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Infectious Diseases and Therapy Sep 2020The ability to predict likely prognosis and infectiousness for patients with COVID-19 would aid patient management decisions. Diagnosis is usually via real-time PCR, and... (Review)
Review
BACKGROUND
The ability to predict likely prognosis and infectiousness for patients with COVID-19 would aid patient management decisions. Diagnosis is usually via real-time PCR, and it is unclear whether the semi-quantitative capability of this method, determining viral load through cycle threshold (Ct) values, can be leveraged.
OBJECTIVES
We aim to review available knowledge on correlations between SARS-COV-2 Ct values and patient- or healthcare-related outcomes to determine whether Ct values provide useful clinical information.
SOURCES
A PubMed search was conducted on 1 June 2020 based on a search strategy of (Ct value OR viral load) AND SARS-CoV-2. Data were extracted from studies reporting on the presence or absence of an association between Ct values, or viral loads determined via Ct value, and clinical outcomes.
CONTENT
Data from 18 studies were relevant for inclusion. One study reported on the correlation between Ct values and mortality and one study reported on the correlation between Ct values and progression to severe disease; both reported a significant association (p < 0.001 and p = 0.008, respectively). Fourteen studies reported on the correlation between Ct value or viral loads determined via Ct value and disease severity, and an association was observed in eight (57%) studies. Studies reporting on the correlation of viral load with biochemical and haematological markers showed an association with at least one marker, including increased lactate dehydrogenase (n = 4), decreased lymphocytes (n = 3) and increased high-sensitivity troponin I (n = 2). Two studies reporting on the correlation with infectivity showed that lower Ct values were associated with higher viral culture positivity.
IMPLICATIONS
Data suggest that lower Ct values may be associated with worse outcomes and that Ct values may be useful in predicting the clinical course and prognosis of patients with COVID-19; however, further studies are warranted to confirm clinical value.
PubMed: 32725536
DOI: 10.1007/s40121-020-00324-3 -
Clinical Orthopaedics and Related... Oct 2019Clinical research in orthopaedics typically reports the presence of an association after rejecting a null hypothesis of no association using an alpha threshold of 0.05... (Review)
Review
BACKGROUND
Clinical research in orthopaedics typically reports the presence of an association after rejecting a null hypothesis of no association using an alpha threshold of 0.05 at which to evaluate a calculated p value. This arbitrary value is a factor that results in the current difficulties reproducing research findings. A proposal is gaining attention to lower the alpha threshold to 0.005. However, it is currently unknown how alpha thresholds are used in orthopaedics and the distribution of p values reported.
QUESTIONS/PURPOSES
We sought to describe the use of alpha thresholds in two orthopaedic journals by asking (1) How frequently are alpha threshold values reported? (2) How frequently are power calculations reported? (3) How frequently are p values between 0.005 and 0.05 reported for the main hypothesis? (4) Are p values less than 0.005 associated with study characteristics such as design and reporting power calculations?
METHODS
The 100 most recent original clinical research articles from two leading orthopaedic journals at the time of this proposal were reviewed. For studies without a specified primary hypothesis, a main hypothesis was selected that was most consistent with the title and abstract. The p value for the main hypothesis and lowest p value for each study were recorded. Study characteristics including details of alpha thresholds, beta, and p values were recorded. Associations between study characteristics and p values were described. Of the 200 articles (100 from each journal), 23 were randomized controlled trials, 141 were cohort studies or case series (defined as a study in which authors had access to original data collected for the study purpose), 31 were database studies, and five were classified as other.
RESULTS
An alpha threshold was reported in 166 articles (83%) with all but two reporting a value 0.05. Forty-two articles (21%) reported performing a power calculation. The p value for the main hypothesis was less than 0.005 for 88 articles (44%), between 0.05 and 0.005 for 67 (34%), and greater than 0.05 for 29 (15%). The smallest p value was between 0.05 and 0.005 for 39 articles (20%), less than 0.005 for 143 (72%), and either not provided or greater than 0.05 for 18 (9%). Although 50% (65 of 130) cohort and database papers had a main hypothesis p value less than 0.005, only 26% (6 of 23) randomized controlled trials did. Only 36% (15 of 42) articles reporting a power calculation had a p value less than 0.005 compared with 51% (73 of 142) that did not report one.
