SARS-CoV-2 antigen rapid detection tests: test performance during the COVID-19 pandemic and the impact of COVID-19 vaccination.

BACKGROUND: SARS-CoV-2 antigen rapid detection tests (RDTs) emerged as point-of-care diagnostics alongside reverse transcription polymerase chain reaction (RT-qPCR) as reference. METHODS: In a prospective performance assessment from 12 November 2020 to 30 June 2023 at a single centre tertiary care hospital, the sensitivity and specificity (primary endpoints) of RDTs from three manufacturers (NADAL®, Panbio™, MEDsan®) were compared to RT-qPCR as reference standard among patients, accompanying persons and staff aged ≥ six month in large-scale, clinical screening use. Regression models were used to assess influencing factors on RDT performance (secondary endpoints). FINDINGS: Among 78,798 paired RDT/RT-qPCR results analysed, overall RDT sensitivity was 34.5% (695/2016; 95% CI 32.4-36.6%), specificity 99.6% (76,503/76,782; 95% CI 99.6-99.7%). Over the pandemic course, sensitivity decreased in line with a lower rate of individuals showing typical COVID-19 symptoms. The lasso regression model showed that a higher viral load and typical COVID-19 symptoms were directly significantly correlated with the likelihood of a positive RDT result in SARS-CoV-2 infection, whereas age, sex, vaccination status, and the Omicron VOC were not. INTERPRETATION: The decline in RDT sensitivity throughout the pandemic can primarily be attributed to the reduced prevalence of symptomatic infections among vaccinated individuals and individuals infected with Omicron VOC. RDTs remain valuable for detecting SARS-CoV-2 in symptomatic individuals and offer potential for detecting other respiratory pathogens in the post-pandemic era, underscoring their importance in infection control efforts. FUNDING: German Federal Ministry of Education and Research (BMBF), Free State of Bavaria, Bavarian State Ministry of Health and Care.

Comparative assessment of the performance of a commercial fluorescent microsphere immunoassay and three commercial ELISAs for Mycoplasma hyopneumoniae serum antibody detection.

Mycoplasma hyopneumoniae (M. hyopneumoniae) is a significant porcine respiratory disease complex pathogen, prompting many swine farms and production systems to pursue M. hyopneumoniae elimination strategies. Antibody testing is cost-effective in demonstrating sustained freedom from M. hyopneumoniae, often replacing PCR testing on deep tracheal swabs. The process typically involves testing a subpopulation of the herd using an M. hyopneumoniae screening antibody ELISA, with non-negative results further assessed through confirmatory testing, such as PCR. Recently, a commercial (Biovet) fluorescent microsphere immunoassay (FMIA) for detecting M. hyopneumoniae antibodies has been introduced as an alternative to ELISA. Its performance was compared to three commercial ELISAs (Idexx, Hipra, and Biochek) using experimental serum samples from pigs inoculated with M. hyopneumoniae, M. hyorhinis, M. hyosynoviae, M. flocculare, or mock-inoculated with Friis medium. FMIA consistently detected M. hyopneumoniae at earlier time points than the ELISAs, although two false-positive results were encountered using the manufacturer's recommended cutoff. ROC analysis allowed for the evaluation of various cutoffs depending on testing objectives. Poisson regression of misclassification error counts detected no difference in the Biovet FMIA and Hipra ELISA but significantly fewer misclassification errors than Idexx and Biocheck ELISAs. This study showed FMIA as a suitable alternative to traditional ELISAs for screening purposes due to its superior antibody detection rate at early stages. Alternatively, adopting a more stringent cutoff to improve diagnostic specificity could position the FMIA as a viable confirmatory test option. Overall, FMIA is an optimal choice for M. hyopneumoniae antibody surveillance testing, offering versatility in testing strategies (e.g., triplex FMIA M. hyopneumoniae/PRRSV types 1 and 2) and contributing to improved diagnostic capabilities in porcine health management.

Sensitivity of transferrin isoform analysis for PMM2-CDG.

