Methodology in the epidemiological research of respiratory diseases and environmental pollution

There are complex and diverse methodological problems involved in the clinical and epidemiological study of respiratory diseases and their etiological factors. The association of urban growth, industrialization and environmental deterioration with respiratory diseases makes it necessary to pay more attention to this research area with a multidisciplinary approach. Appropriate study designs and statistical techniques to analyze and improve our understanding of the pathological events and their causes must be implemented to reduce the growing morbidity and mortality through better preventive actions and health programs. The objective of the article is to review the most common methodological problems in this research area and to present the most available statistical tools used.

Prevalence of anemia and associated factors in older adults: evidence from the SABE Study

OBJECTIVE To assess the prevalence of anemia and associated factors in older adults. METHODS The prevalence and factors associated with anemia in older adults were studied on the basis of the results of the Saúde, Bem-Estar e Envelhecimento (SABE – Health, Welfare and Aging) study. A group of 1,256 individuals were interviewed during the third wave of the SABE study performed in Sao Paulo, SP, in 2010. The study included 60.4% females; the mean age of the participants was 70.4 years, and their average education was 5.3 years. The dependent variable was the presence of anemia (hemoglobin levels: 12 g/dL in women and 13 g/dL in men). Descriptive analysis and hierarchical logistic regression were performed. The independent variables were as follows: a) demographics: gender, age, and education and b) clinical characteristics: self-reported chronic diseases, presence of cognitive decline and depression symptoms, and body mass index. RESULTS The prevalence of anemia was 7.7% and was found to be higher in oldest adults. There was no difference between genders, although the hemoglobin distribution curve in women showed a displacement toward lower values in comparison with the distribution curve in men. Advanced age (OR = 1.07; 95%CI 0.57;1.64; p < 0.001), presence of diabetes (OR = 2.30; 95%CI 1.33;4.00; p = 0.003), cancer (OR = 2.72; 95%CI 1.2;6.11; p = 0.016), and presence of depression symptoms (OR = 1.75; 95%CI 1.06;2.88; p = 0.028) remained significant even after multiple analyses. CONCLUSIONS The prevalence of anemia in older adults was 7.7% and was mainly associated with advanced age and presence of chronic diseases. Thus, anemia can be an important marker in the investigation of health in older adults because it can be easily diagnosed and markedly affects the quality of life of older adults.

Functional disability of adults in Brazil: prevalence and associated factors

ABSTRACT OBJECTIVE To estimate the prevalence and factors associated with functional disability in adults in Brazil. METHODS We used information from the health supplement of the National Household Sample Survey in 2008. The dependent variable was the functional disability among adults of 18 to 65 years, measured by the difficulty of walking about 100 meters; independent variables were: health plan membership, region of residence, state of domicile, education level, household income, economic activity, self-perception of health, hospitalization, chronic diseases, age group, sex, and color. We calculated the gross odds ratios (OR), and their respective confidence intervals (95%), and adjusted them for variables of study by ordinal logistic regression, following hierarchical model. Sample weights were considered in all calculations. RESULTS We included 18,745 subjects, 74.0% of whom were women. More than a third of adults reported having functional disability. The disability was significantly higher among men (OR = 1.17; 95%CI 1.09;1.27), people from 35 to 49 years (OR = 1.30; 95%CI 1.17;1.45) and 50 to 65 years (OR = 1.38; 95%CI 1.24;1.54); economically inactive individuals (OR = 2.21; 95%CI 1.65;2.96); adults who reported heart disease (OR = 1.13; 95%CI 1.03;1.24), diabetes mellitus (OR = 1.16; 95%CI 1.05;1.29), arterial systemic hypertension (OR = 1.10; 95%CI 1.02;1.18), and arthritis/rheumatism (OR = 1.24; 95%CI 1.15;1.34); and participants who were admitted in the last 12 months (OR = 2.35; 95%CI 1.73;3.2). CONCLUSIONS Functional disability is common among Brazilian adults. Hospitalization is the most strongly associated factor, followed by economic activity, and chronic diseases. Sex, age, education, and income are also associated. Results indicate specific targets for actions that address the main factors associated with functional disabilities and contribute to the projection of interventions for the improvement of the well-being and promotion of adults' quality of life.

