Population-based Case Study Research Articles

Temporal Trends of Hypovitaminosis D: A Population-Based Study of Cases Under 19 Years of Age

There is a growing epidemic of hypovitaminosis D in the western hemisphere, however the exact incidence is not known. Additionally, vitamin D has been shown to be associated with atopic and infectious disorders. We aimed to determine the incidence of hypovitaminosis D in a population-based cohort, as well as the prevalence of other comorbidities. We performed a historical cohort study of residents under 19 years of age in Olmsted County, Minnesota, during a 16-year period from January 2, 2002 through December 31, 2017, using the Rochester Epidemiology Project. Using each patient’s first total 25-hydroxyvitamin D concentration less than 30.0 ng/mL, a patient was classified as having either a vitamin D deficiency (<20 ng/mL) or insufficiency (20.1-30.0 ng/mL). Comorbidities at that index date were abstracted from the medical record. The age-and sex-adjusted incidence (per 100,000 person-years) of vitamin D deficiency/insufficiency increased significantly each year from 31.3 (95%CI, 18.7-43.8) in 2002-2003 to 589.7 (95%CI, 535.7-643.6) in 2012-2013, stabilizing at 606.0 in 2014-2015 and 580.1 in 2016-2017. The overall age-adjusted incidence was significantly higher for females compared to males (388.2 (95%CI, 365.9-410.5) vs. 257.4 (95%CI 239.8-275.1), respectively). The prevalence of allergic rhinitis (31.6% vs. 25.9%) and atopic dermatitis (21.7% vs. 17.4%) were significantly higher among patients with a vitamin D insufficiency (N=1353) compared to those with deficiency (N=634). The incidence of hypovitaminosis D increased significantly during 2002 to 2012, with stabilization afterward. The association of hypovitaminosis D in atopic conditions may warrant further inquiry.

Effect of centralization on complex surgical care: A population-based case study of radical cystectomy.

We sought to determine whether non-mandated or passive centralization of radical cystectomy (RC) to higher-volume centers leads to enhanced processes of care and outcomes. This is a population-based, retrospective, cohort study that used the Ontario Cancer Registry (OCR) to identify all incident patients who underwent RC from 1994-2013. Electronic records of treatment were linked to OCR; pathology records were obtained for all cases and reviewed by a team of trained data abstractors. The primary objective was to describe annual provider RC volumes. Secondary objectives included investigating process and outcome measures. For the 5574 patients identified, the mean annual surgeon volume and hospital volume of RC from 1994-2008 was 4.5 (95% confidence interval [CI] 4.4-4.7) and 12.2 (95% CI 11.8-12.5), respectively. From 2009-2013, these volumes significantly increased to 6.8 (95% CI 6.5-7. 1) and 16.4 (95% CI 15.8-16.9). Process variables improved over time, including the use of neoadjuvant chemotherapy. Over the study period, there was a substantial improvement in cancer-specific survival (CSS): hazard ratio (HR) 0.60 (95% CI 0.53-0.67) for 2009-2013. During the most recent era, there was still evidence of a provider volume effect on both process measures and CSS. There has been recent passive centralization of RC to higher-volume providers in the province of Ontario, with measurable improvements in processes of quality care. Although centralization was also associated with improvement in CSS, in the most recent era, there continues to be low-volume providers with a residual volume-outcome effect.

