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Patterns (New York, N.Y.) Dec 2023Since the 18th century, the p value has been an important part of hypothesis-based scientific investigation. As statistical and data science engines accelerate,... (Review)
Review
Since the 18th century, the p value has been an important part of hypothesis-based scientific investigation. As statistical and data science engines accelerate, questions emerge: to what extent are scientific discoveries based on p values reliable and reproducible? Should one adjust the significance level or find alternatives for the p value? Inspired by these questions and everlasting attempts to address them, here, we provide a systematic examination of the p value from its roles and merits to its misuses and misinterpretations. For the latter, we summarize modest recommendations to handle them. In parallel, we present the Bayesian alternatives for seeking evidence and discuss the pooling of p values from multiple studies and datasets. Overall, we argue that the p value and hypothesis testing form a useful probabilistic decision-making mechanism, facilitating causal inference, feature selection, and predictive modeling, but that the interpretation of the p value must be contextual, considering the scientific question, experimental design, and statistical principles.
PubMed: 38106615
DOI: 10.1016/j.patter.2023.100878 -
Briefings in Bioinformatics Jul 2023DNA methylation plays a crucial role in transcriptional regulation. Reduced representation bisulfite sequencing (RRBS) is a technique of increasing use for analyzing...
DNA methylation plays a crucial role in transcriptional regulation. Reduced representation bisulfite sequencing (RRBS) is a technique of increasing use for analyzing genome-wide methylation profiles. Many computational tools such as Metilene, MethylKit, BiSeq and DMRfinder have been developed to use RRBS data for the detection of the differentially methylated regions (DMRs) potentially involved in epigenetic regulations of gene expression. For DMR detection tools, as for countless other medical applications, P-values and their adjustments are among the most standard reporting statistics used to assess the statistical significance of biological findings. However, P-values are coming under increasing criticism relating to their questionable accuracy and relatively high levels of false positive or negative indications. Here, we propose a method to calculate E-values, as likelihood ratios falling into the null hypothesis over the entire parameter space, for DMR detection in RRBS data. We also provide the R package 'metevalue' as a user-friendly interface to implement E-value calculations into various DMR detection tools. To evaluate the performance of E-values, we generated various RRBS benchmarking datasets using our simulator 'RRBSsim' with eight samples in each experimental group. Our comprehensive benchmarking analyses showed that using E-values not only significantly improved accuracy, area under ROC curve and power, over that of P-values or adjusted P-values, but also reduced false discovery rates and type I errors. In applications using real RRBS data of CRL rats and a clinical trial on low-salt diet, the use of E-values detected biologically more relevant DMRs and also improved the negative association between DNA methylation and gene expression.
Topics: Animals; Rats; DNA Methylation; Sequence Analysis, DNA; ROC Curve; CpG Islands
PubMed: 37369639
DOI: 10.1093/bib/bbad241 -
Nutrients Oct 2023Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, and it has two main pathological aspects: reproductive and metabolic. Overweight/obesity...
Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, and it has two main pathological aspects: reproductive and metabolic. Overweight/obesity is a risk factor in terms of adverse effects during hormone stimulation, a reduced response to ovulation induction regimens, reduced success of IVF, and an increased risk of obstetric complications. To resolve this vicious cycle of pathological events, weight loss and lifestyle modifications are promising strategies. Among these possible approaches, the consumption of a very-low-calorie ketogenic diet (VLCKD) or Mediterranean diet (MD) represents a valid option. In our study, 84 obese/overweight PCOS patients were recruited to evaluate the effects induced by the VLCKD and MD on weight, hormonal, and metabolic parameters. BMI decreased significantly among the VLKCD patients compared to the MD patients (both presenting values < 0.0001 at 90 and 120 days), and a significant reduction in body circumference was observed. At the same time, HOMA index values statistically decreased for the VLCKD patients compared to those on the MD ( value < 0.001 at 90 days and value < 0.05 at 120 days), and this phenomenon was also observed for AFC at 90 and 120 days (both values < 0.001) and AMH at 90 days ( value < 0.05). Interestingly, the ovarian hyperstimulation syndrome (OHSS) incidence was statistically lower in the VLKCD patients compared to the MD patients ( < 0.001). We state that these dietary regimes may improve anthropometric parameters (such as BMI) and women's reproductive health, restore menstrual regularity, and reduce the risk of OHSS. Regarding the different nutritional therapies, the results suggest that the VLCKD is an optimal choice for entry into IVF, especially in terms of the time range in which these results are achieved.