Genomic and environmental factors influence Wolbachia-Drosophila symbiosis

Intracellular, vertically transmitted bacteria form complex and intimate relationships with their hosts. Wolbachia, maternally transmitted α- proteobacteria, live within the cells of numerous arthropod species. Wolbachia are famous master manipulators of insect reproduction: to favour their own spread they can induce male killing, parthenogenesis or cytoplasmic incompatibility. Wolbachia can also protect various insects from pathogens, which makes them a promising tool for the control of vector-borne diseases. Mosquitoes with Wolbachia have already been released in the wild to eliminate dengue. Yet, how Wolbachia manipulate their hosts remains largely unknown.(...)

Biological, behavioral, and socioeconomic factors associated with death from AIDS in Brasília, Brazil, in 2007

INTRODUCTION: In the jurisdiction of Brasília, Brazil, significant reductions in mortality rates and lethality resulting from acquired immunodeficiency syndrome (AIDS) were observed shortly after the introduction of highly active antiretroviral therapy. In recent years, however, the decline of these rates has not been as significant. Non-adherence to treatment and delayed diagnosis appear to be the main factors that increase the risk of death from AIDS. Behavioral, socioeconomic, and biological factors could also be associated with increased risk of death due to AIDS. This study aimed to identify which of these factors were associated with deaths from AIDS in Brasília. METHODS: A case-control study was undertaken using the data recorded in the Information System of Notifiable Diseases. Cases consisted of AIDS deaths occurring in 2007, residing in Brasília, and over 12 years of age. Controls consisted of AIDS patients who did not die until December 31 2007, also residing in Brasília, and over 12 years of age. For each group, frequency and proportion tables for the variables were prepared. The statistical association of each factor in isolation with the occurrence of the deaths was verified through a model of multivariate analysis using logistic regression. RESULTS: The factors that were associated with an increased risk of death were intravenous drug use, age 50 years or more, and residing in a region whose residents have low per capita income. CONCLUSIONS: We identified factors associated with death due to AIDS that can guide health planning.

Susceptibility and prognostic factors in portuguese patients with juvenile idiopathic arthritis

ABSTRACT: Objectives: This study aimed to confirm whether 15 single nucleotide polymorphisms (SNPs) of selected genes are also associated with susceptibility for Juvenile idiopathic Arthritis (JIA) in thePortuguese population. Methods: Our study was conducted on Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA receiving biological therapies and synthetic Disease Modifying Anti Rheumatic Drugs (DMARDs) since June 2001. Fifteen SNPs were investigated using Taqman® SNP genotyping assays in 291 Portuguese patients with JIA and 300 ethnically matched healthy controls. Results: Prior to Bonferroni correction for multiple testing, significant genotype association between one SNP and overall group of JIA was observed (PTPN22 rs2476601). In subgroup analysis, associations between six SNPs and the subgroup of patients with rheumatoid factor (RF)-positive Polyarticular (PTPN2 rs7234029), Extended oligoarticular (PTPN22 rs2476601), Systemic (PTPRC rs10919563, ANGPT1 rs7151781 and TNF rs361525) and Psoriatic JIA (IL2RA/CD25 rs2104286) were found. After Bonferroni correction for multiple testing, 3 genotype associations remained significant in the subgroup of patients with RF-positive polyarticular JIA (PTPN2 rs7234029 [corrected P 0.026]), extended oligoarticular (PTPN22 rs2476601 [corrected P 0.026]) and systemic JIA (ANGPT1 rs7151781 [corrected P 0.039]). Conclusion: Our results provide additional evidence for an association between polymorphisms in genes PTPN2, PTPN22 and ANGPT1 and the risk of RF-positive polyarticular, extended oligoarticular and systemic JIA, respectively, in a Portuguese population.

