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Nevin Manimala Statistics

Researcher degrees of freedom in statistical software contribute to unreliable results: A comparison of nonparametric analyses conducted in SPSS, SAS, Stata, and R

Behav Res Methods. 2022 Aug 11. doi: 10.3758/s13428-022-01932-2. Online ahead of print.

ABSTRACT

Researcher degrees of freedom can affect the results of hypothesis tests and consequently, the conclusions drawn from the data. Previous research has documented variability in accuracy, speed, and documentation of output across various statistical software packages. In the current investigation, we conducted Pearson’s chi-square test of independence, Spearman’s rank-ordered correlation, Kruskal-Wallis one-way analysis of variance, Wilcoxon Mann-Whitney U rank-sum tests, and Wilcoxon signed-rank tests, along with estimates of skewness and kurtosis, on large, medium, and small samples of real and simulated data in SPSS, SAS, Stata, and R and compared the results with those obtained through hand calculation using the raw computational formulas. Multiple inconsistencies were found in the results produced between statistical packages due to algorithmic variation, computational error, and statistical output. The most notable inconsistencies were due to algorithmic variations in the computation of Pearson’s chi-square test conducted on 2 × 2 tables, where differences in p-values reported by different software packages ranged from .005 to .162, largely as a function of sample size. We discuss how such inconsistencies may influence the conclusions drawn from the results of statistical analyses depending on the statistical software used, and we urge researchers to analyze their data across multiple packages to check for inconsistencies and report details regarding the statistical procedure used for data analysis.

PMID:35953660 | DOI:10.3758/s13428-022-01932-2

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Nevin Manimala Statistics

Computed Tomography-Guided Coeliac Plexus Neurolysis in Palliative in-Patients with Intra-Abdominal Malignancy: Retrospective Evaluation of Neurolytic Solution Spread as a Predictive Factor

Pain Ther. 2022 Aug 11. doi: 10.1007/s40122-022-00423-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Computed tomography (CT)-guided coeliac plexus neurolysis (CPN) is considered effective at controlling pain in patients with intra-abdominal malignancies. The primary objective was to correlate pain outcomes with the spread of neurolytic solution in the coeliac area and to evaluate the predictive value for the spread of injectate for pain outcomes and side effects.

METHODS: Blinded CT scans were reviewed. The coeliac area was divided into nine quadrants. Assessors evaluated quadrants according to contrast spread, needle tip position, and the contact between the injectate and other organs and plexuses. Efficacy of CPN and complications were estimated.

RESULTS: In 54.9% there was complete spread of the neurolytic in the coeliac area with no correlation between pain relief and spread of injectate. In 85% the neurolytic had contact with viscera with no correlation with pain relief or complications. There was no correlation between needle tip position and spread of the neurolytic and contact of the neurolytic with viscera. In 71.6% the injectate was found to have spread into “other” plexuses. In 13.3% hampered spread of the injectate was observed. There was no correlation between patterns of injectate spread and pain relief, pain relief and spread of injectate in any particular quadrants, and expected and documented post-procedural pain scores.

CONCLUSIONS: Based on the spread of contrast medium clinicians can neither correctly anticipate the pain relief or post-procedural NRS, nor the duration of pain relief and complications. It is not essential to have the perfect sickle-shaped spread of the injectate for adequate pain control.

PMID:35953656 | DOI:10.1007/s40122-022-00423-8

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Nevin Manimala Statistics

Coenzyme Q10, Biochanin A and Phloretin Attenuate Cr(VI)-Induced Oxidative Stress and DNA Damage by Stimulating Nrf2/HO-1 Pathway in the Experimental Model

Biol Trace Elem Res. 2022 Aug 12. doi: 10.1007/s12011-022-03358-5. Online ahead of print.

