General Population Control Subjects Research Articles

Cardiovascular Outcomes in Patients With Both Diabetes and Phenotypic Familial Hypercholesterolemia: A Nationwide Register-Based Cohort Study.

Patients with diabetes or familial hypercholesterolemia (FH) have an increased incidence of cardiovascular diseases compared with the population, but whether this risk is exacerbated in patients with combined traits is unknown. In this Swedish nationwide, register-based cohort study, patients with diabetes were included between 2002 and 2020. Adjusted Cox proportional hazards models were used to assess the risk of cardiovascular events in patients with or without phenotypic FH (≥6 points for phenotypic FH according to Dutch Lipid Clinic Network criteria) compared with general population control subjects without diabetes as reference. A total of 45,585 patients with type 1 diabetes (227,923 control subjects) and 655,250 patients with type 2 diabetes (655,250 control subjects) were followed for a median of 14.1 and 7.9 years, respectively. Of those, 153 and 7,197, respectively, had phenotypic FH. Compared with control subjects, patients with diabetes and phenotypic FH had higher risk of cardiovascular mortality (type 1: hazard ratio 21.3 [95% CI 14.6-31.0]; type 2: 2.40 [2.19-2.63]) and of a cardiovascular event (type 1: 15.1 [11.1-20.5]; type 2: 2.73 [2.58-2.89]). Further, patients with diabetes and phenotypic FH had higher LDL-cholesterol levels during observation (P < 0.05) and increased risk of all major cardiovascular outcomes (P < 0.0001) than patients with diabetes but without FH. The proportion receiving lipid-lowering treatment was higher in patients with phenotypic FH (P < 0.0001). Patients with both diabetes and phenotypic FH are more at risk for adverse cardiovascular outcomes and have higher LDL-cholesterol levels despite receiving intensified lipid-lowering therapy.

Association Between Collagenous and Lymphocytic Colitis and Risk of Severe Coronavirus Disease 2019

Association Between Collagenous and Lymphocytic Colitis and Risk of Severe Coronavirus Disease 2019

IgA Antibodies Directed Against Citrullinated Protein Antigens Are Elevated in Patients With Idiopathic Pulmonary Fibrosis

The etiology of idiopathic pulmonary fibrosis (IPF) is unknown. Because it shares genetic, histopathologic, and radiographic features with the fibrosing interstitial lung disease seen in rheumatoid arthritis (RA), the goal of this study was to investigate RA-related autoantibodies in IPF. The study included patients with IPF from two separate cohorts at National Jewish Health and Brigham Women's Hospital (n= 181), general population control subjects (n= 160), and control subjects with disease (n= 86 [40 with RA-usual interstitial pneumonia and 46 with hypersensitivity pneumonitis]). Serum was tested for RA-associated antibodies (including IgG and IgA) to citrullinated protein antigens (ACPA). Lung tissue in 11 patients with IPF was examined for ectopic lymphoid aggregates. An increased prevalence of ACPA positivity was found in two separate IPF cohorts. In particular, positivity for IgA-ACPA was increased in these two IPF cohorts compared with general population control subjects (21.3%and 24.8%vs5.6%; P< .01). Patients with IPF were more likely to be IgA-ACPA-positive than IgG-ACPA-positive (23.2%vs8.3%; P< .01), whereas patients with RA were more likely to be IgG-ACPA-positive than IgA-ACPA-positive (72.5%vs52.5%; P= .04). There was a strong correlation between IgA-ACPA level and the number of ectopic lymphoid aggregates on lung histologic examination in IPF (r= 0.72; P= .01). In this study, IgA-ACPA was elevated in patients with IPF and correlated with lymphoid aggregates in the lung, supporting the theory that IgA-ACPA may play a role in lung disease pathogenesis in a subset of individuals with IPF. Future studies are needed to determine whether this subset of ACPA-positive patients with IPF is distinct from patients with IPF but without antibodies.

