scholarly journals Statistical Power Considerations Show the Endocrine Disruptor Low-Dose Issue in a New Light

2007 ◽  
Vol 115 (Suppl 1) ◽  
pp. 84-90 ◽  
Author(s):  
Martin Scholze ◽  
Andreas Kortenkamp
Keyword(s):  
Endocrine Disruptor ◽  
Statistical Power ◽  
Low Dose

scholarly journals Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects

2012 ◽  
Vol 108 (9) ◽  
pp. 1652-1657 ◽  
Author(s):  
Elke Theuwissen ◽  
Ellen C. Cranenburg ◽  
Marjo H. Knapen ◽  
Elke J. Magdeleyns ◽  
Kirsten J. Teunissen ◽  
...  
Keyword(s):  
Vitamin K ◽  
Statistical Power ◽  
Thrombin Generation ◽  
Low Dose ◽  
Coagulation Factors ◽  
Peak Height ◽  
Matrix Gla Protein ◽  
High Dose ◽  
Age Related ◽  
Intervention Trials

Vitamin K is required for the carboxylation of Gla-proteins in the liver (coagulation factors) and extra-hepatic tissues, such as bone (osteocalcin, OC), and arterial wall (matrix Gla-protein, MGP). Although the coagulation factors are essentially fully carboxylated under normal conditions, 10–40 % of OC and MGP remains undercarboxylated. We were therefore interested to study the dose–response effects of extra intake of menaquinones on the carboxylation of the extra-hepatic Gla-proteins. A total of forty-two healthy Dutch men and women aged between 18 and 45 years were randomised into seven groups to receive: placebo capsules or menaquinone-7 (MK-7) capsules at a daily dose of 10, 20, 45, 90, 180 or 360 μg. Circulating uncarboxylated OC (ucOC), carboxylated OC (cOC) and desphospho-uncarboxylated MGP were measured by ELISA. The ucOC:cOC ratio was calculated from circulating ucOC and cOC values. Endogenous thrombin potential and peak height were determined by calibrated automated thrombography. To increase the statistical power, we collapsed the treatment groups into three dosage groups: placebo, low-dose supplementation (doses below RDA, Commission Directive 2008/100/EC), and high-dose supplementation (doses around RDA, Commission Directive 2008/100/EC). MK-7 supplementation at doses in the order of the RDA (Commission Directive 2008/100/EC) increased the carboxylation of circulating OC and MGP. No adverse effects on thrombin generation were observed. Extra MK-7 intake at nutritional doses around the RDA (Commission Directive 2008/100/EC) improved the carboxylation of the extra-hepatic vitamin K-dependent proteins. Whether this improvement contributes to public health, i.e. increasing the protection against age-related diseases needs further investigation in specifically designed intervention trials.

Intranasal Steroids for Adenoidal Nasal Obstruction

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P65-P65
Author(s):  
Neil K Chadha ◽  
Linjie Zhang ◽  
Raul Mendoza-Sassi ◽  
Juraci Cesar
Keyword(s):  
Nasal Obstruction ◽  
Statistical Power ◽  
Low Dose ◽  
Current Evidence ◽  
Inclusion Criteria ◽  
Intranasal Corticosteroids ◽  
Randomized Controlled ◽  
Intranasal Steroids ◽  
Symptom Scores ◽  
Adenoidal Hypertrophy

Objective 1) To systematically review the evidence for intranasal steroids in the treatment of nasal obstruction caused by adenoidal hypertrophy, in children. 2) To determine the risk of adverse events of treatment. Methods We performed a systematic review and metaanalysis following a specified protocol. Databases searched (May 2007) included Cochrane CENTRAL, MEDLINE, EM-BASE, CINAHL, AMED, LILACS, KoreaMed, IndMED, SIGLE, Cambridge Scientific Abstracts, mRCT, National Research Register, ISRCTN, and ISI Web of Science. Results 56 studies were identified, with 4 randomized controlled trials (RCTs) meeting the inclusion criteria. Trial 1: an 8-week crossover RCT demonstrating 4-weeks beclomethasone (336 mcg/day) showed a 45% reduction in symptom scores (p<0.01). Trial 2: a 4-week crossover RCT demonstrating a reduction in nasal obstruction index by 50% in patients treated with beclomethasone (400 micrograms/day) for 2 weeks (p<0.0001). Trial 3: a 40-day parallel RCT which showed that 77.7% of patients treated with mometasone (100 micrograms/day) demonstrated an improvement in nasal obstruction symptoMS Trial 4: an 8-week parallel RCT demonstrated no significant improvement in nasal obstruction symptoms after 8-weeks treatment with beclomethasone (200 micrograms/day). Low statistical power and low dose of beclomethasone may have contributed to this negative result. Conclusions Current evidence suggests that intranasal corticosteroids may significantly improve nasal obstruction symptoms in children with adenoidal hypertrophy, and this improvement was associated with a reduction of adenoid size. Given the safety and tolerability of intranasal corticosteroids, it seems reasonable to recommend the use of these drugs as an effective treatment for children with adenoidal hypertrophy when adenoidectomy is not urgently required.