Transferrin isoform analysis is an established laboratory test for congenital disorders of glycosylation (CDG). Despite its long history of clinical use, little has been published about its empirical sensitivity for specific conditions. We conducted a retrospective analysis of ten years of testing data and report our experience with transferrin testing for type I profiles and its sensitivity for the most common congenital disorder of glycosylation, PMM2-CDG. The data demonstrate 94% overall test sensitivity for PMM2-CDG and importantly demonstrate two known, recurrent variants enriched in false positive cases highlighting an important limitation of the test. The data confirm the clinical validity of transferrin isotype analysis as a screening test for disorders of protein N-linked glycosylation and as functional test for PMM2 genotypes of uncertain significance.

Influence of learning strategies and motivation on anatomy test performance of undergraduate medical students.

To learn and comprehend the large amount of information in gross anatomy, undergraduate students must self-regulate their learning to be properly prepared for the exams within the available time. Even though there are many studies on learning strategies and their influence on test results and motivation, the aim of this study is to investigate characteristics of learning strategies in detail and in relation to the anatomy course of first semester students and how their use is related to anatomy test performance. For assessing the learning strategies, we used the short version of the questionnaire "Learning Strategies of University Students" (LIST-K) (Klingsieck, 2018). Further, we investigated potential influences of motivation and resources used during the self-regulated learning process. The participants in this study (N = 108) filled in the above-mentioned questionnaire LIST-K and a written multiple-choice anatomy test. A k-means cluster analysis revealed three groups of students differing in their self-reported use of learning strategies. Students used either (1) predominantly metacognitive and resource-related strategies, (2) predominantly cognitive strategies, or (3) no specific learning strategies at all. We found no significant overall relationships between the use of learning strategies and test performance. A stepwise linear regression identified the use of cognitive learning strategies (ß =.269) as a significant predictor for test performance (R² =.149, p =.003), possibly as these specific learning strategies help with a systematic and effective approach while studying anatomy and retrieving large amount of memorized information. Further, motivation was identified as a negative predictor (ß = -.277), which might be a result of the short time periods students have to study for exams. Overall findings underline the importance of self-regulated learning as a positive predictor for academic performance. By understanding these factors, a more student-centered approach could be adopted by educators to improve medical education and equip students with valuable approaches for their continuous education, even beyond university.

Diagnostic test performance of the Mentzer index in evaluating Saudi children with microcytosis.

Background: Anemia is a global public health concern, affecting both developing and industrialized countries at a rate of 39.8%. It is defined by low hemoglobin concentration, and anemia varies in severity based on age: <11 g/dL (6-59 months), <11.5 g/dL (5-11 years), and < 12 g/dL (12-14 years). Aim: This study evaluates the Mentzer index's reliability in differentiating iron deficiency anemia from the thalassemia trait. Methods: A total of 434 children (≤16 years) with hemoglobin electrophoresis previously screened for microcytosis (MCV <80 FL) and an iron profile were included. Children with other hematological conditions were excluded. Results: Out of 434 children, 181 were diagnosed with thalassemia, and 345 had iron deficiency anemia. The Mentzer index showed 74% sensitivity and 63% specificity for the beta-thalassemia trait, with 61% sensitivity and 36% specificity for iron deficiency anemia. The beta-thalassemia trait group had the highest negative predictive value (98%), while iron deficiency anemia had the highest positive predictive value (79%). Conclusion: Our study, which is consistent with previous literature, suggests that the Mentzer index is not highly reliable in distinguishing iron deficiency anemia from the thalassemia trait among children in Saudi Arabia.

Introduction of a nationwide first-trimester anomaly scan in the Dutch national screening program.