Gastrointestinal Infection Increases Odds of Inflammatory Bowel Disease in a Nationwide Case–Control Study

Gastrointestinal infections have been associated with later development of inflammatory bowel diseases (IBD). However, studies have produced conflicting results. We performed a nationwide case-control study in Sweden to determine whether gastroenteritis is associated with the development of Crohn's disease (CD) or ulcerative colitis (UC). Using the Swedish National Patient Register, we identified 44,214 patients with IBD (26,450 with UC; 13,387 with CD; and 4377 with IBD-unclassified) from 2002 to 2014 and matched them with 436,507 individuals in the general population (control subjects). We then identified patients and control subjects with reported episodes of gastroenteritis (from 1964 to 2014) and type of pathogen associated. We collected medical and demographic data and used logistic regression to estimate odds ratios (ORs) for IBD associated with enteric infection. Of the patients with IBD, 3105 (7.0%) (1672 with UC, 1050 with CD, and 383 with IBD-unclassified) had a record of previous gastroenteritis compared with 17,685 control subjects (4.1%). IBD cases had higher odds for an antecedent episode of gastrointestinal infection (aOR, 1.64; 1.57-1.71), bacterial gastrointestinal infection (aOR, 2.02; 1.82-2.24), parasitic gastrointestinal infection (aOR, 1.55; 1.03-2.33), and viral gastrointestinal infection (aOR, 1.55; 1.34-1.79). Patients with UC had higher odds of previous infection with Salmonella, Escherichia coli, Campylobacter, or Clostridium difficile compared to control subjects. Patients with CD had higher odds of previous infection with Salmonella, Campylobacter, Yersinia enterocolitica, Cdifficile, amoeba, or norovirus compared to control subjects. Increasing numbers of gastroenteritis episodes were associated with increased odds of IBD, and a previous episode of gastroenteritis remained associated with odds for IBD more than 10 years later (aOR, 1.26; 1.19-1.33). In an analysis of the Swedish National Patient Register, we found previous episodes of gastroenteritis to increase odds of later development of IBD. Although we cannot formally exclude misclassification bias, enteric infections might induce microbial dysbiosis that contributes to the development of IBD in susceptible individuals.

Duration of psoriatic arthritis as a risk factor for myocardial infarction.

ObjectivesThe aim was to examine the association between disease duration and risk of myocardial infarction (MI) in patients with PsA.MethodsWe used nationwide registry data from Denmark to estimate incidence rates per 1000 person-years and the risk of MI [adjusted hazard ratios (HRs) with 95% CIs] in rheumatologist-diagnosed patients with PsA using Cox regression models. The study period was between 1 January 2008 and 31 December 2012.ResultsThe study population comprised a total of 8071 patients with PsA and 4 348 857 general population control subjects. A total of 156 and 54 215 MIs occurred during follow-up among patients with PsA and the reference population, respectively. There was a significant association between the duration of PsA and risk of MI (adjusted HR = 1.02; 95% CI: 1.01, 1.03 for each additional year after PsA diagnosis). Stratified based on short (<2 years) and long (≥2 years) disease duration, the adjusted HRs were 0.96 (95% CI: 0.60, 1.52; P = 0.8487) and 1.29 (95% CI: 1.09, 1.53; P = 0.0026), respectively. Other significant predictors included age, sex, socio-economic status, smoking, alcohol abuse, diabetes, hypertension and previous cardiovascular disease.ConclusionsWe observed an increased risk of MI associated with longer duration of PsA. Our findings call for increased focus on disease duration in the cardiovascular risk assessment among patients with PsA.

Association of FGFR2 (rs2981579) gene polymorphism with the risk of mesial occlusion

The molecular-genetic testing of the polymorphic rs2981579 (C>T) locus of the FGFR2 gene as the marker of increased predisposition to the development of mesial occlusion was carried out in 110 patients with mesial occlusion and 103 general-population control subjects from Ukraine. It was shown that polymorphism rs2981579 in gene FGFR2 is associated with mesial occlusion (OR = 1.67, 95% CI = 1.14–2.45, p = 0.009). Compared to CC carriers, TT+CT carriers had a 3.21-fold higher risk of mesial occlusion (95% CI = 1.57–6.57, p = 0.001). We found the protective effect of the homozygous allele C on mesial occlusion development (OR = 0.31, p = 0.001). This is the first published data on FGFR2 polymorphisms rs2981579 (C>T) in patients with mesial occlusion.

