A Decision-Analytic Approach to Addressing the Evidence About Football and Chronic Traumatic Encephalopathy

2019 ◽  
Vol 40 (04) ◽  
pp. 450-460
Author(s):  
Kevin P. Brand ◽  
Adam M. Finkel
Keyword(s):  
Public Health ◽  
Chronic Traumatic Encephalopathy ◽  
Health Effect ◽  
False Negative ◽  
Weight Of Evidence ◽  
False Negatives ◽  
Head Impacts ◽  
Alternative Hypotheses ◽  
Research Questions ◽  
Logical Fallacies

AbstractDoubts can be raised about almost any assertion that a particular exposure can lead to an increase in a given adverse health effect. Even some of the most well-accepted causal associations in public health, such as that linking cigarette smoking to increased lung cancer risk, have intriguing research questions remaining to be answered. The inquiry whether an exposure causes a disease is never wholly a yes/no question but ought to follow from an appraisal of the weight of evidence supporting the positive conclusion in light of any coherent theories casting doubt on this evidence and the data supporting these. More importantly, such an appraisal cannot be made sensibly without considering the relative consequences to public health and economic welfare of specific actions based on unwarranted credulity (false positives) versus unwarranted skepticism (false negatives). Here we appraise the weight of evidence for the premise that repeated head impacts (RHIs) in professional football can increase the incidence of chronic traumatic encephalopathy (CTE) and, in turn, cause a variety of cognitive and behavioral symptoms. We first dismiss four logical fallacies that should not affect the appraisal of the weight of evidence. We then examine four alternative hypotheses in which RHI is not associated with CTE or symptoms (or both), and we conclude that the chances are small that the RHI→ CTE→ symptoms link is coincidental or artifactual. In particular, we observe that there are many specific interventions for which, even under a skeptical appraisal of the weight of evidence, the costs of a false positive are smaller than the false negative costs of refusing to intervene.

Clinically Meaningful Change

Methodology ◽  
2019 ◽  
Vol 15 (3) ◽  
pp. 97-105
Author(s):  
Rodrigo Ferrer ◽  
Antonio Pardo
Keyword(s):  
Effect Size ◽  
False Negative ◽  
False Negative Rate ◽  
Point Of View ◽  
Skewed Distribution ◽  
Effect Sizes ◽  
False Negatives ◽  
Large Size ◽  
Before And After ◽  
Post Test

Abstract. In a recent paper, Ferrer and Pardo (2014) tested several distribution-based methods designed to assess when test scores obtained before and after an intervention reflect a statistically reliable change. However, we still do not know how these methods perform from the point of view of false negatives. For this purpose, we have simulated change scenarios (different effect sizes in a pre-post-test design) with distributions of different shapes and with different sample sizes. For each simulated scenario, we generated 1,000 samples. In each sample, we recorded the false-negative rate of the five distribution-based methods with the best performance from the point of view of the false positives. Our results have revealed unacceptable rates of false negatives even with effects of very large size, starting from 31.8% in an optimistic scenario (effect size of 2.0 and a normal distribution) to 99.9% in the worst scenario (effect size of 0.2 and a highly skewed distribution). Therefore, our results suggest that the widely used distribution-based methods must be applied with caution in a clinical context, because they need huge effect sizes to detect a true change. However, we made some considerations regarding the effect size and the cut-off points commonly used which allow us to be more precise in our estimates.

scholarly journals No evidence of false-negative Plasmodium falciparum rapid diagnostic results in Monrovia, Liberia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mandella King ◽  
Alexander E. George ◽  
Pau Cisteró ◽  
Christine K. Tarr-Attia ◽  
Beatriz Arregui ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
False Negative ◽  
Malaria Diagnosis ◽  
Rapid Diagnostic Tests ◽  
Molecular Testing ◽  
False Negatives ◽  
Gene Deletions ◽  
History Of ◽  
Catholic Hospital ◽  
Or History

