underwent MRI. Imaging was considered positive if either sonography or MRI suggested PAS. Histopathology was the gold standard for diagnosis of PAS. We assessed the pretest and negative imaging-test probability, and resources required. We identified 82 high-risk patients with the following: (1) a history of≥1 cesarean section and/or intrauterine gynecologic procedure and placenta previa in the index pregnancy; (2) a history of >3 cesarean deliveries and/or gynecologic procedures regardless of placental location; (3) prior PAS disorder, or retained placenta requiring manual extraction and/or curettage, complicated by postpartum hemorrhage; and (4) suspected cesarean section scar pregnancy. Histopathology confirmed PAS in 52 patients, with pretest probability of 63%. Imaging correctly identified 44/50 cases with PAS, and excluded this condition in 24/30 cases. Thus, the positive and negative post-test probability for PAS following negative imaging was 88 and 20%, respectively. Of the six patients with false-negative imaging, all had either surgical complications or required care beyond that for routine cesarean section. Although diagnostic imaging is sensitive, the negative posttest probability remains high in women with high pretest probability for PAS. Therefore, women at high risk for PAS should be managed in experienced centers by a multidisciplinary team even if imaging is negative.

Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical probability: prospective diagnostic management study

ObjectiveTo evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT.DesignProspective diagnostic management study.SettingUniversity based...

Expert consensus for the use of home sleep apnea test in the diagnosis of obstructive sleep apnea in adults

With the advancement of home sleep apnea test (HSAT) technology and the increase of encouraging evidence of home-based management approach for obstructive sleep apnea (OSA), HSAT devices using different types of biosignal acquisition technology are more and more widely used for the diagnosis of OSA in adults. HSAT for the diagnosis of OSA should be performed in combination with a comprehensive clinical and sleep evaluation. HSAT can be used as a diagnostic tool for uncomplicated OSA with a high pretest probability of moderate to severe OSA. A negative HSAT result cannot exclude the diagnosis of OSA for subjects with high clinical suspicion. Polysomnography (PSG) is preferred for the diagnosis of OSA in patients with significant comorbid medical conditions. The clinical application of HSAT in the diagnosis of complicated OSA needs to refer to the severity of clinical condition, comorbid disease, personal preference, local medical insurance policy and the accessibility of medical resources. HSAT may be indicated for the diagnosis of OSA in patients for whom attended PSG is not possible by virtue of immobility, safety, or critical illness. HSAT can be used for the screening of OSA in subjects with cardiocerebrovascular diseases. Follow-up HSAT or PSG is recommended to evaluate therapeutic response with non-positive airway pressure (PAP) interventions. Follow-up HSAT or PSG can be used for reassessment for patients with clinically significant weight fluctuation, persistent or recurrent symptoms under good PAP adherence, emergence or changes in cardiovascular diseases. Due to limitations of current automatic scoring algorithms that restrict the diagnostic accuracy, it is mandatory to review the raw data of type 3 devices. The selection of HSAT equipment, interpretation of monitoring results and the development of management plan should be under the guidance of physicians with sleep medicine training. Consumer-grade technologies are not appropriate for the clinical diagnosis of OSA due to lack of validation.

Pretest probability of coronary artery disease as a factor for optimizing invasive diagnostics in routine clinical practice

According to the European Society of Cardiology guidelines, patients with chest pain requires the calculation of pretest probability (PTP) of coronary artery disease (CAD), followed by the identification of diagnostic tactics.Aim. To analyze the registry of patients with stable CAD in order to assess the frequency of PTP calculation, as well as the validity of diagnostic tactics choice depending on its level.Material and methods. The data of the registry of patients with stable CAD for the periods from 2012 to 2014 and from 2017 to 2019 were analyzed. We assessed the number of CAD patients, proportion of men, and distribution of patients depending on angina functional class. In addition, data on PTP calculation, as well as distribution of patients and diagnostic strategy selected depending on its value was analyzed. To assess differences (p) in pairwise comparisons, Student’s t-test was used. Differences were considered significant at p<0,05. Statistical analysis was performed using Microsoft Office Excel 2010 (Microsoft, USA) and STATISTICA 6.0 (StatSoft Inc., USA).Results. In 2017-2019, the number of detected CAD cases and proportion of men increased. In both time periods, an insufficient level of calculating PTP of CAD remains. In patients with intermediate PTP, 15-85% of priority tactics are invasive interventions, and with high PTP, the percentage of invasive methods does not reach the proper level, which does not correspond to modern guidelines for the management of CAD patients and leads to misappropriation of funds and healthcare resources.Conclusion. According to medical records, PTP can be determined in less than half of patients. In CAD patients with intermediate PTP, non-invasive studies are not carried out in full, since coronary angiography is preferred. In patients with a high PTP, invasive diagnostics is insufficient.

Multifaceted approach to limit ordering of IgE food testing

Food allergy is an IgE-mediated, systemic reaction, that begins within minutes of ingestion. Positive food serum IgE testing done without appropriate history and high pre-test probability are not necessarily indicative of a true food allergy. Inappropriate ordering and interpretation can lead to false food allergy diagnoses. We reviewed a 6-year period to evaluate the effectiveness of a multifaceted approach to address over ordering of serum food IgE testing.