Survival and Predictive Factors of Lethality in Hemodyalisis: D/I Polymorphism of The Angiotensin I-Converting Enzyme and of the Angiotensinogen M235T Genes

Background: End-stage kidney disease patients continue to have markedly increased cardiovascular disease morbidity and mortality. Analysis of genetic factors connected with the renin-angiotensin system that influences the survival of the patients with end-stage kidney disease supports the ongoing search for improved outcomes. Objective: To assess survival and its association with the polymorphism of renin-angiotensin system genes: angiotensin I-converting enzyme insertion/deletion and angiotensinogen M235T in patients undergoing hemodialysis. Methods: Our study was designed to examine the role of renin-angiotensin system genes. It was an observational study. We analyzed 473 chronic hemodialysis patients in four dialysis units in the state of Rio de Janeiro. Survival rates were calculated by the Kaplan-Meier method and the differences between the curves were evaluated by Tarone-Ware, Peto-Prentice, and log rank tests. We also used logistic regression analysis and the multinomial model. A p value ≤ 0.05 was considered to be statistically significant. The local medical ethics committee gave their approval to this study. Results: The mean age of patients was 45.8 years old. The overall survival rate was 48% at 11 years. The major causes of death were cardiovascular diseases (34%) and infections (15%). Logistic regression analysis found statistical significance for the following variables: age (p = 0.000038), TT angiotensinogen (p = 0.08261), and family income greater than five times the minimum wage (p = 0.03089), the latter being a protective factor. Conclusions: The survival of hemodialysis patients is likely to be influenced by the TT of the angiotensinogen M235T gene.

Circulating soluble CR1 (CD35). Serum levels in diseases and evidence for its release by human leukocytes.

C receptor type 1 (CR1, CD35) is present in a soluble form in plasma (sCR1). Soluble CR1 was measured with a specific ELISA assay in normal individuals and in patients with different diseases. The mean serum concentration of sCR1 in 31 normal donors was 31.4 +/- 7.8 ng/ml, and was identical in plasma. An increase in sCR1 was observed in 36 patients with end-stage renal failure on dialysis (54.8 +/- 11.7 ng/ml, p &lt; 0.0001), and in 22 patients with liver cirrhosis (158.3 +/- 49.9 ng/ml, p &lt; 0.0001). The mean sCR1 levels dropped from 181 +/- 62.7 to 52.1 +/- 24.0 ng/ml (p &lt; 0.001) in nine patients who underwent liver transplantation, and was 33.5 +/- 7.3 in 10 patients with functioning renal grafts, indicating that the increase in sCR1 was reversible. Soluble CR1 was elevated in some hematologic malignancies (&gt; 47 ng/ml), which included B cell lymphoma (12/19 patients), Hodgkin's lymphoma (4/4), and chronic myeloproliferative syndromes (4/5). By contrast, no increase was observed in acute myeloid or lymphoblastic leukemia (10) or myeloma (5). In two patients with chronic myeloproliferative syndromes, sCR1 decreased rapidly after chemotherapy. The mean concentration of sCR1 was not significantly modified in 181 HIV-infected patients at various stages of the disease (34.8 +/- 14.4 ng/ml), and in 13 patients with active SLE (38.3 +/- 19.6 ng/ml), although in both groups the number of CR1 was diminished on E. There was a weak but significant correlation between sCR1 and CR1 per E in HIV infection and SLE (r = 0.39, p &lt; 0.0001, and r = 0.60, p &lt; 0.03 respectively). In vitro, monocytes, lymphocytes, and neutrophils were found to release sCR1 into culture supernatants. In vivo, sCR1 was detected in the serum of SCID mice populated with human peripheral blood leukocytes. The sCR1 levels correlated with those of human IgG (r = 0.97, p &lt; 0.0001), suggesting synthesis of sCR1 by the transferred lymphocytes. The mechanisms underlining the increased levels of sCR1 and its biologic consequences remain to be defined.

Mandibular osteoradionecrosis in squamous cell carcinoma of the oral cavity and oropharynx: incidence and risk factors.

Objective. Mandibular osteoradionecrosis (ORN) is a serious complication of radiotherapy (RT) in head and neck cancer patients. The aim of this study was to analyze the incidence of and risk factors for mandibular ORN in squamous cell carcinoma (SCC) of the oral cavity and oropharynx.Study Design. Case series with chart review.Setting. University tertiary care center for head and neck oncology.Subjects and Methods. Seventy-three patients treated for stage I to IV SCC of the oral cavity and oropharynx between 2000 and 2007, with a minimum follow-up of 2 years, were included in the study. Treatment modalities included both RT with curative intent and adjuvant RT following tumor surgery. The log-rank test and Cox model were used for univariate and multivariate analyses.Results. The incidence of mandibular ORN was 40% at 5 years. Using univariate analysis, the following risk factors were identified: oral cavity tumors (P < .01), bone invasion (P < .02), any surgery prior to RT (P < .04), and bone surgery (P < .0001). By multivariate analysis, mandibular surgery proved to be the most important risk factor and the only one reaching statistical significance (P < .0002).Conclusion. Mandibular ORN is a frequent long-term complication of RT for oral cavity and oropharynx cancers. Mandibular surgery before irradiation is the only independent risk factor. These aspects must be considered when planning treatment for these tumors.

