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Nevin Manimala Statistics

Analysis of 567,758 randomized controlled trials published over 30 years reveals trends in phrases used to discuss results that do not reach statistical significance

PLoS Biol. 2022 Feb 18;20(2):e3001562. doi: 10.1371/journal.pbio.3001562. Online ahead of print.

ABSTRACT

The power of language to modify the reader’s perception of interpreting biomedical results cannot be underestimated. Misreporting and misinterpretation are pressing problems in randomized controlled trials (RCT) output. This may be partially related to the statistical significance paradigm used in clinical trials centered around a P value below 0.05 cutoff. Strict use of this P value may lead to strategies of clinical researchers to describe their clinical results with P values approaching but not reaching the threshold to be “almost significant.” The question is how phrases expressing nonsignificant results have been reported in RCTs over the past 30 years. To this end, we conducted a quantitative analysis of English full texts containing 567,758 RCTs recorded in PubMed between 1990 and 2020 (81.5% of all published RCTs in PubMed). We determined the exact presence of 505 predefined phrases denoting results that approach but do not cross the line of formal statistical significance (P < 0.05). We modeled temporal trends in phrase data with Bayesian linear regression. Evidence for temporal change was obtained through Bayes factor (BF) analysis. In a randomly sampled subset, the associated P values were manually extracted. We identified 61,741 phrases in 49,134 RCTs indicating almost significant results (8.65%; 95% confidence interval (CI): 8.58% to 8.73%). The overall prevalence of these phrases remained stable over time, with the most prevalent phrases being “marginally significant” (in 7,735 RCTs), “all but significant” (7,015), “a nonsignificant trend” (3,442), “failed to reach statistical significance” (2,578), and “a strong trend” (1,700). The strongest evidence for an increased temporal prevalence was found for “a numerical trend,” “a positive trend,” “an increasing trend,” and “nominally significant.” In contrast, the phrases “all but significant,” “approaches statistical significance,” “did not quite reach statistical significance,” “difference was apparent,” “failed to reach statistical significance,” and “not quite significant” decreased over time. In a random sampled subset of 29,000 phrases, the manually identified and corresponding 11,926 P values, 68,1% ranged between 0.05 and 0.15 (CI: 67. to 69.0; median 0.06). Our results show that RCT reports regularly contain specific phrases describing marginally nonsignificant results to report P values close to but above the dominant 0.05 cutoff. The fact that the prevalence of the phrases remained stable over time indicates that this practice of broadly interpreting P values close to a predefined threshold remains prevalent. To enhance responsible and transparent interpretation of RCT results, researchers, clinicians, reviewers, and editors may reduce the focus on formal statistical significance thresholds and stimulate reporting of P values with corresponding effect sizes and CIs and focus on the clinical relevance of the statistical difference found in RCTs.

PMID:35180228 | DOI:10.1371/journal.pbio.3001562

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Nevin Manimala Statistics

Goal management training and psychoeducation / mindfulness for treatment of executive dysfunction in Parkinson’s disease: A feasibility pilot trial

PLoS One. 2022 Feb 18;17(2):e0263108. doi: 10.1371/journal.pone.0263108. eCollection 2022.

ABSTRACT

INTRODUCTION: As there is currently no pharmacological treatment for Parkinson’s Disease Mild Cognitive Impairment (PD-MCI) with executive dysfunctions, specific cognitive interventions must be investigated. Most previous studies have tested bottom-up cognitive training programs but have not shown very good results.

OBJECTIVES: The aim of this study was to test ease of implementation, differential safety and preliminary efficacy of two top-down (strategy-learning) home-based, individualized, cognitive interventions: Goal Management Training (GMT), adapted for PD-MCI (Adapted-GMT), and a psychoeducation program combined with mindfulness exercises (PSYCH-Mind).

