False-positive Test Research Articles

Evaluating xanthochromia in the diagnosis of subarachnoid haemorrhage in Scotland in the Era of modern computed tomography.

Cerebrospinal fluid (CSF) analysis for xanthochromia is routinely used to exclude subarachnoid haemorrhage (SAH). In this study, we evaluated the sensitivity and specificity of xanthochromia (by NEQAS-spectrophotometry) in routine clinical practice in three acute hospitals, in patients with suspected SAH. We explored whether including CSF red cell count (RCC) with xanthochromia improved diagnostic accuracy. In this retrospective analysis, all xanthochromia results were assessed over three consecutive years. Clinical information and Registry data were analysed to find all patients diagnosed with SAH. We correlated xanthochromia data with clinical and radiological findings. There were 1761 xanthochromia performed. Of these, 26 (1.5%) were positive, 1624 (92%) negative and 72 (4.1%) were inconclusive. Of the 26 tests that were positive, 9 (35%) had confirmed SAH, 17 (65%) were falsely positive, with no false negative tests in our series. Xanthochromia identified 6% of all SAH diagnosed in the study. Incorporating RCC <1000 with xanthochromia, reducing false positive tests by 38% and inconclusive test by 85%. The positive yield of xanthochromia is low but identified 6% of SAH. NEQAS-spectrophotometry is an excellent diagnostic method with 100% sensitivity, 99% specificity. Incorporating RCC markedly reduces false positive and inconclusive tests reducing need for further imaging.

The Effects of Clinical Factors and Neonatal Morbidities on Hearing Screening among Neonatal Admissions.

Hearing loss is an important disorder affecting newborns admitted to NICU. A national hearing screening program using otoacoustic emission testing is an essential tool to identify hearing loss early in neonates, enabling early intervention to avoid further challenges of pediatric deafness. On the other hand, a delay of the auditory pathway maturation in preterm babies compared to term newborns has already been suggested in the literature. Taking this information into account, in this paper, we aim to identify the best time to perform NICU infant hearing screening tests. We aim to study the clinical factors and neonatal morbidities that may affect neonatal hearing screening results using otoacoustic emission test in order to decrease the false-positive test results that increase parental anxiety and increase the need for subsequent investigations. This is a prospective cross-sectional study that included 204 infants who were admitted to a tertiary referral hospital NICU unit between September 2017 and May 2018. Both transients evoked otoacoustic emissions (TEOAE), and distortion product otoacoustic emission (DPOAE) screening tests were performed in order to screen hearing loss. Our study included 204 infants, 52.9 % of which were males and 47.1 % females. There were correlations between both hyperbilirubinemia and ventilation ≥ 5 days and the failure rate of the first OAE test results among NICU infants where the P-values were (p=0.0133) and (p=0.0456), respectively. Moreover, 165 babies (80.9 %) passed the first OAE with a mean birth weight of 2759 gram and mean maternal age of 30.6 years, while 39 babies (19.1 %) failed the test with a mean birth weight of 2436 gram and a mean maternal age of 32 years. There was no statistically significant relation between both maternal age and birth weight with failure of the first screening test. Our study suggests a higher failure rate of the first OAE in NICU infants who had hyperbilirubinemia or ventilation ≥ 5 days. Therefore, our recommendation is to postpone the first phase of hearing screening for those infants until the first scheduled vaccine appointment to achieve high compliance to attendance and decrease distress to the family that can be associated with false-negative results of the test.

Analysis of the characteristics of patients with false-positive HIV screening assay results

ObjectiveTo investigate the clinical characteristics of patients with false-positive human immunodeficiency virus (HIV) screening test results and provide a theoretical basis to interpret the results of HIV screening tests. MethodsThis retrospective study evaluated the incidence of false-positive results for HIV screening tests and characterized false-positive reactions during HIV screening in a large-scale study at Zhongshan Hospital, Xiamen University. ResultsFalse-positive HIV test results occurred for 264 of 275,263 (0.10%) serum samples. Although the incidence of a false-positive HIV screening result did not differ between male and female patients (screening χ2 = 1.194; P = 0.275), it increased with age (χ2 = 25.759; P < 0.01). False-positive reactions were associated with 16 disease categories, including 101 diseases, some of which have never been reported previously to be associated with false-positive HIV screening results. ConclusionsThe occurrence of false-positive HIV screening test results may indicate underlying serious disorders. Characterization of patients with false-positive HIV screening test results can help identify potential diseases unrelated to HIV.

