Nested Case Control Study Design Research Articles

Finnish Prenatal Study of Bipolar Disorders (FIPS-B): Overview, design and description of the sample

Background: Bipolar disorders (BPD) are chronic mental illnesses, the development of which involves genetic factors and environmental influences. Aims: The aim of this paper is to provide an overall description of the Finnish Prenatal Study of Bipolar Disorders (FIPS-B), including the study design, national registers and linkage of the registers. Methods: FIPS-B is a population-based prenatal epidemiological study of BPD with a nested case–control study design using several national registers. The registers used are: the Finnish Medical Birth Register (FMBR), the Finnish Hospital Discharge Register (FHDR), the Population Central Register and the Finnish Maternity Cohort (FMC), which are linked using the unique personal identity code (PIC). FIPS-B includes all children born from January 1, 1983 to December 31, 1998 and diagnosed with BPD in Finland by December 31, 2008. Results: The total number of cases included in the FIPS-B is 1887. The age at first diagnosis ranged from 4 to 25 years. Half (50.4%) of the cases utilized only outpatient services, 12.7% only inpatient services and the rest (36.9%) utilized both services. Offspring of mothers with the lowest educational level had an increased odds of BPD (OR = 1.46, 95% CI 1.13–1.88). The cumulative incidence of BPD in the population aged 25 years or younger was 11.6/10,000 in 2008. Conclusions: FIPS-B has all the strengths of a register-based prenatal epidemiological study, along with the availability of maternal biomarkers, enabling it to examine several prenatal, perinatal and familial risk factors for BPD.

Factors Associated with Tuberculosis Treatment Default in an Endemic Area of the Brazilian Amazon: A Case Control-Study

SettingTreatment default is a serious problem in tuberculosis control because it implies persistence of infection source, increased mortality, increased relapse rates and facilitates the development of resistant strains.ObjectiveThis study analyzed tuberculosis treatment default determinants in the Amazonas State to contribute in planning appropriate control interventions.DesignObservational study with a retrospective cohort using Brazilian Disease Notification System data from 2005 to 2010. A nested case control study design was used. Patients defaulting from treatment were considered as ‘cases’ and those completing treatment as ‘controls’. In the analysis, 11,312 tuberculosis patients were included, 1,584 cases and 9,728 controls.ResultsTreatment default was observed to be associated to previous default (aOR 3.20; p<0.001), HIV positivity (aOR 1.62; p<0.001), alcoholism (aOR 1.51; p<0.001), low education level (aOR 1.35; p<0.001) and other co-morbidities (aOR 1.31; p = 0.05). Older patients (aOR 0.98; p = 0.001) and DOT (aOR 0,72; p<0.01) were considered as protective factor for default.ConclusionsAssociated factors should be considered in addressing care and policy actions to tuberculosis control. Information on disease and treatment should be intensified and appropriate to the level of education of the population, in order to promote adherence to treatment and counter the spread of multidrug resistance to anti-TB drugs.

C-Reactive Protein, Interleukin 6, Fibrinogen and Risk of Sudden Death in European Middle-Aged Men: The PRIME Study

To examine prospectively the association of high-sensitivity C-reactive protein, interleukin 6, and fibrinogen with sudden death in asymptomatic European men. Among the 9771 men from the Etude PRospective de l'Infarctus du Myocarde (PRIME) Study, 664 had a first coronary heart disease over 10 years, including 50 sudden deaths, 34 nonsudden coronary deaths, and 580 nonfatal coronary heart disease events. For each outcome, 2 matched controls, who were free of coronary heart disease at the index date, were randomly selected from the initial cohort (nested case control study design). There was a 3-fold increased risk (95% CI, 1.20 to 7.81) of sudden death between the upper and the lower third of interleukin 6 after adjustment for baseline confounders in conditional logistic regression analysis. Neither high-sensitivity C-reactive protein (hazard ratio(third versus first tertile)=1.27; 95% CI, 0.51 to 3.17) nor fibrinogen (hazard ratio(third versus first tertile)=1.90; 95% CI, 0.76 to 4.75) was associated with sudden death. For comparison, there was a 6-fold increased risk of nonsudden coronary death from the highest compared with the lowest tertile of fibrinogen and a trend toward an association with higher C-reactive protein and higher interleukin 6. All 3 inflammatory biomarkers were moderately, but significantly, associated with nonfatal coronary heart disease. Interleukin 6, but not high-sensitivity C-reactive protein or fibrinogen, is an independent predictor of sudden death in asymptomatic European men.