METHODS: This was a single-blind block-randomized between-group comparative study. Twelve PD-MCI with mild executive dysfunctions were divided in four blocks and randomly assigned to any of the two interventions. The participants were included if they had PD-MCI diagnosis (no dementia), with stabilized medication. Both groups (Adapted-GMT and PSYCH-mind) received five intervention sessions each lasting 60-90 minutes for five weeks. Measures were collected at baseline, mid-point, one-week, four-week and 12-week follow-ups. Executive functions were assessed with the Dysexecutive questionnaire (DEX) and the Zoo Map Test (ZMT). Quality of life (QoL) and psychiatric symptoms were also evaluated. Repeated measures ANCOVAs (mixed linear analysis) were applied to all outcomes.

RESULTS: There was one drop out, and both interventions were feasible and acceptable. Despite the small sample size limiting statistical power, patients of both groups significantly improved executive functions per the DEX-patient (Time: F(4,36) = 2.96, p = 0.033, CI95%: 10.75-15.23) and DEX-caregiver scores (Time: F(4,36) = 6.02, p = 0.017, CI95%: 9.63-17.23). Both groups significantly made fewer errors between measurement times on the ZMT (Time: F(3,36) = 16.66, p = 0.001, CI95%: 1.07-2.93). However, QoL significantly increased only in PSYCH-Mind patients at four-week follow-up (interaction Time*Group: F(4,36) = 5.31, p = 0.002, CI95%: 15.33-25.61).

CONCLUSION: Both interventions were easily implemented and proved to be safe. Because both interventions are arguably cost-effective, these pilot findings, although promising, need to be replicated in large samples.

CLINICALTRIALS.GOV IDENTIFIER: NCT04636541.

PMID:35180229 | DOI:10.1371/journal.pone.0263108

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Nevin Manimala Statistics

Phylogenetic inference of changes in amino acid propensities with single-position resolution

PLoS Comput Biol. 2022 Feb 18;18(2):e1009878. doi: 10.1371/journal.pcbi.1009878. Online ahead of print.

ABSTRACT

Fitness conferred by the same allele may differ between genotypes and environments, and these differences shape variation and evolution. Changes in amino acid propensities at protein sites over the course of evolution have been inferred from sequence alignments statistically, but the existing methods are data-intensive and aggregate multiple sites. Here, we develop an approach to detect individual amino acids that confer different fitness in different groups of species from combined sequence and phylogenetic data. Using the fact that the probability of a substitution to an amino acid depends on its fitness, our method looks for amino acids such that substitutions to them occur more frequently in one group of lineages than in another. We validate our method using simulated evolution of a protein site under different scenarios and show that it has high specificity for a wide range of assumptions regarding the underlying changes in selection, while its sensitivity differs between scenarios. We apply our method to the env gene of two HIV-1 subtypes, A and B, and to the HA gene of two influenza A subtypes, H1 and H3, and show that the inferred fitness changes are consistent with the fitness differences observed in deep mutational scanning experiments. We find that changes in relative fitness of different amino acid variants within a site do not always trigger episodes of positive selection and therefore may not result in an overall increase in the frequency of substitutions, but can still be detected from changes in relative frequencies of different substitutions.

PMID:35180226 | DOI:10.1371/journal.pcbi.1009878

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Nevin Manimala Statistics

The impact of COVID-19 on cryptocurrency markets: A network analysis based on mutual information

PLoS One. 2022 Feb 18;17(2):e0259869. doi: 10.1371/journal.pone.0259869. eCollection 2022.

ABSTRACT

The purpose of our study is to figure out the transitions of the cryptocurrency market due to the outbreak of COVID-19 through network analysis, and we studied the complexity of the market from different perspectives. To construct a cryptocurrency network, we first apply a mutual information method to the daily log return values of 102 digital currencies from January 1, 2019, to December 31, 2020, and also apply a correlation coefficient method for comparison. Based on these two methods, we construct networks by applying the minimum spanning tree and the planar maximally filtered graph. Furthermore, we study the statistical and topological properties of these networks. Numerical results demonstrate that the degree distribution follows the power-law and the graphs after the COVID-19 outbreak have noticeable differences in network measurements compared to before. Moreover, the results of graphs constructed by each method are different in topological and statistical properties and the network’s behavior. In particular, during the post-COVID-19 period, it can be seen that Ethereum and Qtum are the most influential cryptocurrencies in both methods. Our results provide insight and expectations for investors in terms of sharing information about cryptocurrencies amid the uncertainty posed by the COVID-19 pandemic.