Abstract WP211: Exome Association Analysis of Small Vessel Young Onset Ischemic Stroke

Background: Cerebral small vessel disease accounts for ~25-30% of strokes and is a leading cause of age- and hypertension-related cognitive decline and disability. Specific treatments for cerebral small vessel disease are lacking, and therapeutic options for secondary prevention are limited as compared to other common causes of stroke. Identifying stroke-associated protein coding variants is a promising tool to better understand disease etiology and identify novel targets. Methods: The GEOS Study was initiated as a biracial population-based study of cases with first-ever ischemic stroke 15 to 49 years of age and controls. All participants had prior GWAS and underwent Illumina exome-chip genotyping. Logistic regression analysis was conducted to identify associated variants after accounting for population substructure using Principal Component Analysis based on GWAS array data. Gene-based aggregation testing (SKAT) and meta-analysis were performed using seqMeta with ethnicity-specific GWAS PCs. Covariates for these analyses included age and gender. This was followed by Ingenuity Pathway Analyses on the top genes. Results: Gene-based testing using a filter (cumulative MAC&gt;40, # of SNPs per gene≥2, missingness=0) was performed on 7448 genes in 123 small vessel cases and 727 non-stroke controls. Two genes reached exome wide statistical significance (p&lt;6.7*10 -6 ) in the meta-analyses: FNDC9 (Fibronectin type III domain containing 9, p=9.2*10 -7 ) and ASXL1 (ASXL Transcriptional Regulator 1, p=3.4*10 -7 ). Although no individual SNPs reached genome-wide significance (3x10 -7 ), a rare missense variant in ASXL1 (MAF=0.02, p=3.5*10 -6 ) was near the threshold. ASXL1 SNPs have been associated with an increased risk of CVD. Pathway analyses of the top 438 genes (p&lt;0.05) from the gene-based results identified the nuclear receptor signaling pathway related to lipid/glucose metabolism, and the neurotransmitter glutamate receptor signaling and neurodevelopment notch signaling pathways. Efforts to replicate these findings in independent data sets are ongoing. Conclusion: Exome-based analyses of small vessel young-onset ischemic stroke is a promising methodology to identify novel genetic risk variants, genes and pathways.

Decreasing income inequality and adolescent emotional distress: a population-based case study of Icelandic adolescents 2006-2016.

In this study, we aim to test whether changes in community income inequality influence adolescent emotional distress. We take advantage of the unique combination of data and history available in Iceland. This affluent welfare society has experienced extreme shifts in income inequality, allowing us to test whether changes in community income inequality are related to changes in adolescent emotional distress. Combining adolescent survey data (n = 24,107) with tax registry data on 76 neighborhood communities, we used a multilevel approach to model the data as longitudinal in order to test whether changes in community income inequality are related to changes in symptoms of anxiety and depression among adolescents. The results showed that, after adjusting for relevant individual and community covariates, decreases in community income inequality were associated with decreases in symptoms of anxiety among adolescents (b = - 0.367, p ≤ 0.001), but not with decreases in symptoms of depression. While the results provide a partial support for the income inequality thesis, we call for replications from other cultures and studies exploring the mediating role of social psychological processes.

Early death in Danish stage I lung cancer patients: a population-based case study

Objective: Clinical stage (c-stage) at diagnosis is the most significant prognostic marker for patients with cancer, where 1- and 5-year survival rates as main landmarks when assessing outcomes. This is a population-based case study of Danish c-stage I lung cancer patients who were considered candidates for curative therapy and then died within 1 year after diagnosis (cases). Cases were identified in the Danish Lung Cancer Register (DLCR), and medical records were used to retrieve treatment details and cause of death (CoD). Our aims were, if possible, to identify and describe clusters of patients, in terms of CoD and treatment modality at risk for an adverse short-term outcome.Results: Patients who died early were more frequently male, older, had squamous-cell histology, were less frequently surgically treated and generally had a higher burden of comorbidity. In terms of CoD, 29% died of lung cancer with distant recurrence (DR) as the most common type of recurrence (55%). Death from co-morbidity occurred for 23%, where the largest proportion (36%) died from another cancer. Nineteen percentage died from treatment complications, with the majority being male (p < .001). The remainder died of unknown or other causes.Conclusions: Lung cancer with DR remains the most common CoD. Identifying and accordingly treating patients at risk for DR could potentially improve outcomes. Further studies of the predominantly male subgroup of patients who die of treatment complications are needed. Death from co-morbidity especially in patients with another cancer is a significant CoD and when assessing the quality of lung cancer care a competing event.