Analysis of nucleic acids extracted from rapid diagnostic tests reveals a significant proportion of false positive test results associated with recent malaria treatment

BackgroundSurveillance programmes often use malaria rapid diagnostic tests (RDTs) to determine the proportion of the population carrying parasites in their peripheral blood to assess the malaria transmission intensity. Despite an increasing number of reports on false-negative and false-positive RDT results, there is a lack of systematic quality control activities for RDTs deployed in malaria surveillance programmes.MethodsThe diagnostic performance of field-deployed RDTs used for malaria surveys was assessed by retrospective molecular analysis of the blood retained on the tests.ResultsOf the 2865 RDTs that were collected in 2018 on Bioko Island and analysed in this study, 4.7% had a false-negative result. These false-negative RDTs were associated with low parasite density infections. In 16.6% of analysed samples, masked pfhrp2 and pfhrp3 gene deletions were identified, in which at least one Plasmodium falciparum strain carried a gene deletion. Among all positive RDTs analysed, 28.4% were tested negative by qPCR and therefore considered to be false-positive. Analysing the questionnaire data collected from the participants, this high proportion of false-positive RDTs could be explained by P. falciparum histidine rich protein 2 (PfHRP2) antigen persistence after recent malaria treatment.ConclusionMalaria surveillance depending solely on RDTs needs well-integrated quality control procedures to assess the extent and impact of reduced sensitivity and specificity of RDTs on malaria control programmes.

High False-Positive Rate of (1,3)-β-D-Glucan in Onco-Hematological Patients Receiving Immunoglobulins and Therapeutic Antibodies.

Immunoglobulins and/or therapeutic antibody preparations are associated with a high rate of false-positive (1,3)-β-D-glucan (BDG) tests in onco-hematological patients routinely screened for fungal infections. The benefit of BDG monitoring shall be balanced against the risk of false-positive tests leading to unnecessary investigations and costs in this population.

False Positive Results on Dobutamine Stress Echocardiography: A New Marker of Risk for Ischemic Events

Background: Although dobutamine stress echocardiography (DSE) has a high specificity, there is still a subset of patients with false positive tests (FP); whether these results have prognostic value remains unclear. Aims: To identify the clinical and echocardiographic predictors of FP on DSE and to evaluate the prognostic impact of FP on DSE. Methods: Retrospective study of 355 consecutive patients who underwent DSE for ischemia assessment over a one-year period: 134 (37,7%) women, 70,3 ± 0,57 years. Demographics, risk factors, clinical and laboratorial parameters and DSE variables were evaluated. Patients were divided into 2 groups regarding the presence (FP+) or the absence (FP0) of a FP result on DSE and a comparative analysis was performed to characterize the groups and identify potencial predictors of FP results. Patients were followed for 2 years to assess acute myocardial infarction, hospitalization for acute heart failure (HF) and mortality. Results: The FP rate was 4,5%. Comparing to FP0, patients in group FP+ were younger, baseline wall motion abnormalities were more frequent, had higher mean blood pressure values at rest and at peak stage and more often hypertensive response. There were no significant differences regarding previous coronary artery disease, medication or complete left bundle branch block. By multivariate analysis, only mean blood pressure values at rest (OR 0,01; 95%CI 0,005-0,02; p=0,003) and at peak stage (OR 0,02; 95%CI 0,000-0,004; p=0,003) were independent predictors of FP. During follow-up was observed: acute myocardial infarction (FP+: 12,5% vs FP0: 1,8%, p=0,046), HF (FP+: 6,3% vs FP0: 11,5%, p=0,44) and mortality (FP+: 6,3% vs FP0: 6,2%, p=0,65). After adjustment for age, sex and comorbidities, there were no diferences between the groups regarding HF and mortality, but the group FP+ mantained a higher rate of acute myocardial infarction (OR 0,21; 95%CI 0,065-0,354; p=0,005). Conclusion: A FP result on DSE was associated with higher mean blood pressure values during the test and with higher rates of acute myocardial infarction during follow-up. This result on DSE should therefore be faced as a risk marker for ischemic events and can identify patients that may benefit from aggressive risk factor control and careful clinical follow-up.

Aluminum-Allergen of the Year 2022.