PMID:35180208 | DOI:10.1371/journal.pone.0259869

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Nevin Manimala Statistics

Log-Transformed Electromyography Amplitude Power Output Relationship: Nondominant vs. Dominant Limb

J Strength Cond Res. 2022 Mar 1;36(3):851-856. doi: 10.1519/JSC.0000000000004222.

ABSTRACT

Boccomino, HL, Daoud, BT, Hudas, A, North, WA, and Malek, MH. Log-transformed electromyography amplitude power output relationship: nondominant vs. dominant limb. J Strength Cond Res 36(3): 851-856, 2022-Findings from studies that examine bilateral differences between the nondominant and dominant limb during whole-body (i.e., cycle ergometry) are equivocal. This may, in part, be because of the mode of exercise (i.e., whole-body) and how the data are analyzed. Surface electromyography (EMG) is a noninvasive method of examining motor unit recruitment and activation during exercise. The log-transformed electromyography amplitude power output relationship provides y-intercept and slope terms on a subject-by-subject basis that can therefore be statistically analyzed. The purpose of this study, therefore, was to identify potential differences in the muscle for the nondominant and dominant limb using the log-transformed EMG amplitude power output relationship for continuous exercise that isolates the quadricep femoris muscles. Nine healthy college-aged men (mean ± SEM: age, 22.6 ± 1.2 years; mass, 68.6 ± 10.4 kg; and height, 1.76 ± 0.03 m) volunteered as subjects for the current study. Each subject visited the laboratory on a single occasion, had EMG electrodes placed on their rectus femoris muscle for their nondominant and dominant limb, and performed an incremental double-leg knee-extensor ergometry to voluntary exhaustion. The subjects achieved a mean power output (75 ± 8 W) for the exercise test. In addition, a mean end-exercise heart rate (155 ± 8 b·min-1) corresponded to 79 ± 4% of the age-predicted heart rate using the formula 220-age. Separate paired t tests for the slope (t[8] = 0.929 p = 0.38) and y-intercept (t[8] = 0.368, p = 0.72) terms revealed no significant mean differences between the 2 limbs. The results of the present study indicate that there are no differences in muscle activation between the nondominant and dominant limbs for continuous exercise that isolates the muscle.

PMID:35180194 | DOI:10.1519/JSC.0000000000004222

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Nevin Manimala Statistics

The effect of root canal rinsing protocol on the push-out bond strength to the dentin cementation of the fiber post

Folia Med Cracov. 2021 Dec 28;61(4):81-92. doi: 10.24425/fmc.2021.140006.

ABSTRACT

B a c k g r o u n d: Studies on the effect of root canal rinsing protocols on fiber post bonding to dentin are inconclusive. This study reports investigation of this topic. O b j e c t i v e s: to determine effects of irrigation protocol by means of a push-out test on the strength of adhesion between the post and dentin in an in vitro study. Materials and Method: Thirty human single-rooted teeth were prepared using hand instruments and the step-back technique, filled with gutta-percha, sealed with AH Plus (Dentsply), and divided into three groups: A: rinsed with NaCl; B: rinsed with 2% chlorhexidine (CHX); C: not rinsed before cementation of posts. The fiber posts were set using RelyX and Built-it. The tooth roots were sliced and the push-out test was performed. The area of contact between the post and dentin was calculated and the destroying force was established. The results were statistically analyzed. R e s u l t s: The mean adhesive strength was 10.69 MPa in group A, 16.33 MPa in group B, and 16.72 MPa in C. The adhesive strength in group B and C was statistically significantly higher than in group A (p = 0.0016, ANOVA). Conclusion: Rinsing root canals with CHX seems to be the most effective method prior to setting a fiber post.

PMID:35180204 | DOI:10.24425/fmc.2021.140006

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Nevin Manimala Statistics

Thrombin Generation in Cardiac Versus Noncardiac Surgical Cohorts

Anesth Analg. 2022 Mar 1;134(3):606-614. doi: 10.1213/ANE.0000000000005840.