ABSTRACT

Hexavalent chromium [Cr(VI)] has emerged as a prevailing environmental and occupational contaminant over the past few decades. However, the knowledge is sparse regarding Cr(VI)-induced neurological aberrations, and its remediation through natural bioactive compounds has not been fully explored. This study intended to probe the possible invigorative effects of nutraceuticals such as coenzyme Q10 (CoQ10), biochanin A (BCA), and phloretin (PHL) on Cr(VI) intoxicated Swiss albino mice with special emphasis on Nrf2/HO-1/NQO1 gene expressions. Mice received potassium dichromate (75 ppm) through drinking water and were simultaneously co-treated intraperitoneally with CoQ10 (10 mg/kg), BCA, and PHL (50 mg/kg) each for 30-day treatment period. The statistics highlight the elevated levels of lipid peroxidation (LPO) and protein carbonyl content (PCC) with a concomitant reduction in the superoxide dismutase (SOD), glutathione-S-transferase (GST), reduced glutathione (GSH), total thiols (TT), catalase (CAT), and cholinesterase activities in the Cr(VI)-exposed mice. The collateral assessment of DNA fragmentation, DNA breakages, and induced histological alterations was in conformity with the above findings in conjugation with the dysregulation in the Nrf2 and associated downstream HO-1 and NQO1 gene expressions. Co-treatment with the selected natural compounds reversed the above-altered parameters significantly, thereby bringing cellular homeostasis in alleviating the Cr(VI)-induced conciliated impairments. Our study demonstrated that the combination of different bioactive compounds shields the brain better against Cr(VI)-induced neurotoxicity by revoking the oxidative stress-associated manifestations. These compounds may represent a new potential combination therapy due to their ability to modulate the cellular antioxidant responses by upregulating the Nrf2/HO-1/NQO1 signaling pathway against Cr(VI)-exposed population. HIGHLIGHTS: Cr(VI)-associated heavy metal exposure poses a significant threat to the environment, especially to living organisms. Cr(VI) exposure for 30 days resulted in the free radical’s generation that caused neurotoxicity in the Swiss albino mice. Natural compounds such as coenzyme Q10, biochanin A, and phloretin counteracted the neurotoxic effect due to Cr(VI) exposure in scavenging of free radicals by enhancing Nrf2/HO-1/NQO1 gene expressions in maintaining the cellular homeostasis.

PMID:35953644 | DOI:10.1007/s12011-022-03358-5

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Nevin Manimala Statistics

Global prevalence of cerebral palsy: A systematic analysis

Dev Med Child Neurol. 2022 Aug 11. doi: 10.1111/dmcn.15346. Online ahead of print.

ABSTRACT

AIM: To determine trends and current estimates in regional and global prevalence of cerebral palsy (CP).

METHOD: A systematic analysis of data from participating CP registers/surveillance systems and population-based prevalence studies (from birth year 1995) was performed. Quality and risk of bias were assessed for both data sources. Analyses were conducted for pre-/perinatal, postnatal, neonatal, and overall CP. For each region, trends were statistically classified as increasing, decreasing, heterogeneous, or no change, and most recent prevalence estimates with 95% confidence intervals (CI) were calculated. Meta-analyses were conducted to determine current birth prevalence estimates (from birth year 2010).

RESULTS: Forty-one regions from 27 countries across five continents were represented. Pre-/perinatal birth prevalence declined significantly across Europe and Australia (11 out of 14 regions), with no change in postneonatal CP. From the limited but increasing data available from regions in low- and middle-income countries (LMICs), birth prevalence for pre-/perinatal CP was as high as 3.4 per 1000 (95% CI 3.0-3.9) live births. Following meta-analyses, birth prevalence for pre-/perinatal CP in regions from high-income countries (HICs) was 1.5 per 1000 (95% CI 1.4-1.6) live births, and 1.6 per 1000 (95% CI 1.5-1.7) live births when postneonatal CP was included.

INTERPRETATION: The birth prevalence estimate of CP in HICs declined to 1.6 per 1000 live births. Data available from LMICs indicated markedly higher birth prevalence.

PMID:35952356 | DOI:10.1111/dmcn.15346

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Nevin Manimala Statistics

Change in reflective functioning in interpersonal psychotherapy and cognitive behavioral therapy for major depressive disorder

Psychother Res. 2022 Aug 11:1-8. doi: 10.1080/10503307.2022.2109443. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with Major Depressive Disorder (MDD) have been found to have restricted capacity for mentalization, and it is possible that this constitutes a vulnerability factor for developing depression. Due to its focus on linking depressive symptomatology to emotions and interpersonal relations, it was hypothesized that Interpersonal Psychotherapy (IPT) would improve mentalization more than Cognitive Behavioral Therapy (CBT).

METHODS: In a randomized controlled trial of 90 patients undergoing IPT and CBT for MDD, Reflective Functioning (RF) was rated from Adult Attachment and from Depression-Specific Reflective Functioning (DSRF) Interviews before and after therapy. Treatment outcome was assessed using the Beck Depression Inventory-II.

RESULTS: The interaction between time and treatment approach was statistically significant, with RF improving significantly more in IPT than in CBT. Change in RF was not correlated with change in depression. The difference in DSRF ratings before and after therapy was not statistically significant for any of the treatments.

CONCLUSIONS: IPT may improve mentalization more than CBT. However, although RF increased significantly in IPT, the mean level was still low after therapy. A limitation of the study is the large amount of post-treatment missing data. More research is needed to understand the potential role of mentalization in symptom reduction.