CONCLUSIONS
Although a lower alpha threshold may theoretically increase the reproducibility of research findings across orthopaedics, this would preferentially select findings from lower-quality studies or increase the burden on higher quality ones. A more-nuanced approach could be to consider alpha thresholds specific to study characteristics. For example, randomized controlled trials with a prespecified primary hypothesis may still be best evaluated at 0.05 while database studies with an abundance of statistical tests may be best evaluated at a threshold even below 0.005.
CLINICAL RELEVANCE
Surgeons and scientists in orthopaedics should understand that the default alpha threshold of 0.05 represents an arbitrary value that could be lowered to help reduce type-I errors; however, it must also be appreciated that such a change could increase type-II errors, increase resource utilization, and preferentially select findings from lower-quality studies.
Topics: Biomedical Research; Mathematical Concepts; Orthopedic Procedures; Research Design
PubMed: 31283730
DOI: 10.1097/CORR.0000000000000843 -
Ceska a Slovenska Oftalmologie :... 2022The aim of the study was to analyse the values of the anteroposterior corneal optical power ratio (AP ratio), to compare the resulting values with those of theoretical...
AIMS
The aim of the study was to analyse the values of the anteroposterior corneal optical power ratio (AP ratio), to compare the resulting values with those of theoretical models of the eye, and to define the effect of using an individual ratio value on the approximation of the total corneal power.
MATERIAL AND METHODS
A total of 406 eyes were included. Each patient underwent an OCT (RTVue XR) examination, according to which the AP ratio of the cornea was determined, as well as the biometric parameters of the eye (Lenstar LS900). The correlation between the biometric parameters of the eye and the individual AP ratio values was evaluated using Pearsons correlation coefficient. In the analysis, the AP ratio results were compared with selected schematic models of the eye. Using Gaussian equations, a theoretical calculation of the total corneal optical power (KG) was performed, by fitting the AP ratio value and comparing it with the actually measured total corneal power (TCP).
RESULTS
The mean value of the individually determined AP ratio was 1.17 ±0.02. The most frequently represented interval (33.74 %) was 1.17 to 1.18 AP ratio values, with the vast majority of eyes (79.56 %) in the range of 1.15 to 1.20. Individual values of total corneal optical power were statistically significantly different (p < 0.05) from the theoretical values of TCP (except in the Liu-Brennan eye model, where p = 0.06). The lowest mean difference of values was found for the Navarro schematic model. The dependence of the measured AP ratio values and biometric parameters reached a moderate negative correlation (r = -0.50 for p < 0.05) with the parameter corneal posterior surface curvature (Rp), as well as a weak negative correlation with limbal diameter WtW (r = -0.26 for p < 0.05) and a weak positive correlation with central corneal thickness CCT (r = 0.17 for p < 0.05).
CONCLUSION
The assumption of a constant value of the AP ratio according to the selected schematic models of the eye is statistically significantly different from the actual measured values and was defined to have only a negative weak correlation with the size of the limbus diameter. Using the resulting average value of the determined AP ratio (1.17 ±0.02), a lower difference between real and calculated total corneal optical power was achieved.
Topics: Biometry; Cornea; Humans; Reproducibility of Results; Tomography, Optical Coherence
PubMed: 36220362
DOI: 10.31348/2022/23 -
Statistics in Medicine Sep 2019Null hypothesis significance testing has received a great amount of attention in recent years in the light of the reproducibility crisis of science. Recently, there have...