C-C3-04: Using Electronic Health Record Data to Predict Heart Failure Diagnosis

Background: Heart Failure (HF) is one of the most common and serious progressive illnesses among elderly patients. It is usually detected at a relatively advanced stage, after irreversible damage has occurred. Early detection offers the potential to substantially reduce patient disability and health care costs. Objective: To develop a novel detection strategy, making use of longitudinal electronic health record (EHR) data to create an HF early detection prediction model. Methods: All data for this study were obtained from Geisinger Clinic’s EHR among patients who had a primary care provider. A prediction model was developed using a nested case control study design, where HF cases diagnosed between 2003–2006 were identified and controls were randomly selected matched on sex, age, and clinic. We used conditional logistic regression to model the relation between EHR data and detection of HF 6+ months and 18+ months before the actual date of diagnosis. Variables for the model included diagnoses, the most recent lab and clinical (e.g., SBP, DBP, pulse pressure) measures, medication orders and ambulatory care use in the previous two years, and smoking status. Data were only used if they occurred in the record either 6+ months or 18+ months before the diagnosis date, depending on the specific model. Model results were validated by combining a bootstrap re-sampling approach with a backwards elimination selection method. Results: We identified at least one matching control for 2,239 of the 2,764 cases; 9 or 10 controls were identified for 81% of the cases. A total of 24,249 controls were selected. The model for detecting HF 6+ months before usual diagnosis had an AUC of 0.80; the parallel model for detecting HF 18+ months before usual diagnosis had an AUC of 0.75 (95% CI: 0.73, 0.79). The AUC findings were similar for separate models completed on systolic HF and diastolic HF. Conclusions: In practice, clinicians do not have the time or ability to process seemingly disparate data points over a series of visits that might suggest a preclinical HF for a given patient. Our analysis of EHR data indicate that HF can be detected 6 or more months before usual diagnosis with good AUC and high specificity. These findings suggest that routine evaluation of EHR data may be useful in screening for patients at high risk of HF, creating numerous opportunities for early and aggressive intervention and potentially altering the natural history of heart failure for many patients.

Low Levels of Antibodies Against Phosphorylcholine Predict Development of Stroke in a Population-Based Study From Northern Sweden

Natural immunoglobulin M antibodies specific for phosphorylcholine (anti-PC) have been implicated in atherosclerosis. We have shown previously that high levels of anti-PC predict a slower progression of atherosclerosis in humans and that low levels of anti-PC are associated with higher risk for cardiovascular disease. Here we determine the association between anti-PC and the incidence of stroke. Using a nested case control study design, we examined 227 incident cases (125 men and 102 women) of first-time stroke and 455 age- and sex-matched controls identified during a 13-year time period (1985 to 1999) within the population-based cohorts of the Västerbotten Intervention Project (VIP) and the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (WHO MONICA) project in Northern Sweden. Odds ratios of stroke with 95% CIs with adjustments for age, gender, smoking, serum cholesterol, diabetes, body mass index, and blood pressure were determined. Anti-PC levels were measured using ELISA. A significant association between low levels of anti-PC at baseline and incident stroke was seen for the whole group of anti-PC levels below the 30th percentile (multivariately adjusted odds ratio, 1.62; CI, 1.11 to 2.35). Analyses of gender-specific associations indicated fairly strong associations for females, especially at the lowest 30th percentile (multivariately adjusted odds ratio, 2.65; CI, 1.41 to 4.95). No associations were noted for men. Low anti-PC is a novel independent risk marker for development of stroke. Measurements of anti-PC could be used to identify immunodeficient subjects at an increased risk for stroke. The possibility that such subjects might be targets for novel modes of treatment such as immunotherapies deserves further investigation.