Abstract Background Malaria diagnosis in many malaria-endemic countries relies mainly on the use of rapid diagnostic tests (RDTs). The majority of commercial RDTs used in Africa detect the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). pfhrp2/3 gene deletions can therefore lead to false-negative RDT results. This study aimed to evaluate the frequency of PCR-confirmed, false-negative P. falciparum RDT results in Monrovia, Liberia. Methods PfHRP2-based RDT (Paracheck Pf®) and microscopy results from 1038 individuals with fever or history of fever (n = 951) and pregnant women at first antenatal care (ANC) visit (n = 87) enrolled in the Saint Joseph’s Catholic Hospital (Monrovia) from March to July 2019 were used to assess the frequency of false-negative RDT results. True–false negatives were confirmed by detecting the presence of P. falciparum DNA by quantitative PCR in samples from individuals with discrepant RDT and microscopy results. Samples that were positive by 18S rRNA qPCR but negative by PfHRP2-RDT were subjected to multiplex qPCR assay for detection of pfhrp2 and pfhrp3. Results One-hundred and eighty-six (19.6%) and 200 (21.0%) of the 951 febrile participants had a P. falciparum-positive result by RDT and microscopy, respectively. Positivity rate increased with age and the reporting of joint pain, chills and shivers, vomiting and weakness, and decreased with the presence of coughs and nausea. The positivity rate at first ANC visit was 5.7% (n = 5) and 8% (n = 7) by RDT and microscopy, respectively. Out of 207 Plasmodium infections detected by microscopy, 22 (11%) were negative by RDT. qPCR confirmed absence of P. falciparum DNA in the 16 RDT-negative but microscopy-positive samples which were available for molecular testing. Among the 14 samples that were positive by qPCR but negative by RDT and microscopy, 3 only amplified pfldh, and among these 3 all were positive for pfhrp2 and pfhrp3. Conclusion There is no qPCR-confirmed evidence of false-negative RDT results due to pfhrp2/pfhrp3 deletions in this study conducted in Monrovia (Liberia). This indicates that these deletions are not expected to affect the performance of PfHRP2-based RDTs for the diagnosis of malaria in Liberia. Nevertheless, active surveillance for the emergence of PfHRP2 deletions is required.

scholarly journals Testing Segmentation Popular Loss and Variations in Three Multiclass Medical Imaging Problems

2021 ◽  
Vol 7 (2) ◽  
pp. 16
Author(s):  
Pedro Furtado
Keyword(s):  
False Negative ◽  
Magnetic Resonance Images ◽  
Medical Image Segmentation ◽  
Cross Entropy ◽  
Loss Functions ◽  
Optic Disk ◽  
False Negatives ◽  
Convolutional Network ◽  
Percentage Points ◽  
Class Background

Image structures are segmented automatically using deep learning (DL) for analysis and processing. The three most popular base loss functions are cross entropy (crossE), intersect-over-the-union (IoU), and dice. Which should be used, is it useful to consider simple variations, such as modifying formula coefficients? How do characteristics of different image structures influence scores? Taking three different medical image segmentation problems (segmentation of organs in magnetic resonance images (MRI), liver in computer tomography images (CT) and diabetic retinopathy lesions in eye fundus images (EFI)), we quantify loss functions and variations, as well as segmentation scores of different targets. We first describe the limitations of metrics, since loss is a metric, then we describe and test alternatives. Experimentally, we observed that DeeplabV3 outperforms UNet and fully convolutional network (FCN) in all datasets. Dice scored 1 to 6 percentage points (pp) higher than cross entropy over all datasets, IoU improved 0 to 3 pp. Varying formula coefficients improved scores, but the best choices depend on the dataset: compared to crossE, different false positive vs. false negative weights improved MRI by 12 pp, and assigning zero weight to background improved EFI by 6 pp. Multiclass segmentation scored higher than n-uniclass segmentation in MRI by 8 pp. EFI lesions score low compared to more constant structures (e.g., optic disk or even organs), but loss modifications improve those scores significantly 6 to 9 pp. Our conclusions are that dice is best, it is worth assigning 0 weight to class background and to test different weights on false positives and false negatives.

Engaging Undergraduate Public Health Students Through a Textbook Creation Project

2020 ◽  
pp. 237337992096241
Author(s):  
Jessica Sloan Kruger ◽  
Christopher Hollister
Keyword(s):  
Public Health ◽  
Future Research ◽  
Open Educational Resource ◽  
Educational Resource ◽  
Final Version ◽  
Primary Motivation ◽  
Course Content ◽  
Health Course ◽  
Research Questions ◽  
Undergraduate Public Health

