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PloS One 2017In Sub-Saharan African (SSA) resource limited settings, Cluster of Differentiation 4 (CD4) counts continue to be used for clinical decision making in antiretroviral... (Review)
Review
INTRODUCTION
In Sub-Saharan African (SSA) resource limited settings, Cluster of Differentiation 4 (CD4) counts continue to be used for clinical decision making in antiretroviral therapy (ART). Here, HIV-infected people often remain with CD4 counts <350 cells/μL even after 5 years of viral load suppression. Ongoing immunological monitoring is necessary. Due to varying statistical modeling methods comparing immune response to ART across different cohorts is difficult. We systematically review such models and detail the similarities, differences and problems.
METHODS
'Preferred Reporting Items for Systematic Review and Meta-Analyses' guidelines were used. Only studies of immune-response after ART initiation from SSA in adults were included. Data was extracted from each study and tabulated. Outcomes were categorized into 3 groups: 'slope', 'survival', and 'asymptote' models. Wordclouds were drawn wherein the frequency of variables occurring in the reviewed models is indicated by their size and color.
RESULTS
69 covariates were identified in the final models of 35 studies. Effect sizes of covariates were not directly quantitatively comparable in view of the combination of differing variables and scale transformation methods across models. Wordclouds enabled the identification of qualitative and semi-quantitative covariate sets for each outcome category. Comparison across categories identified sex, baseline age, baseline log viral load, baseline CD4, ART initiation regimen and ART duration as a minimal consensus set.
CONCLUSION
Most models were different with respect to covariates included, variable transformations and scales, model assumptions, modelling strategies and reporting methods, even for the same outcomes. To enable comparison across cohorts, statistical models would benefit from the application of more uniform modelling techniques. Historic efforts have produced results that are anecdotal to individual cohorts only. This study was able to define 'prior' knowledge in the Bayesian sense. Such information has value for prospective modelling efforts.
Topics: Africa South of the Sahara; Anti-Retroviral Agents; CD4 Lymphocyte Count; HIV; HIV Infections; Humans; Models, Statistical; Viral Load
PubMed: 28199360
DOI: 10.1371/journal.pone.0171658 -
OncoTargets and Therapy 2016The prognostic significance of claudin 4 (CLDN4) in patients with gastric cancer (GC) is controversial. This meta-analysis aims to assess the correlation between CLDN4...
BACKGROUND
The prognostic significance of claudin 4 (CLDN4) in patients with gastric cancer (GC) is controversial. This meta-analysis aims to assess the correlation between CLDN4 expression and clinicopathological characteristics and assess the prognostic significance of CLDN4 in GC.
METHODS
We searched the PubMed and Embase databases. We performed the meta-analysis with odds ratio (OR), hazard ratio (HR), and 95% confidence interval (CI) as effect values.
RESULTS
Fourteen studies containing 2,106 patients with GC were analyzed. The overall analysis showed that CLDN4 expression was associated with increasing pT category, tumor size, and lymph node metastasis in patients with GC (pT3-T4 vs pT1-T2: OR =1.56, 95% CI =1.13-2.16; P<0.01; large tumor size vs small tumor size: OR =1.64, 95% CI =1.15-2.34; P<0.01; positive lymph node metastasis vs negative lymph node metastasis: OR =1.49, 95% CI =1.12-1.97; P<0.01). CLDN4 expression was associated with histological differentiation (differentiated type vs undifferentiated type: OR =2.90, 95% CI =1.32-6.37; P=0.01; Lauren intestinal type vs diffuse type: OR =3.51, 95% CI =1.48-8.28; P<0.01). CLDN4 expression was also strongly associated with sex and age. This meta-analysis found no significant association between CLDN4 expression and prognosis for overall survival in patients with GC (HR =0.74, 95% CI =0.43-1.27; P=0.28).
CONCLUSION
Present study indicates that aberrant CLDN4 expression plays an important role in the clinicopathological characteristics of GC.
PubMed: 27313466
DOI: 10.2147/OTT.S99461 -
Journal of Neuroinflammation Jun 2015Animal studies show that peripheral inflammatory stimuli may activate microglial cells in the brain implicating an important role for microglia in sepsis-associated... (Review)
Review
BACKGROUND
Animal studies show that peripheral inflammatory stimuli may activate microglial cells in the brain implicating an important role for microglia in sepsis-associated delirium. We systematically reviewed animal experiments related to the effects of systemic inflammation on the microglial and inflammatory response in the brain.