Ten-year mortality is increased after hospitalization for atopic dermatitis compared with the general population, but reduced compared with psoriasis

Psoriasis and atopic dermatitis (AD) are chronic inflammatory skin disorders. Mortality is increased in psoriasis, yet no studies on mortality in AD are currently available. We investigated 10-year mortality after hospitalization for AD compared with psoriasis and the general population. Between 1996 and 2002 all Danes aged 18years or older with a first-time hospitalization as a result of AD or psoriasis and AD-matched healthy control subjects were examined in nationwide registers. Multivariable (adjusted for age, sex, socioeconomic status, Charlson Comorbidity Index score, smoking, and medication) hazard ratios were estimated by Cox regression. The study comprised 576 and 951 hospitalized patients with AD and psoriasis, respectively, with a maximum follow-up time of 10years. During the study period, there were 65 and 286 deaths among patients with AD and psoriasis. Risk of death was decreased in patients with AD versus psoriasis (hazard ratio 0.75; 95% confidence interval 0.57-1.00), but higher than in general population control subjects (n=5760) (hazard ratio 1.71; 95% confidence interval 1.20-2.44). Patients hospitalized with AD died on average 8.3years younger than control subjects. Lifestyle may have affected the risk. The 10-year mortality was significantly lower after hospitalization for AD compared withpsoriasis, but increased when compared with the general population.

Suicide in Tourette’s and Chronic Tic Disorders

BackgroundPersons with neuropsychiatric disorders are at increased risk of suicide, but there is little data concerning Tourette’s and chronic tic disorders (TD/CTD). We aimed to quantify the risk of suicidal behavior in a large nationwide cohort of patients with TD/CTD, establish the contribution of psychiatric comorbidity to this risk, and identify predictors of suicide. MethodsUsing a validated algorithm, we identified 7736 TD/CTD cases in the Swedish National Patient Register during a 44-year period (1969–2013). Using a matched case-cohort design, patients were compared with general population control subjects (1:10 ratio). Risk of suicidal behavior was estimated using conditional logistic regressions. Predictors of suicidal behavior in the TD/CTD cohort were studied using Cox regression models. ResultsIn unadjusted models, TD/CTD patients, compared with control subjects, had an increased risk of both dying by suicide (odds ratio: 4.39; 95% confidence interval [CI]: 2.89–6.67) and attempting suicide (odds ratio: 3.86; 95% CI: 3.50–4.26). After adjusting for psychiatric comorbidities, the risk was reduced but remained substantial. Persistence of tics beyond young adulthood and a previous suicide attempt were the strongest predictors of death by suicide in TD/CTD patients (hazard ratio: 11.39; 95% CI: 3.71–35.02, and hazard ratio: 5.65; 95% CI: 2.21–14.42, respectively). ConclusionsTD/CTD are associated with substantial risk of suicide. Suicidal behavior should be monitored in these patients, particularly in those with persistent tics, history of suicide attempts, and psychiatric comorbidities. Preventive and intervention strategies aimed to reduce the suicidal risk in this group are warranted.

Allelic polymorphism C-590T of the IL4 gene as a probable genetic marker for the increased predisposition to the development of recurrent episodes of acute obstructive bronchitis in children

Acute respiratory infections (ARIs) hold the first place among all infections throughout the world. ARIs are frequently complicated by the development of acute obstructive bronchitis (AOB). According to different authors, the frequency of developing AOB due to ARIs in children ranges from 5 to 40%. The growing occurrences of ARIs in children and the formation of bronchoobstructive syndrome that frequently ends up in the development of bronchial asthma, leading children to invalidity, specify a new priority research area—molecular genetic markers sought for to identify an increased predisposition to certain socially important illnesses. The molecular-genetic testing of the polymorphic C-590T locus of the IL4 gene as the marker of increased predisposition to the development of recurrent episodes of AOB were conducted in 31 children with frequent ARIs and recurrent episodes of AOB and in 50 general-population control subjects. The level of IgE in the blood serum was studied in 31 children with frequent recurrent episodes of AOB and compared with the data of 35 control children with acute bronchitis. The comparative molecular genetic analysis of the results in children with recurrent episodes of AOB and the data obtained from the subjects of a general population control group has shown that the frequency of the CT genotype at the polymorphic C-590T locus of the IL4 gene was noticeably higher in children with recurrent AOB episodes. The markedly higher frequency of the CC genotype at the polymorphic C-590T locus of the IL4 gene was recorded in the control group subjects and compared to the data of children from the main group. It was established that carrying the 590 CT genotype with the allelic polymorphism of the IL4 gene increases the risk of recurrent episodes of AOB in children by three times. The level of IgE in the blood serum in the majority of sick children from the main group was four times higher than in the control children.

Risk factors and analysis of long-term headache in sporadic vestibular schwannoma: a multicenter cross-sectional study.

