Epidemiological Questions Research Articles

Possible immunosuppressive effects of drug exposure and environmental and nutritional effects on infection and vaccination.

A variety of drugs which are not primarily considered to be immunosuppressive agents have been described to modulate the humoral and cellular immune response in humans or animals. Thereby they may have an influence on the effectiveness and possible side effects of vaccines. This mini review lists some of the different substance classes and also some of endogeneous, infectious, nutritional, and environmental influences with suspected capability to interfere with immunizations. Studies in most cases focused on substances with known immunosuppressive functions, but there is growing evidence for immunomodulatory effects also of commonly used drugs with wide distribution. In particular combinations of those antiproliferative and antiphlogistic side effects of different substance classes have not been studied in detail but may substantially interfere with the development of a functional humoral and cellular immune response. The drugs of importance include antipyretics, anticoagulants, tranquilizers, and substances influencing lipid metabolism but also commonly used drugs of abuse like alcohol or cannabinoids. Additional substances of environmental, nutritional, or microbiological origin may also play a role but their combinatory/synergistic effects have been disregarded so far due to the lack of systematic data and the complex study designs necessary to elucidate those complex epidemiologic questions.

Development of rapid direct PCR assays to identify downy and powdery mildew and grey mould in <em>Vitis vinifera</em> tissues

<p style="text-align: justify;"><strong>Aims</strong>: The development of a rapid and reliable direct PCR method to detect fungal propagules in grapevine tissues without prior DNA purification steps, and illustration of its potential use with different examples.</p><p style="text-align: justify;"><strong>Methods and results</strong>: Different grapevine samples crushed in the presence of polyvinylpolypyrrolidone (PVPP) were used as templates for direct PCR amplification with primers specifie for <em>Erysiphe necator</em>, <em>Plasmopara viticola</em>, <em>Botrytis cinerea</em> and <em>Vitis vinifera</em>. Sequencing of the PCR products confirmed the specificity of the amplifications. The sensitivity tested using conidia/sporangia dilution series was high, ranging from five sporangia for <em>P. viticola</em> to one conidium for <em>E. necator</em>. The potential of this technique is illustrated through the study of four epidemiological questions. Fungal propagules were observed in dormant buds using microscopy, but the responsible species could not be identified. Direct PCR revealed the presence of <em>E. necator</em> and<em> B. cinerea</em> in 29 % and 65 % of the buds, respectively. Downy mildew could be detected in asymptomatic leaves sampled in fields after potentially infectious events. In bunch, microscopic analysis of rachis sections showed the presence of hyphae growing in the green tissue. Direct PCR identified the presence of <em>P. viticola</em>.</p><p style="text-align: justify;"><strong>Conclusion</strong>: A direct PCR method without DNA purification was demonstrated to be a simple and reliable method for the detection and identification of fungal pathogens in grapevine tissues. This method, together with microscopy, is a very interesting tool that can be used to study various epidemiological problems in the grapevine, including important unanswered questions such as the route of infection that leads to brown rot caused by downy mildew.</p><p style="text-align: justify;"><strong>Significance and impact of the study</strong>: Direct PCR was shown to be a simple and versatile technique for the study of epidemiological questions in the grapevine. This technique could be extended to other pathosystems with minor adaptations.</p>

Metaprop: a Stata command to perform meta-analysis of binomial data.

BackgroundMeta-analyses have become an essential tool in synthesizing evidence on clinical and epidemiological questions derived from a multitude of similar studies assessing the particular issue. Appropriate and accessible statistical software is needed to produce the summary statistic of interest.MethodsMetaprop is a statistical program implemented to perform meta-analyses of proportions in Stata. It builds further on the existing Stata procedure metan which is typically used to pool effects (risk ratios, odds ratios, differences of risks or means) but which is also used to pool proportions. Metaprop implements procedures which are specific to binomial data and allows computation of exact binomial and score test-based confidence intervals. It provides appropriate methods for dealing with proportions close to or at the margins where the normal approximation procedures often break down, by use of the binomial distribution to model the within-study variability or by allowing Freeman-Tukey double arcsine transformation to stabilize the variances. Metaprop was applied on two published meta-analyses: 1) prevalence of HPV-infection in women with a Pap smear showing ASC-US; 2) cure rate after treatment for cervical precancer using cold coagulation.ResultsThe first meta-analysis showed a pooled HPV-prevalence of 43% (95% CI: 38%-48%). In the second meta-analysis, the pooled percentage of cured women was 94% (95% CI: 86%-97%).ConclusionBy using metaprop, no studies with 0% or 100% proportions were excluded from the meta-analysis. Furthermore, study specific and pooled confidence intervals always were within admissible values, contrary to the original publication, where metan was used.Electronic supplementary materialThe online version of this article (doi:10.1186/2049-3258-72-39) contains supplementary material, which is available to authorized users.