BACKGROUND: A significant proportion of major fetal structural anomalies can be detected in the first trimester by ultrasound examination. However, the test performance of the first-trimester anomaly scan performed in a low-risk population as part of a nationwide prenatal screening program is unknown. Potential benefits of the first-trimester anomaly scan include early detection of fetal anomalies, providing parents with more time for reproductive decision-making. OBJECTIVE: To investigate the uptake, test performance, and time to a final prenatal diagnosis after referral. STUDY DESIGN: A nationwide implementation study was conducted in the Netherlands (November 2021-November 2022). The FTAS was performed between 12+3 and 14+3 weeks of gestation by certified sonographers using a standard protocol. Women were referred to a tertiary care center if anomalies were suspected. Uptake, test performance, and time to a final prenatal diagnosis (days between referral and date of final diagnosis/prognosis for reproductive decision-making) were determined. Test performance was calculated for first-trimester major congenital anomalies, such as anencephaly and holoprosencephaly and all diagnosed anomalies <24 weeks of gestation. RESULTS: The first-trimester anomaly scan uptake was 74.9% (129,704/173,129). In 1.0% (1313/129,704), an anomaly was suspected, of which 54.9% (n=721) had abnormal findings on the detailed first-trimester diagnostic scan and 44.6% (n=586) showed normal results. In 0.5% (n=6), intrauterine fetal death occurred. In the total group of 721 cases with abnormal findings, 332 structural anomalies, 117 genetic anomalies, 82 other findings (abnormal fetal biometry, sonomarkers, placental/umbilical cord anomaly, an-/oligohydramnios), and 189 cases with transient findings (defined as ultrasound findings which resolved <24 weeks of gestation) were found, with 1 case having an unknown outcome. 0.9% (n=1164) of all cases with a normal first-trimester anomaly scan were diagnosed with a fetal anomaly in the second trimester. Test performance included a sensitivity of 84.6% (126/149) for first-trimester major congenital anomalies and 31.6% (537/1701) for all types of anomalies. Specificity for all anomalies was 99.2% (98,055/98,830); positive predictive value 40.9% (537/1312); negative predictive value 98.8% (98,055/99,219); positive likelihood ratio 40.3; negative likelihood ratio 0.7; false positive rate 0.8% (775/98,830), and false negative rate 68.4% (1164/1701). The median time to diagnosis for structural anomalies was 20 days (6-43 days; median gestational age 16+3), for genetic anomalies 17 days (8.5-27.5 days; median gestational age 15+6 weeks), and for first-trimester major congenital anomalies 9 days (5-22 days; median gestational age 14+6 weeks). CONCLUSION: The performance of a newly introduced nationwide first-trimester anomaly scan in a low-risk population showed a high sensitivity for first-trimester major congenital anomalies and a lower sensitivity for all anomalies combined. The program was accompanied by a referral rate of 1.0%, of which 59.1% involved cases where anomalies were either not confirmed or resolved before 24 weeks gestation. Timing of diagnosis was around 16 weeks of gestation for referred cases. To evaluate the balance between benefits and potential harm of the first-trimester anomaly scan within a nationwide prenatal screening program, it is essential to assess the effectiveness of the program over time and to consider the perspectives of both women and their partners, as well as healthcare professionals.

External Quality Assessment (EQA) scheme for serological diagnostic test for SARS-CoV-2 detection in Sicily Region (Italy), in the period 2020-2022.

OBJECTIVES: Since December 2019, worldwide public health has been exposed to a severe acute respiratory syndrome caused by Coronavirus-2. Serological testing is necessary for retrospective assessment of seroprevalence rates, and the determination of vaccine response and duration of immunity. For this reason, it was necessary to introduce a panel of tests able to identify and quantify Covid-19 antibodies. METHODS: As a Regional Reference Centre, the CRQ Laboratory (Regional Laboratory for the Quality Control) developed and conducted an External Quality Assessment (EQA) panel of assays, to evaluate the quality of various methods, that were used by 288 Sicilian laboratories, previously authorized on behalf of the Public Health Service. RESULTS: The performance test was based on pooled samples with different levels of concentration of antibodies. 97 , 98, and 95 % of the participating laboratories tested all samples correctly in 2020, 2021, and 2022 respectively. The best performance was observed in the test of total Ig. The general performance of laboratories improved over the years. CONCLUSIONS: The incorrect diagnosis had and could still have important implications on vaccination cycles. Only through the effort of laboratory professionals, and the extension of the EQA scheme, a better harmonization of methods, protocols, and thus results, to guarantee a better healthcare system, will be possible.