Null hypothesis significance testing has received a great amount of attention in recent years in the light of the reproducibility crisis of science. Recently, there have been calls to retire the dichotomization of study results into "significant" or "not significant" depending on whether the P value crosses some threshold or not. Ways of improving the interpretation of P values and confidence intervals are therefore needed. We illustrate the use of P value functions, which display confidence limits and P values for any confidence level for a parameter. P value functions accessibly display a wealth of information: point estimate for the parameter, one-sided and two-sided confidence limits at any level, and one-sided and two-sided P values for any null and non-null value and the counternull value. Presenting several recent examples from the literature, we show how P value functions can be applied to present evidence and to make informed statistical inferences without resorting to dichotomization. We argue that P value functions are more informative than commonly used summaries of study results such as single P values or confidence intervals. P value functions require minimal retraining, are easily interpreted, and show potential to fix many of the common misinterpretation of P values and confidence intervals. To facilitate the adoption of P value functions, we released an R package for creating P value functions for several commonly used estimates.
Topics: Biometry; Confidence Intervals; Data Interpretation, Statistical; Humans
PubMed: 31270842
DOI: 10.1002/sim.8293 -
Journal of Magnetic Resonance Imaging :... Aug 2022Currently, multi-parametric prostate MRI (mpMRI) consists of a qualitative T , diffusion weighted, and dynamic contrast enhanced imaging. Quantification of T imaging...
BACKGROUND
Currently, multi-parametric prostate MRI (mpMRI) consists of a qualitative T , diffusion weighted, and dynamic contrast enhanced imaging. Quantification of T imaging might further standardize PCa detection and support artificial intelligence solutions.
PURPOSE
To evaluate the value of T mapping to detect prostate cancer (PCa) and to differentiate PCa aggressiveness.
STUDY TYPE
Retrospective single center cohort study.
POPULATION
Forty-four consecutive patients (mean age 67 years; median PSA 7.9 ng/mL) with mpMRI and verified PCa by subsequent targeted plus systematic MR/ultrasound (US)-fusion biopsy from February 2019 to December 2019.
FIELD STRENGTH/SEQUENCE
Standardized mpMRI at 3 T with an additionally acquired T mapping sequence.
ASSESSMENT
Primary endpoint was the analysis of quantitative T values and contrast differences/ratios (CD/CR) between PCa and benign tissue. Secondary objectives were the correlation between T values, ISUP grade, apparent diffusion coefficient (ADC) value, and PI-RADS, and the evaluation of thresholds for differentiating PCa and clinically significant PCa (csPCa).
STATISTICAL TESTS
Mann-Whitney test, Spearman's rank (r ) correlation, receiver operating curves, Youden's index (J), and AUC were performed. Statistical significance was defined as P < 0.05.
RESULTS
Median quantitative T values were significantly lower for PCa in PZ (85 msec) and PCa in TZ (75 msec) compared to benign PZ (141 msec) or TZ (97 msec) (P < 0.001). CD/CR between PCa and benign PZ (51.2/1.77), respectively TZ (19.8/1.29), differed significantly (P < 0.001). The best T -mapping threshold for PCa/csPCa detection was for TZ 81/86 msec (J = 0.929/1.0), and for PZ 110 msec (J = 0.834/0.905). Quantitative T values of PCa did not correlate significantly with the ISUP grade (r = 0.186; P = 0.226), ADC value (r = 0.138; P = 0.372), or PI-RADS (r = 0.132; P = 0.392).
DATA CONCLUSION
Quantitative T values could differentiate PCa in TZ and PZ and might support standardization of mpMRI of the prostate. Different thresholds seem to apply for PZ and TZ lesions. However, in the present study quantitative T values were not able to indicate PCa aggressiveness.
LEVEL OF EVIDENCE
2 TECHNICAL EFFICACY: Stage 2.
Topics: Aged; Artificial Intelligence; Cohort Studies; Diffusion Magnetic Resonance Imaging; Humans; Magnetic Resonance Imaging; Male; Prostate; Prostatic Neoplasms; Retrospective Studies
PubMed: 35038203
DOI: 10.1002/jmri.28061 -
Perspectives on Psychological Science :... May 2021Because of the strong overreliance on values in the scientific literature, some researchers have argued that we need to move beyond values and embrace practical...