Gynecologic Cancer InterGroup (GCIG) consensus review for cervical adenocarcinoma.

Cervical adenocarcinoma is known to be less common than squamous cell carcinoma of the cervix comprising approximately 25% of all cervical carcinomas. Differences in associated human papillomavirus types, patterns of spread, and prognosis call for treatments that are not always like those for squamous cancers. In this review, we report a consensus developed by the Gynecologic Cancer InterGroup surrounding cervical adenocarcinoma for epidemiology, pathology, treatment, and unanswered questions. Prospective clinical trials are needed to help develop treatment guidelines.

Epidemiologic data and pathogen genome sequences: a powerful synergy for public health.

Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional ‘line lists’ (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.

A Practical and Evidence-Based Approach to Common Symptoms

Physical symptoms account for more than half of all outpatient visits, yet the predominant disease-focused model of care is inadequate for many of these symptom-prompted encounters. Moreover, the amount of clinician training dedicated to understanding, evaluating, and managing common symptoms is disproportionally small relative to their prevalence, impairment, and health care costs. This narrative review regarding physical symptoms addresses 4 common epidemiologic questions: cause, diagnosis, prognosis, and therapy. Important findings include the following: First, at least one third of common symptoms do not have a clear-cut, disease-based explanation (5 studies in primary care, 1 in specialty clinics, and 2 in the general population). Second, the history and physical examination alone contribute 73% to 94% of the diagnostic information, with costly testing and procedures contributing much less (5 studies of multiple types of symptoms and 4 of specific symptoms). Third, physical and psychological symptoms commonly co-occur, making a dualistic approach impractical. Fourth, because most patients have multiple symptoms rather than a single symptom, focusing on 1 symptom and ignoring the others is unwise. Fifth, symptoms improve in weeks to several months in most patients but become chronic or recur in 20% to 25%. Sixth, serious causes that are not apparent after initial evaluation seldom emerge during long-term follow-up. Seventh, certain pharmacologic and behavioral treatments are effective across multiple types of symptoms. Eighth, measuring treatment response with valid scales can be helpful. Finally, communication has therapeutic value, including providing an explanation and probable prognosis without "normalizing" the symptom.

First nationwide survey of hypertrophic pachymeningitis in Japan not only solves epidemiological questions, but also leads to the proposal of new questions

First nationwide survey of hypertrophic pachymeningitis in Japan not only solves epidemiological questions, but also leads to the proposal of new questions

Seroepidemiology of Toxoplasma gondii in elderly individuals treated under the Family Health Strategy, Porto Alegre, Rio Grande do Sul, Brazil

The aim of this study was to evaluate the seroprevalence of Toxoplasma gondii and relate it to the socioeconomic, hygienic, sanitary and health conditions of the elderly of the Family Health Strategy (FHS) in the city of Porto Alegre, Rio Grande do Sul, Brazil. The research involved a cross-sectional study in which a questionnaire with epidemiologic questions was applied and blood samples were taken. The assessment of IgG and IgM anti-T. gondii was performed using the ELISA technique. Seroprevalence was evaluated among 599 elderly individuals with 88% for IgG anti-T. gondii and with 0.8% for IgM. In the multivariate analysis, the variables that associated themselves independently with positive IgG were age range, personal income and wearing spectacles. Those associated with positive IgM were age, self-rated health and wearing spectacles. The results call attention to the high prevalence of IgG anti-T. gondii in elderly individuals in the FHS in Porto Alegre, generating concern in the event that the reactivation of toxoplasmosis and the development of more severe symptoms of this infection occur.

Regression discontinuity designs in epidemiology: causal inference without randomized trials.

When patients receive an intervention based on whether they score below or above some threshold value on a continuously measured random variable, the intervention will be randomly assigned for patients close to the threshold. The regression discontinuity design exploits this fact to estimate causal treatment effects. In spite of its recent proliferation in economics, the regression discontinuity design has not been widely adopted in epidemiology. We describe regression discontinuity, its implementation, and the assumptions required for causal inference. We show that regression discontinuity is generalizable to the survival and nonlinear models that are mainstays of epidemiologic analysis. We then present an application of regression discontinuity to the much-debated epidemiologic question of when to start HIV patients on antiretroviral therapy. Using data from a large South African cohort (2007-2011), we estimate the causal effect of early versus deferred treatment eligibility on mortality. Patients whose first CD4 count was just below the 200 cells/μL CD4 count threshold had a 35% lower hazard of death (hazard ratio = 0.65 [95% confidence interval = 0.45-0.94]) than patients presenting with CD4 counts just above the threshold. We close by discussing the strengths and limitations of regression discontinuity designs for epidemiology.