Exposure to elemental aluminum and its salts is unavoidable. Aluminum as a metal is present in transport, construction, packaging, and electronic equipment. Aluminum salts are present in consumer products, food items and drinking water, vaccines, drugs, and antiperspirants. Aluminum in vaccines and preparations for allergen-specific immunotherapy are the major sensitization sources. The predominent clinical manifestations of aluminum allergy are pruritic subcutaneous nodules and eczematous dermatitis. Patch testing shall be performed with aluminum chloride hexahydrate (ACH) in petrolatum. The preparation with ACH 10% detects substantially more aluminum allergy than ACH 2%. A patch test with elemental aluminum, for example, an empty Finn Chamber, is only positive when there is a strong aluminum allergy. A patch test reading should be performed 1 week after the application so as not to miss 15% to 20% of aluminum allergy. Aluminum should be included in any baseline patch test series for children and investigated for a possible inclusion in baseline series for adults. Aluminum test chambers can interfere with the testing resulting in both false-negative and false-positive patch test reactions to nonaluminum contact sensitizers.

Conditions Other than Severe Combined Immune Deficiency Found on SCID Newborn Screening

Severe combined immune deficiency (SCID) is caused by a wide variety of genetic variants that result in absent or diminished levels of mature and functional T cells. SCID Newborn Screening programs that detect T cell receptor excision circles have resulted in early intervention and improvement in survival rates in infants with SCID but have also identified other conditions with low T cells. These conditions trigger what could be thought of as false positive tests for SCID, but for the most part they do reflect low T cells in conditions other than SCID. The scope of this review is entities other than severe combined immune deficiency that cause low T cell receptor excision circles (TRECs) and are thus identified on newborn screening. Secondary immune deficiencies from prematurity, neonatal medical conditions, hypomorphic or incomplete variants of SCID, transient T cell lymphopenia of infancy, and primary immune deficiencies that do not qualify as SCID are all elaborated. Identification and treatment options for these conditions leading to low TRECs are discussed.

Budget impact of the Oncotype DX® test compared to other gene expression tests in patients with early breast cancer in Germany

PurposeGene expression tests can inform decisions on whether to recommend chemotherapy for patients with HR+, HER2- early breast cancer. The goal of this analysis was to compare treatment costs by an expanded budget impact model of reimbursed gene expression tests in Germany. MethodsA cost comparison was constructed as an expanded budget impact model to calculate average total costs per patient covered by public health insurance. Based on the strong clinical evidence from the prospective randomized controlled trial TAILORx including more than 10,000 patients with HR+ and node negative breast cancer, the assumption was made that the Oncotype DX® test accurately predicts chemotherapy benefit and clinical outcomes. For the further reimbursed tests (EndoPredict®, MammaPrint®, Prosigna®), results from comparative studies – aligned with prognosis studies – as analyzed in IQWiG Rapid Report D19–01 were applied. ResultsThe use of the Oncotype DX test led to estimated average savings per patient of 2,500 € vs. EndoPredict, 1,936 € vs. MammaPrint, and 649 € vs. Prosigna. Savings were achieved by reduction of unnecessary chemotherapy use, a consequence of false-positive test results (EndoPredict 73%, MammaPrint 42%, Prosigna 20%). False-negative test results (EndoPredict 5%, MammaPrint 22%, Prosigna 49%) reduced necessary chemotherapies, which initially results in cost savings, but may lead to increased long-term costs associated with management of progressive disease. ConclusionThe results from this model suggest that the use of the Oncotype DX test reduces the cost of health care in Germany making it the most cost effective test compared to the further tests.

Suitability of Different Diagnostic Platforms for Virological Testing of Blood Samples from Cornea Donors

