Dataset Information

Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics.

ABSTRACT:

Background

Human immunology is a growing field of research in which experimental, clinical, and analytical methods of many life science disciplines are utilized. Classic epidemiological study designs, including observational longitudinal birth cohort studies, offer strong potential for gaining new knowledge and insights into immune response to pathogens in humans. However, rigorous discussion of methodological issues related to designs and statistical analysis that are appropriate for longitudinal studies is lacking.

Methods

In this communication we address key questions of quality and validity of traditional and recently developed statistical tools applied to measures of immune responses. For this purpose we use data on humoral immune response (IR) associated with the first cryptosporidial diarrhea in a birth cohort of children residing in an urban slum in south India. The main objective is to detect the difference and derive inferences for a change in IR measured at two time points, before (pre) and after (post) an event of interest. We illustrate the use and interpretation of analytical and data visualization techniques including generalized linear and additive models, data-driven smoothing, and combinations of box-, scatter-, and needle-plots.

Results

We provide step-by-step instructions for conducting a thorough and relatively simple analytical investigation, describe the challenges and pitfalls, and offer practical solutions for comprehensive examination of data. We illustrate how the assumption of time irrelevance can be handled in a study with a pre-post design. We demonstrate how one can study the dynamics of IR in humans by considering the timing of response following an event of interest and seasonal fluctuation of exposure by proper alignment of time of measurements. This alignment of calendar time of measurements and a child's age at the event of interest allows us to explore interactions between IR, seasonal exposures and age at first infection.

Conclusions

The use of traditional statistical techniques to analyze immunological data derived from observational human studies can result in loss of important information. Detailed analysis using well-tailored techniques allows the depiction of new features of immune response to a pathogen in longitudinal studies in humans. The proposed staged approach has prominent implications for future study designs and analyses.

SUBMITTER: Sarkar R

PROVIDER: S-EPMC3359263 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics.

Sarkar Rajiv R Ajjampur Sitara S SS Ward Honorine D HD Kang Gagandeep G Naumova Elena N EN

BMC medical research methodology 20120103

<h4>Background</h4>Human immunology is a growing field of research in which experimental, clinical, and analytical methods of many life science disciplines are utilized. Classic epidemiological study designs, including observational longitudinal birth cohort studies, offer strong potential for gaining new knowledge and insights into immune response to pathogens in humans. However, rigorous discussion of methodological issues related to designs and statistical analysis that are appropriate for lo ...[more]

PMID: 22214542

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Project description:IntroductionTobacco is the leading cause of death and disease in India. This study examines the effect of training intervention in behavioral counseling on intention to quit tobacco in primary healthcare settings in India. The intervention included training to improve behavioral counseling practices of primary care physicians (PCPs) based on the 5As approach to increase patients' motivation to quit tobacco.MethodsA quasi-experimental design was used for the study. The intervention consists of training of primary care physicians in the behavioral intervention in tobacco cessation. The intervention was conducted in twelve districts of two states in India (Rajasthan and Odisha) in 2016-2017. Four districts were randomly sampled for the study. A total of 1314 participants (intervention and control) were recruited for the study in the baseline and end-line surveys, respectively. Intention to quit in 30 days was the primary outcome measure. Difference-in-difference (DiD) logistic regression models were used separately for smokers and smokeless tobacco users to estimate the odds of intention to quit. Analysis was done in STATA Version 14.ResultsThe intervention and time variable had a significantly positive influence on the intention to quit tobacco among smokers. Smokers in the intervention districts had higher odds of intention to quit (OR=9.82; 95% CI: 1.67-57.72) compared to smokers in the control districts. Smokeless tobacco (SLT) users had higher odds of intention to quit (OR=3.06; 95% CI: 1.35-6.98) in the end-line survey compared to baseline survey.ConclusionsOur findings indicate that building capacity in behavioral intervention in primary care settings can help increase the intention to quit among smokers. The observed difference in intention to quit between smokers and SLT users suggests the need of tailored counseling interventions for SLT users. There is a need for further research to design and evaluate training and behavioral interventions for SLT and dual (smoking and SLT) users in primary care settings in low- and middle-income countries.

