scholarly journals Stepwise Procedure for Toxicological Assessment Based on Ratio of Mean Differences for a Normally Distributed Data

Author(s):  
Michael J. Adjabui ◽  
Jakperik Dioggban ◽  
Nathaniel K. Howard

We propose a new stepwise confidence set procedure for toxicity study based on ratio of mean difference. Statistical approaches for evaluating toxicity studies that properly control familywise error rate (FWER) for difference of means between treatments and a control already exist. However, in some therapeutic areas, ratio of mean differences is desirable. Therefore, we construct stepwise confidence procedure based on Fieller's confidence intervals for multiple ratio of mean difference without multiplicity adjustment for toxicological evaluation. Simulation study revealed that the FWER is well controlled at prespecified nominal level α. Also, the power of our approach increases with increasing sample size and ratio of mean differences.

2021 ◽  
Vol 16 (3) ◽  
pp. 2911-2922
Author(s):  
Michael Jackson Adjabui ◽  
John Ayuekanbey Awaab ◽  
Jakperik Dioggban

This paper proposes a stepwise confidence set procedure for identifying equivalence or safety of compounds in a toxicity study under heteroscedasticity of variances for a normally distributed data. The problem of statistical methodology for drug safety is the control of the familywise error rate (FWER). Hence, we construct a confidence set procedure for toxicological evaluation and incorporating the partitioning principle with a case of heteroscedascity of variances under normal assumption. Our simulation studies demonstrated that the power of the procedures for heterogeneity of variances increases with increasing in ratio of means.


2021 ◽  
pp. bjophthalmol-2020-317664
Author(s):  
Carly SY Lam ◽  
Wing Chun Tang ◽  
Paul H Lee ◽  
Han Yu Zhang ◽  
Hua Qi ◽  
...  

AimsTo determine myopia progression in children who continued to wear the defocus incorporated multiple segments (DIMS) lenses or switched from single vision (SV) to DIMS lenses for a 1-year period following a 2-year myopia control trial.Methods128 children participated in this study. The children who had worn DIMS lenses continued to wear DIMS lenses (DIMS group), and children who had worn SV lenses switched to wear DIMS lenses (Control-to-DIMS group). Cycloplegic spherical equivalent refraction (SER) and axial length (AL) were measured at 6-month interval. Historical controls were age matched to the DIMS group at 24 months and used for comparing the third-year changes.ResultsOver 3 years, SER and AL changes in the DIMS group (n=65) were −0.52±0.69D and 0.31±0.26 mm; these changes were not statistically significant over time (repeated measures analysis of variance, p>0.05).SER (−0.04±0. 38D) and AL (0.08±0.12 mm) changes in the Control-to-DIMS group (n=55) in the third year were less compared with the first (mean difference=0.45 ± 0.30D, 0.21±0.11 mm, p<0.001) and second (0.34±0.30D, 0.12±0.10 mm, p<0.001) years.Changes in SER and AL in both groups over that period were significantly less than in the historical control group (DIMS vs historical control: mean difference=−0.18±0.42D, p=0.012; 0.08±0.15 mm, p=0.001; Control-to-DIMS versus historical control: adjusted mean differences=−0.30±0.42D, p<0.001; 0.12±0.16 mm, p<0.001).ConclusionsMyopia control effect was sustained in the third year in children who had used the DIMS spectacles in the previous 2 years and was also shown in the children switching from SV to DIMS lenses.


2021 ◽  
Vol 11 (15) ◽  
pp. 6994
Author(s):  
Hasnain Q. R. B. Khan ◽  
Gwendolen C. Reilly

The aim was to explore the body of literature focusing on protective treatments against endothelial glycocalyx degradation in surgery. A comprehensive systematic review of relevant articles was conducted across databases. Inclusion criteria: (1) treatments for the protection of the endothelial glycocalyx in surgery; (2) syndecan-1 used as a biomarker for endothelial glycocalyx degradation. Outcomes analysed: (1) mean difference of syndecan-1 (2) correlation between glycocalyx degradation and inflammation; (3) correlation between glycocalyx degradation and extravasation. A meta-analysis was used to present mean differences and 95% confidence intervals. Seven articles with eight randomised controlled trials were included. The greatest change from baseline values in syndecan-1 concentrations was generally from the first timepoint measured post-operatively. Interventions looked to either dampen the inflammatory response or fluid therapy. Methylprednisolone had the highest mean difference in plasma syndecan-1 concentrations. Ulinastatin showed correlations between alleviation of degradation and preserving vascular permeability. In this systematic review of 385 patients, those treated were more likely than those treated with placebo to exhibit less shedding of the endothelial glycocalyx. Methylprednisolone has been shown to specifically target the transient increase of glycocalyx degradation immediately post-operation and has displayed anti-inflammatory effects. We have proposed suggestions for improved uniformity and enhanced confidence for future randomised controlled trials.


