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Expert Review of Clinical Pharmacology May 2023Immunoassay urine drug screen (UDS) is frequently used in clinical practice for initial screening process, being generally available, fast, and inexpensive. Exposure to... (Review)
Review
INTRODUCTION
Immunoassay urine drug screen (UDS) is frequently used in clinical practice for initial screening process, being generally available, fast, and inexpensive. Exposure to widely prescribed drugs might determine false-positive UDS amphetamines, leading to diagnostic issues, wrong therapeutic choices, impairment of physician-patient relationship, and legal implications.
AREAS COVERED
To summarize and comment on a comprehensive list of compounds responsible for UDS false positives for amphetamines, we conducted a literature review on PubMed along with a comparison with Real-World Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database analysis between 2010 and 2022. Forty-four articles and 125 Individual Case Safety Reports (ICSR) involving false-positive amphetamine UDS in psychiatric patients were retrieved from FAERS.
EXPERT OPINION
False-positive results were described in literature for antidepressants, atomoxetine, methylphenidate, and antipsychotics, but also for non-psychiatric drugs of common use, such as labetalol, fenofibrate, and metformin. Immunoassay method is usually responsible for false-positive results, and in most cases, mass spectrometry (MS) does not eventually confirm the UDS positivity. Physicians should be aware of immunoassays' limitations and when turning to a confirmatory test. Any new cross-reaction should be reported to pharmacovigilance activities.
Topics: United States; Humans; Pharmacovigilance; United States Food and Drug Administration; Substance Abuse Detection; Amphetamines; Immunoassay
PubMed: 37147189
DOI: 10.1080/17512433.2023.2211261 -
Annals of the Rheumatic Diseases Jun 2021Lack of effective biomarkers in anti-citrullinated protein antibody (ACPA)-negative rheumatoid arthritis (RA) impedes early diagnosis and treatment. This study aimed to...
OBJECTIVES
Lack of effective biomarkers in anti-citrullinated protein antibody (ACPA)-negative rheumatoid arthritis (RA) impedes early diagnosis and treatment. This study aimed to identify novel autoantibodies in RA and verify their diagnostic values in ACPA-negative RA based on protein microarray technology.
METHODS
A total of 1011 sera from 559 RA (276 ACPA-positive and 283 ACPA-negative), 239 disease controls (DCs) and 213 healthy controls (HCs) were collected and sampled on two sequential microarrays and ELISA and western blot (WB) detection, for novel autoantibodies discovery, validation and verification, respectively. The high-density protein microarray printed with a broad spectrum of recombinant human proteins was first employed to screen candidate autoantibodies, then focused microarrays composed of candidate autoantigens were used for validation, followed by ELISA and WB to verify the presence of the most promising candidates in ACPA-negative RA.
RESULTS
Nine novel autoantibodies were identified by two sequential microarrays with positivity 17.93%-27.59% and specificities >90% in ACPA-negative RA. Among these, anti-PTX3 and anti-DUSP11 autoantibodies presented with the highest sensitivity and were consistently verified by ELISA and WB. Pooling samples of all cohorts, the positivities of anti-PTX3 and anti-DUSP11 in ACPA-negative RA were 27.56% and 31.80%, respectively, similar to those in ACPA-positive RA, and significantly higher than in HCs (4.69% and 2.35%) and DCs (10.04% and 8.49%) (p<0.0001). Combination of anti-PTX3 with anti-DUSP11 significantly increased the diagnostic sensitivity (38.00%) with specificity of 88.72%, regardless of ACPA status.
CONCLUSION
Anti-PTX3 and anti-DUSP11 autoantibodies are newly identified biomarkers for diagnosis of ACPA-negative RA.
Topics: Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Biomarkers; Humans; Peptides, Cyclic
PubMed: 33452006
DOI: 10.1136/annrheumdis-2020-218460 -
Psychonomic Bulletin & Review Oct 2022A fundamental goal of scientific research is to generate true positives (i.e., authentic discoveries). Statistically, a true positive is a significant finding for which... (Review)
Review
A fundamental goal of scientific research is to generate true positives (i.e., authentic discoveries). Statistically, a true positive is a significant finding for which the underlying effect size (δ) is greater than 0, whereas a false positive is a significant finding for which δ equals 0. However, the null hypothesis of no difference (δ = 0) may never be strictly true because innumerable nuisance factors can introduce small effects for theoretically uninteresting reasons. If δ never equals zero, then with sufficient power, every experiment would yield a significant result. Yet running studies with higher power by increasing sample size (N) is one of the most widely agreed upon reforms to increase replicability. Moreover, and perhaps not surprisingly, the idea that psychology should attach greater value to small effect sizes is gaining currency. Increasing N without limit makes sense for purely measurement-focused research, where the magnitude of δ itself is of interest, but it makes less sense for theory-focused research, where the truth status of the theory under investigation is of interest. Increasing power to enhance replicability will increase true positives at the level of the effect size (statistical true positives) while increasing false positives at the level of theory (theoretical false positives). With too much power, the cumulative foundation of psychological science would consist largely of nuisance effects masquerading as theoretically important discoveries. Positive predictive value at the level of theory is maximized by using an optimal N, one that is neither too small nor too large.