This study examines students’ perceptions of an open pedagogy experiment in which they created their own textbook for an undergraduate public health course. The lead author’s primary motivation for developing this assignment was the high cost associated with the traditional textbooks that were otherwise needed to cover the breadth of subject matter in the course. The resulting open textbook included 19 chapters, covering all the required components of the course, and the final version was published in a statewide open educational resource repository. Students provided feedback about this undertaking by way of an end-of-term survey. The results showed high percentages of students who associated the textbook creation project with greater engagement and satisfaction than the passive use of traditional textbooks. Students also reported their perception of a learning benefit related to the creation of course content. Pedagogical implications of this study are discussed, and future research questions are proposed.

scholarly journals Characteristics of patients who had a stroke not initially identified during emergency prehospital assessment: a systematic review

2021 ◽  
pp. emermed-2020-209607
Author(s):  
Stephanie P Jones ◽  
Janet E Bray ◽  
Josephine ME Gibson ◽  
Graham McClelland ◽  
Colette Miller ◽  
...  
Keyword(s):  
Systematic Review ◽  
Diagnostic Accuracy ◽  
False Negative ◽  
Visual Disturbance ◽  
Screening Tools ◽  
False Negatives ◽  
Presenting Symptoms ◽  
Ischaemic Attack ◽  
Stroke Type ◽  
Key Terms

BackgroundAround 25% of patients who had a stroke do not present with typical ‘face, arm, speech’ symptoms at onset, and are challenging for emergency medical services (EMS) to identify. The aim of this systematic review was to identify the characteristics of acute stroke presentations associated with inaccurate EMS identification (false negatives).MethodWe performed a systematic search of MEDLINE, EMBASE, CINAHL and PubMed from 1995 to August 2020 using key terms: stroke, EMS, paramedics, identification and assessment. Studies included: patients who had a stroke or patient records; ≥18 years; any stroke type; prehospital assessment undertaken by health professionals including paramedics or technicians; data reported on prehospital diagnostic accuracy and/or presenting symptoms. Data were extracted and study quality assessed by two researchers using the Quality Assessment of Diagnostic Accuracy Studies V.2 tool.ResultsOf 845 studies initially identified, 21 observational studies met the inclusion criteria. Of the 6934 stroke and Transient Ischaemic Attack patients included, there were 1774 (26%) false negative patients (range from 4 (2%) to 247 (52%)). Commonly documented symptoms in false negative cases were speech problems (n=107; 13%–28%), nausea/vomiting (n=94; 8%–38%), dizziness (n=86; 23%–27%), changes in mental status (n=51; 8%–25%) and visual disturbance/impairment (n=43; 13%–28%).ConclusionSpeech problems and posterior circulation symptoms were the most commonly documented symptoms among stroke presentations that were not correctly identified by EMS (false negatives). However, the addition of further symptoms to stroke screening tools requires valuation of subsequent sensitivity and specificity, training needs and possible overuse of high priority resources.

scholarly journals Validity of negative bone biopsy in suspicious bone lesions

2021 ◽  
Vol 10 (7) ◽  
pp. 205846012110306
Author(s):  
Mine B Lange ◽  
Lars J Petersen ◽  
Michael B Nielsen ◽  
Helle D Zacho
Keyword(s):  
Bone Biopsy ◽  
False Negative ◽  
Exclusion Criterion ◽  
Bone Lesions ◽  
False Negatives ◽  
Patient Morbidity ◽  
Bone Biopsies ◽  
Initial Biopsy ◽  
Valid Criterion

Background The presence of malignant cells in bone biopsies is considered gold standard to verify occurrence of cancer, whereas a negative bone biopsy can represent a false negative, with a risk of increasing patient morbidity and mortality and creating misleading conclusions in cancer research. However, a paucity of literature documents the validity of negative bone biopsy as an exclusion criterion for the presence of skeletal malignancies. Purpose To investigate the validity of a negative bone biopsy in bone lesions suspicious of malignancy. Material and Method A retrospective cohort of 215 consecutive targeted non-malignant skeletal biopsies from 207 patients (43% women, 57% men, median age 64, and range 94) representing suspicious focal bone lesions, collected from January 1, 2011, to July 31, 2013, was followed over a 2-year period to examine any additional biopsy, imaging, and clinical follow-up information to categorize the original biopsy as truly benign, malignant, or equivocal. Standard deviations and 95% confidence intervals were calculated. Results 210 of 215 biopsies (98%; 95% CI 0.94–0.99) showed to be truly benign 2 years after initial biopsy. Two biopsies were false negatives (1%; 95% CI 0.001–0.03), and three were equivocal (lack of imaging description). Conclusion Our study documents negative bone biopsy as a valid criterion for the absence of bone metastasis. Since only 28% had a confirmed diagnosis of prior cancer and not all patients received adequately sensitive imaging, our results might not be applicable to all cancer patients with suspicious bone lesions.