Because of the strong overreliance on values in the scientific literature, some researchers have argued that we need to move beyond values and embrace practical alternatives. When proposing alternatives to values statisticians often commit the "statistician's fallacy," whereby they declare which statistic researchers really "want to know." Instead of telling researchers what they want to know, statisticians should teach researchers which questions they can ask. In some situations, the answer to the question they are most interested in will be the value. As long as null-hypothesis tests have been criticized, researchers have suggested including minimum-effect tests and equivalence tests in our statistical toolbox, and these tests have the potential to greatly improve the questions researchers ask. If anyone believes values affect the quality of scientific research, preventing the misinterpretation of values by developing better evidence-based education and user-centered statistical software should be a top priority. Polarized discussions about which statistic scientists should use has distracted us from examining more important questions, such as asking researchers what they want to know when they conduct scientific research. Before we can improve our statistical inferences, we need to improve our statistical questions.
Topics: Humans; Knowledge; Probability; Research; Research Personnel; Software
PubMed: 33560174
DOI: 10.1177/1745691620958012 -
BMC Medical Research Methodology Sep 2020Researchers often misinterpret and misrepresent statistical outputs. This abuse has led to a large literature on modification or replacement of testing thresholds and... (Review)
Review
BACKGROUND
Researchers often misinterpret and misrepresent statistical outputs. This abuse has led to a large literature on modification or replacement of testing thresholds and P-values with confidence intervals, Bayes factors, and other devices. Because the core problems appear cognitive rather than statistical, we review some simple methods to aid researchers in interpreting statistical outputs. These methods emphasize logical and information concepts over probability, and thus may be more robust to common misinterpretations than are traditional descriptions.
METHODS
We use the Shannon transform of the P-value p, also known as the binary surprisal or S-value s = -log(p), to provide a measure of the information supplied by the testing procedure, and to help calibrate intuitions against simple physical experiments like coin tossing. We also use tables or graphs of test statistics for alternative hypotheses, and interval estimates for different percentile levels, to thwart fallacies arising from arbitrary dichotomies. Finally, we reinterpret P-values and interval estimates in unconditional terms, which describe compatibility of data with the entire set of analysis assumptions. We illustrate these methods with a reanalysis of data from an existing record-based cohort study.
CONCLUSIONS
In line with other recent recommendations, we advise that teaching materials and research reports discuss P-values as measures of compatibility rather than significance, compute P-values for alternative hypotheses whenever they are computed for null hypotheses, and interpret interval estimates as showing values of high compatibility with data, rather than regions of confidence. Our recommendations emphasize cognitive devices for displaying the compatibility of the observed data with various hypotheses of interest, rather than focusing on single hypothesis tests or interval estimates. We believe these simple reforms are well worth the minor effort they require.
Topics: Bayes Theorem; Cognition; Cohort Studies; Confidence Intervals; Humans; Probability; Semantics
PubMed: 32998683
DOI: 10.1186/s12874-020-01105-9 -
Frontiers in Bioinformatics 2022The human mind shows extraordinary capability at recognizing patterns, while at the same time tending to underestimate the natural scope of random processes. Taken... (Review)
Review
The human mind shows extraordinary capability at recognizing patterns, while at the same time tending to underestimate the natural scope of random processes. Taken together, this easily misleads researchers in judging whether the observed characteristics of their data are of significance or just the outcome of random effects. One of the best tools to assess whether observed features fall into the scope of pure randomness is statistical significance testing, which quantifies the probability to falsely reject a chosen null hypothesis. The central parameter in this context is the -value, which can be calculated from the recorded data sets. In case of -values smaller than the level of significance, the null hypothesis is rejected, otherwise not. While significance testing has found widespread application in many sciences including the life sciences, it is hardly used in (bio-)physics. We propose here that significance testing provides an important and valid addendum to the toolbox of quantitative (single molecule) biology. It allows to support a quantitative judgement (the hypothesis) about the data set with a probabilistic assessment. In this manuscript we describe ways for obtaining valid -values in two selected applications of single molecule microscopy: (i) Nanoclustering in single molecule localization microscopy. Previously, we developed a method termed 2-CLASTA, which allows to calculate a valid -value for the null hypothesis of an underlying random distribution of molecules of interest while circumventing overcounting issues. Here, we present an extension to this approach, yielding a single overall -value for data pooled from multiple cells or experiments. (ii) Single molecule trajectories. Data from a single molecule trajectory are inherently correlated, thus prohibiting a direct analysis via conventional statistical tools. Here, we introduce a block permutation test, which yields a valid -value for the analysis and comparison of single molecule trajectory data. We exemplify the approach based on FRET trajectories.