Traffic Marker?: Early Exposure to Air Pollution Associated with Childhood Asthma

Vol. 118, No. 2 NewsOpen AccessTraffic Marker?: Early Exposure to Air Pollution Associated with Childhood Asthma Laura Alderson Laura Alderson Search for more papers by this author Published:1 February 2010https://doi.org/10.1289/ehp.118-a80bCited by:2AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Asthma is now the most common chronic disease for children and a major cause of emergency room visits, hospitalizations, and school absences, according to the World Health Organization. Now a large population-based study has shown an association between elevated exposure to air pollution in utero and during the first year of life and a higher risk of asthma in preschool-aged children [EHP118:284–290; Clark et al.].There are multiple known risk factors for developing asthma, including genetic factors, diet, and exposure to secondhand tobacco smoke and allergens. The speed with which the disease has risen in most developed and developing countries suggests environmental exposures probably play a prominent role. Although air pollution is known to worsen existing asthma, a succession of recent studies is building evidence for an additional association between exposure to traffic-related air pollution and initial onset of asthma in children.Using a nested case–control study design, researchers looked at administrative and health care data for nearly 3,500 children born in southwest British Columbia, Canada, in 1999 and 2000 who were diagnosed with asthma by age 4 years. Each case was age- and sex-matched to 5 randomly chosen controls born in the same region and time period.To estimate air pollutant exposures, the researchers mapped the residential history of each child against air pollution data obtained from regulatory monitoring, land use regression modeling, and proximity to stationary pollution sources and to roads. These metrics were used to calculate average exposures for the duration of the mother’s pregnancy and the child’s first year of life. Nine pollutant exposures were evaluated: carbon monoxide, nitric oxide, nitrogen dioxide, particulate matter (PM10 and PM2.5), ozone, sulfur dioxide, black carbon, and wood smoke.The highest risk of asthma was associated with exposure to the traffic-related pollutants carbon monoxide, nitric oxide, nitrogen dioxide, and black carbon; lesser associations were seen with exposure to PM10 and sulfur dioxide, as well as with proximity to industrial point sources. Proximity to roads was not associated with increased risk, but only a small number of children resided near major roads in the study population. Associations between air pollution and asthma were generally greater in girls than in boys, although asthma was significantly more common in boys, consistent with other populations. The authors observe that other researchers also have reported stronger associations in girls, although the finding is not entirely consistent.This is one of the few studies to examine the effect of in utero exposure on pediatric asthma risk. However, because of relatively high correlation between in utero and first-year exposures, the relative importance of these periods could not be discerned.FiguresReferencesRelatedDetailsCited by Dietert R (2011) Maternal and childhood asthma: Risk factors, interactions, and ramifications, Reproductive Toxicology, 10.1016/j.reprotox.2011.04.007, 32:2, (198-204), Online publication date: 1-Sep-2011. Gonzalez P, Minkler M, Garcia A, Gordon M, Garzón C, Palaniappan M, Prakash S and Beveridge B (2011) Community-Based Participatory Research and Policy Advocacy to Reduce Diesel Exposure in West Oakland, California, American Journal of Public Health, 10.2105/AJPH.2010.196204, 101:S1, (S166-S175), Online publication date: 1-Dec-2011. Vol. 118, No. 2 February 2010Metrics About Article Metrics Publication History Originally published1 February 2010Published in print1 February 2010 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Predictors of major infections in systemic lupus erythematosus