Identification of Alcohol Use Prior to Major Cancer Surgery: Timeline Follow Back Interview Compared to Four Other Markers.

BACKGROUND: The postoperative complication rate is 30-64% among patients undergoing muscle-invasive and recurrent high-risk non-muscle-invasive bladder cancer surgery. Preoperative risky alcohol use increases the risk. The aim was to evaluate the accuracy of markers for identifying preoperative risky alcohol. METHODS: Diagnostic test sub-study of a randomized controlled trial (STOP-OP trial), based on a cohort of 94 patients scheduled for major bladder cancer surgery. Identification of risky alcohol use using Timeline Follow Back interviews (TLFB) were compared to the AUDIT-C questionnaire and three biomarkers: carbohydrate-deficient transferrin in plasma (P-CDT), phosphatidyl-ethanol in blood (B-PEth), and ethyl glucuronide in urine (U-EtG). RESULTS: The correlation between TLFB and AUDIT-C was strong (ρ = 0.75), while it was moderate between TLFB and the biomarkers (ρ = 0.55-0.65). Overall, sensitivity ranged from 56 to 82% and specificity from 38 to 100%. B-PEth showed the lowest sensitivity at 56%, but the highest specificity of 100%. All tests had high positive predictive values (79-100%), but low negative predictive values (42-55%). CONCLUSIONS: Despite high positive predictive values, negative predictive values were weak compared to TLFB. For now, TLFB interviews seem preferable for preoperative identification of risky alcohol use.

Factors that indicate performance on the MoCA 7.3 in healthy adults over 50 years old.

Human aging is a physiological, progressive, heterogeneous global process that causes a decline of all body systems, functions, and organs. Throughout this process, cognitive function suffers an incremental decline with broad interindividual variability.The first objective of this study was to examine the differences in the performance on the MoCA test (v. 7.3) per gender and the relationship between the performance and the variables age, years of schooling, and depressive symptoms .The second objective was to identify factors that may influence the global performance on the MoCA test (v. 7.3) and of the domains orientation, language, memory, attention/calculation, visuospatial and executive function, abstraction, and identification.A cross-sectional study was carried out in which five hundred seventy-three (573) cognitively healthy adults ≥ 50 years old were included in the study. A sociodemographic questionnaire, the GDS-15 questionnaire to assess depression symptoms and the Spanish version of the MoCA Test (v 7.3) were administered. The evaluations were carried out between the months of January and June 2022. Differences in the MoCA test performance per gender was assessed with Student's t-test for independent samples. The bivariate Pearson correlation was applied to examine the relationship between total scoring of the MoCA test performance and the variables age, years of schooling, and depressive symptoms. Different linear multiple regression analyses were performed to determine variables that could influence the MoCA test performance.We found gender-related MoCA Test performance differences. An association between age, years of schooling, and severity of depressive symptoms was observed. Age, years of schooling, and severity of depressive symptoms influence the MoCA Test performance, while gender does not.

An ELISA test using a circulating Mycobacterium bovis peptide for detecting bovine tuberculosis in dairy cattle.

This study aimed to determine the sensitivity (Se) and specificity (Sp) of a circulating pathogen-specific biomarker (polyketide synthetase 5, Pks5)-based enzyme-linked immunosorbent assay (ELISA) independently or in conjunction with a caudal fold tuberculin (CFT) test for bovine tuberculosis (bTB) screening in dairy cattle. We enrolled 987 dairy cows from 34 herds in Chiang Mai province, Thailand. A conditionally independent Bayesian model with a single population was inferred from the test results. The percentage of positive results for the Pks5-ELISA using 0.4 OD cutoff test and CFT test were 9.0% (89/987) and 10.5% (104/987), respectively. The median of posterior estimates of Se for the Pks5-ELISA test was 90.2% (95% posterior probability interval [PPI] = 76.6-97.4%), while the estimated Sp was slightly higher (median = 92.9, 95% PPI = 91.0-94.5%). The median estimated Se of the CFT test was 85.9% (95% PPI = 72.4-94.6%), while the estimated Sp was higher, with a median of 90.7% (95% PPI = 88.7-92.5%). The posterior estimate for true disease prevalence was 2.4% (95% PPI = 1.2-3.9%). The Pks5-ELISA test yielded characteristics at or above the acceptable standards for bTB detection. Therefore, the pathogen-specific biomarker, Pks5, is a potential detection system for bTB screening and may be applied as an ancillary test together with the currently applied standard method (CFT test) to reinforce the bTB control and eradication programs.