Background: To minimize the risk of disease transmission in cornea transplantation, donor screening for blood-derived viral infections is mandatory. Ideally, pre-mortem blood samples are used, but based on availability, cadaveric blood samples of cornea donors may also be used. However, serological and nucleic acid amplification tests (NATs) need to be validated for the use of cadaveric specimens. Methods: Hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV) 1/2, and Treponema pallidum (syphilis)-specific serological and/or NAT assays were validated on different platforms (Abbott Alinity i, Alinity m, Roche Cobas 6800, and Roche Cobas AmpliPrep/Cobas TaqMan (CAP/CTM)) using (un)spiked paired pre- and post-mortem cornea donor blood samples from the same individual (up to 23.83 h after death) of 28 individuals in accordance with the specifications of the German Federal Institute for Vaccines and Biomedicines (Paul-Ehrlich-Institut [PEI]). In addition, routinely HBV-, HCV- and HIV-PCR-negative tested post-mortem blood samples of 24 individuals were used to assess NAT specificity. Results: For the majority of serological parameters on the Abbott Alinity i (HBsAg, anti-HBc, anti-HBs, anti-HCV, anti-HIV, anti-HTLV 1/2, and anti-Treponema pallidum), ratios of generated test results of (un)spiked paired pre- and post-mortem blood samples differed ≤25%, with an agreement of qualitative pre- and post-mortem test results ranging from 91.2 to 100%. For NAT parameters (HBV, HCV, and HIV) on the Cobas 6800, Alinity m, and CAP/CTM, no significant deviation in virus concentrations (factor >5) of spiked pre- and post-mortem blood samples could be observed. Ct-values of corresponding internal controls did also not differ significantly (>1.5 Ct-values). In addition, no false-positive test results were generated when specificity was assessed. Conclusion: Overall, fluctuations of test results for serological and NAT parameters in pre- and post-mortem blood samples examined in this study, were only limited and within the range of what is also observed when routinely testing fresh patient specimens. We conclude that all examined assays are eligible for the screening of blood samples taken up to about 24 h after the occurrence of death.

Annual adult health screening: barriers, challenges and effectiveness

Although it has been well-established that screening for early detection and intervention practices has been associated with favorable outcomes, there have been many concerns about the potential of these approaches to cause harm to the patients. In addition, evidence also shows some associated barriers and challenges to these approaches that need to be considered by healthcare authorities when planning for such approaches. The present literature review discusses annual adult health screening programs' effectiveness, barriers, and challenges. There is no doubt that these screening programs can help identify undiagnosed disorders among many patients with various conditions, like diabetes mellitus, hypertension, and different cancers. Moreover, the effectiveness of these screening programs can be best highlighted by the premarital screening program in Saudi Arabia, which targets high-risk couples for developing certain conditions and infections. However, it should be noted that there are many barriers and challenges to conducting health screening campaigns, like cultural and economic factors. Other challenges might also include the rates of false-positive tests, overdiagnosis, and knowledge about the screening programs.

Biomarkers in the Degenerative Human Intervertebral Disc Tissue and Blood.

Patients with back pain comprise a large proportion of the outpatient practice among physiatrists. Diagnostic tools are limited to clinical history, physical examinations, and imaging. Nonsurgical treatments are largely empirical, encompassing medications, physical therapy, manual treatments, and interventional spinal procedures. A body of literature is emerging confirming elevated levels of biomarkers including inflammatory cytokines in patients with back pain and/or radiculopathy, largely because the protein assay sensitivity has increased. These biomarkers may serve as tools to assist diagnosis and assess outcomes.The presence of inflammatory mediators in the intervertebral disc tissues and blood helped to confirm the inflammatory underpinnings of back pain related to intervertebral disc degeneration. Literature reviewed here suggests that biomarkers could assist clinical diagnosis and monitor physiological outcomes during and after treatments for spine-related pain. Biomarkers must be measured in a large and diverse asymptomatic population, in the context of age and comorbidities to prevent false-positive tests. These levels can then be rationally compared with those in patients with back disorders including discogenic back pain, radiculopathy, and spinal stenosis. While studies reviewed here used "candidate marker" approaches, future nonbiased approaches in clearly defined patient populations could uncover novel biomarkers in clinical management of patients.

The role of first-trimester ultrasound screening for women with positive noninvasive prenatal testing results.

This study aimed to assess the utility of ultrasound screening for pregnancies with positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. We performed a retrospective analysis of positive noninvasive prenatal testing results and first-trimester ultrasound screening at our department between 2013 and 2019. Invasive genetic testing was performed if the patient had positive noninvasive prenatal testing results. Fetal ultrasound and cytogenetic data were collected. Noninvasive prenatal testing was performed in the women for advanced maternal age, nuchal translucency thickness, or history of abnormality in the previous child or relative. Forty-one pregnant women had positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. Twenty-three women had positive results for trisomy 21, 13 had positive results for trisomy 18, and 5 had positive results for trisomy 13 at 11 to 14 weeks of gestation. The positive predictive value of noninvasive prenatal testing was 100% for trisomy 21, 84.6% for trisomy 18, and 100% for trisomy 13. The positive predictive value of positive noninvasive prenatal testing results and fetal morphological abnormalities was 100% for trisomy 21, trisomy 18, and trisomy 13. Combining an ultrasound examination with noninvasive prenatal testing resulted in a higher positive predictive value for trisomy 18. Normal ultrasound examination results can help alleviate stress caused by false-positive noninvasive prenatal testing results. In contrast, the positive predictive value and negative predictive value for trisomy 21 were not altered by adding an ultrasound examination to noninvasive prenatal testing.

