scholarly journals Stimulation of Nucleotide Oligomerization Domain and Toll-Like Receptors 2 to Enhance the Effect of Bacillus Calmette Guerin Immunization for Prevention of Mycobacterium Tuberculosis Infection: Protocol for a Series of Preclinical Randomized Controlled Trials

10.2196/13045 ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. e13045 ◽  
Author(s):  
Michael Eisenhut
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Randomized Controlled Trials ◽  
Controlled Trials ◽  
Bacillus Calmette Guerin ◽  
Mycobacterium Tuberculosis Infection ◽  
Randomized Controlled ◽  
Nucleotide Oligomerization ◽  
Stimulation Of ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

scholarly journals Stimulation of Nucleotide Oligomerization Domain and Toll-Like Receptors 2 to Enhance the Effect of Bacillus Calmette Guerin Immunization for Prevention of Mycobacterium Tuberculosis Infection: Protocol for a Series of Preclinical Randomized Controlled Trials (Preprint)

2018 ◽  
Author(s):  
Michael Eisenhut
Keyword(s):  
Innate Immunity ◽  
Mycobacterium Tuberculosis ◽  
Bacillus Calmette Guerin ◽  
Infection Rates ◽  
Ifn Gamma ◽  
Prevention Of Infection ◽  
Nucleotide Oligomerization ◽  
Stimulation Of ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

BACKGROUND Bacillus calmette guerin (BCG) immunization has been associated with a reduction in Mycobacterium tuberculosis (MTB) infection. BCG immunization has been shown to enhance innate immunity. This effect of BCG can be explained by an enhancing effect on innate immunity. OBJECTIVE This study aimed to test the following hypotheses: (1) BCG immunization can prevent infection with MTB, (2) prevention of infection occurs via stimulation of NOD2 (nucleotide oligomerization domain) and toll-like receptors 2 (TLR2), and (3) the effect of BCG immunization on prevention of infection with MTB can be enhanced by giving stimulators of NOD2 and TLR2. METHODS To detect the influence of immunization on infection rates, the ultralow dose (ULD) infection model is used. The infection rate of mice vaccinated with BCG and exposed after 6 weeks to ULD of MTB and unvaccinated mice are compared via cultures of lung homogenates and interferon (IFN) gamma release assay. If a reduced infection rate by BCG immunization is confirmed, the experiment is repeated by giving BCG combined simultaneously or in time sequence with the enhancers of innate immunity murabutide or beta-glycan. The influence of murabutide or beta-glycan alone on infection rates is investigated. To quantify the contribution of innate immunity levels of tumor necrosis factor, IFN gamma expression, histone H3 K4me3 trimethylation, and concentrations of monocytes with features of activation of innate immunity as defined by the Ly6Chigh as well as CD11b positive phenotype in immunized versus unimmunized infected and uninfected mice in the various immunization protocols is compared. The experiments will be repeated with prior application of the inhibitors of epigenetic programming of innate immunity histone methyltransferase inhibitor 5’-deoxy-5’-methylthio-adenosine and histone acetyl transferase inhibitor epigallocatechin-3-gallate. The influence of BCG on innate immunity is further corroborated by a prospective observational study in human infants. RESULTS Investigations of derivatives of muramyl dipeptide (MDP) to enhance early immunity in the C57BL/6 mouse strain (mice aged 7 weeks) by another group used 300 micrograms per mouse of oil-associated 6-0-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP) 50/50 mixed with Freund’s incomplete adjuvant. Comparison of colony-forming unit (CFU) count in the lungs 3 weeks after aerosol challenge with Mycobacterium bovis of groups (n=5) between groups receiving mycol-MDP in oil emulsion (see above) versus controls (n=5) showed a significantly lower CFU count of 94.5 x106 (SD 22.0) in cases versus controls with 204.0 X 106 (SD 77.6). It is important to note that after elimination of T-cells in this model, a reduction of CFU in lungs of mice treated with mycol-MDP persisted albeit without statistical significance, which was possibly related to the small number of animals used. CONCLUSIONS Demonstration of a reduction of MTB infection by enhancement of innate immunity could show a new approach to improving vaccine efficacy against this pathogen. INTERNATIONAL REGISTERED REPOR PRR1-10.2196/13045

scholarly journals Effectiveness of Stimulation of Acupoint KI 1 byArtemisia vulgaris(Moxa) for the Treatment of Essential Hypertension: A Systematic Review of Randomized Controlled Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaochen Yang ◽  
Xingjiang Xiong ◽  
Guoyan Yang ◽  
Jie Wang
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Randomized Controlled Trials ◽  
Antihypertensive Drugs ◽  
Controlled Trials ◽  
Lower Blood Pressure ◽  
Clinical Trial Registry ◽  
Randomized Controlled ◽  
Lower Blood ◽  
Stimulation Of

