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Archives of Pathology & Laboratory... Oct 2019Protein C (PC) deficiency is a heritable or acquired risk factor for thrombophilia, with presentations varying from asymptomatic to venous thromboembolism to neonatal... (Review)
Review
Protein C (PC) deficiency is a heritable or acquired risk factor for thrombophilia, with presentations varying from asymptomatic to venous thromboembolism to neonatal purpura fulminans, a life-threatening disorder. Hereditary PC deficiency is caused by mutation in the PC () gene located on chromosome 2q14.3. Heterozygous and acquired PC deficiencies are more common than homozygous deficiency. The recommended initial laboratory test measures PC activity using either clot-based or chromogenic methods. There are numerous potential interferences in PC activity testing that may result in either false-positive (falsely low activity) or false-negative (falsely normal or elevated activity) results. In the present review, we discuss common clinical presentations; laboratory testing, with a focus on potential assay interferences; treatment options; and prognosis in patients with PC deficiency.
Topics: Blood Coagulation Tests; Humans; Mutation; Protein C Deficiency; Purpura Fulminans; Thrombophilia; Venous Thromboembolism
PubMed: 30702334
DOI: 10.5858/arpa.2017-0403-RS -
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 -
CytoJournal 2021Effusion fluid cytology has propensity for both false positives (in up to 0.5%) and false negatives (in up to 30%) results. Methodical approach from collection step to... (Review)
Review
Effusion fluid cytology has propensity for both false positives (in up to 0.5%) and false negatives (in up to 30%) results. Methodical approach from collection step to final interpretation stage could prevent both false positives and false negatives, if the interpreter is familiar with various factors responsible for diagnostic pitfalls in effusion fluid cytology. For this discussion, these factors are categorized as mentioned below: Surface tension-related alterations in cytomorphologyImproper specimen processingMany faces of reactive mesothelial cells, overlapping with those of cancer cellsProliferation-related featuresDegenerative changes, such as nuclear hyperchromasia and cytoplasmic vacuolationUnexpected patterns and unusual entities.
PubMed: 35126611
DOI: 10.25259/CMAS_02_04_2021 -
Annals of Family Medicine 2015We undertook a study to assess whether women with false-positive mammography have worse psychosocial consequences if managed with a workup that involves a biopsy...
PURPOSE
We undertook a study to assess whether women with false-positive mammography have worse psychosocial consequences if managed with a workup that involves a biopsy (invasive group) than if managed with only additional imaging (noninvasive group).
METHODS
We performed subgroup analysis of a cohort study of 454 women with abnormal screening mammography and 908 matched control women with normal results. Using a condition-specific questionnaire (Consequences of Screening in Breast Cancer), we assessed 12 psychosocial consequences at 5 time points (0, 1, 6, 18, and 36 months after final diagnosis) and compared the 2 groups of women with false-positives (invasive and noninvasive management groups).
RESULTS
Among the 252 women with false-positive mammography eligible for this study, psychosocial consequences were similar for those managed invasively and those managed noninvasively during the 36 months of follow-up. In 60 comparisons (12 scales and 5 time points), differences between the groups were never statistically significant (P <.01) and the point estimates for the differences were always close to zero. The psychosocial consequences of women with false-positive results, regardless of management, fell between those of women with normal mammography and those of women determined to have breast cancer.
CONCLUSIONS
We found no evidence that use of more invasive diagnostics was associated with worse psychosocial consequences. It is therefore reasonable to pool subgroups of women with false-positives in a single analysis. The invasiveness of subsequent diagnostic procedures does not help to identify women at higher risk for adverse psychosocial consequences of false-positive mammography.
Topics: Aged; Biopsy, Fine-Needle; Breast Neoplasms; Cohort Studies; Early Detection of Cancer; False Positive Reactions; Female; Humans; Mammography; Mass Screening; Middle Aged; Stress, Psychological; Surveys and Questionnaires; Time Factors
PubMed: 25964402
DOI: 10.1370/afm.1762 -
BMJ Open Aug 2016Many published meta-analyses are underpowered. We explored the role of trial sequential analysis (TSA) in assessing the reliability of conclusions in underpowered... (Review)
Review
OBJECTIVE
Many published meta-analyses are underpowered. We explored the role of trial sequential analysis (TSA) in assessing the reliability of conclusions in underpowered meta-analyses.
METHODS
We screened The Cochrane Database of Systematic Reviews and selected 100 meta-analyses with a binary outcome, a negative result and sufficient power. We defined a negative result as one where the 95% CI for the effect included 1.00, a positive result as one where the 95% CI did not include 1.00, and sufficient power as the required information size for 80% power, 5% type 1 error, relative risk reduction of 10% or number needed to treat of 100, and control event proportion and heterogeneity taken from the included studies. We re-conducted the meta-analyses, using conventional cumulative techniques, to measure how many false positives would have occurred if these meta-analyses had been updated after each new trial. For each false positive, we performed TSA, using three different approaches.