Assessing How Consumers Interpret and Act on Results From At-Home COVID-19 Self-test Kits

The US Food and Drug Administration (FDA) authorized SARS-CoV-2 rapid at-home self-test kits for individuals with and without symptoms. How appropriately users interpret and act on the results of at-home COVID-19 self-tests is unknown. To assess how users of at-home COVID-19 self-test kits interpret and act on results when given instructions authorized by the FDA, instructions based on decision science principles, or no instructions. A randomized clinical trial was conducted of 360 adults in the US who were recruited in April 2021 to complete an online survey on their interpretation of at-home COVID-19 self-test results. Participants were given 1 of 3 instruction types and were presented with 1 of 4 risk scenarios. Participants were paid $5 and had a median survey completion time of 8.7 minutes. Data analyses were performed from June to July 2021. Participants were randomized to receiving either the FDA-authorized instructions (authorized), the intervention instructions (intervention), or no instructions (control), and to 1 of 4 scenarios: 3 with a high pretest probability of infection (COVID-19 symptoms and/or a close contact with COVID-19) and 1 with low pretest probability (no symptoms and no contact). The intervention instructions were designed using decision science principles. Proportion of participants in the high pretest probability scenarios choosing to quarantine per federal recommendations and perceived probabilities of infection given a negative or positive COVID-19 test result. A Bonferroni correction accounted for multiple comparisons (3 instruction types × 4 scenarios; α = 0.004). After excluding 22 individuals who completed the survey too quickly, the responses of 338 participants (median [IQR] age, 38 [31 to 48] years; 154 (46%) women; 215 (64%) with a college degree or higher) were included in the study analysis. Given a positive test result, 95% (322 of 338; 95% CI, 0.92 to 0.97) of the total participants appropriately chose to quarantine regardless of which instructions they had received. Given a negative test result, participants in the high pretest probability scenarios were more likely to fail to quarantine appropriately with the authorized instructions (33%) than with the intervention (14%; 95% CI for the 19% difference, 6% to 31%; P = .004) or control (24%; 95% CI for the 9% difference, -4% to 23%; P = .02). In the low pretest probability scenario, the proportion choosing unnecessary quarantine was higher with the authorized instructions (31%) than with the intervention (22%; 95% CI for the 9% difference, -14% to 31%) or control (10%; 95% CI for the 21% difference, 0.5% to 41%)-neither comparison was statistically significant (P = .05 and P = .20 respectively). The findings of this randomized clinical trial indicate that at-home COVID-19 self-test kit users relying on the authorized instructions may not follow the Centers for Disease Control and Prevention's quarantine recommendations, producing unintended risks and unnecessary disruptions. Redesigned instructions that follow decision science principles may improve compliance. ClinicalTrials.gov Identifier: NCT04758299.

Comparison of Three Real-Time PCR Assays for the Detection of Cyclospora cayetanensis in Stool Samples Targeting the 18S rRNA Gene and the hsp70 Gene.

Diagnostic real-time PCR for the detection of Cyclospora cayetanensis in human stool samples has been applied for two decades. However, recent comparative assessments between in-house and commercial assays suggested room for improvement regarding the agreement of positive signals of the applied real-time PCRs. In order to assess the effect of the choice of the target sequence, 3 inhouse real time PCR assays targeting the 18S rRNA gene (n = 2, one of them later referred to as SSU rRNA gene assay to avoid confusion) and the hsp70 gene of C. cayetanensis were compared in a head-to-head comparison with 905 samples with high pretest probability for C. cayetanensis infections from Ghanaian HIV patients in a test comparison without a reference standard. Only slight agreement kappa of 0.095 was observed. In the assays targeting the SSU rRNA gene, the 18S rRNA gene, and hsp70, positive signals were recorded in 63, 45, and 0 instances, respectively, with latent class analysis-based estimation of sensitivity of 32.2%, 23.3%, 0% as well as of specificity of 99.7%, 99.9% and 100%, respectively. High cycle threshold values with an average of about 35 indicated low quantities of target DNA in the samples with similar Ct values in concordantly and discordantly positive samples. In conclusion, the study suggested target-gene-specific differences in the diagnostic accuracy of real-time PCR-based diagnosis of C. cayetanensis as well as an ongoing need for further standardization of this diagnostic approach.

A Multicenter Retrospective Evaluation of Direct Oral Anticoagulants for the Treatment of Heparin-Induced Thrombocytopenia.

Direct oral anticoagulants (DOACs) represent an off-label but potential alternative to traditional therapies for heparin-induced thrombocytopenia (HIT). The objective of this study was to evaluate the efficacy and safety of DOACs in patients with a diagnosis of laboratory-confirmed HIT. A multicenter retrospective cohort study of adult patients with HIT treated with apixaban, rivaroxaban, or dabigatran between 1 January 2013 and 1 January 2020 was performed. Patients with an intermediate or high pre-test probability for HIT and a positive antiplatelet factor 4/heparin complex assay, latex immunoturbidimetric assay, or serotonin release assay were included for analysis. The primary outcome was the composite of newly diagnosed venous or arterial thromboembolism, gangrene, or severe limb ischemia requiring amputation at 3 months following DOAC initiation. This study was approved by local institutional review boards, and the requirement for informed consent was waived. A total of 77 patients from four health systems were included. The median 4Ts score was 5 (interquartile range 4.5-6), and 38 patients (49.4%) had a diagnosis of HIT with thrombosis. The most frequently used DOAC was apixaban (n = 51), followed by rivaroxaban (n = 24) and dabigatran (n = 2). In total, 63 (81.8%) patients received parenteral non-heparin anticoagulation prior to DOAC initiation. Nine patients (11.7%) experienced the primary outcome of HIT-related thrombotic events. Of the 14 patients who exclusively received DOAC therapy, none experienced the primary outcome. Major bleeding occurred in five (6.5%) patients. In this retrospective cohort study, DOACs were associated with rates of thrombotic and hemorrhagic events similar to those with other therapies currently used in the treatment of HIT.