The performance of single and combination test strategies using visual inspection, cytology, high-risk HPV DNA and HPV16/18 to screen South African women with and without HIV-infection.

BACKGROUND: Cervical cancer screening strategies should ideally be informed by population-specific data. Strategies recommended for secondary prevention, are often inadequately studied in populations with high cervical disease burdens. This report describes the test performance measured against CIN2 + /CIN3 + histology in HIV-positive women (HPW) and HIV-negative women (HNW) with the aim to determine the most effective strategies to identify South African women at risk. METHODS: Primary screening using visual inspection, cytology and HPV DNA (cobas®) was performed in two South African provinces on 456 HPW and 639 HNW participating in the multicentric DiaVACCS trial. Histology was obtained for 91.7% screen-positive and 42.7% screen-negative participants, and unavailable histology was determined by multiple imputation to adjust for verification bias. Cross-sectional test performance was calculated for single and combination test strategies with and without intermediate risk categories using different cut-offs. Minimum acceptability for sensitivity and specificity, treatment and follow-up numbers were considered to evaluate strategies. RESULTS: The only single test to reach acceptability in HPW was cytology (LSIL) [sensitivity 71.2%; specificity 90.5%; treatment 33.4%]; in HNW only HPV (hr) qualified [sensitivity 68.2%; specificity 85.2%; treatment 23.5%]. The universally best performing strategy which also resulted in smaller treatment numbers without intermediate risk group was primary HPV(hr), with treatment of both HPV(16/18) and cytology (ASCUS +) [HPW: sensitivity 73.6%; specificity 89.7%; treatment 34.7%. HNW: sensitivity 59.1%; specificity 93.6%; treatment 13.9%]. DNA testing for hrHPV (any) and hrHPV (16/18) was the best universally acceptable strategy with an intermediate risk category (early follow-up) in HPW [sensitivity 82.1%; specificity 96.4%; treatment 17.1%; follow-up 31.4%] and HNW [sensitivity 68.2%; specificity 96.7%; treatment 7.6%; follow-up 15.9%]. In comparison, using both HPV (16/18) and cytology (ASCUS +) as secondary tests in hrHPV positive women, decreased follow-up [HPW 13.8%, HNW 9.6%], but increased treatment [HPW 34.7%, HNW 13.9%]. CONCLUSION: Using hrHPV (any) as primary and both HPV16/18 and cytology as secondary tests, was universally acceptable without an intermediate risk group. Strategies with follow-up groups improved screening performance with smaller treatment numbers, but with effective management of the intermediate risk group as prerequisite.

Technical and health governance aspects of the external quality assessment system for classical and new psychoactive substances analysis testing in blood.