Abstract WP160: Exome Array Analysis of Early-Onset Ischemic Stroke

Background: The genetic architecture of ischemic stroke (IS) is poorly understood and may differ by age of onset. To identify stroke susceptibility variants, genes and pathways for IS in young adults, we genotyped participants in the Genetics of Early-Onset Stroke (GEOS) with an exome array to interrogate the protein-coding portion of genes. Methods: The GEOS Study was initiated as a biracial population-based study of cases with first-ever ischemic stroke 15 to 49 years of age (n=828) and controls (n=850). All participants had prior GWAS and underwent Illumina exome-chip genotyping. Mixed model regression in EMMAX was conducted to calculate variant-specific associations using pooled European-Caucasians (EUR) and African-Americans (AA) samples, with population structure controlled by kinship matrix relationships using GWAS data. Gene-based burden testing and meta-analysis were performed using seqMeta with ethnicity-specific GWAS PCs. In both analyses covariates included age and gender. This was followed by Ingenuity Pathway Analyses on the top genes. Results: While no individual SNPs reached chip-wide significance (3x10 -7 ), several were near, including one exonic variant in TRAPPC11 (rs67383011, p=1.7*10 -6 ). Gene-based burden testing using a filter (cumulative MAC&gt;40, # of SNPs per gene≥2, missingness=0) was performed on 6934 genes in EURs and 9423 genes in AAs. While several interesting genes were identified, notably in methylation pathways, none reached statistical significance in the ethnicity-stratified (p=3.3*10 -4 ) or meta-analyses (p=1.1*10 -4 ). Pathway analyses on the top 448 genes (p&lt;0.05) from the gene-based results identified several metabolism and signaling pathways, including: (1) those implicated in the risk for vascular diseases: glucose metabolism, lipid metabolism, and inflammation (leukocyte extravasation, IL-17A); (2) neurotrophic signaling: CTNF and NGF, and; (3) neurotransmitter and neuroactive compound signaling: GABA receptor signaling and tryptophan degradation pathways. Efforts in additional data sets to replicate these findings are ongoing. Conclusion: Exome-based analyses in the setting of early-onset stroke is a promising methodology to identify novel genetic risk variants, loci and pathways.

Abstract 56: An Exome Array Analysis of Ischemic Stroke in the Genetics of Early Onset Stroke Study

Background: Ischemic stroke is a heterogeneous trait and its genetic architecture is poorly understood. The genetic contribution may be stronger for stroke occurring at younger (vs. older) ages. To identify additional stroke susceptibility variants, we genotyped participants in the Genetics of Early Onset Stroke (GEOS) with the exome array and conducted association analyses with the goal of identifying functional risk variants by interrogating the protein-coding portion of genes. Methods: The GEOS Study was initiated as a biracial population-based study of cases with first-ever ischemic stroke 15 to 49 years of age (n=828) and matched controls (n=850). All participants underwent exome-chip genotyping. Logistic regression was used to calculate associations in European-Caucasians (EUR) and African-Americans (AA), and summary results were combined by meta-analysis. Results: Our analyses revealed four highly associated variants for all-stroke and several others that were stroke subtype specific. Among these for all-stroke, we identified a missense variant in VWDE (rs6460939 (K (AA G ) --&gt; N (AA C )), which encodes the Von Willebrand Factor D and EGF domain-containing protein. This protein plays a role in intracellular calcium ion binding within a variety of cell-types. The association was present in both European-Caucasians (OR = 1.34, p = 0.002) and African-Americans (OR = 1.32, p = 0.01), and was strengthened in a meta-analysis of both ethnic groups (OR = 1.41, p = 8.95 х 10 -6 ). The frequency of the effect C allele was 0.46 in EUR and 0.55 in AA. Efforts in additional data sets to further replicate this association, and the others identified, are ongoing. Conclusion: Exome-based analyses in the setting of young-onset stroke is a productive methodology to identify genetic risk variants.