ABSTRACT

BACKGROUND: Bleeding can be a significant problem after cardiac surgery. As a result, venous thromboembolism (VTE) or anticoagulation or both following mechanical valve implantation are often delayed in these patients. The calibrated automated thrombin (CAT) generation assay has become the gold standard to evaluate thrombin generation, a critical step in clot formation independent of other hemostatic processes (eg, platelet activation, fibrin cross-linking, and fibrinolysis), and is increasingly used to examine thrombotic and hemorrhagic outcomes. No study has currently used this assay to compare the thrombin generation profiles of cardiac surgical patients to noncardiac surgical patients. We hypothesize that noncardiac patients may be less prone to postoperative changes in thrombin generation.

METHODS: A prospective, observational, cohort study was undertaken using blood samples from 50 cardiac and 50 noncardiac surgical patients preoperatively, immediately postoperatively, and on postoperative days 1 to 4. Platelet-poor plasma samples were obtained from patients preoperatively, on arrival to the postanesthesia care unit (PACU) or intensive care unit (ICU), and daily on postoperative days 1 to 4 if patients remained inpatient. Samples were evaluated for CAT measurements. Patient and surgical procedure characteristics were obtained from the electronic medical record.

RESULTS: The primary outcome variable, median endogenous thrombin potential (ETP), measured in nanomolar × minutes (nM × min), was decreased 100% in cardiac surgical versus 2% in noncardiac patients (P < .001). All parameters of thrombin generation were similarly depressed. Cardiac (versus noncardiac) surgical type was associated with -76.5% difference of percent change in ETP on multivariable regression analysis (95% confidence interval [CI], -87.4 to -65.5; P value <.001).

CONCLUSIONS: Cardiac surgical patients exhibit a profound decrease in thrombin generation postoperatively compared with noncardiac surgical patients evaluated by this study. Hemodilution and coagulation factor depletion likely contribute to this decreased thrombin generation after cardiac surgery.

PMID:35180177 | DOI:10.1213/ANE.0000000000005840

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Nevin Manimala Statistics

Association Between Changes in Postoperative Opioid Utilization and Long-Term Health Care Spending Among Surgical Patients With Chronic Opioid Utilization

Anesth Analg. 2022 Mar 1;134(3):515-523. doi: 10.1213/ANE.0000000000005865.

ABSTRACT

BACKGROUND: There is growing interest in identifying and developing interventions aimed at reducing the risk of increased, long-term opioid use among surgical patients. While understanding how these interventions impact health care spending has important policy implications and may facilitate the widespread adoption of these interventions, the extent to which they may impact health care spending among surgical patients who utilize opioids chronically is unknown.

METHODS: This study was a retrospective analysis of administrative health care claims data for privately insured patients. We identified 53,847 patients undergoing 1 of 10 procedures between January 1, 2004, and September 30, 2018 (total knee arthroplasty, total hip arthroplasty, laparoscopic cholecystectomy, open cholecystectomy, laparoscopic appendectomy, open appendectomy, cesarean delivery, functional endoscopic sinus surgery, transurethral resection of the prostate, or simple mastectomy) who had chronic opioid utilization (≥10 prescriptions or ≥120-day supply in the year before surgery). Patients were classified into 3 groups based on differences in opioid utilization, measured in average daily oral morphine milligram equivalents (MMEs), between the first postoperative year and the year before surgery: “stable” (<20% change), “increasing” (≥20% increase), or “decreasing” (≥20% decrease). We then examined the association between these 3 groups and health care spending during the first postoperative year, using a multivariable regression to adjust for observable confounders, such as patient demographics, medical comorbidities, and preoperative health care utilization.

RESULTS: The average age of the sample was 62.0 (standard deviation [SD] 13.1) years, and there were 35,715 (66.3%) women. Based on the change in average daily MME between the first postoperative year and the year before surgery, 16,961 (31.5%) patients were classified as “stable,” 15,463 (28.7%) were classified as “increasing,” and 21,423 (39.8%) patients were classified as “decreasing.” After adjusting for potential confounders, “increasing” patients had higher health care spending ($37,437) than “stable” patients ($31,061), a difference that was statistically significant ($6377; 95% confidence interval [CI], $5669-$7084; P < .001), while “decreasing” patients had lower health care spending ($29,990), a difference (-$1070) that was also statistically significant (95% CI, -$1679 to -$462; P = .001). These results were generally consistent across an array of subgroup and sensitivity analyses.