PMID:35952325 | DOI:10.1080/10503307.2022.2109443

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Nevin Manimala Statistics

Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients With Non-Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

JCO Precis Oncol. 2022 Aug;6:e2100372. doi: 10.1200/PO.21.00372.

ABSTRACT

PURPOSE: As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed through a standardized approach by assessing clinical trial data from five independent studies.

PATIENTS AND METHODS: Patient-level clinical and ctDNA data were pooled and harmonized from 200 patients across five independent clinical trials investigating the treatment of patients with non-small-cell lung cancer with programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1)-directed monotherapy or in combination with chemotherapy. CtDNA levels were measured using different ctDNA assays across the studies. Maximum variant allele frequencies were calculated using all somatic tumor-derived variants in each unique patient sample to correlate ctDNA changes with overall survival (OS) and progression-free survival (PFS).

RESULTS: We observed strong associations between reductions in ctDNA levels from on-treatment liquid biopsies with improved OS (OS; hazard ratio, 2.28; 95% CI, 1.62 to 3.20; P < .001) and PFS (PFS; hazard ratio 1.76; 95% CI, 1.31 to 2.36; P < .001). Changes in the maximum variant allele frequencies ctDNA values showed strong association across different outcomes.

CONCLUSION: In this pooled analysis of five independent clinical trials, consistent and robust associations between reductions in ctDNA and outcomes were found across multiple end points assessed in patients with non-small-cell lung cancer treated with an ICI. Additional tumor types, stages, and drug classes should be included in future analyses to further validate this. CtDNA may serve as an important tool in clinical development and an early indicator of treatment benefit.

PMID:35952319 | DOI:10.1200/PO.21.00372

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Nevin Manimala Statistics

Immunoscore Is Prognostic in Low-Risk and High-Risk Stage III Colon Carcinomas Treated With Adjuvant Infusional Fluorouracil, Leucovorin, and Oxaliplatin in a Phase III Trial

JCO Precis Oncol. 2022 Aug;6:e2200010. doi: 10.1200/PO.22.00010.

ABSTRACT

PURPOSE: The recommended duration of adjuvant fluoropyrimidine and oxaliplatin chemotherapy for patients with stage III colon cancer is based on tumor classification into clinically low-risk (T1-3 N1) and high-risk (T4 or N2) groups. We determined whether Immunoscore can enhance prognostication within these risk groups.

MATERIALS AND METHODS: Patients with stage III colon carcinomas (N = 600) were randomly selected from the infusional fluorouracil, leucovorin, and oxaliplatin arm of adjuvant trial NCCTG N0147 (Alliance for Clinical Trials in Oncology). Tumors were evaluated for Immunoscore that quantifies CD3+ and CD8+ T-cell densities in the tumor center and invasive margin by digital image analysis. Disease-free survival (DFS) by Immunoscore was analyzed using a multivariable Cox regression model in each risk group with adjustment for covariates including KRAS, BRAFV600E, and mismatch repair status.

RESULTS: Of 559 cancers with Immunoscore data, 299 (53.5%) were classified as clinically low-risk (T1-3 N1) and 260 (46.5%) as clinically high-risk (T4 and/or N2). Among patients with low-risk tumors, those with Immunoscore-Low versus Immunoscore-High tumors had significantly worse 5-year DFS rates (77.5% v 91.8%; hazard ratio, 1.70; 95% CI, 1.03 to 2.79; P = .037). Among patients with high-risk tumors, those with Immunoscore-Low versus Immunoscore-High tumors also had significantly worse DFS (55.3% v 70.3%; hazard ratio, 1.65; 95% CI, 1.11 to 2.47; P = .013). Tumors that were low-risk/Immunoscore-Low had similar outcomes as did tumors that were high-risk/Immunoscore-High (P = .174). Prognostication was significantly improved in multivariable models where Immunoscore was added to clinical risk parameters and limited biomarkers (likelihood ratio test P = .0003).

CONCLUSION: Immunoscore can refine patient prognosis beyond clinical risk group classification, suggesting its potential utility for adjuvant decision making.

PMID:35952316 | DOI:10.1200/PO.22.00010

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Nevin Manimala Statistics

Ultrasound-guided Targeted vs. Regional Flooding: A Comparative Study for Improving the Clinical Outcome in Soft Tissue Filler Vascular Adverse Event Management

Aesthet Surg J. 2022 Aug 11:sjac227. doi: 10.1093/asj/sjac227. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse vascular event management following hyaluronic acid-based aesthetic injections relies on the administration of hyaluronidase which is capable to enzymatically degrade the injected product and to improve clinical symptoms. Two protocols are currently available to manage such complications: “ultrasound guided targeted” and “flooding”.