Epidemiology of Tuberculosis in Immigrants in a Large City with Large-Scale Immigration (1991-2013).

BackgroundThe increase in immigration in Barcelona between 2000 and 2008 forced a reorganization of the control of tuberculosis (TB). TB clinical units (TBCU) were created and community health workers (CHW) were gradually included.ObjectiveTo understand trends in the incidence of TB among immigrants, their main characteristics and treatment compliance during the period 1991–2013.DesignWe conducted a cross-sectional population-based study of cases detected among immigrants by the Tuberculosis Program in Barcelona, Spain. Sociodemographic, clinical characteristics and risk factors were described. The annual incidence was calculated for various periods and geographical areas of origin. In the linear trend analysis, a p-value of <0.05 was considered statistically significant.ResultsWe detected 3,284 cases. Incidence decreased from 144.8/100,000 inhabitants in 1991 to 53.4/100,000 in 2013. Individuals born in Pakistan-India-Bangladesh had the highest average annual incidence (675/100,000). In all, 2,156 cases (65.7%) were male. 2,272 (69.2%) had pulmonary TB, of which 48.2% were smear-positive. 33% of the cases (1,093) lived in the inner city. Contact tracing (CT) coverage in smear-positive individuals rose from 56.8% in 1991–1999 to 81.4% in 2000–2013 (p<0.01); this value was less than 50% in people from Africa and Eastern European countries. The case fatality rate was 3.6% overall and 9.8% among those born in high-income countries (p<0.01). The highest rate of treatment default (12.8%) was observed among cases from the Maghreb. The rate of successful treatment increased from 69.9% in 1991–1999 to 87.5% in 2000–2013 (p<0.01).ConclusionThe incidence of TB in immigrants is decreasing in Barcelona. Organizational actions, such as incorporating CHWs and TBCUs, have been decisive for the observed improvements.

Awareness among mothers of Down syndrome children on the importance of folic acid consumption during pregnancy

Objective: The maternal use of folic acid supplementation particularly during the preconception period has been suggested to thwart Down syndrome, thus the awareness among the mothers of Down syndrome children regarding folic acid consumption and other factors was assessed in this study. Methods: In this population-based case study, mothers of children with Down syndrome [n=192] living in the city of Riyadh, Kingdom of Saudi Arabia, were enrolled through schools run by The Down syndrome society. Using a specially structured questionnaire that included questions on socio-demographic variables, women’s knowledge about folic acid supplementation, and timing of supplementation was evaluated. Results: Analysis of data indicated children born to mothers who were 35 and above failed to follow recommended Folic acid supplementation. Around 70% percent of the DS mothers started taking supplementation after a confirmed pregnancy. Children were more likely to be born with DS if they were the 4th or more, child born to the same mother in the family. The rate was observed to be higher if they were born to mothers with even higher parity [>4]. Conclusion: The results of this study imply that folic acid supplementation is crucial for the prevention of Down syndrome before conception, as well as for the post-conception period in all women, especially for women who are 35 years and over and women with high parity.

Integrated Strategies for the Control of Leishmaniasis in the Municipality of Teodoro Sampaio, SP, from a Geographical Perspective, Supported by Geoprocessing