scholarly journals Issues in Interpreting Epidemiologic Studies of Populations Exposed to Low-Dose, High-Energy Photon Radiation

2020 ◽  
Vol 2020 (56) ◽  
pp. 176-187 ◽  
Author(s):  
Ethel S Gilbert ◽  
Mark P Little ◽  
Dale L Preston ◽  
Daniel O Stram
Keyword(s):  
Measurement Errors ◽  
Statistical Power ◽  
Low Dose ◽  
Risk Model ◽  
Atomic Bomb ◽  
Statistical Tests ◽  
High Energy ◽  
Epidemiologic Studies ◽  
Photon Radiation ◽  
High Dose

Abstract This article addresses issues relevant to interpreting findings from 26 epidemiologic studies of persons exposed to low-dose radiation. We review the extensive data from both epidemiologic studies of persons exposed at moderate or high doses and from radiobiology that together have firmly established radiation as carcinogenic. We then discuss the use of the linear relative risk model that has been used to describe data from both low- and moderate- or high-dose studies. We consider the effects of dose measurement errors; these can reduce statistical power and lead to underestimation of risks but are very unlikely to bring about a spurious dose response. We estimate statistical power for the low-dose studies under the assumption that true risks of radiation-related cancers are those expected from studies of Japanese atomic bomb survivors. Finally, we discuss the interpretation of confidence intervals and statistical tests and the applicability of the Bradford Hill principles for a causal relationship.

Low-Dose Exposure to Endocrine Disruptor Dichlorodiphenyltrichloroethane (DDT) Affects Transcriptional Regulation of Adrenal Zona Reticularis in Male Rats

2021 ◽  
Vol 170 (5) ◽  
pp. 682-685
Author(s):  
N. V. Yaglova ◽  
S. S. Obernikhin ◽  
V. V. Yaglov ◽  
S. V. Nazimova ◽  
E. P. Timokhina ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Endocrine Disruptor ◽  
Low Dose ◽  
Male Rats ◽  
Zona Reticularis

Mortality benefit in the COMPASS trial: is it related to superior statistical power or better efficacy and safety?

2021 ◽  
Vol 17 (1) ◽  
pp. 175-182 ◽  
Author(s):  
Krishnan Shyamkumar ◽  
Jack Hirsh ◽  
Vinai C Bhagirath ◽  
Smita Sinha ◽  
Ke Xu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Statistical Power ◽  
Low Dose ◽  
The Other ◽  
Mortality Reduction ◽  
Efficacy And Safety ◽  
Mortality Benefit ◽  
Antithrombotic Agent ◽  
Net Clinical Benefit ◽  
Significant Mortality

Until recently, attempts to improve the benefit of aspirin by adding another antithrombotic agent have not resulted in a mortality reduction in patients with chronic symptomatic atherosclerosis. In this population, COMPASS is the only one among six trials to show a significant mortality reduction, thereby providing evidence of a clear net clinical benefit with the combination of low-dose rivaroxaban plus aspirin. In this systematic review, we sought to determine whether the mortality benefit of the combination arm in COMPASS is best explained by greater statistical power or by a more favorable efficacy–safety profile than the other regimens evaluated in patients with chronic symptomatic atherosclerosis.

scholarly journals Hemodynamic modeling of aspirin effects on BOLD responses at 7T

2020 ◽  
Author(s):  
Cao-Tri Do ◽  
Zina-Mary Manjaly ◽  
Jakob Heinzle ◽  
Dario Schöbi ◽  
Lars Kasper ◽  
...  
Keyword(s):  
Statistical Power ◽  
Low Dose ◽  
Hand Movement ◽  
7 Tesla ◽  
Parameter Estimates ◽  
Bold Signal ◽  
Bold Response ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Potential Confound