Prevalence of and risk factors for biliary carriage of bacteria showing worrisome and unexpected resistance traits.

Data on biliary carriage of bacteria and, specifically, of bacteria with worrisome and unexpected resistance traits (URB) are lacking. A prospective study (April 2010 to December 2011) was performed that included all patients admitted for <48 h for elective laparoscopic cholecystectomy in a Spanish hospital. Bile samples were cultured and epidemiological/clinical data recorded. Logistic regression models (stepwise) were performed using bactobilia or bactobilia by URB as dependent variables. Models (P < 0.001) showing the highest R(2) values were considered. A total of 198 patients (40.4% males; age, 55.3 ± 17.3 years) were included. Bactobilia was found in 44 of them (22.2%). The presence of bactobilia was associated (R(2) Cox, 0.30) with previous biliary endoscopic retrograde cholangiopancreatography (ERCP) (odds ratio [OR], 8.95; 95% confidence interval [CI], 2.96 to 27.06; P < 0.001), previous admission (OR, 2.82; 95% CI, 1.10 to 7.24; P = 0.031), and age (OR, 1.09 per year; 95% CI, 1.05 to 1.12; P < 0.001). Ten out of the 44 (22.7%) patients with bactobilia carried URB: 1 Escherichia coli isolate (CTX-M), 1 Klebsiella pneumoniae isolate (OXA-48), 3 high-level gentamicin-resistant enterococci, 1 vancomycin-resistant Enterococcus isolate, 3 Enterobacter cloacae strains, and 1 imipenem-resistant Pseudomonas aeruginosa strain. Bactobilia by URB (versus those by non-URB) was only associated (R(2) Cox, 0.19) with previous ERCP (OR, 11.11; 95% CI, 1.98 to 62.47; P = 0.006). For analyses of patients with bactobilia by URB versus the remaining patients, previous ERCP (OR, 35.284; 95% CI, 5.320 to 234.016; P < 0.001), previous intake of antibiotics (OR, 7.200; 95% CI, 0.962 to 53.906; P = 0.050), and age (OR, 1.113 per year of age; 95% CI, 1.028 to 1.206; P = 0.009) were associated with bactobilia by URB (R(2) Cox, 0.19; P < 0.001). Previous antibiotic exposure (in addition to age and previous ERCP) was a risk driver for bactobilia by URB. This may have implications in prophylactic/therapeutic measures.

Individual, family and environmental factors associated with pediatric excess weight in Spain: a cross-sectional study.

BACKGROUND There is a growing worldwide trend of obesity in children. Identifying the causes and modifiable factors associated with child obesity is important in order to design effective public health strategies.Our objective was to provide empirical evidence of the association that some individual and environmental factors may have with child excess weight. METHOD A cross-sectional study was performed using multi-stage probability sampling of 978 Spanish children aged between 8 and 17 years, with objectively measured height and weight, along with other individual, family and neighborhood variables. Crude and adjusted odds ratios were calculated. RESULTS In 2012, 4 in 10 children were either overweight or obese with a higher prevalence amongst males and in the 8-12 year age group. Child obesity was associated negatively with the socio-economic status of the adult responsible for the child's diet, OR 0.78 (CI95% 0.59-1.00), girls OR 0.75 (CI95% 0.57-0.99), older age of the child (0.41; CI95% 0.31-0.55), daily breakfast (OR 0.59; p = 0.028) and half an hour or more of physical activity every day. No association was found for neighborhood variables relating to perceived neighborhood quality and safety. CONCLUSION This study identifies potential modifiable factors such as physical activity, daily breakfast and caregiver education as areas for public health policies. To be successful, an intervention should take into account both individual and family factors when designing prevention strategies to combat the worldwide epidemic of child excess weight.