Project description:UnlabelledThe ability of human cytomegalovirus (HCMV) to establish lifelong persistence and reactivate from latency is critical to its success as a pathogen. Here we describe a short-term in vitro model representing the events surrounding HCMV latency and reactivation in circulating peripheral blood monocytes that was developed in order to study the immunological consequence of latent virus carriage. Infection of human CD14(+) monocytes by HCMV resulted in the immediate establishment of latency, as evidenced by the absence of particular lytic gene expression, the transcription of latency-associated mRNAs, and the maintenance of viral genomes. Latent HCMV induced cellular differentiation to a macrophage lineage, causing production of selective proinflammatory cytokines and myeloid-cell chemoattractants that most likely play a role in virus dissemination in the host. Analysis of global cellular gene expression revealed activation of innate immune responses and the modulation of protein and lipid synthesis to accommodate latent HCMV infection. Remarkably, monocytes harboring latent virus exhibited selective responses to secondary stimuli known to induce an antiviral state. Furthermore, when challenged with type I and II interferon, latently infected cells demonstrated a blockade of signaling at the level of STAT1 phosphorylation. The data demonstrate that HCMV reprograms specific cellular pathways in monocytes, most notably innate immune responses, which may play a role in the establishment of, maintenance of, and reactivation from latency. The modulation of innate immune responses is likely a viral evasion strategy contributing to viral dissemination and pathogenesis in the host.ImportanceHCMV has the ability to establish a lifelong infection within the host, a phenomenon termed latency. We have established a short-term model system in human peripheral blood monocytes to study the immunological relevance of latent virus carriage. Infection of CD14(+) monocytes by HCMV results in the generation of latency-specific transcripts, maintenance of viral genomes, and the capacity to reenter the lytic cycle. During short-term latency in monocytes the virus initiates a program of differentiation to inflammatory macrophages that coincides with the modulation of cytokine secretion and specific cellular processes. HCMV-infected monocytes are hindered in their capacity to exert normal immunoprotective mechanisms. Additionally, latent virus disrupts type I and II interferon signaling at the level of STAT1 phosphorylation. This in vitro model system can significantly contribute to our understanding of the molecular and inflammatory factors that initiate HCMV reactivation in the host and allow the development of strategies to eradicate virus persistence.

Project description:BackgroundThe magnitude of the benefit associated with screening has been debated. We present a meta-analysis of quasi-experimental studies on the effects of mammography screening.MethodsWe searched MEDLINE/PubMed and Embase for articles published through January 31, 2013. Studies were included if they reported: 1) a population-wide breast cancer screening program using mammography with 5+ years of data post-implementation; 2) a comparison group with equal access to therapies; and 3) breast cancer mortality. Studies excluded were: RCTs, case-control, or simulation studies. We defined quasi-experimental as studies that compared either geographical, historical or birth cohorts with a screening program to an equivalent cohort without a screening program. Meta-analyses were conducted in Stata using the metan command, random effects. Meta-analyses were conducted separately for ages screened: under 50, 50 to 69 and over 70 and weighted by population and person-years.ResultsAmong 4,903 published papers that were retrieved, 19 studies matched eligibility criteria. Birth cohort studies reported a significant benefit for women screened <age 50, but not for women screened ages 50-69. Significant reductions in breast cancer mortality were observed in historical comparisons. For geographical comparisons, there was a significant 20% reduction in mortality for women <age 50 and a significant 21-22% reduction for women ages 50-69. Studies that tested the interaction of geographical and historical comparisons produced a pooled, significant 13-17% reduction in incident breast cancer mortality for women ages 50-69, but the effects in most individual studies were non-significant. All studies of women ages 70+ were non-significant.ConclusionsMammography screening may have modest effects on cancer mortality between the ages of 50 and 69 and non-significant effects for women older than age 70. Results are consistent with meta-analyses of RCTs. Effects on total mortality could not be assessed because of the limited number of studies.

Dataset Information

Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics.

Background

Methods

Results

Conclusions

Publications

Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics.

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