AbstractAspirin is considered a potential confound for functional magnetic resonance imaging (fMRI) studies. This is because aspirin affects the synthesis of prostaglandin, a vasoactive mediator centrally involved in neurovascular coupling, a process that underlies the blood oxygenated level dependent (BOLD) response. Aspirin-induced changes in BOLD signal are a potential confound for fMRI studies of patients (e.g. with cardiovascular conditions or stroke) who receive low-dose aspirin prophylactically and are compared to healthy controls that do not take aspirin. To examine the severity of this potential confound, we combined high field (7 Tesla) MRI during a simple hand movement task with a biophysically informed hemodynamic model. Comparing elderly volunteers with vs. without aspirin medication, we tested for putative effects of low-dose chronic aspirin on the BOLD response. Specifically, we fitted hemodynamic models to BOLD signal time courses from 14 regions of the human motor system and examined whether model parameter estimates were significantly altered by aspirin. While our analyses indicate that hemodynamics differed across regions, consistent with the known regional variability of the BOLD response, we neither found a significant main effect of aspirin (i.e., an average effect across brain regions) nor an expected drug×region interaction. While our sample size is not sufficiently large to rule out small-to-medium global effects of aspirin, we had adequate statistical power for detecting the expected interaction. Altogether, our analysis suggests that low-dose aspirin, as used for prophylactic purposes, does not strongly affect BOLD signals and may not represent a critical confound for fMRI studies.

A review on sources and health impacts of bisphenol A

2020 ◽  
Vol 35 (2) ◽  
pp. 201-210 ◽  
Author(s):  
Anna Abraham ◽  
Paromita Chakraborty
Keyword(s):  
Bisphenol A ◽  
Epoxy Resins ◽  
Endocrine Disruptor ◽  
Low Dose ◽  
Prolonged Exposure ◽  
Cellular Responses ◽  
Developing Nations ◽  
Health Impacts ◽  
Health Studies ◽  
Animal Exposure

AbstractBisphenol-A (BPA) is a synthetic chemical used in the manufacturing of polycarbonates and epoxy resins. This paper is a review of studies reporting the occurrences and concentrations of BPA in the environment and associated impact on human health. Studies have found that at high temperature conditions such as open burning of dumped waste in developing nations can relocate BPA from plastic waste into the environment. BPA is a proven endocrine disruptor capable of mimicking or blocking the receptors and altering hormone concentrations and its metabolism. Even though it is consumed in a low dose, it can stimulate cellular responses and affect body functions. Biomonitoring studies show that human and animal exposure to BPA is rapid and continuous. In-depth studies are needed to understand the fate of these compounds particularly in the developing nations and the associated adverse health impacts of BPA due to prolonged exposure.

scholarly journals Effect of prenatal exposure to the endocrine disruptor bisphenol A on mammary gland morphology and gene expression signature

2007 ◽  
Vol 196 (1) ◽  
pp. 101-112 ◽  
Author(s):  
Raquel Moral ◽  
Richard Wang ◽  
Irma H Russo ◽  
Coral A Lamartiniere ◽  
Julia Pereira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Bisphenol A ◽  
Endocrine Disruptor ◽  
Dose Group ◽  
Low Dose ◽  
Gene Expression Signature ◽  
High Dose ◽  
Proliferative Index ◽  
Induced Changes

Bisphenol A (BPA), known as an environmental endocrine disruptor, is widely used as a plasticizer. This study aims to investigate whether exposure in utero to BPA alters the architecture, proliferative index, and genomic signature of the rat mammary gland during critical stages of development. Pregnant rats were gavaged with 25 μg BPA/kg body weight (BW; low-dose group) or 250 μg BPA/kg BW (high-dose group) from day 10 post-conception to delivery. Female litters were euthanized at 21, 35, 50, and 100 days, and mammary glands were collected. Analysis of gland morphology was performed from whole-mounted mammary tissue, while proliferative index was determined by detection of bromodeoxyuridine incorporation in the epithelial cells. Genomic profiles were obtained by microarray analysis, and some genes were validated by real-time RT-PCR. BPA exposure induced changes in the mammary gland that were time and dose specific. High-dose exposure resulted in architectural modifications, mainly in the number of undifferentiated epithelial structures of the breast tissue. Proliferative index did not show remarkable differences by the effect of BPA. Low and high doses of BPA changed the gene expression signature of the mammary gland following a different fashion: low dose had the highest effect by 50 days, while high dose had a highest influence on gene expression by 100 days. Both doses presented a significant cluster of up-modulated genes related to the immune system at the age of maximal changes. Moreover, high-dose exposure induced changes in genes related to differentiation suggesting alterations in the normal development of the gland. The increase of undifferentiated structures and the changes in the gene expression profile at different ages suggest that prenatal exposure to BPA can affect the susceptibility of the mammary gland to transformation.

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