New psychoactive substances (NPS) are uncontrolled analogues of existing drugs or newly synthesized chemicals that exhibit psychopharmacological effects. Due to their diverse nature, composition, and increasing prevalence, they present significant challenges to the healthcare system and drug control policies. In response, healthcare system laboratories have developed analytical methods to detect NPS in biological samples. As a Regional Reference Centre, the Sicilian CRQ Laboratory (Regional Laboratory for Quality Control) developed and conducted an External Quality Assessment (EQA) study to assess, in collaboration with the Istituto Superiore di Sanità (ISS), the ability of different Italian laboratories to identify NPS and traditional drugs of abuse (DOA) in biological matrices. Two blood samples were spiked with substances from various drug classes, including synthetic cannabinoids, cathinones, synthetic opiates, and benzodiazepines, at concentrations ranging from 2 to 10 ng/mL. The blood samples were freeze-dried to ensure the stability of DOA and NPS. Twenty-two laboratories from the Italian healthcare system participated in this assessment. The information provided by the laboratories during the registration in an in-house platform included a general description of the laboratory, analytical technique, and the chosen panels of analytes. The same platform was employed to collect and statistically analyze the data and record laboratory feedback and comments. The evaluation of the results revealed that the participating laboratories employed three different techniques for analyzing the samples: GC-MS, LC-MS, and immunoenzymatic methods. Approximately 90 % of the laboratories utilized LC-MS techniques. Around 40 % of false negative results were obtained, with the worst results in the identification of 5-chloro AB PINACA. The results showed that laboratories that used LC-MS methods obtained better specificity and sensitivity compared to the laboratories using other techniques. The results obtained from this first assessment underscore the importance of external quality control schemes in identifying the most effective analytical techniques for detecting trace molecules in biological matrices. Since the judicial authorities have not yet established cut-off values for NPS, this EQA will enable participating laboratories to share their analytical methods and expertise, aiming to establish common criteria for NPS identification.

Evaluation of a Revised Point-of-Care Test for the Detection of Feline Leukaemia p27 Antigen and Anti-p15E Antibodies in Cats.

The first point-of-care (PoC) test (v-RetroFel®; modified version 2021) determining the presence of FeLV p27 antigen and FeLV anti-p15E antibodies has become recently commercially available to identify different feline leukaemia virus (FeLV) infection outcomes. This study aimed to assess this PoC test's performance concerning FeLV p27 antigen and FeLV anti-p15E antibody detection. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were assessed after ten minutes (recommended) and 20 min (prolonged) incubation times. The test results were evaluated as either positive or negative. Serum samples from 934 cats were included, originating from Italy (n = 269), Portugal (n = 240), Germany (n = 318), and France (n = 107). FeLV p27 antigen and anti-p15E antibodies were measured by reference standard ELISAs and compared to the PoC test results. The PoC test was easy to perform and the results easy to interpret. Sensitivity and specificity for FeLV p27 antigen were 82.8% (PPV: 57.8%) and 96.0% (NPV: 98.8%) after both, ten and 20 minues of incubation time. Sensitivity and specificity for anti-p15E antibodies were 31.4% (PPV: 71.6%) and 96.9% (NPV: 85.1%) after ten minutes incubation time; sensitivity was improved by a prolonged incubation time (20 min) to 40.0% (PPV: 76.3%), while specificity remained the same (96.9%, NPV: 86.7%). Despite the improved sensitivity using the prolonged incubation time, lower than ideal sensitivities for both p27 antigen and especially anti-p15E antibodies were found, indicating that the PoC test in its current version needs further improvement prior to application in the field.

Comparing Polymerase Chain Reaction Testing of Nasopharyngeal Swab and Lower Respiratory Tract Specimens for the Diagnosis of Pneumocystis jirovecii Pneumonia.

Using nasopharyngeal (NP) swab samples instead of lower respiratory tract specimens for polymerase chain reaction (PCR) to diagnose Pneumocystis jirovecii pneumonia (PJP) may be better tolerated and improve diagnostic accessibility. In this 2-year Australian retrospective cohort study of patients with clinically suspected PJP, P jirovecii PCR on NP swab samples had perfect specificity but low sensitivity (0.66).

Positive predictive value of myositis antibody line blot testing in patients with suspected idiopathic inflammatory myopathy.