2018 ◽  
Vol 7 (5) ◽  
pp. 419-424
Author(s):  
Abiodun Olusoji Owoade ◽  
◽  
Adewale Adetutu ◽  
Augustine Ikhueoya Airaodion ◽  
Olufemi Ogundeji Ogundipe ◽  
...  

This study evaluated the acute and subacute toxicity effects of Bridelia ferrugelia leaf extract. Observation of the acute group showed that LD50 of the extract is greater than 2000 mg/kg. The subacute investigation was determined by administering 200 mg/kg, 400 mg/kg and 600 mg/kg of the methanolic leaf extract to male Wistar rats for 28 days with distilled water as a control. Haematological and biochemical parameters, as well as lipid levels of vital organs, were examined. Toxicological evaluation of the extract did not produce any significant change in haematological and biochemical parameters in rats. In addition, blood lipids levels were not significantly affected, while dyslipidaemia effect observed in some vital organs were found to be nonlipotoxic. Administration of Bridelia ferrugelia at a dose of 200, 400 and 600 mg/kg for 28 days resulted in reduction of cardiac cholesterol level by 37.16%, 39.36% and 17.64% respectively, reduction of pulmonary cholesterol by 22.17%, 28.08% and 6.24 % respectively and dose-dependent decrease in pulmonary triglyceride level by 16.17, 29.14 and 54.25% respectively. This study indicates that Bridelia ferrugelia extract administered at 200, 400 and 600 mg/kg did not show any toxic effect on the parameters investigated in rats. Thus, the extract can be considered safe when administered orally


2021 ◽  
Vol 8 ◽  
Author(s):  
Alberto Domínguez-Rodríguez ◽  
Pedro Abreu-González ◽  
Néstor Báez-Ferrer ◽  
Russel J. Reiter ◽  
Pablo Avanzas ◽  
...  

Myocardial ischemia/reperfusion (IR) injury represents a critical problem associated with interventional approaches for coronary reperfusion. Pharmacological cardioprotective interventions are advocated to ameliorate IR injury. Melatonin is an anti-inflammatory and antioxidant agent with a wide range of therapeutic properties that may contribute to its cardioprotective effects. No systematic review or meta-analysis has compared melatonin vs. placebo as a cardioprotective agent in humans. The present study, based on a systematic review and meta-analysis, was carried out to assess melatonin's efficacy as a cardioprotective treatment. We performed a systematic review of the available literature. Randomized controlled trials (RCTs) were identified and information was extracted using predefined data extraction forms. The primary outcomes were (a) left ventricular ejection fraction (LVEF) and (b) blood troponin levels in patients who underwent myocardial revascularization and were randomized to melatonin or placebo. The inverse-variance random-effects method was used to pool the estimates. Heterogeneity and publication bias were assessed. Weighted mean differences or standardized mean differences were calculated. A total of 283 records were screened and seven RCTs met all the inclusion criteria. After the pooled analysis, the results on LVEF were consistent across all studies, and a significant heterogeneity was found in the results on troponin levels. The melatonin-treated patients had on average higher LVEF than the placebo-treated individuals with a weighted mean difference = 3.1% (95% CI 0.6–5.5, p = 0.01). Five works compared the levels of troponin after melatonin or placebo treatment. The melatonin-treated patients had lower levels of troponin with a standardized mean difference = −1.76 (95% CI −2.85 to −0.67, p = 0.002). The findings of this meta-analysis revealed that melatonin administration in humans as a cardioprotective agent attenuated heart dysfunction with a favorable effect on the LVEF.


2018 ◽  
Vol 43 (10) ◽  
pp. 1027-1032
Author(s):  
Tiago V. Barreira ◽  
Jessica G. Redmond ◽  
Tom D. Brutsaert ◽  
John M. Schuna ◽  
Emily F. Mire ◽  
...  

The purpose of this study was to test whether estimates of bedtime, wake time, and sleep period time (SPT) were comparable between an automated algorithm (ALG) applied to waist-worn accelerometry data and a sleep log (LOG) in an adult sample. A total of 104 participants were asked to log evening bedtime and morning wake time and wear an ActiGraph wGT3X-BT accelerometer at their waist for 24 h/day for 7 consecutive days. Mean difference and mean absolute difference (MAD) were computed. Pearson correlations and dependent-sample t tests were used to compare LOG-based and ALG-based sleep variables. Effect sizes were calculated for variables with significant mean differences. A total of 84 participants provided 2+ days of valid accelerometer and LOG data for a total of 368 days. There was no mean difference (p = 0.47) between LOG 472 ± 59 min and ALG SPT 475 ± 66 min (MAD = 31 ± 23 min, r = 0.81). There was no significant mean difference between bedtime (2348 h and 2353 h for LOG and ALG, respectively; p = 0.14, MAD = 25 ± 21 min, r = 0.92). However, there was a significant mean difference between LOG (0741 h) and ALG (0749 h) wake times (p = 0.01, d = 0.11, MAD = 24 ± 21 min, r = 0.92). The LOG and ALG data were highly correlated and relatively small differences were present. The significant mean difference in wake time might not be practically meaningful (Cohen’s d = 0.11), making the ALG useful for sample estimates. MAD, which gives a better estimate of the expected differences at the individual level, also demonstrated good evidence supporting ALG individual estimates.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Sverre Nestaas ◽  
Vigdis Rosseland ◽  
Knut Haakon Steensaeth ◽  
Jo Kramer-Johansen