scholarly journals Incorporating false negative tests in epidemiological models for SARS-CoV-2 transmission and reconciling with seroprevalence estimates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rupam Bhattacharyya ◽  
Ritoban Kundu ◽  
Ritwik Bhaduri ◽  
Debashree Ray ◽  
Lauren J. Beesley ◽  
...  
Keyword(s):  
False Negative ◽  
Population Based ◽  
Training Data ◽  
Epidemiological Models ◽  
Rt Pcr ◽  
Antibody Prevalence ◽  
Igg Antibody ◽  
False Negatives ◽  
Seir Model ◽  
Study Population

AbstractSusceptible-Exposed-Infected-Removed (SEIR)-type epidemiologic models, modeling unascertained infections latently, can predict unreported cases and deaths assuming perfect testing. We apply a method we developed to account for the high false negative rates of diagnostic RT-PCR tests for detecting an active SARS-CoV-2 infection in a classic SEIR model. The number of unascertained cases and false negatives being unobservable in a real study, population-based serosurveys can help validate model projections. Applying our method to training data from Delhi, India, during March 15–June 30, 2020, we estimate the underreporting factor for cases at 34–53 (deaths: 8–13) on July 10, 2020, largely consistent with the findings of the first round of serosurveys for Delhi (done during June 27–July 10, 2020) with an estimated 22.86% IgG antibody prevalence, yielding estimated underreporting factors of 30–42 for cases. Together, these imply approximately 96–98% cases in Delhi remained unreported (July 10, 2020). Updated calculations using training data during March 15-December 31, 2020 yield estimated underreporting factor for cases at 13–22 (deaths: 3–7) on January 23, 2021, which are again consistent with the latest (fifth) round of serosurveys for Delhi (done during January 15–23, 2021) with an estimated 56.13% IgG antibody prevalence, yielding an estimated range for the underreporting factor for cases at 17–21. Together, these updated estimates imply approximately 92–96% cases in Delhi remained unreported (January 23, 2021). Such model-based estimates, updated with latest data, provide a viable alternative to repeated resource-intensive serosurveys for tracking unreported cases and deaths and gauging the true extent of the pandemic.

scholarly journals Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jonathan D. Cherry ◽  
Camille D. Esnault ◽  
Zachary H. Baucom ◽  
Yorghos Tripodis ◽  
Bertrand R. Huber ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chronic Traumatic Encephalopathy ◽  
Temporal Cortex ◽  
Head Impacts ◽  
Hippocampal Subfields ◽  
Mild Disease ◽  
Tau Isoforms ◽  
Ghost Tangles

AbstractChronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease, characterized by hyperphosphorylated tau, found in individuals with a history of exposure to repetitive head impacts. While the neuropathologic hallmark of CTE is found in the cortex, hippocampal tau has proven to be an important neuropathologic feature to examine the extent of disease severity. However, the hippocampus is also heavily affected in many other tauopathies, such as Alzheimer’s disease (AD). How CTE and AD differentially affect the hippocampus is unclear. Using immunofluorescent analysis, a detailed histologic characterization of 3R and 4R tau isoforms and their differential accumulation in the temporal cortex in CTE and AD was performed. CTE and AD were both observed to contain mixed 3R and 4R tau isoforms, with 4R predominating in mild disease and 3R increasing proportionally as pathological severity increased. CTE demonstrated high levels of tau in hippocampal subfields CA2 and CA3 compared to CA1. There were also low levels of tau in the subiculum compared to CA1 in CTE. In contrast, AD had higher levels of tau in CA1 and subiculum compared to CA2/3. Direct comparison of the tau burden between AD and CTE demonstrated that CTE had higher tau densities in CA4 and CA2/3, while AD had elevated tau in the subiculum. Amyloid beta pathology did not contribute to tau isoform levels. Finally, it was demonstrated that higher levels of 3R tau correlated to more severe extracellular tau (ghost tangles) pathology. These findings suggest that mixed 3R/4R tauopathies begin as 4R predominant then transition to 3R predominant as pathological severity increases and ghost tangles develop. Overall, this work demonstrates that the relative deposition of tau isoforms among hippocampal subfields can aid in differential diagnosis of AD and CTE, and might help improve specificity of biomarkers for in vivo diagnosis.