Evaluating the Efficacy of a Screening Protocol for Severe Acute Respiratory Syndrome Coronavirus 2 Virus in Asymptomatic Preoperative/Preprocedural Patients at a Military Hospital.

ABSTRACTIntroductionFacing the COVID-19 pandemic, many hospitals implemented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening protocols before aerosol-generating procedures (AGPs) in an effort to protect patients and health care workers. Given the limited prior evidence on the effectiveness of such protocols, we report the process improvement experience at a military treatment facility.Materials and MethodsWe evaluated the outcomes of patients undergoing AGPs from March to September 2020, divided into three cohorts: a preprotocol (PP) cohort who did not receive screening, an early testing (ET) cohort representing the early months of the screening protocol, and a late testing (LT) cohort managed under adaptive modifications to the screening protocol. We recorded identifiable post-procedure COVID-19 diagnoses. The study was approved as a process improvement protocol and was determined not to meet criteria for human subject research through an institutional approval process.ResultsAcross the three cohorts, 4520 procedures were performed: 422 PP, 1297 ET, and 2801 LT. Among 4098 procedures in the ET and LT cohorts, 12 asymptomatic patients tested positive for SARS-CoV-2 (0.29% positivity rate). One left the health system before completing the procedure and another proceeded urgently under COVID precautions, while 10 were rescheduled and completed at a later date; 7 were cleared using a test-based strategy, while 3 were cleared using a time-based strategy. Of 445 patients who had SARS-CoV-2 tests performed within 30 days following their procedures, three patients with negative preoperative tests had a positive test within 30 days, all in the LT cohort but had evidence of acquiring the infection after the procedure or had a false-positive test.ConclusionsOur strategy of preprocedural SARS-CoV-2 testing successfully identified asymptomatic infected patients before surgery. Care was delayed for most of these patients without apparent detriment. Adaptation to a time-based strategy for clearance might reduce such delays, but other considerations may still influence how soon procedures should be completed after a positive test.

Serial antigen rapid testing in staff of a large acute hospital

Serial antigen rapid testing in staff of a large acute hospital

1163. HIV-1 NAAT Pitfalls in B-cell Lymphoblastic Leukemia Patients Following CAR-T Cell Therapy

BackgroundCAR-T Cell Therapy is approved for the treatment of pediatric patients with relapsed/refractory B-ALL. Lentiviral vector technology, highly modified from HIV-1, is used to induce stable, long-term transgene expression by integration into the host genome. This integration may interfere with HIV-1 NAAT producing false-positive results. MethodsA retrospective chart review of Pre-B ALL patients who underwent to CAR T cell therapy with KYMRIAH(tisagenlecleucel) at a single institution between January 2019 and May 2021 to assess for patients whose CAR-T infusion interfered with post-infusion HIV-1 testing. All patients had HIV NAAT pre and post CAR T-cell therapy (using platform, Roche COBAS AmpliPrep/Quantitative TaqMan HIV-1 T). Reactive HIV NAAT by Roche test were subsequently tested using different HIV-1 assay platforms to rule out or confirm HIV infection.ResultsWe report three cases in which interpretation of HIV-1 NAAT testing was complicated by CAR T cell therapy. Case 1: 1-year-old male with refractory infantile leukemia was found to have a reactive HIV NAAT post CAR-T in routine infectious screening prior to SCT. Case 2: 3-year-old refractory ALL planned for SCT who had a reactive HIV NAAT 9 months post CART. Fourth-generation HIV-1 testing (targeting the p24 antigen and anti-HIV-1 antibodies) was negative pre and post CART. Viral loads were also undetectable indicating false-positive post-CAR-T HIV-1 NAT test results. Case 3: 21-year-old sexually active female with relapsed B cell ALL. Post CAR-T HIV NAAT was reactive, and a quantitative viral load was positive at 176 copies/mm3 one day prior to start of stem cell transplant conditioning regimen. Aptima HIV testing is typically used as confirmatory test for CAR-T associated false positive HIV NAT cases, but surprisingly, the Aptima test was also reactive. Additional testing with Abbott m2000 Realtime HIV-1 assay and 4th generation p24 antigen-based testing were both negative. Table 1 Summary of reported patients with false-positive HIV-1 NAAT test results following CAR T cell therapy and Table 2, HIV platforms used for screening and diagnosis with interpretations following CAR T cell therapy.ConclusionClinicians need to be aware of potential false-positive HIV testing after CAR-T therapy. HIV testing platforms with targets not used in lentiviral vectors (4th generation test/P24, or Abbott test/integrase region) are highly recommended to avoid delays in subsequent therapy and unwanted stress for the patients, families, and cliniciansDisclosures All Authors: No reported disclosures