Topics: Pregnancy; Humans; Female; Overweight; Polycystic Ovary Syndrome; Obesity; Hormones; Fertilization in Vitro
PubMed: 37892519
DOI: 10.3390/nu15204444 -
Perspectives on Medical Education 2024The use of the p-value in quantitative research, particularly its threshold of "P < 0.05" for determining "statistical significance," has long been a cornerstone of...
The use of the p-value in quantitative research, particularly its threshold of "P < 0.05" for determining "statistical significance," has long been a cornerstone of statistical analysis in research. However, this standard has been increasingly scrutinized for its potential to mislead findings, especially when the practical significance, the number of comparisons, or the suitability of statistical tests are not properly considered. In response to controversy around use of p-values, the American Statistical Association published a statement in 2016 that challenged the research community to abandon the term "statistically significant". This stance has been echoed by leading scientific journals to urge a significant reduction or complete elimination in the reliance on p-values when reporting results. To provide guidance to researchers in health professions education, this paper provides a succinct overview of the ongoing debate regarding the use of p-values and the definition of p-values. It reflects on the controversy by highlighting the common pitfalls associated with p-value interpretation and usage, such as misinterpretation, overemphasis, and false dichotomization between "significant" and "non-significant" results. This paper also outlines specific recommendations for the effective use of p-values in statistical reporting including the importance of reporting effect sizes, confidence intervals, the null hypothesis, and conducting sensitivity analyses for appropriate interpretation. These considerations aim to guide researchers toward a more nuanced and informative use of p-values.
Topics: Humans; Data Interpretation, Statistical; Research Design
PubMed: 38680196
DOI: 10.5334/pme.1324 -
Medical Hypothesis, Discovery &... 2023Proper correction of spherical aberration using intraocular lenses requires precise selection of the sphericity of intraocular lens surfaces based on individual...
BACKGROUND
Proper correction of spherical aberration using intraocular lenses requires precise selection of the sphericity of intraocular lens surfaces based on individual biometric data and corneal asphericity coefficient (Q value). This study aimed to determine and analyze the corneal Q value and its related factors among Saudi participants.
METHODS
In this cross-sectional study, normal right eyes of healthy Saudi participants aged 17 - 58 years who visited Al-Kahhal Medical Complex, Dammam, Saudi Arabia, were included. The Pentacam rotating Scheimpflug camera was used to determine the average Q value at 6-mm diameter. Q values were obtained from each quadrant (superior, nasal, inferior, and temporal) and two meridians (horizontal and vertical). Mean Q values of the anterior and posterior corneal surfaces were also obtained. Other factors including age, sex, refractive error, and central corneal radius were documented.