IntroductionInfections commonly complicate the course of systemic lupus erythematosus (SLE). Our aim is to investigate the clinical predictors of major infections in patients with SLE.MethodsA nested case–control study design was used within the prospective Lupus-Cruces cohort. The endpoints of the study were major infections. Cases were defined as patients with a major infection. Two controls (SLE patients without major infections), matched for time of follow-up until the event and age at diagnosis, were selected for each case. Univariate analysis and logistic regression models were used for the analysis of data.ResultsTwo hundred and forty-nine patients (83 cases, 166 controls) were selected. Eighty-three episodes of major infections were analyzed; E. coli, S. aureus, M. tuberculosis and S. pneumoniae being the most frequent isolates. Univariate analysis identified several variables related with infection: lung and renal involvement, at or previous to the study point; leukopenia at the study point; antiphospholipid antibody-positivity and treatment with prednisone within 3 months previous to the study point, and the dose of prednisone received. Treatment with antimalarials, on the other hand, showed a strong inverse association with major infections. Logistic regression models identified treatment with antimalarials (odds ratio (OR) = 0.06, 95% confidence interval (CI) = 0.02 to 0.18), prednisone dose (OR = 1.12, 95% CI = 1.04 to 1.19) and lung involvement (OR = 4.41, 95% CI = 1.06 to 18.36) as significant and independent predictors of major infections. No significant interactions among these three variables were found. Further adjustment for potential confounders related with antimalarial treatment did not change the results.ConclusionsThe risk of major infections in patients with SLE is mostly influenced by treatment. Prednisone treatment, even at moderate doses, increases the risk, whilst antimalarials have a protective effect.

Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design.

Research methods for biomarker evaluation lag behind those for evaluating therapeutic treatments. Although a phased approach to development of biomarkers exists and guidelines are available for reporting study results, a coherent and comprehensive set of guidelines for study design has not been delineated. We describe a nested case–control study design that involves prospective collection of specimens before outcome ascertainment from a study cohort that is relevant to the clinical application. The biomarker is assayed in a blinded fashion on specimens from randomly selected case patients and control subjects in the study cohort. We separately describe aspects of the design that relate to the clinical context, biomarker performance criteria, the biomarker test, and study size. The design can be applied to studies of biomarkers intended for use in disease diagnosis, screening, or prognosis. Common biases that pervade the biomarker research literature would be eliminated if these rigorous standards were followed.

Genetic Associations between Delusional Disorder and Paranoid Schizophrenia: A Novel Etiologic Approach

Genetic associations between delusional disorder and paranoid schizophrenia are not well understood, although involvement of biological factors has been suspected. We investigated the incidence of human leukocyte antigen (HLA) class I alleles in patients with delusional disorder and paranoid schizophrenia, first, to explore a possible immunogenetic etiology of these paranoid disorders and, second, to determine whether they share similar etiologic mechanisms. We employed a nested case-control study design. Psychiatric reference data were available for 38,500 patients attending a hospital-based psychiatric outpatient department between 1998 and 2005. We enrolled 100 patients with delusional disorder and 50 patients with paranoid schizophrenia as the subject cases, using DSM-IV criteria. We considered equivalent numbers of healthy volunteers matched for age and ethnic background as control subjects. All subjects came from an India-born Bengali population. We applied the polymerase chain reaction-based molecular typing method to all patients and healthy subjects. The HLA-A*03 gene is significantly associated with delusional disorder as well as with paranoid schizophrenia. This HLA gene alone or in linkage disequilibrium with other HLA genes or other closely linked non-HLA genes may influence susceptibility to delusional disorder and paranoid schizophrenia. The study reveals important associations between HLA genes and paranoid disorders. Delusional disorder and paranoid schizophrenia may share similar etiologic mechanisms. This preliminary observation may help our understanding of the genetic basis of these paranoid disorders.

Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke

Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke. A nested case-control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene. The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87; 95% CI, 1.12 to 3.15 in study A; OR of 4G homozygosity, 1.56; 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke. Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene-environment interaction.