Time to get real with qPCR controls: The frequency of sample contamination and the informative power of negative controls in environmental DNA studies.

Environmental (e)DNA methods have enabled rapid, sensitive and specific inferences of taxa presence throughout diverse fields of ecological study. However, use of eDNA results for decision-making has been impeded by uncertainties associated with false positive tests putatively caused by sporadic or systemic contamination. Sporadic contamination is a process that is inconsistent across samples and systemic contamination occurs consistently over a group of samples. Here, we used empirical data and laboratory experiments to (i) estimate the sporadic contamination rate for each stage of a common, targeted eDNA workflow employing best practice quality control measures under simulated conditions of rare and common target DNA presence, (ii) determine the rate at which negative controls (i.e., "blanks") detect varying concentrations of systemic contamination, and (iii) estimate the effort that would be required to consistently detect sporadic and systemic contamination. Sporadic contamination rates were very low across all eDNA workflow steps, and, therefore, an intractably high number of negative controls (>100) would be required to determine occurrence of sporadic contamination with any certainty. Contrarily, detection of intentionally introduced systemic contamination was more consistent; therefore, very few negative controls (<5) would be needed to consistently alert to systemic contamination. These results have considerable implications to eDNA study design when resources for sample analyses are constrained.

What Is the Impact of Automated Synovial Cell Counting on Different Aseptic Causes and Periprosthetic Conditions Associated With Revision THA?

Studies have suggested that automated synovial cell counting may overestimate the white blood cell (WBC) count, resulting in false positive tests when evaluating patients for the possibility of periprosthetic joint infection (PJI) after THA. However, associations between WBC counts high enough to mimic PJI in patients whose arthroplasties are not infected but rather are experiencing a variety of aseptic problems-including but not limited to metallosis, polyethylene wear, and recurrent dislocation-have not, to our knowledge, been adequately addressed. In addition, there is a lack of analyses about the polymorphonuclear percentage (PMN%) when assessed by automated analyzers in this context. In the context of different indications for aseptic revision and different periprosthetic hip pathologic findings, we asked: (1) What were the synovial WBC count levels, and what proportion of values were above the 2018 International Consensus Meeting (ICM) cutoff (3000 cells/μL)? (2) What were the synovial PMN% levels, and what proportion of values were above the 2018 ICM (70%)? We retrospectively studied the preoperative cell count analyses of synovial fluid in patients who underwent revision THA for aseptic reasons at our tertiary referral arthroplasty center between January 2015 and December 2017. We considered all revisions performed on patients during that time potentially eligible, and after prespecified exclusions were applied (exclusions mainly included 15% [197 of 1306] sporadic missing data and 12% [155 of 1306] insufficient synovial fluid obtained in the aspirate), a total of 702 patients undergoing revision THA for aseptic reasons remained for the final analysis. As far as we know, no patients underwent re-revision for PJI at a mean follow-up of 46 ± 11 months, which tends to confirm our impression that indeed these hips did not have PJI. Cell count analyses were conducted using an automated analyzer. Clinical findings, preoperative radiographs, and surgical reports--confirmed by available histologic results--were used to establish diagnoses. We evaluated these hips considering the recommendations of the 2018 ICM (WBC count of 3000 cells/μL and PMN% of 70%) to see what proportion of them would have been characterized as likely having PJI on basis of those cutoff values. The mean WBC count for the entire cohort was 2120 ± 2395 cells/μL. The mean PMN% for the entire cohort was 36% ± 22%. Compared with aseptic loosening and recurrent dislocation, polyethylene wear had the highest mean WBC count (3817 ± 3711 cells/μL; p < 0.001). Of the investigated periprosthetic conditions, wear-induced synovitis had the highest value (4464 ± 3620 cells/μL; p < 0.001). Considering the ICM threshold, polyethylene wear showed the highest proportion of WBC counts above 3000 cells/μL among the indications for aseptic revision (60% [25 of 42]; p < 0.001). Of the periprosthetic conditions, wear-induced synovitis showed the highest proportion beyond the ICM cutoff (60% [50 of 83]; p < 0.001). The mean PMN% for aseptic causes ranged between 28% and 44% without differences among them (p = 0.12). Patients with metallosis had the highest mean PMN% of the periprosthetic conditions investigated (45% ± 25%; p = 0.007). Regarding the ICM threshold, metallosis resulted in the largest proportion of patients with a PMN% above 70% (21% [10 of 47]; p = 0.003), and that for wear-induced synovitis was 6% (5 of 83; p = 0.42) and for osteolysis was 3% (1 of 33; p = 0.51). There were no differences among aseptic loosening, recurrent dislocation, and polyethylene wear in terms of the proportion above 70% among the aseptic revision causes. Using automated cell counting, we found that WBC counts differ widely across indications for aseptic revision THA, and a high proportion of patients who underwent revision THA for aseptic reasons had WBC counts above the commonly used threshold of 3000 cells/μL. However, the PMN% was much less affected in several common indications for aseptic revision THA, making this measure more reliable for interpreting aspiration results using an automated analyzer. Based on the data distributions we observed, manual counting techniques might be considered in particular among patients with polyethylene wear, metal-on-metal bearing surfaces, or suspected metallosis. However, an elevated WBC count alone, observed using an automated analyzer in the context of polyethylene wear, should not be considered to be strongly suggestive of PJI, since that finding occurred so commonly among patients without infection. Level III, diagnostic study.