The TraumaRegister DGU® as data source for monitoring severe injuries

The TraumaRegister DGU® of the German Society for Trauma Surgery (TR-DGU) has collected data on the treatment of severely injured accident victims in Germany since 1993. Due to the current number of more than 600 participating clinics which regularly receive quality comparison reports, these register data are becoming an increasingly more valuable source for healthcare research. The aims of this article are to describe the potential of the TR-DGU for dealing with epidemiological questions and for describing the quality of the process and results for treatment of severely injured patients. The TR-DGU includes approximately 100 details per patient on the person, the circumstances of the accident, the injury pattern, the preclinical and hospital treatment, the condition of the patient and the outcome. Using comparative analyses the observed mortality is adjusted by considering prognostically relevant findings. Some key features of the register are reported for patients who were treated in German hospitals between 2002 and 2012 with an injury severity score (ISS) of ≥9 points. Since 1993 more than 122,000 patients have been included in the register. The majority are traffic accident victims (57 %), followed by patients with falls from low heights (< 3 m, 17 %) or greater heights (> 3 m, 16 %). Among the traffic accident victims approximately one half are car drivers or passengers (46 %), one quarter are motorbike drivers (25 %) and the rest are cyclists (14 %) and pedestrians (13 %). The mortality of patients with an ISS ³ 9 is 12.8 %. This value is approximately 1-2 % below the expected prognosis based on data from the 1990s. The TR-DGU is not only a successful instrument for external quality assurance of the treatment of severely injured patients but also an increasingly more valuable source for scientific evaluation within the framework of healthcare research. The introduction of regional trauma networks by the DGU has made a substantial contribution to the comprehensive compilation of severely injured patients and allows increasingly more detailed information on the epidemiology of severe injuries in Germany to be compiled.

Comparative analyses of the complete mitochondrial genomes of the two ruminant hookworms Bunostomum trigonocephalum and Bunostomum phlebotomum

Bunostomum trigonocephalum and Bunostomum phlebotomum are blood-feeding hookworms of sheep and cattle, causing considerable economic losses to the live stock industries. Studying genetic variability within and among hookworm populations is critical to addressing epidemiological and ecological questions. Mitochondrial (mt) DNA is known to provide useful markers for investigations of population genetics of hookworms, but mt genome sequence data are scant. In the present study, the complete mitochondrial DNA (mtDNA) sequences of the sheep and goat hookworm B. trigonocephalum were determined for the first time, and the mt genome of B. phlebotomum from yak in China was also sequenced for comparative analyses of their gene contents and genome organizations. The lengths of mt DNA sequences of B. trigonocephalum sheep isolate, B. trigonocephalum goat isolate and B. phlebotomum China yak isolate were 13,764bp, 13,771bp and 13,803bp in size, respectively. The identity of the mt genomes was 99.7% between B. trigonocephalum sheep isolate and B. trigonocephalum goat isolate. The identity of B. phlebotomum China yak isolate mt genomes was 85.3% with B. trigonocephalum sheep isolate, and 85.2% with B. trigonocephalum goat isolate. All the mt genes of the two hookworms were transcribed in the same direction and gene arrangements were consistent with those of the GA3 type, including 12 protein-coding genes, 2 rRNA genes and 22 tRNA genes, but lacking ATP synthetase subunit 8 gene. The mt genomes of B. trigonocephalum and B. phlebotomum were similar to prefer bases A and T, the contents of A+T are 76.5% (sheep isolate), 76.4% (goat isolate) and 76.9% (China yak isolate), respectively. Phylogenetic relationships reconstructed using concatenated amino acid sequences of 12 protein-coding genes with three methods (maximum likelihood, Bayesian inference and neighbor joining) revealed that the B. trigonocephalum and B. phlebotomum represent distinct but closely-related species. These data provide novel and useful genetic markers for studying the systematics, and population genetics of the two ruminant hookworms.