Introduction: Recommended chest compression depth during cardiopulmonary resuscitation (CPR) for adults was increased to 5-6 cm in 2010. According to the cardiac pump theory each compression squeezes blood from the heart and the amount of blood per compression would be expected to be limited by the blood filled structures directly underneath the compression point. Methods: Cardiovascular MR (CMR) survey axial scans acquired from consenting patients referred for CMR were analyzed. We measured the external anterior-posterior (AP) diameter (AP) and the cumulative height of blood-filled structures in the perpendicular line in an axial plane from the compression point in the center of the inter-nipple line (INL) (Compression line). Results are means with standard deviation (SD) and mean differences with 95 % confidence intervals (CI), P-values from unpaired, two-sided t-test. Results: We included 144 patients, age 52 (17), 110 (76 %) males, 74 (60 %) having one or more pathological finding from the exam. The most prominent structure identified in the studied midline was (decreasing order): Left Atrium (41 %), Right Ventricle (31 %), Right Atrium (12 %), Left Ventricular Outflow Tract (LVOT)/Root of Aorta (8 %), Pulmonary Outflow Tract (2 %), other (6 %). Altogether, LVOT was present in 35 % and Left Ventricle in only 2 % of compression lines. Mean (SD) AP diameter for males and females was 25 (2) cm and 22 (2) cm (mean difference 2 cm (95 % CI 1, 3; P<0.001)), and the blood filled length of the compression line (APblood) were 6.5 cm (2) and 4.7 cm (2) (mean difference 1.8 cm (95 % CI 1.1, 2.5, P<0.001)), respectively. This comprised 22 % (10) and 26 % (7) of the AP diameter, for men and women, respectively. In a linear regression gender, body mass index (BMI), but not pathological findings were significant predictors of external AP diameter. Only gender was found to predict APblood. Conclusions: In the average male 5-6 cm chest compression depth at the level of the INL seems feasible, but for over half of the women compressions deeper than 5 cm would probably compress connective and muscle tissue rather than just squeeze blood from the heart, even though the blood-filled proportion of the AP diameter was larger in women than in men.


2019 ◽  
Vol 73 (8) ◽  
pp. 786-792 ◽  
Author(s):  
Anne Marie Darling ◽  
Martha M Werler ◽  
David E Cantonwine ◽  
Wafaie W Fawzi ◽  
Thomas F McElrath

BackgroundInterpolation of missing weight values is sometimes used in studies of gestational weight gain, but the accuracy of these methods has not been established. Our objective was to assess the accuracy of estimated weight values obtained by interpolating from the nearest observed weight values and by linear and spline regression models when compared with measured weight values.MethodsThe study population included participants enrolled in the LIFECODES cohort at Brigham and Women’s Hospital. We estimated weights at 28 (n=764) and 40 (n=382) weeks of gestation using participants’ two nearest observed weights and subject-specific slopes and intercepts derived from repeated measures mixed effects models. In separate models, gestational age was parameterised as a linear and restricted cubic spline variable. Mean differences, absolute error measures and correlation coefficients comparing observed and estimated weights were calculated.ResultsMean differences and mean absolute error for weights derived from the 28-week linear model (0.18 lbs (SD 6.92), 2.73 lbs (SD 6.35)) and 40-week linear model (−0.40 lbs (SD 5.43) and 2.84 lbs (SD 4.65)) were low. Mean differences were somewhat greater at 28 weeks for weight values derived from the nearest two observed values (mean difference −1.97 lbs (SD 8.74)) and from spline models (mean difference −2.25 lbs (SD 7.13)). Results were similar at 40 weeks.ConclusionsOverall, weight values estimated using this interpolation approach showed good agreement with observed values. When repeated measures of weight are available, mixed effects models may be used to interpolate of missing weight values with minimal error.