Objective. A systematic review of randomized controlled trials has been performed to assess the effectiveness of stimulation of acupoint KI 1 byArtemisia vulgaris(the Japanese name is moxa) to lower blood pressure compared to antihypertensive drugs.Methods and Findings. Articles published from 1980 to August 2013 in databases of CENTRAL, Pubmed, CBM, CNKI, VIP, and online clinical trial registry websites were searched. Studies included were randomized controlled trials (RCTs); moxibustion-type intervention on KI 1 compared with antihypertensive drugs; meta-analysis showed superior effects of moxibustion plus antihypertensive drugs on systolic blood pressure (WMD: −4.91 [−7.54, −2.28];P=0.0003) but no superior effects on diastolic blood pressure (WMD: −6.38 [−17.17, 4.41];P=0.25).Conclusions. Our systematic review of the current literature shows a beneficial effect of using moxibustion interventions on KI 1 to lower blood pressure compared to antihypertensive drugs. However, the results are influenced by the existing differences in design of the current trials.

Therapeutic Stimulation of the Ictal Onset Zone

2018 ◽  
pp. 476-486
Author(s):  
Mathieu Sprengers ◽  
Sofie Carrette ◽  
Kristl Vonck ◽  
Paul Boon
Keyword(s):  
Randomized Controlled Trials ◽  
Brain Stimulation ◽  
Alternative Treatment ◽  
Refractory Epilepsy ◽  
Brain Structures ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Open Label ◽  
Randomized Controlled ◽  
Stimulation Of

Brain stimulation has emerged as an alternative treatment for patients with refractory epilepsy and an increasing number of trials evaluating its efficacy and safety have been published. Various brain structures have been targeted, focusing either on the ictal onset zone or on remote epileptogenic network structures. This chapter focuses on stimulation of the ictal onset zone. The rationale for these targets and the results obtained in open-label and randomized controlled trials (RCTs), when available, are discussed. It is concluded that promising results have been published, although mainly in open-label trials. More RCTs are needed to establish the value of ictal onset stimulation for the treatment of epilepsy.

The Effect of Partly Missing Covariates on Statistical Power in Randomized Controlled Trials With Discrete-Time Survival Endpoints

Methodology ◽  
2017 ◽  
Vol 13 (2) ◽  
pp. 41-60
Author(s):  
Shahab Jolani ◽  
Maryam Safarkhani
Keyword(s):  
Randomized Controlled Trials ◽  
Discrete Time ◽  
Treatment Effect ◽  
Survival Data ◽  
Controlled Trials ◽  
Missing Covariates ◽  
Indicator Method ◽  
Imputation Methods ◽  
Randomized Controlled ◽  
Baseline Covariates

Abstract. In randomized controlled trials (RCTs), a common strategy to increase power to detect a treatment effect is adjustment for baseline covariates. However, adjustment with partly missing covariates, where complete cases are only used, is inefficient. We consider different alternatives in trials with discrete-time survival data, where subjects are measured in discrete-time intervals while they may experience an event at any point in time. The results of a Monte Carlo simulation study, as well as a case study of randomized trials in smokers with attention deficit hyperactivity disorder (ADHD), indicated that single and multiple imputation methods outperform the other methods and increase precision in estimating the treatment effect. Missing indicator method, which uses a dummy variable in the statistical model to indicate whether the value for that variable is missing and sets the same value to all missing values, is comparable to imputation methods. Nevertheless, the power level to detect the treatment effect based on missing indicator method is marginally lower than the imputation methods, particularly when the missingness depends on the outcome. In conclusion, it appears that imputation of partly missing (baseline) covariates should be preferred in the analysis of discrete-time survival data.

Interventions for suicide and self-injury: A meta-analysis of randomized controlled trials across nearly 50 years of research.

2020 ◽  
Vol 146 (12) ◽  
pp. 1117-1145
Author(s):  
Kathryn R. Fox ◽  
Xieyining Huang ◽  
Eleonora M. Guzmán ◽  
Kensie M. Funsch ◽  
Christine B. Cha ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Self Injury
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