Topics: Humans; Sample Size
PubMed: 35501547
DOI: 10.3758/s13423-022-02098-w -
Papillomavirus Research (Amsterdam,... Jun 2019In cervical cancer screening, HPV testing is best at reassuring women when they are negative, but proper management of HPV positives is still evolving. Most HPV...
In cervical cancer screening, HPV testing is best at reassuring women when they are negative, but proper management of HPV positives is still evolving. Most HPV infections are benign, and over-reacting clinically to HPV positivity can cause psychological and possible iatrogenic physical (e.g., obstetrical) harm. We describe the built-in false positives in current tests, and the real harm that can result when the meaning of such false positive HPV tests is misunderstood. We suggest steps that could reduce harm being done by flawed tests and excessive clinical responses to positive HPV testing. We focus the discussion by presenting an illustrative case.
Topics: Early Detection of Cancer; False Positive Reactions; Female; Humans; Molecular Diagnostic Techniques; Papillomaviridae; Uterine Cervical Neoplasms
PubMed: 31029852
DOI: 10.1016/j.pvr.2019.04.012 -
Frontiers in Immunology 2023Purkinje cytoplasmic autoantibody type 1 (PCA-1)/anti-Yo autoimmunity is a common high-risk paraneoplastic neurological disorder, traditionally attributed antigenically...
BACKGROUND
Purkinje cytoplasmic autoantibody type 1 (PCA-1)/anti-Yo autoimmunity is a common high-risk paraneoplastic neurological disorder, traditionally attributed antigenically to cerebellar degeneration-related protein 2 (CDR2), predominantly affecting women with gynecologic or breast adenocarcinoma. Single-modality CDR2 testing may produce false-positive results. We assessed the performance characteristics of the more recently purported major PCA-1/Yo antigen, CDR2-like (CDR2L), side by side with CDR2, in a line blot format.
METHODS
CDR2 and CDR2L were tested in six specimen groups (serum and cerebrospinal fluid (CSF)). Group 1, PCA-1/Yo mouse brain indirect immunofluorescence assay (IFA) positives; Group 2, PCA-1/Yo IFA mimics; Group 3, suspected CDR2 line blot false positives; Group 4, consecutive patient samples tested for neural antibodies over 1 year; Group 5, healthy subject serums; and Group 6, polyclonal (non-specific) immunoglobulin G (IgG)-positive serums.
RESULTS
Group 1: Of 64 samples tested, all but two were CDR2 positive (both CSF samples) and all were CDR2L positive. In individual patients, CDR2L values were always higher than CDR2. The two "CDR2L-only" positives were CSF samples with low titer PCA-1/Yo by IFA with serum negativity but with typical clinical phenotype. Group 2: All 51 PCA-1/Yo mimics were CDR2/CDR2L negative. Group 3: Nine samples [six of 1289 (0.47%) serums and three of 700 CSF samples (0.43%) were PCA-1/Yo IFA negative/CDR2 positive; two of the six available (serums from the same patient) were also CDR2L positive; the other four CDR2L negative had low CDR2 values (17-22). Group 4: Twenty-two patients had unexpected CDR2 or CDR2L positivity; none had tissue IFA positivity. Eleven of the 2,132 serum (0.5%) and three of the 677 CSF (0.4%) samples were CDR2 positive; median value was 19 (range, 11-48). Seven of the 2,132 serum (0.3%) and three of the 677 CSF (0.4%) samples were CDR2L positive; median value was 18 (range, 11-96). Group 5: All 151 healthy serum samples were negative. Group 6: One of the 46 polyclonal serum samples was CDR2L positive. Optimum overall performance was accomplished by requiring both CDR2 and CDR2L positivity in serum (sensitivity, 100%; and specificity, 99.9%) and positivity for CDR2L in CSF (sensitivity, 100%; and specificity, 99.6%).