RESULTS
Five hundred right eyes from 500 participants were included. The mean (standard deviation [SD]) (range) age was 27.2 (7.1) (18 - 58) years. The mean (SD) (range) Q value of 500 eyes was - 0.24 (0.10) (- 0.71 to + 0.09) anteriorly and - 0.16 (0.14) (- 0.70 to + 0.23) posteriorly, being significantly more prolate anteriorly ( < 0.05). The corneas were significantly more prolate in the nasal than in the temporal quadrant, in the superior than in the inferior quadrant, and in the horizontal than in the vertical meridian (all < 0.05). There were statistically significant differences in anterior, nasal, temporal, inferior, horizontal, and vertical Q values among age groups (all < 0.05) but not in the superior or posterior Q values (both > 0.05). The corneas became less prolate with increasing age ( < 0.05). However, Q values were comparable between the sexes (all > 0.05). There was no significant correlation between anterior (r = + 0.08; = 0.095) or posterior (r = - 0.08; = 0.092) Q value and spherical equivalent, but a significant trend was detected toward more prolate shape with increasing myopia in the temporal and inferior quadrants (r = + 0.19; < 0.001, r = + 0.10; = 0.022, respectively). There was a significant negligible correlation between the posterior Q value and central corneal radius (r = - 0.18; < 0.001) but no significant correlation between the anterior Q value and central corneal radius (r = + 0.02; = 0.673).
CONCLUSIONS
Most corneas in this Saudi population were prolate in contour. Anterior corneal asphericity was positively correlated with age and was not significantly related to sex, refractive error, or central corneal radius. Further studies are needed to verify our preliminary findings.
PubMed: 38476574
DOI: 10.51329/mehdiophthal1479 -
Journal of Medical Biochemistry Aug 2023The aim was examination of the intimamedia thickness of carotid arteries in COVID-19 infection.
BACKGROUND
The aim was examination of the intimamedia thickness of carotid arteries in COVID-19 infection.
METHODS
In 50 patients, the thickness of the intimomedial complex (IMT) in the common carotid arteries was measured. The values were compared with the control group in 2006-9. The condition of the lungs was assessed by ultrasound score (It score) (0-42) as mild (0-14) or mediumsevere (15-28) Covid. IMT thickening risk factors and the value of fibrinogen, IL-6 and CRP were recorded. Two IMT prediction models were formed. The socio-epidemiological model predicts the development of IMT based on epidemiological factors. Apart from these factors, the second model also includes the values of the mentioned biomarkers.
RESULTS
It score 20±6, IMT values right: median 0.99 mm, p25=0.89, p75=1.14; left: 1±0.22 mm. Control: IMTright: median 0.7 mm, p25=0.68 mm; p75=0-9 mm; left: median=0.75 mm, p25=0.6 mm, p75=1.0 mm. The group/control difference is highly significant. Epide mio - logical model: logit (IMT)= 4.463+(2.021+value for GEN)+(0.055x AGE value)+(-3.419x RF value)+(-4.447x SM value)+(5.115x HTA value)+(3.56x DM value)+ (22.389x LIP value)+(24.206x CVD value)+(1.449x other value)+(-0.138x It score value)+(0.19xBMI value). Epidemiological-inflammatory model: logit (IMT)=5.204+ (2.545x GEN value)+(0.076x AGE value)+(-6.132x RF value)+(-7.583x SM value)+(8.744x HTA value)+(6.838x DM value)+(25.446x LIP value)+(28.825x CVD value)+ (2.487x other value)+(-0.218xIt score value)+(0.649x BMI value) +(-0.194x fibrinogen value)+(0.894x IL-6 value)+(0.659x CRP value). Values for both models Exp(B)=4.882; P of sample=0.83; logit=-0.19; OR= 23.84; model accuracy for the first model 87% and for the second 88%; Omnibus test of the first model c2=34.324; p=0.000; reliability coefficient -2LogLH=56.854; Omnibus test of the second model c2=39.774; p=0.000; and -2LogLH=51.403.
CONCLUSIONS
The ageing of blood vessels in COVID-19 can be predicted.
PubMed: 37814624
DOI: 10.5937/jomb0-39602 -
Biomedicines Oct 2023The ferritin-lymphocyte ratio (FLR) is a novel inflammatory biomarker for the assessment of acute COVID-19 patients. However, the prognostic value of FLR for predicting...