The primary goals of this study were: 1) to examine the influence of disease and treatment on headache in patients with sporadic vestibular schwannoma (VS); and 2) to identify clinical predictors of long-term headache disability. This was a cross-sectional observational study with international multicenter enrollment. Patients included those with primary sporadic <3-cm VS and a separate group of general population control subjects without tumors. Interventions included a postal survey incorporating the Headache Disability Inventory (HDI), the Hospital Anxiety and Depression Scale, and a VS symptom questionnaire. The main outcome measures were univariate and multivariable associations with HDI total score. The overall survey response rate was 79%. Data from 538 patients with VS were analyzed. The mean age at time of survey was 64 years, 56% of patients were female, and the average duration between treatment and survey was 7.7 years. Twenty-seven percent of patients received microsurgery, 46% stereotactic radiosurgery, and 28% observation. Patients with VS who were managed with observation were more than twice as likely to have severe headache disability compared with 103 control subjects without VS. When accounting for baseline differences, there was no statistically significant difference in HDI outcome between treatment modalities at time of survey. Similarly, among the microsurgery cohort, the long-term risk of severe headache disability was not different between surgical approaches. Multivariable regression demonstrated that younger age, greater anxiety and depression, and a preexisting diagnosis of headache were the primary predictors of severe long-term headache disability, while tumor size and treatment modality had little influence. At a mean of almost 8 years following treatment, approximately half of patients with VS experience headaches of varying frequency and severity. Patient-driven factors including age, sex, mental health, and preexisting headache syndrome are the strongest predictors of long-term severe headache disability. Tumor size and treatment modality have less impact. These data may assist with patient counseling regarding long-term expectations following diagnosis and treatment.

Risk Factors for Cardiovascular Disease in People With Idiopathic Pulmonary Fibrosis

People with idiopathic pulmonary fibrosis (IPF) have been shown to be at an increased risk for cardiovascular (CV) disease, but reasons for this are unknown. The aim of this study was to compare the prevalence of common CV risk factors in people with IPF and the general population and establish the incidence of ischemic heart disease (IHD) and stroke after the diagnosis of IPF, controlling for these risk factors. We used data from a large, UK primary care database to identify incident cases of IPF and matched general-population control subjects. We compared the prevalence of risk factors for CV disease and prescription of CV medications in people with IPF (before diagnosis) with control subjects from the general population and assessed the incidence of IHD and stroke in people with IPF (after diagnosis) compared with control subjects. We identified 3,211 cases of IPF and 12,307 control subjects. Patients with IPF were more likely to have a record of hypertension (OR, 1.31; 95% CI, 1.19-1.44), and diabetes (OR, 1.20; 95% CI, 1.07-1.34) compared with control subjects; they were also more likely to have been prescribed several CV drugs. The rate of first-time IHD events was more than twice as high in patients than control subjects (rate ratio, 2.32; 95% CI, 1.85-2.93; P < .001), but the incidence of stroke was only marginally higher (P = .09). Rate ratios for IHD and stroke were not altered substantially after adjusting for CV risk factors. Several CV risk factors were more prevalent in people with IPF; however, this did not account for the increased rate of IHD in this group of patients.

Population-Based, Multigenerational Family Clustering Study of Obsessive-compulsive Disorder

Controlled family studies have consistently found that obsessive-compulsive disorder (OCD) aggregates in families but have typically relied on samples recruited from specialist clinics. Furthermore, previous studies could not disentangle genetic from environmental factors contributing to the observed familiality. To provide unbiased estimates of familial risk for and heritability of OCD at the population level. Population-based, multigenerational, case-control family and twin studies using the Swedish National Patient Register, Multi-Generation Register, and Twin Register. All individuals diagnosed as having OCD between January 1, 1969, and December 31, 2009 (n = 24 768) and all their available first-, second-, and third-degree relatives, as well as nonbiological relatives and matched general population control subjects. Twins (n = 16 383) were included from the population-based Twin Register. The risk for OCD among relatives of OCD probands. The risk for OCD among relatives of OCD probands increased proportionally to the degree of genetic relatedness. The risk for first-degree relatives was significantly higher than that for second- and third-degree and nonbiological relatives. Second-degree relatives had higher risk for OCD than third-degree relatives. Relatives at similar genetic distances had similar risks for OCD, despite different degrees of shared environment. Separate twin modeling analyses confirmed that familial risk for OCD was largely attributable to additive genetic factors (47%; 95% CI, 42%-52%), with no significant effect of shared environment. Nonbiological relatives (spouses or partners who have at least 1 child together) also had an elevated risk for OCD (odds ratio, 2.61; 95% CI, 1.99-3.42). Early-onset probands (3907 individuals; mean age, 13.7 years) had slightly (nonsignificantly) higher familial risk than the total sample, although this was substantially lower than previously reported. There were no significant sex differences in the familial pattern or heritability estimates. Obsessive-compulsive disorder clusters in families primarily due to genetic factors. Nonshared environmental factors are at least as important. The quest for candidate genes, nonshared environmental risk factors, and their possible correlation or interaction should continue. The finding of possible assortative mating in OCD is intriguing and should be investigated further.