Genetics of calcium homeostasis in humans: continuum between monogenic diseases and continuous phenotypes

Extracellular calcium participates in several key physiological functions, such as control of blood coagulation, bone calcification or muscle contraction. Calcium homeostasis in humans is regulated in part by genetic factors, as illustrated by rare monogenic diseases characterized by hypo or hypercalcaemia. Both serum calcium and urinary calcium excretion are heritable continuous traits in humans. Serum calcium levels are tightly regulated by two main hormonal systems, i.e. parathyroid hormone and vitamin D, which are themselves also influenced by genetic factors. Recent technological advances in molecular biology allow for the screening of the human genome at an unprecedented level of detail and using hypothesis-free approaches, such as genome-wide association studies (GWAS). GWAS identified novel loci for calcium-related phenotypes (i.e. serum calcium and 25-OH vitamin D) that shed new light on the biology of calcium in humans. The substantial overlap (i.e. CYP24A1, CASR, GATA3; CYP2R1) between genes involved in rare monogenic diseases and genes located within loci identified in GWAS suggests a genetic and phenotypic continuum between monogenic diseases of calcium homeostasis and slight disturbances of calcium homeostasis in the general population. Future studies using whole-exome and whole-genome sequencing will further advance our understanding of the genetic architecture of calcium homeostasis in humans. These findings will likely provide new insight into the complex mechanisms involved in calcium homeostasis and hopefully lead to novel preventive and therapeutic approaches. Keyword: calcium, monogenic, genome-wide association studies, genetics.

What is the value of hypothermia in acute neurologic diseases and status epilepticus?

Patients with status epilepticus that proves refractory to anesthetic agents represent a daunting challenge for treating clinicians. Animal data support the neuroprotective action of brain hypothermia, and its efficacy in status epilepticus models. This approach, targeting a core temperature of about 33°C for at least 24 hours together with pharmacological sedation, has been described in adults and children. However, although relatively safe if concomitant barbiturates are avoided, it seems that mild hypothermia rarely allows a sustained control of ongoing status epilepticus, since seizures tend to recur in normothermia. Conversely, mild hypothermia has a high-evidence level and is increasingly used in postanoxic encephalopathy, both in newborns and adults. Due to the paucity of available clinical data, prospective studies are needed to assess the value of hypothermia in status epilepticus.

Protective and Aggravating Effects of Nlrp3 Inflammasome Activation in IBD Models: Influence of Genetic and Environmental Factors.

Background: Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation due to dysregulation of the mucosal immune system. The cytokines IL-1β and IL-18 appear early in intestinal inflammation and their pro-forms are processed via the caspase-1-activating multiprotein complex, the Nlrp3 inflammasome. Previously, we reported that the uptake of dextran sodium sulfate (DSS) by macrophages activates the Nlrp3 inflammasome and that Nlrp3(-/-) mice are protected in the acute DSS colitis model. Of note, other groups have reported opposing effects in regards to DSS susceptibility in Nlrp3(-/-) mice. Recently, mice lacking inflammasomes were found to develop a distinct intestinal microflora. Methods: To reconcile the contradicting observations, we investigated the role of Nlrp3 deficiency in two different IBD models: acute DSS colitis and TNBS (2,4,6-trinitrobenzene sulfonic acid)-induced colitis. In addition, we investigated the impact of the intestinal flora on disease severity by performing cohousing experiments of wild-type and Nlrp3(-/-) mice, as well as by antibiotic treatment. Results: Nlrp3(-/-) mice treated with either DSS or TNBS exhibited attenuated colitis and lower mortality. This protective effect correlated with an increased frequency of CD103+ lamina propria dendritic cells expressing a tolerogenic phenotype in Nlrp3(-/-) mice in steady state conditions. Interestingly, after cohousing, Nlrp3(-/-) mice were as susceptible as wild-type mice, indicating that transmission of endogenous bacterial flora between the two mouse strains might increase susceptibility of Nlrp3(-/-) mice towards DSS-induced colitis. Accordingly, treatment with antibiotics almost completely prevented colitis in the DSS model. Conclusions: The composition of the intestinal microflora significantly influences disease severity in IBD models comparing wild-type and Nlrp3(-/-) mice. This observation may - at least in part - explain contradictory results concerning the role of the inflammasome in different labs. Further studies are required to define the role of the Nlrp3 inflammasome in noninflamed mucosa under steady state conditions and in IBD.