The ferritin-lymphocyte ratio (FLR) is a novel inflammatory biomarker for the assessment of acute COVID-19 patients. However, the prognostic value of FLR for predicting adverse clinical outcomes in COVID-19 remains unclear, which hinders its clinical translation. We characterised the prognostic value of FLR in COVID-19 patients, as compared to established inflammatory markers. In 217 study patients (69 years [IQR: 55-82]; 60% males), FLR was weakly correlated with CRP (R = 0.108, = 0.115) and white cell count (R = -0.144; = 0.034). On ROC analysis, an FLR cut-off of 286 achieved a sensitivity of 86% and a specificity of 30% for predicting inpatient mortality (AUC 0.60, 95% CI: 0.53-0.67). The negative predictive values of FLR for ruling out mortality, non-invasive ventilation requirement and critical illness (intubation and/or ICU admission) were 86%, 85% and 93%, respectively. FLR performed similarly to CRP (AUC 0.60 vs. 0.64; = 0.375) for predicting mortality, but worse than CRP for predicting non-fatal outcomes (all < 0.05). On Kaplan-Meier analysis, COVID-19 patients with FLR values > 286 had worse inpatient survival than patients with FLR ≤ 286, = 0.041. FLR has prognostic value in COVID-19 patients, and appears unrelated to other inflammatory markers such as CRP and WCC. FLR exhibits high sensitivity and negative predictive values for adverse clinical outcomes in COVID-19, and may be a good "rule-out" test. Further work is needed to improve the sensitivity of FLR and validate its role in prospective studies for guiding clinical management.
PubMed: 37893192
DOI: 10.3390/biomedicines11102819 -
Psychopharmacology Dec 2023Inadequate responses to current schizophrenia treatments have accelerated research into novel therapeutic approaches. (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE
Inadequate responses to current schizophrenia treatments have accelerated research into novel therapeutic approaches.
OBJECTIVES
This study investigated the efficacy and tolerability of adjunctive L-theanine, an ingredient with neuroimmunomodulatory and neuroprotective properties, for chronic schizophrenia.
METHODS
Eighty chronic schizophrenia inpatients were equally assigned to receive risperidone (6 mg/day) plus either L-theanine (400 mg/day) or matched placebo in this 8-week, randomized, parallel-group, double-blind, placebo-controlled trial. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS) by recording the results of subscales at baseline and weeks 4 and 8 to measure treatment efficacy. Additionally, the participants were assessed for the Hamilton Depression Rating Scale (HDRS) and adverse events, including the Extrapyramidal Symptom Rating Scale (ESRS).
RESULTS
Sixty patients, 30 in each group, were included in the analyses. All baseline demographic and clinical characteristics were comparable between the groups (p-values > 0.05). The reduction rates from baseline to endpoint in negative, general psychopathology, and total scores of PANSS were greater in the L-theanine group (p-values = 0.03, 0.01, and 0.04, respectively). Regarding general psychopathology scores, the reduction in the L-theanine group was also greater until week 4 (p-value < 0.01). The time × treatment interaction effect was significant on negative (p-value = 0.03), general psychopathology (p-value < 0.01), and total (p-value = 0.04) scores of PANSS, indicating additional improvements in the L-theanine group. The HDRS and side effects were comparable between the groups (p-values > 0.05).
CONCLUSIONS
L-Theanine adjunct to risperidone safely and tolerably outperformed adjunctive placebo for schizophrenia, and promising evidence indicated its effects on primary negative symptoms, which need to be scrutinized in further studies.
TRIAL REGISTRATION
The study protocol was registered and published prospectively in the Iranian Registry of Clinical Trials ( http://www.irct.ir ; registration number: IRCT20090117001556N133) on 2020-12-12.
Topics: Humans; Risperidone; Schizophrenia; Antipsychotic Agents; Inpatients; Iran; Drug Therapy, Combination; Psychiatric Status Rating Scales; Treatment Outcome; Double-Blind Method
PubMed: 37697164
DOI: 10.1007/s00213-023-06458-9 -
Canadian Association of Radiologists... Aug 2023P-hacking, the tendency to run selective analyses until they become significant, is prevalent in many scientific disciplines.