Introduction: This study is justified since very little is known of the relationship between Leishmaniasis and the spatial transformation process. In the past, the municipality of Teodoro Sampaio has spread ACL and recently cases of visceral Leishmaniasis have been found in dogs in the urban area, making the municipality a likely area for the convergence of both manifestations of the disease. The overall aim is to relate recent spatial transformations with the pattern of spatial distribution of the infection’s vectors and hosts, keeping in mind the integrated geographic distribution of ACL and AVL. Methods: The study has two levels of aggregation: (a) a population-based case study of the municipality of Teodoro Sampaio, Pontal do Paranapanema, in the state of São Paulo, designed to be quantitative, descriptive and cross-sectional, and (b) population-based across the municipalities of São Paulo state, designed to be retrospective, quantitative, observational and descriptive. The choice of two approaches to the study is justified by a consideration of the articulations which enable the formation of production circuits for Leishmaniasis in the region. The gathering of data for the Teodoro Sampaio case study underwent two phases: field study and by means of secondary official data sources. Data concerning the state of São Paulo comes from secondary sources. Conclusion: As it is a focal disease, the data presented allows us to infer that AVL spreads from Sector 1 of the urban area to Sector 3, because the vector relevant to transmission is within the former. The ACL pattern in Teodoro Sampaio is thought to be based in the woodlands surrounding the urban area, in general terms, based in the Parque Estadual do Morro do Diabo (PEMD), the edge of which is five kilometres from the centre of the district. Exchanges take place between the urban area of the municipality, the PEMD, the settlement of Ribeirão Bonito, which forms part of the transect making up the geosystem of Teodoro Sampaio, and Pontal do Paranapanema. Human intervention can be seen as the main agent in promoting these exchanges between environments due to the transit of people between subgeosystems and the interrelationship with other municipalities encouraging the spread of the disease. The only municipalities to be among those with a high incidence of AVL are Araçatuba and Presidente Prudente, although the number of cases is growing and becoming more concentrated. The state presents a circumscribed hub of AVL cases in the region of Campinas and Piracicaba, and another in Pontal do Paranapanema. This interaction borders on Mato Grosso do Sul, giving rise to the main circuit AVL instances of the Southeast. ACL has a hub at Itapetininga, which is next to Vale do Paraiba Paulista, also leading to interactions across the border with the state of Rio de Janeiro and its principal circumscribed centres of transmission of ACL. This will be Brazil’s next ACL production circuit. It was possible to identify areas in the state of São Paulo particularly vulnerable to Leishmaniasis with particular distributions for each of the two types of the disease, sometimes existing together. Outbreaks of canine VL do not depend on distribution rules on a small scale, although the effect of many outbreaks together clarifies a spatial pattern, as seen in the state of São Paulo. Patterns of transmission of Leishmaniasis are established in the state of São Paulo and the data analyzed helps to verify these patterns.

Arsenicosis and its relationship with nutritional status in two arsenic affected areas of West Bengal, India

Incidence of chronic arsenicosis in the lower Gangetic plain has led to intensive research on arsenic (As) contamination in groundwater and potential health crisis associated with exposure to groundwater As. Arsenic toxicity of local inhabitants and their nutritional status were investigated in two As affected villages (Nonaghata and Doulatpur) of West Bengal, India. Population-based case study on randomly selected subjects was used to assess chronic As exposure through medical evaluation and individual health survey. Groundwater As concentrations were found as high as 870μg/L and 1752μg/L in Nonaghata and Doulatpur respectively at a depth 50–100ft. In Nonaghata, 26.7% of people (among 385 surveyed) showed dermatological manifestation and As skin lesions were dominant in age group of 15–30 and 30–45years old. In both the age groups, cases of melanosis were higher (22.5% and 31.5%) compared to keratosis (15.4% and 12.5%). In Doulatpur 27.4% of people (among 440 surveyed) was found with dermatological manifestations and As skin lesions were dominant in age group of 15–30 and 30–45years old. Cases of melanosis are higher (27.2% and 31.4%) compared to keratosis (10.8% and 30.7%) in these two age groups. Assessment on calories intake (mainly carbohydrate and protein) by local inhabitants showed that 67.5% and 66.8% people of these two villages belongs to poor nutrition. Assessment of odds ratios (OR) suggested that the stronger associations were with low nutrition which may increase susceptibility to arsenical skin lesions. Thus it is a matter of concern that nutritional status may be an important factor causing prevalence of As toxicity among local inhabitants.