A Study of HLA-Linked Genes in a Monosymptomatic Psychotic Disorder in an Indian Bengali Population

The etiology of delusional disorder is imperfectly understood. Involvement of biological factors has long been suspected. We examined the incidence of class I human leukocyte antigens (HLAs) in patients with delusional disorder to understand the role of HLA genes and explore a possible immunogenetic etiology for delusional disorder. We used a nested case-control study design. Psychiatric reference data were available for 27 500 patients registered between 1998 and 2003. Initially, we enrolled 150 patients with delusional disorder from the India-born Bengali population, using DSM-IV diagnostic criteria. After longitudinal follow-up, 80 patients were found to have only delusional disorder, while the remaining 70 patients represented different illnesses with paranoid symptoms and were excluded. We performed serological typing on all 150 patients and applied the polymerase chain reaction-based high-resolution molecular typing method to the 80 patients with delusional disorder. Eighty healthy donors of the same ethnic background, matched for age, sex, and other socioeconomic variables, formed the control group. Some of the HLA alleles were associated with delusional disorder, and the gene HLA-A*03 was found to be significantly more frequent. This gene may influence patients' susceptibility to delusional disorder. The study reveals important associations between HLA genes and delusional disorder. This preliminary observation may help our understanding of this disorder's genetic basis.

Faktor-faktor yang Mempengaruhi Kejadian Malnutrisi Pasien Dewasa di Ruang Rawat Inap Rumah Sakit

Background : Nutrient intakes may influence nutritional status of patients during health care. It was reported that nutritional status of 75% of hospitalized patients declined during hospitalization.Objective: The objectives of this study was to assess factors that may influence malnutrition among adult patients in hospital.Methods: This study was done using a nested case control study design. Subjects were inpatients of internal and neurology departments of Sanglah, Sardjito and M. Jamil hospitals. They were all given oral feeding, inconsciousness condition, cooperative, and non-ascites. Data on food consumption were obtained using comstock methods, while nutritional status were measured using Subjective Global Assessment.Results: Low energy intake, length of stay, infection, and special diet were all associated with a higher risk of hospital malnutrition. Patients with low energy intakes were 2.4 (OR=2.4, 95%CI= 1.17-4.92) times more likely to be malnourished than those with sufficient energy intakes. Patients with length of stay &gt;= 7 days were 8 (OR=8.15, 95% CI =1.87-35.51) times more likely to be malnourished than those with length of stay &lt; 7 days. Patients with infectious diseases were 3 (OR= 0.33, 95% CI= 0.17-0.64) times less likely to be malnourished than those with non infectious diseases. Lastly, patients with special diet were 2 (OR=1.96, 95% CI= 1.05-3.68) times more likely to be malnourished than those without special diet.Conclusions: Low energy intake, length of stay, non infectious diseases, and special diet are risk factors of malnutrition in adult hospitalized patients.

Family history of psychiatric disorders and age at first contact in schizophrenia: an epidemiological study.

The risk for schizophrenia has been associated with a family history of this and other psychiatric disorders. The relationship between age at first contact and family history of psychiatric illness is not certain. To estimate the risks for schizophrenia associated with a range of psychiatric diagnoses in family members and to investigate the relationship between these risks and age at first contact for schizophrenia. A nested case-control study design was employed. Psychiatric admission data and socio-economic data were available for 7704 cases admitted between 1981 and 1998 in Denmark, 192,590 gender- and age-matched controls, and for the parents and siblings of all subjects. Controlling for socio-economic factors, risk for schizophrenia was associated with a family history of all psychiatric disorders except substance misuse and independently with a family history of suicide. The risk for schizophrenia associated with a family history of psychiatric disorders decreased as age at first contact increased. Risk for schizophrenia is associated with a range of psychiatric disorders in family members and these risks are not constant across the risk period.