COPD and the Risk of Tuberculosis - A Population-Based Cohort Study

BackgroundBoth chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) primarily affect the lungs and are major causes of morbidity and mortality worldwide. COPD and TB have common risk factors such as smoking, low socioeconomic status and dysregulation of host defence functions. COPD is a prevalent co-morbid condition, especially in elderly with TB but in contrast to other diseases known to increase the risk of TB, relatively little is known about the specific relationship and impact from COPD on TB-incidence and mortality.Methods and FindingsAll individuals ≥40 years of age, discharged with a diagnosis of COPD from Swedish hospitals 1987–2003 were identified in the Swedish Inpatient Register (n = 115,867). Records were linked to the Swedish Tuberculosis Register 1989–2007 and the relative risk of active TB in patients with COPD compared to control subjects randomly selected from the general population (matched for sex, year of birth and county of residence) was estimated using Cox regression. The analyses were stratified by year of birth, sex and county of residence and adjusted for immigration status, socioeconomic status (SES) and inpatient co-morbidities previously known to increase the risk of TB. COPD patients had a three-fold increased hazard ratio (HR) of developing active TB (HR 3.0 (95% confidence interval 2.4 to 4.0)) that was mainly dependent on an increased risk of pulmonary TB. In addition, logistic regression estimates showed that COPD patients who developed active TB had a two-fold increased risk of death from all causes within first year after the TB diagnosis compared to the general population control subjects with TB (OR 2.2, 95% confidence interval 1.2 to 4.1).ConclusionsThis population-based study comprised of a large number of COPD patients shows that these patients have an increased risk of developing active TB compared to the general population. The results raise concerns that the increasing global burden of COPD will increase the incidence of active TB. The underlying contributory factors need to be disentangled in further studies.

Polymorphisms of FAS and FAS ligand genes in preeclamptic women

Objectives This study investigated the influence that Fas and Fas ligand gene polymorphisms might have on preeclampsia. The pathogenesis of preeclampsia is still enigmatic and several studies have proposed that it may, in part, be determined by genetic susceptibility. Therefore, the identification of a gene polymorphism associated with an increased risk of preeclampsia might well represent a useful tool in the identification of at risk pregnant women enabling the setup of preventive therapy. Apoptosis has also been implied in the pathogenesis of preeclampsia and since Fas and Fas ligand are the main apoptotic pathway members, they may represent candidate genes involved in the development of preeclampsia. A polymorphism at the 670 position (A–G) in the Fas gene has been found more frequently in Hungarian women with preeclampsia. Study design The study cohort was a group of 50 women with preeclampsia and 142 healthy control subjects from the general Italian population. They were studied, by RFLP analysis, to validate the role that the 670 G Fas gene polymorphism plays in preeclampsia, and to evaluate the Fas ligand IVS2nt 124 G polymorphism. The Fisher's exact test was used to compute the statistical difference between groups. Results The presence of the 670 G Fas gene variant was observed in 42 preeclamptic patients (84%) and 96 members of the general population control group (67.6%) ( p = 0.029). Regarding the Fas ligand gene, the IVS2nt 124 G variant was present in 14 preeclamptic patients (28%) and in 47 of the general population control subjects (33.1%) ( p = 0.6). Conclusions The present study validated the hypothesis that the Fas 670 G variant may have an influencing role in preeclampsia.