Anaphylaxis and reactions to foods in children – a population‐based case study of emergency department visits

Information about acute reactions to foods among children is limited. To describe the overall incidence of anaphylaxis in a paediatric emergency department (ED) setting and to describe reactions to foods in relation to sex and age, clinical characteristics and management. In a review of medical records, children with ED visits at any of three paediatric hospitals in Stockholm County during 2007 were targeted. Inclusion criteria were any adverse reaction to foods or anaphylaxis. 383 children fulfilled the inclusion criteria of which 371 had had reactions to foods. The incidence of anaphylaxis was 32 per 100000 person years irrespective of cause and food was involved in 92%. Tree nuts, particular cashew, and peanut were the most common eliciting foods, and in children under 3years, reactions to these two food allergens were as common as reactions to milk and egg. Pollen-allergic children seemed to be admitted due to food-induced anaphylaxis more often during the deciduous tree pollen season compared with the rest of the year (P=0.015). Symptoms from the lower airways occurred in 49% of children with anaphylaxis but without underlying asthma compared with 72% of children with anaphylaxis and asthma, P<0.01. Reactions to peanut and tree nuts are as common as reactions to milk and egg in early life. Concomitant exposure to airborne allergens seems to increase the risk of anaphylaxis to foods. Among children with anaphylaxis, wheeze is prevalent even in children without asthma diagnosis.

Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study

Ionizing radiation (IR) is a breast carcinogen that induces DNA double-strand breaks (DSBs), and variation in genes involved in the DNA DSB response has been implicated in radiation-induced breast cancer. The Women's Environmental, Cancer, and Radiation Epidemiology (WECARE) study is a population-based study of cases with contralateral breast cancer (CBC) and matched controls with unilateral breast cancer. The location-specific radiation dose received by the contralateral breast was estimated from radiotherapy records and mathematical models. One hundred fifty-two SNPs in six genes (CHEK2, MRE11A, MDC1, NBN, RAD50, TP53BP1) involved in the DNA DSBs response were genotyped. No variants or haplotypes were associated with CBC risk (649 cases and 1,284 controls) and no variants were found to interact with radiation dose. Carriers of a RAD50 haplotype exposed to ≥1 gray (Gy) had an increased risk of CBC compared with unexposed carriers (Rate ratios [RR] = 4.31 [95% confidence intervals [CI] 1.93-9.62]); with an excess relative risk (ERR) per Gy = 2.13 [95% CI 0.61-5.33]). Although the results of this study were largely null, carriers of a haplotype in RAD50 treated with radiation had a greater CBC risk than unexposed carriers. This suggests that carriers of this haplotype may be susceptible to the DNA-damaging effects of radiation therapy associated with radiation-induced breast cancer.

Variables asociadas al riesgo de depresión posparto. Edinburgh Postnatal Depression Scale

To find some of the variables associated with values on the Edinburgh Postnatal Depression Scale (EPDS) which suggest postnatal depression in women living in the province of Soria. Population-based case study with controls. Soria Health Region. Women living in Soria giving birth in the INSALUD General Hospital between January and October 2000. Questionnaire sent by mail, containing socio-economic variables, pathology background, gynaecological and obstetric details, the EPDS and the APGAR Family score. Those questionnaires filled in between the third and eighth week after birth were considered valid. 340 questionnaires out of 556 sent out were received back (61.2% reply rate). 34 were excluded for lack of data or evident mistakes. 15.7% (95%, CI, 11.6-19.8) of the women scored 13 or more on the EPDS and were at risk of suffering postnatal depression. The independent variables associated with postnatal depression were: age of mother, poor or very poor economic situation, personal history of disturbed states of mind, being anaesthetised during birth and family dysfunction. The risk of postnatal depression was mainly related to socio-economic and family variables. Identification of these variables along with application of the EPDS after giving birth raises the alarm for a possible postnatal depression, and enables the study and follow-up in benefit of the mother and of the subsequent evolution of the new-born to be initiated.