Evaluation of Positive T- and B-Cell Gene Rearrangement Studies Among Patients Without a Definitive Diagnosis by Other Assays

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S35-S36
Author(s):  
Hadrian Mendoza ◽  
Christopher Tormey ◽  
Alexa Siddon
Keyword(s):  
T Cell ◽  
False Positive ◽  
Gene Rearrangement ◽  
Hematologic Malignancy ◽  
False Negative ◽  
False Positives ◽  
False Negatives ◽  
True Negative ◽  
Flow Cytometric ◽  
Pathology Reports

Abstract In the evaluation of bone marrow (BM) and peripheral blood (PB) for hematologic malignancy, positive immunoglobulin heavy chain (IG) or T-cell receptor (TCR) gene rearrangement results may be detected despite unrevealing results from morphologic, flow cytometric, immunohistochemical (IHC), and/or cytogenetic studies. The significance of positive rearrangement studies in the context of otherwise normal ancillary findings is unknown, and as such, we hypothesized that gene rearrangement studies may be predictive of an emerging B- or T-cell clone in the absence of other abnormal laboratory tests. Data from all patients who underwent IG or TCR gene rearrangement testing at the authors’ affiliated VA hospital between January 1, 2013, and July 6, 2018, were extracted from the electronic medical record. Date of testing; specimen source; and morphologic, flow cytometric, IHC, and cytogenetic characterization of the tissue source were recorded from pathology reports. Gene rearrangement results were categorized as true positive, false positive, false negative, or true negative. Lastly, patient records were reviewed for subsequent diagnosis of hematologic malignancy in patients with positive gene rearrangement results with negative ancillary testing. A total of 136 patients, who had 203 gene rearrangement studies (50 PB and 153 BM), were analyzed. In TCR studies, there were 2 false positives and 1 false negative in 47 PB assays, as well as 7 false positives and 1 false negative in 54 BM assays. Regarding IG studies, 3 false positives and 12 false negatives in 99 BM studies were identified. Sensitivity and specificity, respectively, were calculated for PB TCR studies (94% and 93%), BM IG studies (71% and 95%), and BM TCR studies (92% and 83%). Analysis of PB IG gene rearrangement studies was not performed due to the small number of tests (3; all true negative). None of the 12 patients with false-positive IG/TCR gene rearrangement studies later developed a lymphoproliferative disorder, although 2 patients were later diagnosed with acute myeloid leukemia. Of the 14 false negatives, 10 (71%) were related to a diagnosis of plasma cell neoplasms. Results from the present study suggest that positive IG/TCR gene rearrangement studies are not predictive of lymphoproliferative disorders in the context of otherwise negative BM or PB findings. As such, when faced with equivocal pathology reports, clinicians can be practically advised that isolated positive IG/TCR gene rearrangement results may not indicate the need for closer surveillance.

scholarly journals Evaluation of vaccines against enteric infections: a clinical and public health research agenda for developing countries

2011 ◽  
Vol 366 (1579) ◽  
pp. 2799-2805 ◽  
Author(s):  
John Clemens
Keyword(s):  
Public Health ◽  
Developing Countries ◽  
Age Groups ◽  
Population Level ◽  
Vaccine Safety ◽  
Public Health Research ◽  
Protective Effects ◽  
Vaccine Protection ◽  
Enteric Infections ◽  
Research Questions

Enteric infections are a major cause of morbidity and mortality in developing countries. To date, vaccines have played a limited role in public health efforts to control enteric infections. Licensed vaccines exist for cholera and typhoid, but these vaccines are used primarily for travellers; and there are two internationally licensed vaccines for rotavirus, but they are mainly used in affluent countries. The reasons that enteric vaccines are little used in developing countries are multiple, and certainly include financial and political constraints. Also important is the need for more cogent evidence on the performance of enteric vaccines in developing country populations. A partial inventory of research questions would include: (i) does the vaccine perform well in the most relevant settings? (ii) does the vaccine perform well in all epidemiologically relevant age groups? (iii) is there adequate evidence of vaccine safety once the vaccines have been deployed in developing countries? (iv) how effective is the vaccine when given in conjunction with non-vaccine cointerventions? (v) what is the level of vaccine protection against all relevant outcomes? and (vi) what is the expected population level of vaccine protection, including both direct and herd vaccine protective effects? Provision of evidence addressing these questions will help expand the use of enteric vaccines in developing countries.

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