CONCLUSIONS: Among patients with chronic opioid utilization before surgery, subsequent increases in opioid utilization during the first postoperative year were associated with increased health care spending during that timeframe, while subsequent decreases in opioid utilization were associated with decreased health care spending.

PMID:35180168 | DOI:10.1213/ANE.0000000000005865

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Nevin Manimala Statistics

Health Services Research in Anesthesia: A Brief Overview of Common Methodologies

Anesth Analg. 2022 Mar 1;134(3):540-547. doi: 10.1213/ANE.0000000000005884.

ABSTRACT

The use of large data sources such as registries and claims-based data sets to perform health services research in anesthesia has increased considerably, ultimately informing clinical decisions, supporting evaluation of policy or intervention changes, and guiding further research. These observational data sources come with limitations that must be addressed to effectively examine all aspects of health care services and generate new individual- and population-level knowledge. Several statistical methods are growing in popularity to address these limitations, with the goal of mitigating confounding and other biases. In this article, we provide a brief overview of common statistical methods used in health services research when using observational data sources, guidance on their interpretation, and examples of how they have been applied to anesthesia-related health services research. Methods described involve regression, propensity scoring, instrumental variables, difference-in-differences, interrupted time series, and machine learning.

PMID:35180171 | DOI:10.1213/ANE.0000000000005884

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Nevin Manimala Statistics

The Association Between Timing of Elective Surgery Scheduling and Operating Theater Utilization: A Cross-Sectional Retrospective Study

Anesth Analg. 2022 Mar 1;134(3):455-462. doi: 10.1213/ANE.0000000000005871.

ABSTRACT

BACKGROUND: Overutilization of operating theaters (OTs) occurs when actual surgery duration exceeds scheduled duration, which could potentially result in delays or cancelations in subsequent surgeries. We investigate the association between the timing of elective surgery scheduling and OT overutilization.

METHODS: A cross-sectional retrospective study was conducted using electronic health record data of 27,423 elective surgeries from July 1, 2016, to July 31, 2018, at a mid-Atlantic academic medical center with 56 OTs. The scheduling precision of each surgery is measured using the ratio of the actual (A) over the scheduled or forecast (F) length of surgery to derive the predictor variable of A/F (actual-to-forecast ratio [AF]). Student t test and χ2 tests analyzed differences between OTs reserved within and over 7 days of surgery for continuous and dichotomous variables, respectively. Hierarchical regression models, controlling for potential confounds from the hospital environment, clinicians’ work experience and workloads, patient factors, scheduled OT length, and operational and team factors isolated the association between OTs reserved within 7 days of the elective surgery with AF.

RESULTS: The Student t test indicates that OTs reserved within 7 days of surgery had significantly higher AF (1.13 ± 0.53 vs 1.08 ± 0.41; P < .001). In-depth Student t test analyses for 4 patient groups, namely, outpatient, extended recovery, admission after surgery, and inpatient, indicate that AF was only significantly different for OTs reserved within 7 days for the admission after surgery group (1.15 ± 0.47 vs 1.09 ± 0.35; P < .001) but did not reach statistical significance among the outpatient, extended recovery, and inpatient groups. After controlling for potential confounds, hierarchical regression for the admission after surgery group reveals that OTs reserved within 7 days took 2.7% longer than the scheduled length of surgery (AFbeta, 0.027; 95% CI, 0.003-0.051; P = .027).

CONCLUSIONS: Elective surgeries scheduled within 7 days of surgery were associated with significantly higher likelihood of OT overutilization for surgical patients who will be admitted after surgery. Further studies at other hospitals and a longer period of time are needed to ascertain a potential “squeeze-in” effect.

PMID:35180161 | DOI:10.1213/ANE.0000000000005871