Evolving Interpretation of Screening and Diagnostic Tests in Allergy

Diagnostic tests for allergy usually are performed to confirm a diagnosis of an allergic disease. If a food allergy suspected, a test can help to determine whether it is present, to monitor its activity over time, and to determine whether the allergy is resolving. In this way, tests are used for diagnosis, monitoring, screening, and prognosis. There are 2 schools of thought for using tests: Frequentist and Bayesian approaches. The Frequentist approach defines probability in terms of the frequency of an event if it were to be repeated numerous times and uses parameters such as sensitivity, specificity, and predictive values to make a diagnosis. In contrast, the Bayesian approach defines probability as the degree of belief or disbelief regarding the diagnosis and asserts that only data are real and that test parameters are to be inferred from the data. There are strengths and limitations to each approach; however, the Bayesian approach provides an algorithm leading to a disease probability. To use the Bayesian approach, test results need to be expressed as a likelihood ratio. This helps to determine how much the result of a test changes the probability of a particular diagnosis. Once a probability of disease is determined, decision thresholds need to be defined so that a treatment decision can be made. Using this Bayesian approach, the concept of a false-positive or false-negative test result becomes obsolete.

Clinical Data Prediction Model to Identify Patients With Early-Stage Pancreatic Cancer.

Pancreatic cancer is an aggressive malignancy with patients often experiencing nonspecific symptoms before diagnosis. This study evaluates a machine learning approach to help identify patients with early-stage pancreatic cancer from clinical data within electronic health records (EHRs). From the Optum deidentified EHR data set, we identified early-stage (n = 3,322) and late-stage (n = 25,908) pancreatic cancer cases over 40 years of age diagnosed between 2009 and 2017. Patients with early-stage pancreatic cancer were matched to noncancer controls (1:16 match). We constructed a prediction model using eXtreme Gradient Boosting (XGBoost) to identify early-stage patients on the basis of 18,220 features within the EHR including diagnoses, procedures, information within clinical notes, and medications. Model accuracy was assessed with sensitivity, specificity, positive predictive value, and the area under the curve. The final predictive model included 582 predictive features from the EHR, including 248 (42.5%) physician note elements, 146 (25.0%) procedure codes, 91 (15.6%) diagnosis codes, 89 (15.3%) medications, and 9 (1.5%) demographic features. The final model area under the curve was 0.84. Choosing a model cut point with a sensitivity of 60% and specificity of 90% would enable early detection of 58% late-stage patients with a median of 24 months before their actual diagnosis. Prediction models using EHR data show promise in the early detection of pancreatic cancer. Although widespread use of this approach on an unselected population would produce high rates of false-positive tests, this technique may be rapidly impactful if deployed among high-risk patients or paired with other imaging or biomarker screening tools.