RESULTS
We screened 4736 systematic reviews to find 100 meta-analyses that fulfilled our inclusion criteria. Using conventional cumulative meta-analysis, false positives were present in seven of the meta-analyses (7%, 95% CI 3% to 14%), occurring more than once in three. The total number of false positives was 14 and TSA prevented 13 of these (93%, 95% CI 68% to 98%). In a post hoc analysis, we found that Cochrane meta-analyses that are negative are 1.67 times more likely to be updated (95% CI 0.92 to 2.68) than those that are positive.
CONCLUSIONS
We found false positives in 7% (95% CI 3% to 14%) of the included meta-analyses. Owing to limitations of external validity and to the decreased likelihood of updating positive meta-analyses, the true proportion of false positives in meta-analysis is probably higher. TSA prevented 93% of the false positives (95% CI 68% to 98%).
Topics: Clinical Trials as Topic; Data Interpretation, Statistical; Humans; Meta-Analysis as Topic; Statistics as Topic
PubMed: 27519923
DOI: 10.1136/bmjopen-2016-011890 -
European Archives of... Oct 2023More studies exploring referral rates and false-positive rates are needed to make hearing screening programs in newborns better and cost-effective. Our aim was to study...
AIM
More studies exploring referral rates and false-positive rates are needed to make hearing screening programs in newborns better and cost-effective. Our aim was to study the referral and false-positivity rates among high-risk newborns in our hearing screening program and to analyze the factors potentially associated with false-positive hearing screening test results.
METHODS
A retrospective cohort study was done among the newborns hospitalized at a university hospital from January 2009 to December 2014 that underwent hearing screening with a two-staged AABR screening protocol. Referral rates and false-positivity rates were calculated and possible risk factors for false-positivity were analyzed.
RESULTS
4512 newborns were screened for hearing loss in the neonatology department. The referral rate for the two-staged AABR-only screening was 3.8% with false-positivity being 2.9%. Our study showed that the higher the birthweight or gestational age of the newborn, the lower the odds of the hearing screening results being false-positive, and the higher the chronological age of the infant at the time of screening, the higher the odds of the results being false-positive. Our study did not show a clear association between the mode of delivery or gender and false-positivity.
CONCLUSION
Among high-risk infants, prematurity and low-birthweight increased the rate of false-positivity in the hearing screening, and the chronological age at the time of the test seems to be significantly associated with false-positivity.
Topics: Infant; Infant, Newborn; Humans; Birth Weight; Neonatal Screening; Retrospective Studies; Evoked Potentials, Auditory, Brain Stem; Hearing; Referral and Consultation
PubMed: 37154942
DOI: 10.1007/s00405-023-07978-y -
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 -
Laboratory Investigation; a Journal of... Sep 2019The external validity of the scientific literature has recently come into question, popularly referred to as the "reproducibility crisis." It is now generally...
The external validity of the scientific literature has recently come into question, popularly referred to as the "reproducibility crisis." It is now generally acknowledged that too many false positive or non-reproducible results are being published throughout the biomedical and social science literature due to misaligned incentives and poor methodology. Pathology is likely no exception to this problem, and may be especially prone to false positives due to common observational methodologies used in our research. Spurious findings in pathology contribute inefficiency to the scientific literature and detrimentally influence patient care. In particular, false positives in pathology affect patients through biomarker development, prognostic classification, and cancer overdiagnosis. We discuss possible sources of non-reproducible pathology studies and describe practical ways our field can improve research habits, especially among trainees.
Topics: False Positive Reactions; Humans; Medical Overuse; Pathologists; Pathology; Reproducibility of Results
PubMed: 31019290
DOI: 10.1038/s41374-019-0257-2 -
Microbial Genomics Aug 2021Minimizing false positives is a critical issue when variant calling as no method is without error. It is common practice to post-process a variant-call file (VCF) using...
Minimizing false positives is a critical issue when variant calling as no method is without error. It is common practice to post-process a variant-call file (VCF) using hard filter criteria intended to discriminate true-positive (TP) from false-positive (FP) calls. These are applied on the simple principle that certain characteristics are disproportionately represented among the set of FP calls and that a user-chosen threshold can maximize the number detected. To provide guidance on this issue, this study empirically characterized all false SNP and indel calls made using real Illumina sequencing data from six disparate species and 166 variant-calling pipelines (the combination of 14 read aligners with up to 13 different variant callers, plus four 'all-in-one' pipelines). We did not seek to optimize filter thresholds but instead to draw attention to those filters of greatest efficacy and the pipelines to which they may most usefully be applied. In this respect, this study acts as a coda to our previous benchmarking evaluation of bacterial variant callers, and provides general recommendations for effective practice. The results suggest that, of the pipelines analysed in this study, the most straightforward way of minimizing false positives would simply be to use Snippy. We also find that a disproportionate number of false calls, irrespective of the variant-calling pipeline, are located in the vicinity of indels, and highlight this as an issue for future development.
Topics: Bacteria; Bacteriological Techniques; Computational Biology; False Positive Reactions; High-Throughput Nucleotide Sequencing; Polymorphism, Single Nucleotide
PubMed: 34346861
DOI: 10.1099/mgen.0.000615