INTRODUCTION/AIMS: Line blot (LB) is in widespread use for myositis antibody detection. Yet, studies of its positive predictive value (PPV) in patients with suspected idiopathic inflammatory myopathy (IIM), which would be of particular relevance to neuromuscular clinicians, are lacking. We aimed to determine the PPV of myositis antibody LB testing in patients with suspected IIM, and examine whether PPV was significantly impacted by intensity of antibody positivity. METHODS: This was a retrospective study of patients who underwent myositis antibody LB testing for suspected IIM between March 2019 and August 2022. RESULTS: Of 70 patients who underwent testing for suspected IIM and had positive myositis antibody LB results, 43 (61%) were female and the median age was 61 years (range: 10-83 years). Forty-four were classified as true-positives, yielding a PPV of 63%. The PPV of patients with weak-positive myositis antibody results (14/30, 47%) was significantly lower than the PPV of patients with moderate-positive or strong-positive myositis antibody results (30/40, 75%) (p = .02). DISCUSSION: Our study found that myositis antibody LB testing in patients with suspected IIM had a modest PPV, underscoring the need for antibody interpretation in the context of all available clinical and ancillary test data to avoid misdiagnosis. The significantly lower PPV in patients with weak-positive results emphasizes the particular importance of clinical correlation in such patients. Further study into the diagnostic performance of various LBs for myositis antibody detection is needed to inform their interpretation in clinical practice.

Comparative methods for quantifying plasma biomarkers in Alzheimer's disease: Implications for the next frontier in cerebral amyloid angiopathy diagnostics.

Plasma amyloid beta (Aß) and tau are emerging as accessible biomarkers for Alzheimer's disease (AD). However, many assays exist with variable test performances, highlighting the need for a comparative assessment to identify the most valid assays for future use in AD and to apply to other settings in which the same biomarkers may be useful, namely, cerebral amyloid angiopathy (CAA). CAA is a progressive cerebrovascular disease characterized by deposition of Aß40 and Aß42 in cortical and leptomeningeal vessels. Novel immunotherapies for AD can induce amyloid-related imaging abnormalities resembling CAA-related inflammation. Few studies have evaluated plasma biomarkers in CAA. Identifying a CAA signature could facilitate diagnosis, prognosis, and a safer selection of patients with AD for emerging immunotherapies. This review evaluates studies that compare the diagnostic test performance of plasma biomarker techniques in AD and cerebrovascular and plasma biomarker profiles of CAA; it also discusses novel hypotheses and future avenues for plasma biomarker research in CAA.

The transition from Mild Cognitive Impairment of the Amnestic Type to early dementia: A phenomenological and neuropsychological case analysis.

The scientific literature on neuropsychological correlates of Mild Cognitive Impairment of the Amnestic Type (MCI-A) often reports large group findings and employs multivariate statistics to describe domains of cognitive impairment associated with the transition of MCI-A to early dementia, typically of the Alzheimer's Type (AD). Individual patients may vary, however, in terms of specific changes in their neuropsychological test performance as they transition from MCI-A to probable AD. The subjective experiences of individuals during this time of transition can also vary but rarely are reported. Tracking both the patient's subjective experiences and their performance on neuropsychological measures provides a more complete picture of the patient's clinical situation. These combined sets of information help the clinical neuropsychologist provide a more individualized and personally relevant service. We present a phenomenological and neuropsychological case analysis of a 67-year-old woman who transitioned from MCI-A to probable early AD in an attempt to illustrate how such a combined analysis is helpful in their psychological care.

The impact of different growth charts on birthweight prediction: obstetrical ultrasound vs magnetic resonance imaging.