SEV – a software toolbox for large scale analysis and visualization of polysomnography data

SEV is a graphical toolbox designed in MATLAB for displaying polysomnography (PSG) signals recorded during sleep studies, prototyping signal-processing algorithms and automating sleep feature extraction methods across large collections or cohorts of such studies. Format imported are European Data Formats and event/hypnogram files. Time-series analysis can be performed using a suite of classifiers, filters and signal decomposition tools (e.g. wavelets) developed internally or implemented from validated methods published by others. Power spectral analysis can be performed using either periodogram averaging or multiple spectrum independent component analysis. The tool is highly configurable and provides a simple framework for classifier optimization and extensibility. MATLAB's parallel processing toolbox is utilized during batch processing. Output formats include MySQL database entry, tab-delimited text and MATLAB archive (.MAT). The tool is well suited for genetic or epidemiological sleep research questions requiring rigorous, robust and reproducible evaluation of a PSG-based sleep study cohort. Current built-in applications include modules to detect and quantify rapid eye movements and spindle activity (using existing algorithms), inter-channel electroencephalography coherence and a detector developed in house to quantify periodic leg movements during sleep. SEV is open source and freely available under a common creative license.

Focussing and funding a longitudinal study of health over 20 years: the MRC National Survey of Health and Development from 16 to 36 years

The first British national birth cohort study was initially concerned principally with health at the birth of its sample in 1946. Throughout its first fifteen years it received only short-term financial support, but still managed to undertake ten follow-up data collections and broaden its focus to include educational and cognitive outcomes. Then in 1962, when cohort members were aged 16 years, the Medical Research Council (MRC) agreed to be the principal funder. Over the next twenty years, during the cohort’s adolescence and early adulthood, discussion about the study’s focus was influenced by the funding source, the cohort’s age, the data, current policy concerns, and current thought and innovations in measurement in epidemiology. That period began with pessimism about the study’s future. However, towards the end of the twenty years, the MRC review of options for continuation revealed new epidemiological questions on mental health and ageing that required life course data. Consequently the study was continued, and extensively revised health outcome indicators and methods of data collection were first used at age 36 years. They provided new baselines against which to measure future health change with age, and new outcomes with which to test life course effects of hypothesised earlier life exposures, experiences and health. This paper shows how the focus of the study was changed and developed by internal and external pressures and influences between 1962 and 1982, when the cohort was aged 16 to 36 years.

Evaluation of generic medical information accessed via mobile phones at the point of care in resource-limited settings

Many mobile phone resources have been developed to increase access to health education in the developing world, yet few studies have compared these resources or quantified their performance in a resource-limited setting. This study aims to compare the performance of resident physicians in answering clinical scenarios using PubMed abstracts accessed via the PubMed for Handhelds (PubMed4Hh) website versus medical/drug reference applications (Medical Apps) accessed via software on the mobile phone. A two-arm comparative study with crossover design was conducted. Subjects, who were resident physicians at the University of Botswana, completed eight scenarios, each with multi-part questions. The primary outcome was a grade for each question. The primary independent variable was the intervention arm and other independent variables included residency and question. Within each question type there were significant differences in 'percentage correct' between Medical Apps and PubMed4Hh for three of the six types of questions: drug-related, diagnosis/definitions, and treatment/management. Within each of these question types, Medical Apps had a higher percentage of fully correct responses than PubMed4Hh (63% vs 13%, 33% vs 12%, and 41% vs 13%, respectively). PubMed4Hh performed better for epidemiologic questions. While mobile access to primary literature remains important and serves an information niche, mobile applications with condensed content may be more appropriate for point-of-care information needs. Further research is required to examine the specific information needs of clinicians in resource-limited settings and to evaluate the appropriateness of current resources in bridging location- and context-specific information gaps.

Restless legs syndrome during pregnancy in czech women

Introduction The objective of this study was to identify the prevalence of restless legs syndrome (RLS) among pregnant Czech women, with questionnaire based survey during the third trimester of pregnancy, and to determine risk factors. Materials and methods It was a cross-sectional study. We surveyed 776 pregnant women (18–49 years old) who came to the prenatal outpatient clinic to consult an obstetrician at the third trimester (36th-38th week of pregnancy). We used the 3 minimal set epidemiological questions to assign RLS status, disease course and frequency of symptoms. Further, we asked for previous pregnancies and comorbidities. Results The prevalence of RLS during pregnancy was 28.0% (95% confidence interval from 24.9% to 31.2%) in our sample, among which 63% of the cases started with their symptoms during the current pregnancy. On the other hand 16.6% reported positive family history of RLS. More than two thirds of the patients (71.0%) presented symptoms more than once per week and the largest proportion of them (49.3%) reported onset or major worsening of previous symptoms in the third trimester. There were no demographic differences between these groups. We did not observe any differences in prevalence of screened comorbidities between RLS positive and RLS negative pregnant women, only leg cramps were marginally more frequent in the RLS group (23% vs. 16%, p = 0,022) and also hypothyreosis (13% vs. 8%, p = 0,033). We also could not confirm higher prevalence of RLS among multiparous women. Conclusion RLS during pregnancy is more frequent than in the general population. Moreover, about two thirds of the pregnant women with RLS suffer from the symptoms frequently. It occurs especially in the third trimester. Despite relatively young age of the patients, family history is positive relatively rarely. Acknowledgements Supported by grant IGA-NT 12141–3 and MSM 0021620849.