PubMed: 36304307
DOI: 10.3389/fbinf.2022.811053 -
Iranian Journal of Otorhinolaryngology Sep 2023Considering the inconsistent results regarding the association between the severity and duration of olfactory dysfunction (OD), and the viral load in coronavirus disease...
INTRODUCTION
Considering the inconsistent results regarding the association between the severity and duration of olfactory dysfunction (OD), and the viral load in coronavirus disease 2019 (COVID-19) patients, we aimed to conduct this study.
MATERIALS AND METHODS
This is a prospective cohort study in which COVID-19 patients were evaluated for the initial cycle threshold value (Ct values) measured by the nasopharyngeal samples along with olfactory function measured by the University of Pennsylvania Smell Identification Test (UPSIT) within 2 months of COVID-19 onset.
RESULTS
Among 309 COVID-19 patients who were included in this study, 108 (34.9%), 112 (36.2%) and 89 (28.8%) were normosmic, hyposmic, and anosmic, respectively based on the UPSIT. The severity of COVID-19 and the rate of hospitalization were higher in anosmic patients (p<0.0001, and p<0.0001, respectively). Moreover, significant associations between the initial Ct value and the severity of OD at admission and follow-ups were detected (p<0.0001 and p<0.0001, respectively). Anosmic patients had higher Ct values in comparison with hyposmic (approx. 3-fold) and normosmic (approx. 12-fold) patients. The recovery rate after one- and two-month follow-ups was 47% and 84%, respectively. At the follow-ups, OD-recovered patients significantly had lower Ct values (mean Ct value: 27.79 ± 2 and 28.21 ± 2.08) in comparison with those who have not recovered yet (mean Ct value: 30.19 ± 3.36, and 33.6 ± 3.37) (p<0.0001, and p<0.0001, respectively).
CONCLUSIONS
Ct value seems to be a significant factor not only in predicting OD severity in COVID-19 patients but also in the OD recovery duration. This finding may be helpful to investigate the underlying mechanisms of OD in COVID-19 patients.
PubMed: 38090619
DOI: 10.22038/IJORL.2023.71462.3429 -
Frontiers in Psychology 2020A widely cited roadblock to bridging ecological psychology and enactivism is that the former identifies with realism and the latter identifies with constructivism, which...
A widely cited roadblock to bridging ecological psychology and enactivism is that the former identifies with realism and the latter identifies with constructivism, which critics charge is subjectivist. A pragmatic reading, however, suggests non-mental forms of constructivism that simultaneously fit core tenets of enactivism and ecological realism. After advancing a pragmatic version of enactive constructivism that does not obviate realism, I reinforce the position with an empirical illustration: , a communal unicellular organism that leaves slime trails that form chemical barriers that it avoids in foraging explorations. Here, environmental building and sensorimotor engagement are part of the same process with coordinating around self-created, affordance-bearing geographies, which nonetheless exist independently in ways described by ecological realists. For ecological psychologists, affordances are values, meaning values are external to the perceiver. I argue that agent-enacted values have the same status and thus do not obviate ecological realism or generate subjectivism. The constructivist-realist debate organizes around the emphasis that enactivists and ecological theorists respectively place on the inner constitution of organisms vs. the structure of environments. Building on alimentary themes introduced in the example and also in Gibson's work, I go on to consider how environment, brain, visceral systems, and even bacteria within them enter perceptual loops. This highlights almost unfathomable degrees of mutually modulating internal and external synchronization. It also shows instances in which internal conditions alter worldly configurations and invert values, in Gibson's sense of the term, albeit without implying subjectivism. My aim is to cut across the somatic focus of enactive constructivism and the external environment-oriented emphasis of ecological realism and show that enactivism can enrich ecological accounts of value.
PubMed: 33192781
DOI: 10.3389/fpsyg.2020.538644