OBJECTIVES: To compare the 2 protocols by means of amount of hyaluronidase volume utilized, and onset and degree of clinical improvement.

METHODS: A comparative case series of 39 patients was retrospectively evaluated which were initially treated with the “flooding” protocol and then treated with the “ultrasound guided targeted” due to no or little improvement.

RESULTS: The “ultrasound-guided targeted” protocol utilized a total of 122.5 iu (34) whereas the “flooding” protocol utilized 1519.4 iu (1137) which represents a statistically significant reduced amount of injected hyaluronidase with p = 0.028. There was no clinical improvement in 92.3% and only little improvement in 7.7% of the treated patients following the first applied “flooding” protocol but there was a 100% immediate improvement when treated with the “ultrasound-guided targeted” protocol. Ultrasound imaging revealed that the application of hyaluronidase normal blood flow was restored both in the perivascular space and in the superficially located subdermal soft tissues.

CONCLUSIONS: Despite its limitations in study design, this retrospectively evaluated case series revealed that the ultrasound guided targeted protocol utilized less hyaluronidase material and restored faster clinically visible symptoms. The effect of this protocol is best explained by the perforasome concept which will need to be investigated further in future studies.

PMID:35951759 | DOI:10.1093/asj/sjac227

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Nevin Manimala Statistics

Mobilization with reduced cyclophosphamide for autologous stem cell transplantation is feasible in patients with systemic sclerosis

Rheumatology (Oxford). 2022 Aug 11:keac455. doi: 10.1093/rheumatology/keac455. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the feasibility of reduced cyclophosphamide dosing in the setting of mobilization chemotherapy prior high dose chemotherapy and autologous stem cell transplantation in patients with systemic sclerosis. The primary end point was the occurrence of ‘poor mobilization’ when using different cyclophosphamide dosing. The second end point was to analyze potential risk factors for difficult stem cell mobilization in this cohort of patients with systemic sclerosis.

METHODS: This single-center study retrospectively reviewed 32 patients with systemic sclerosis who underwent autologous stem cell transplantation. We analyze the occurrence of ‘poor mobilization’ (defined as CD34+ progenitor cell count < 2 x 106/kg body weight, the use of increasing G-CSF dose, the use of plerixafor, or leukapheresis on > 2 consecutive days) in different cyclophosphamide mobilization regimens: We herein compared low dose (2×1-1.5g/m2) cyclophosphamide vs high dose (2x2g/m2) for mobilization.

RESULTS: Higher dosing of cyclophosphamide seems not to be beneficial regarding stem cell collection as there was no significant difference in stem cell yield between high dose and reduced dose cyclophosphamide (6.2 vs 5.2 x106/kg bodyweight after CD34+ enrichment). Furthermore, higher doses of cyclophosphamide might be associated with more side effects, this difference was however not statistically significant. Lower bodyweight and BMI (p< 0.001) as well as Rituximab pre-therapy (p< 0.05) and cardiac involvement (p< 0.01) might negatively impact stem cell collection independently from the chosen regimen.

CONCLUSION: Our data demonstrate that a reduced cyclophosphamide mobilization regimen seems to be feasible. Risk factors for poor mobilization might be low bodyweight, prior rituximab therapy and cardiac involvement.

PMID:35951758 | DOI:10.1093/rheumatology/keac455

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Nevin Manimala Statistics

Approximations to the expectations and variances of ratios of tree properties under the coalescent

G3 (Bethesda). 2022 Aug 11:jkac205. doi: 10.1093/g3journal/jkac205. Online ahead of print.

ABSTRACT

Properties of gene genealogies such as tree height (H), total branch length (L), total lengths of external (E) and internal (I) branches, mean length of basal branches (B), and the underlying coalescence times (T) can be used to study population-genetic processes and to develop statistical tests of population-genetic models. Uses of tree features in statistical tests often rely on predictions that depend on pairwise relationships among such features. For genealogies under the coalescent, we provide exact expressions for Taylor approximations to expected values and variances of ratios Xn/Yn, for all 15 pairs among the variables {Hn, Ln, En, In, Bn, Tk}, considering n leaves and 2 ≤ k ≤ n. For expected values of the ratios, the approximations match closely with empirical simulation-based values. The approximations to the variances are not as accurate, but they generally match simulations in their trends as n increases. Although En has expectation 2 and Hn has expectation 2 in the limit as n → ∞, the approximation to the limiting expectation for En/Hn is not 1, instead equaling π2/3-2 ≈ 1.28987. The new approximations augment fundamental results in coalescent theory on the shapes of genealogical trees.

PMID:35951748 | DOI:10.1093/g3journal/jkac205