CONCLUSION
CDR2L provides additional PCA-1/anti-Yo sensitivity in CSF, and dual positivity with CDR2 provides additional specificity assurance in serum. Combining antigen-specific and tissue-based assays optimizes PCA-1/anti-Yo testing.
Topics: Animals; Mice; Humans; Female; Autoantibodies; Autoimmunity; Paraneoplastic Cerebellar Degeneration; Nerve Tissue Proteins; Cytoplasm; Neurodegenerative Diseases
PubMed: 37841252
DOI: 10.3389/fimmu.2023.1265797 -
Parkinsonism & Related Disorders May 2022Corticobasal degeneration (CBD) is the most common neuropathological substrate for clinically diagnosed corticobasal syndrome (CBS), while identifying CBD pathology in...
INTRODUCTION
Corticobasal degeneration (CBD) is the most common neuropathological substrate for clinically diagnosed corticobasal syndrome (CBS), while identifying CBD pathology in living individuals has been challenging. This study aimed to examine the capability of positron emission tomography (PET) to detect CBD-type tau depositions and neuropathological classification of CBS.
METHODS
Sixteen CBS cases diagnosed by Cambridge's criteria and 12 cognitively healthy controls (HCs) underwent PET scans with C-PiB, C-PBB3, and F-FDG, along with T1-weighted magnetic resonance imaging. Amyloid positivity was assessed by visual inspection of C-PiB retentions. Tau positivity was judged by quantitative comparisons of C-PBB3 binding to HCs.
RESULTS
Sixteen CBS cases consisted of two cases (13%) with amyloid and tau positivities indicative of Alzheimer's disease (AD) pathologies, 11 cases (69%) with amyloid negativity and tau positivity, and three cases (19%) with amyloid and tau negativities. Amyloid(-), tau(+) CBS cases showed increased retentions of C-PBB3 in the frontoparietal areas, basal ganglia, and midbrain, and reduced metabolism in the precentral gyrus and thalamus relative to HCs. The enhanced tau probe retentions in the frontal gray and white matters partially overlapped with metabolic deficits and atrophy and correlated with Clinical Dementia Rating scores.
CONCLUSIONS
PET-based classification of CBS was in accordance with previous neuropathological reports on the prevalences of AD, non-AD tauopathies, and others in CBS. The current work suggests that C-PBB3-PET may assist the biological classification of CBS and understanding of links between CBD-type tau depositions and neuronal deteriorations leading to cognitive declines.
Topics: Alzheimer Disease; Corticobasal Degeneration; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography; tau Proteins
PubMed: 35533530
DOI: 10.1016/j.parkreldis.2022.04.015 -
PloS One 2022The purpose of this study was to analyse whether contextual (perception of motivational climate and positive and negative spontaneous self-talk in sports), personal...
The purpose of this study was to analyse whether contextual (perception of motivational climate and positive and negative spontaneous self-talk in sports), personal (positivity) and situational variables (positive and negative spontaneous self-talk employed in competition and precompetitive anxiety) predict performance in a competition of ensembles of rhythmic gymnastics. 258 female gymnasts between ages14 and 20 (M = 15.24, SD = 1.46) participated in the study, completing pre- and post-competition measures. The results of the path-analysis showed that both the task-involving climate and positivity predicted positive self-talk in sport. This predicted self-confidence which, in turn, positively predicted positive situational self-talk in competition. For its part, the perception of an ego-involving climate positively predicted the use of both negative and positive self-talk in sport. Negative self-talk in sports predicted negative situational self-talk in competition and somatic and cognitive anxiety. In turn, cognitive anxiety positively predicted negative situational self-talk. Finally, performance was positively predicted by positive situational self-talk and negatively by negative situational self-talk. These results explain the functioning of spontaneous self-talk at different levels of generality and its relationship with sports performance.
Topics: Anxiety; Athletic Performance; Female; Gymnastics; Humans; Male; Motivation; Self Concept
PubMed: 35325003
DOI: 10.1371/journal.pone.0265809 -
Frontiers in Psychology 2021Positive emotions are linked to numerous benefits, but not everyone appreciates the same kinds of positive emotional experiences. We examine how distinct positive...