BACKGROUND
P-hacking, the tendency to run selective analyses until they become significant, is prevalent in many scientific disciplines.
PURPOSE
This study aims to assess if p-hacking exists in imaging research.
METHODS
Protocol, data, and code available here https://osf.io/xz9ku/?view_only=a9f7c2d841684cb7a3616f567db273fa. We searched imaging journals Ovid MEDLINE from 1972 to 2021. Text mining using Python script was used to collect metadata: journal, publication year, title, abstract, and -values from abstracts. One -value was randomly sampled per abstract. We assessed for evidence of p-hacking using a p-curve, by evaluating for a concentration of -values just below .05. We conducted a one-tailed binomial test (α = .05 level of significance) to assess whether there were more -values falling in the upper range (e.g., .045 < P < .05) than in the lower range (e.g., .04 < P < .045). To assess variation in results introduced by our random sampling of a single -value per abstract, we repeated the random sampling process 1000 times and pooled results across the samples. Analysis was done (divided into 10-year periods) to determine if p-hacking practices evolved over time.
RESULTS
Our search of 136 journals identified 967,981 abstracts. Text mining identified 293,687 -values, and a total of 4105 randomly sampled -values were included in the p-hacking analysis. The number of journals and abstracts that were included in the analysis as a fraction and percentage of the total number was, respectively, 108/136 (80%) and 4105/967,981 (.4%). P-values did not concentrate just under .05; in fact, there were more -values falling in the lower range (e.g., .04 < < .045) than falling just below .05 (e.g., .045 < < .05), indicating lack of evidence for p-hacking. Time trend analysis did not identify p-hacking in any of the five 10-year periods.
CONCLUSION
We did not identify evidence of p-hacking in abstracts published in over 100 imaging journals since 1972. These analyses cannot detect all forms of p-hacking, and other forms of bias may exist in imaging research such as publication bias and selective outcome reporting.
Topics: Publication Bias; Statistics as Topic
PubMed: 36412994
DOI: 10.1177/08465371221139418 -
Biomedicines Dec 2023The aim of this study was to evaluate whether there were significant sex x time interactions in lipoprotein(a) (Lp(a)) and low-density lipoprotein cholesterol (LDL-C)...
The aim of this study was to evaluate whether there were significant sex x time interactions in lipoprotein(a) (Lp(a)) and low-density lipoprotein cholesterol (LDL-C) response to treatment with the Proprotein Convertase Subtilisin/Kexin type 9 inhibitor (PCSK9i) Evolocumab, in a real-life clinical setting. For this purpose, we pooled data from 176 outpatients (Men: 93; Women: 83) clinically evaluated at baseline and every six months after starting Evolocumab. Individuals who had been on PCSK9i for less than 30 months and nonadherent patients were excluded from the analysis. Over time, absolute values of Lp(a) plasma concentrations significantly decreased in the entire cohort (-value < 0.001) and by sex (-value < 0.001 in men and -value = 0.002 in and women). However, there were no sex-related significant differences. Absolute plasma concentrations of LDL-C significantly decreased over time in the entire cohort and by sex (-value < 0.001 always), with greater improvements in men compared to women. The sex x time interaction was statistically significant in LDL-C (all -values < 0.05), while absolute changes in Lp(a) were not influenced by either sex or time (all -value > 0.05). Our data partially reinforce the presence of differences in response to treatment to PCSK9i between men and women and are essential to gain a better understanding of the relationship between LDL-C and Lp(a) lowering in response to PCSK9i. Further research will clarify whether these sex-related significant differences translate into a meaningful difference in the long-term risk of ASCVD.
PubMed: 38137492
DOI: 10.3390/biomedicines11123271