2016 ◽  
Vol 99 (3) ◽  
pp. 695-704 ◽  
Author(s):  
Shingo Mizuochi ◽  
Maria Nelson

Abstract Nissui Compact Dry YM was originally certified by the AOAC Research Institute Performance Tested MethodsSM (PTM) program (PTM No. 100401) for enumeration of yeasts and molds in fruit products after 7 days of incubation. A matrix extension study, organized by Campden BRI (Chipping Campden, United Kingdom), was conducted to extend the method's claim to cooked deli turkey, fresh whole tomatoes, cheese (Wensleydale), sliced white bread, and mayonnaise. In addition, the method was evaluated at 3 and 7 days to validate the 3 day incubation period. Compact Dry YM is a ready-to-use dry media sheet, containing a cold-soluble gelling agent, selective agents, and chromogenic medium, which are rehydrated by adding 1 mL diluted sample. Yeasts and molds appear as blue colonies, while molds can also have a cottony appearance and the color may vary. Users can obtain total yeast and mold count following 3–7 days of incubation at 25 ± 1°C. Method comparison data for cooked deli turkey, fresh whole tomatoes, cheese (Wensleydale), sliced white bread, and mayonnaise were collected in a single-laboratory evaluation by Campden BRI. A multilaboratory study was conducted on orange juice with 10 laboratories participating including the organizing laboratory. Compact Dry YM was compared to ISO 21527-1:2008, Microbiology of food and animal feeding stuffs–Horizontal method for the enumeration of yeasts and molds – Part 1: Colony count technique in products with water activity greater than 0.95, the current standard at the time of this study. Each matrix was evaluated for total yeasts and molds at each contamination level (including an uncontaminated level). In the single-laboratory evaluation (cooked deli turkey, fresh whole tomatoes, cheese, sliced white bread, and mayonnaise), colony counts were logarithmically transformed, and then the data were analyzed at each level for repeatability (sr), RSD of repeatability (RSDr), and mean difference between methods with a 95% confidence interval (CI). A CI outside a range of (−0.5 to 0.5) on the log10 mean difference between methods was used as the criterion to establish a significant statistical difference. In the multilaboratory study on orange juice, after logarithmic transformation the data were analyzed for sr, RSDr, and mean difference with 95% CIs and also for reproducibility (sR) and RSD of reproducibility (RSDR). Regression analysis was performed on all matrixes and reported as r2. Results from Compact Dry YM at 3 and 7 days were compared separately to ISO 21527-1 and then to each other. In the single-laboratory evaluation, five contamination levels were tested. With the exception of cheese, there were few, if any, colonies recovered at the two lowest contamination levels. As a consequence, differences of a few colonies resulted in significant statistical differences indicated between Compact Dry YM (at both 3 and 7 days) and ISO 21527-1 for most of the foods at these levels. At the three higher contamination levels, statistical differences were seen between Compact Dry YM at 3 days and the ISO method for cooked deli turkey at the middle level, tomatoes at the two middle levels, sliced white bread at the two highest levels, and mayonnaise at the middle level. After 7 days, statistical differences remained between Compact Dry and ISO methods, based on the CIs, but mean differences between methods were &lt;0.5 log10 CFU/g for all foods at the three highest contamination levels. When comparing results between Compact Dry YM at 3 and 7 days, statistical differences were indicated for tomatoes and sliced white bread, both in the second highest contamination level. Otherwise, differences between results at 3 and 7 days were small. The sr and RSDr values were similar for Compact Dry YM (both days) and ISO 21527-1, and r2 values were ≥0.84 for all comparisons. In the multilaboratory study for orange juice, there were no statistical differences between methods across 11 data sets. Four contamination levels were tested, and at all levels mean differences between methods were &lt;0.1 log10 CFU/mL, and CIs were smaller than (−0.05, 0.15), well within the acceptance criterion of (−0.5, 0.5). The sr, RSDr, sR, and RSDr were similar for each method, and r2 was 1.0 in all comparisons. Results indicate that Compact Dry YM offers comparable results at 3 days to the ISO standard plating method at 5 days, in a space-saving, easy-to-use format.


Author(s):  
Shirly Kumala ◽  
Dwi Windi Sapitri

Prasman leaves (Eupatororium triplinerve V) was well documented to have anti cancer benefit in Indonesian traditional medicine history. However, there were no scientific studies including toxicological assessment on the plan extract. The purpose of this study was to investigate the toxicological effect of some fractions of Prasman leaves methanol extract. Phytochemical screening by the Farnsworth method on powder and some fraction of the methanol extract were conducted followed by toxicity test using the “Brine Shrimp Lethality” test (BSLT) method. In the current study results, the phytochemical screening showed the presence of flavonoid, saponin, coumarin, tannin, steroid and volatile oil. LC50 of the n-hexane fraction 238.66 µg/mL, ethyl acetate fraction 24.42 µg/mL,  and n-butanol 64.10 µg/mL.Keywords : BSLT, Toxicity test, Eupatororium triplinerve


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