Positive emotions are linked to numerous benefits, but not everyone appreciates the same kinds of positive emotional experiences. We examine how distinct positive emotions are perceived and whether individuals' perceptions are linked to how societies evaluate those emotions. Participants from Hong Kong and Netherlands rated 23 positive emotions based on their individual perceptions (positivity, arousal, and socially engaging) and societal evaluations (appropriate, valued, and approved of). We found that (1) there were cultural differences in judgments about all six aspects of positive emotions; (2) positivity, arousal, and social engagement predicted emotions being positively regarded at the societal level in both cultures; and (3) that positivity mattered more for the Dutch participants, although arousal and social engagement mattered more in Hong Kong for societal evaluations. These findings provide a granular map of the perception and evaluation of distinct positive emotions in two cultures and highlight the role of cultures in the understanding how positive emotions are perceived and evaluated.
PubMed: 34122207
DOI: 10.3389/fpsyg.2021.579474 -
Microbiology Spectrum Jun 2022The BacT/Alert system has been used for detecting the presence of bacteria in various clinical settings as well as in blood services, but it is associated with a...
The BacT/Alert system has been used for detecting the presence of bacteria in various clinical settings as well as in blood services, but it is associated with a relatively high incidence of false-positive results. We analyzed the results of our quality control sterility testing of blood products by BacT/Alert 3D to understand the mechanism of false-positive results. Anaerobic and aerobic bottles were inoculated with 10 mL of samples and cultured in BacT/Alert 3D for 10 days. Positive-reaction cases were classified as true positive if any bacterium was identified or false positive if the identification test had a negative result. The detection algorithm and the bottle graph pattern of the positive reaction cases were investigated. Among the 43,374 samples, 25 true positives (0.06%) and 29 false positives (0.07%) were observed. Although the detection algorithm of all true positives and 25 of 29 false positives was accelerating production of CO, a steep rise in the bottle graph was observed only in the true positives, and it was not observed in either of the false positives. Four of 29 false positives were dependent on high baseline scatter reflections. Furthermore, evaluating the bottle graph pattern of Streptococcus pneumoniae, a bacterium known to autolyze, we confirmed that no viable bacterium was detected even if a steep rise was observed. In conclusion, the bottle graph pattern of positive reactions allows the differentiation between true positives and false positives. In case of a steep rise without bacterium detection, the bacterium might have autolyzed. Moreover, positive reactions with high baseline scatter reflections, despite immediate loading of bottles after sampling, are potentially false positive. In clinical settings, false-positive results are treated as positive until bacterial identification. It may result in the discarding of blood products in blood centers or affect clinical decisions in hospitals or testing facilities. Moreover, the management of these samples is usually time- and labor-consuming. The results of our study may help clinicians and laboratory staff in making a more precise evaluation of positive reactions in BacT/Alert.
Topics: Bacteria; Bacteriological Techniques; Humans
PubMed: 35467361
DOI: 10.1128/spectrum.00055-22 -
Journal of Affective Disorders Nov 2016Bipolar disorder (BD) is a public health issue; it is one of the leading causes of disability and its late diagnosis heightens the impact of the condition. Screening... (Review)
Review
INTRODUCTION
Bipolar disorder (BD) is a public health issue; it is one of the leading causes of disability and its late diagnosis heightens the impact of the condition. Screening tools for early detection could be extremely useful.
METHODS
Narrative review on screening of BD.
RESULTS
Screening questionnaires have high sensitivity but relatively low specificity if DSM diagnoses are taken as the "gold standard". Critics maintain that an excess of false positives makes such tools unnecessary for identifying cases and of little use in screening studies consisting of two phases. However, "positive" screening was frequently homogeneous with BD in terms of gender, age, level of distress, low social functioning and employment rate, comorbidity with alcohol and substance abuse, heavy recourse to health care, use of mood stabilizers and antidepressants, risk of suicide attempts, and high recurrence of depressive episodes. While none of these components is pathognomonic of BD, their co-occurrence could identify subthreshold "cases". The studies reviewed found positivity at screening to be associated with impaired quality of life, even without BD and independently of comorbidity. Patients with a neurological disease and positive at screening show homogenous brain lesions, different from those of patients screening negative.
CONCLUSIONS
The results are coherent with the hypothesis that positivity identifies a bipolar spectrum of clinical and public health interest, including sub-threshold bipolar cases, which do not fulfil the diagnostic criteria for BD.
Topics: Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Humans; Mass Screening; Public Health; Surveys and Questionnaires
PubMed: 27442457
DOI: 10.1016/j.jad.2016.03.072