METHODS
We searched PubMed between January 1, 1950 and December 1, 2013 and Embase between January 1, 1988 and December 1, 2013 for animal studies on the influence of peripheral inflammatory stimuli on microglia and the brain. Identified studies were systematically scored on methodological quality. Two investigators extracted independently data on animal species, gender, age, and genetic background; number of animals; infectious stimulus; microglial cells; and other inflammatory parameters in the brain, including methods, time points after inoculation, and brain regions.
RESULTS
Fifty-one studies were identified of which the majority was performed in mice (n = 30) or in rats (n = 19). Lipopolysaccharide (LPS) (dose ranging between 0.33 and 200 mg/kg) was used as a peripheral infectious stimulus in 39 studies (76 %), and live or heat-killed pathogens were used in 12 studies (24 %). Information about animal characteristics such as species, strain, sex, age, and weight were defined in 41 studies (80 %), and complete methods of the disease model were described in 35 studies (68 %). Studies were also heterogeneous with respect to methods used to assess microglial activation; markers used mostly were the ionized calcium binding adaptor molecule-1 (Iba-1), cluster of differentiation 68 (CD68), and CD11b. After LPS challenge microglial activation was seen 6 h after challenge and remained present for at least 3 days. Live Escherichia coli resulted in microglial activation after 2 days, and heat-killed bacteria after 2 weeks. Concomitant with microglial response, inflammatory parameters in the brain were reviewed in 23 of 51 studies (45 %). Microglial activation was associated with an increase in Toll-like receptor (TLR-2 and TLR-4), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) messenger ribonucleic acid (mRNA) expression or protein levels.
INTERPRETATION
Animal experiments robustly showed that peripheral inflammatory stimuli cause microglial activation. We observed distinct differences in microglial activation between systemic stimulation with (supranatural doses) LPS and live or heat-killed bacteria.
Topics: Animals; Delirium; Disease Models, Animal; Escherichia coli; Female; Inflammation; Lipopolysaccharides; Male; Mice; Microglia; Rats; Sepsis
PubMed: 26048578
DOI: 10.1186/s12974-015-0332-6 -
BMJ Open Mar 2015To assess effectiveness of school-based smoking prevention curricula keeping children never-smokers. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess effectiveness of school-based smoking prevention curricula keeping children never-smokers.
DESIGN
Systematic review, meta-analysis.
DATA
MEDLINE (1966+), EMBASE (1974+), Cinahl, PsycINFO (1967+), ERIC (1982+), Cochrane CENTRAL, Health Star, Dissertation Abstracts, conference proceedings.
DATA SYNTHESIS
pooled analyses, fixed-effects models, adjusted ORs. Risk of bias assessed with Cochrane Risk of Bias tool.
SETTING
50 randomised controlled trials (RCTs) of school-based smoking curricula.
PARTICIPANTS
Never-smokers age 5-18 (n=143,495); follow-up ≥6 months; all countries; no date/language limitations.
INTERVENTIONS
Information, social influences, social competence, combined social influences/competence and multimodal curricula.
OUTCOME MEASURE
Remaining a never-smoker at follow-up.
RESULTS
Pooling all curricula, trials with follow-up ≤1 year showed no statistically significant differences compared with controls (OR 0.91 (0.82 to 1.01)), though trials of combined social competence/social influences curricula had a significant effect on smoking prevention (7 trials, OR 0.59 (95% CI 0.41 to 0.85)). Pooling all trials with longest follow-up showed an overall significant effect in favour of the interventions (OR 0.88 (0.82 to 0.95)), as did the social competence (OR 0.65 (0.43 to 0.96)) and combined social competence/social influences curricula (OR 0.60 (0.43 to 0.83)). No effect for information, social influences or multimodal curricula. Principal findings were not sensitive to inclusion of booster sessions in curricula or to whether they were peer-led or adult-led. Differentiation into tobacco-only or multifocal curricula had a similar effect on the primary findings. Few trials assessed outcomes by gender: there were significant effects for females at both follow-up periods, but not for males.
CONCLUSIONS
RCTs of baseline never-smokers at longest follow-up found an overall significant effect with average 12% reduction in starting smoking compared with controls, but no effect for all trials pooled at ≤1 year. However, combined social competence/social influences curricula showed a significant effect at both follow-up periods.
SYSTEMATIC REVIEW REGISTRATION
Cochrane Tobacco Review Group CD001293.
Topics: Adolescent; Child; Child, Preschool; Curriculum; Health Education; Humans; Randomized Controlled Trials as Topic; Schools; Sex Factors; Smoking Prevention; Social Skills
PubMed: 25757946
DOI: 10.1136/bmjopen-2014-006976