The Epidemiology of Delirium: Challenges and Opportunities for Population Studies

Delirium is a serious and common acute neuropsychiatric syndrome that is associated with short- and long-term adverse health outcomes. However, relatively little delirium research has been conducted in unselected populations. Epidemiologic research in such populations has the potential to resolve several questions of clinical significance in delirium. Part 1 of this article explores the importance of population selection, case-ascertainment, attrition, and confounding. Part 2 examines a specific question in delirium epidemiology: What is the relationship between delirium and trajectories of cognitive decline? This section assesses previous work through two systematic reviews and proposes a design for investigating delirium in the context of longitudinal cohort studies. Such a design requires robust links between community and hospital settings. Practical considerations for case-ascertainment in the hospital, as well as the necessary quality control of these programs, are outlined. We argue that attention to these factors is important if delirium research is to benefit fully from a population perspective.

Influenza research in the Eastern Mediterranean Region: the current state and the way forward

We searched published literature, surveillance data sources, and sequence databases to analyze the state of influenza virus research and to identify research gaps in the World Health Organization (WHO) Eastern Mediterranean Region. PubMed, Scopus, and other databases were searched for influenza publications and nucleotide sequences. WHO's FluNet was searched to determine virologic reporting from each country. We found that influenza research has increased in recent years with the emergence of H5N1 and pandemic H1N1. In some countries, influenza research is growing and is diversified, covering epidemiologic, veterinary, and basic science aspects. However, the volume and diversity of influenza research is low, especially in light of the burden of influenza in the region. To have contemporary and advanced research in the region, systematic surveillance in humans and animals, as well as at the human-animal interface, needs to be boosted. Surveillance data should then be used to answer more important epidemiologic, virologic, immunologic, and basic science questions.

SP0069 Finding the Right Key for the Right Lock: Choosing the Appropriate Study Design to Answer a Research Question

This lecture relates to the selection of study design for clinical and epidemiological (as opposed to laboratory) questions. Epidemiological studies divide into those which are purely descriptive and those which...

Duração da Terapêutica Antibiótica na Meningite Bacteriana

The duration of antibiotic therapy in bacterial meningitis is a controversial issue. Antibiotic regimens have changed over time along with the criteria used to determine the ideal antibiotic therapy duration. The authors aim to make an historical overview on this matter and simultaneously add the evidence of recent studies, pointing out some issues in results interpretation, namely, their design and the associated demographic and epidemiological questions. Clinical assays on this subject, with statistically significant results, are quite recent. Most of the scientific knowledge has been acquired empirically through the times. The actual investigation paradigm, in what concerns to antibiotic therapy in bacterial meningitis, lays on the dichotomy: "short versus long duration regimens". Nevertheless, so far, the existing studies have not completely cleared this doubt. Thus, despite some evidence suggests that short duration antibiotic regimens are effective for some patients, in patients with severe disease presentations or with other morbidities its use may be questioned.

Dientamoeba fragilis in Denmark: epidemiological experience derived from four years of routine real-time PCR

The intestinal protozoon Dientamoeba fragilis remains a clinical entity of dubious significance. While several previous studies address questions of epidemiology, only a handful have systematically employed and reported on the results from real-time polymerase chain reaction (qPCR), the best currently available diagnostic modality, and the comparison of results from different studies is, therefore, difficult. Since 2007, Statens Serum Institut (Denmark) has utilised qPCR for D. fragilis as routine diagnostic work-up for intestinal parasitosis, testing more than 22,000 samples from 2008 through 2011, and the aim of this study was to report on the results and experiences gained in the process. We demonstrate a staggeringly high proportion (43%) of investigated patients positive for D. fragilis, ranging from 12 to 71% depending on age group, showing a bimodal age distribution peaking in children and adults of parental age, as well as a clear association between exposure to children and risk of D. fragilis infection. We discuss these findings in light of the pinworm egg vector hypothesis and substantiate further our knowledge of risk factors pertaining to D. fragilis carriage.