BACKGROUND: The estimation of fetal weight by fetal magnetic resonance imaging is a simple and rapid method with a high sensitivity in predicting birthweight in comparison with ultrasound. Several national and international growth charts are currently in use, but there is substantial heterogeneity among these charts due to variations in the selected populations from which they were derived, in methodologies, and in statistical analysis of data. OBJECTIVE: This study aimed to compare the performance of magnetic resonance imaging and ultrasound for the prediction of birthweight using 3 commonly used fetal growth charts: the INTERGROWTH-21st Project, World Health Organization, and Fetal Medicine Foundation charts. STUDY DESIGN: Data derived from a prospective, single-center, blinded cohort study that compared the performance of magnetic resonance imaging and ultrasound between 36+0/7 and 36+6/7 weeks of gestation for the prediction of birthweight ≥95th percentile were reanalyzed. Estimated fetal weight was categorized as above or below the 5th, 10th, 90th, and 95th percentile according to the 3 growth charts. Birthweight was similarly categorized according to the birthweight standards of each chart. The performances of ultrasound and magnetic resonance imaging for the prediction of birthweight <5th, <10th, >90th, and >95th percentile using the different growth charts were compared. Data were analyzed with R software, version 4.1.2. The comparison of sensitivity and specificity was done using McNemar and exact binomial tests. P values <.05 were considered statistically significant. RESULTS: A total of 2378 women were eligible for final analysis. Ultrasound and magnetic resonance imaging were performed at a median gestational age of 36+3/7 weeks, delivery occurred at a median gestational age of 39+3/7 weeks, and median birthweight was 3380 g. The incidences of birthweight <5th and <10th percentiles were highest with the Fetal Medicine Foundation chart and lowest with the INTERGROWTH-21st chart, whereas the incidences of birthweight >90th and >95th percentiles were lowest with the Fetal Medicine Foundation chart and highest with the INTERGROWTH-21st chart. The sensitivity of magnetic resonance imaging with an estimated fetal weight >95th percentile in the prediction of birthweight >95th percentile was significantly higher than that of ultrasound across the 3 growth charts; however, its specificity was slightly lower than that of ultrasound. In contrast, the sensitivity of magnetic resonance imaging with an estimated fetal weight <10th percentile for predicting birthweight <10th percentile was significantly lower than that of ultrasound in the INTERGROWTH-21st and Fetal Medicine Foundation charts, whereas the specificity and positive predictive value of magnetic resonance imaging were significantly higher than those of ultrasound for all 3 charts. Findings for the prediction of birthweight >90th percentile were close to those of birthweight >95th percentile, and findings for the prediction of birthweight <5th percentile were close to those of birthweight <10th percentile. CONCLUSION: The sensitivity of magnetic resonance imaging is superior to that of ultrasound for the prediction of large for gestational age fetuses and inferior to that of ultrasound for the prediction of small for gestational age fetuses across the 3 different growth charts. The reverse is true for the specificity of magnetic resonance imaging in comparison with that of ultrasound.

Stool DNA testing for early detection of colorectal cancer: systematic review using the HTA Core Model® for Rapid Relative Effectiveness Assessment.

Background: Stool DNA testing for early detection of colorectal cancer (CRC) is a non-invasive technology with the potential to supplement established CRC screening tests. The aim of this health technology assessment was to evaluate effectiveness and safety of currently CE-marked stool DNA tests, compared to other CRC tests in CRC screening strategies in an asymptomatic screening population. Methods: The assessment was carried out following the guidelines of the European Network for Health Technology Assessment (EUnetHTA). This included a systematic literature search in MED-LINE, Cochrane and EMBASE in 2018. Manufacturers were asked to provide additional data. Five patient interviews helped assessing potential ethical or social aspects and patients' experiences and preferences. We assessed the risk of bias using QUADAS-2, and the quality of the body of evidence using GRADE. Results: We identified three test accuracy studies, two of which investigated a multitarget stool DNA test (Cologuard®, compared fecal immunochemical test (FIT)) and one a combined DNA stool assay (ColoAlert®, compared to guaiac-based fecal occult blood test (gFOBT), Pyruvate Kinase Isoenzyme Type M2 (M2-PK) and combined gFOBT/M2-PK). We found five published surveys on patient satisfaction. No primary study investigating screening effects on CRC incidence or on overall mortality was found. Both stool DNA tests showed in direct comparison higher sensitivity for the detection of CRC and (advanced) adenoma compared to FIT, or gFOBT, respectively, but had lower specificity. However, these comparative results may depend on the exact type of FIT used. The reported test failure rates were higher for stool DNA testing than for FIT. The certainty of evidence was moderate to high for Cologuard® studies, and low to very low for the ColoAlert® study which refers to a former version of the product and yielded no direct evidence on the test accuracy for ad-vanced versus non-advanced adenoma. Conclusions: ColoAlert® is the only stool DNA test currently sold in Europe and is available at a lower price than Cologuard®, but reliable evidence is lacking. A screening study including the current product version of ColoAlert® and suitable comparators would, therefore, help evaluate the effectiveness of this screening option in a European context.