Is Arson the Crime Most Strongly Associated With Psychosis?—A National Case-Control Study of Arson Risk in Schizophrenia and Other Psychoses

The association of psychosis with certain serious crimes, such as homicide, has been clearly demonstrated, but it is uncertain to what extent psychotic disorders are associated with arson. We used a case-control design to investigate the association of being diagnosed with schizophrenia and other psychoses and committing arson. Data were obtained from Swedish national registers for criminal convictions, hospital discharge diagnoses (International Classification of Diseases, Ninth Revision [ICD-9], and International Classification of Diseases, Tenth Revision [ICD-10]), and sociodemographic factors for 1988-2000. We included all convicted arson offenders of both sexes in Sweden (N=1689) and compared them with a random sample of general population control subjects (N=40,560). After adjustment for sociodemographic confounders, arson offenders were more likely to be diagnosed with schizophrenia (in men, adjusted odds ratio [OR]=22.6, 95% confidence interval [CI]=14.8-34.4; in women, adjusted OR=38.7, 95% CI=20.4-73.5) or other psychoses (in men, adjusted OR=17.4, 95% CI=11.1-27.5; in women, adjusted OR=30.8, 95% CI=18.8-50.6). Individuals with schizophrenia and other psychoses have significantly increased risks of an arson conviction. These risk estimates are higher than those reported for other violent crimes and place arson in the same category as homicide as crimes that are most strongly associated with psychotic disorders.

Treatment wetlands: Cost-effective practice for intercepting nitrate before it reaches and adversely impacts surface waters

<b>Objective:</b> To examine factors influencing obtaining a driver’s license and subsequent prognosis among people with epilepsy vs control subjects. <b>Methods:</b> Eighty-one patients from a population-based cohort with childhood-onset epilepsy, followed prospectively for 45 years, and 96 general population control subjects were compared with regard to driving licensing, seizure relapses, and accidents. <b>Results:</b> By the end of the follow-up period, all 81 subjects had achieved at least one 2-year seizure-free interval in adulthood and were eligible for a driver’s license. Of these, 64 vs 90% of control subjects had obtained a license (<i>p</i> &lt; 0.0001). On multivariable analysis, factors associated with not obtaining a driver’s license among subjects were female gender (relative risk [RR] 2.4, 95% CI 1.0 to 5.5, <i>p</i> = 0.02), nonidiopathic etiology (RR 2.0, 95% CI 1.1 to 3.8, <i>p</i> = 0.02), and presence of learning disabilities (RR 2.0, 95% CI 1.2 to 3.2, <i>p</i> = 0.02). Having a driver’s license was associated with a higher rate of employment (RR 1.9, 95% CI 1.2 to 3.0, <i>p</i> = 0.0002). Relapses of seizures had occurred in 37% of the 81 patients theoretically eligible for a license but only in 25% of the 52 subjects who actually obtained one (<i>p</i> = 0.003). Shortening the eligibility period from 2 to 1 year would not significantly alter the relapse rate in this population. The accident rate was not increased among patients vs control subjects. <b>Conclusions:</b> During a long-term follow-up, differences in driving licensing between patients with uncomplicated epilepsy and healthy control subjects persist despite legal eligibility. The lower actual relapse rates among those with epilepsy who obtain a license than in those who are eligible suggest that those at higher risk of relapse are less likely to obtain a license.

Mitochondrial Variant G4132A is Associated with Familial Non-Arteritic Anterior Ischemic Optic Neuropathy in One Large Pedigree

Objective: To identify the genetic factors associated with familial non-arteritic anterior ischemic optic neuropathy (NA-AION) in a large pedigree. Methods: Eleven family members of a single pedigree, including six affected with NA-AION, underwent detailed clinical examinations. The mitochondrial DNA of the proband was sequenced in its entirety in search of disease-causing mutations associated with NA-AION in the pedigree. A control panel comprising 1488 patients suspected of having Leber hereditary optic neuropathy (LHON) and 97 general-population control subjects was screened for the mitochondrial sequence variant identified in the family. Results: Affected family members were all male and exhibited classic features of NA-AION. Their mean age was 50.2 ± 5.0 years. A total of 23 sequence variations were detected in the mitochondrial genome of the proband, including one novel sequence variation (G4132A, Ala276Thr) in the NADH dehydrogenase subunit 1 gene (ND1). The G4132A mitochondrial variant was detected in six members of a single pedigree with NA-AION. The G4132A variation was not observed in any of the 1585 subjects in the control panel. Moreover, this variant was not identified in over 2469 ethnically diverse individuals previously evaluated through the Human Mitochondrial Genome Database. None of the three major mutations associated with LHON (G3460A, G11778A, T14484C) were identified in the family. Conclusion: The G4132A mitochondrial variation is associated with familial NA-AION in our pedigree.

Risk Factors of Differentiated Thyroid Cancers in Child- and Young Adulthood in France: A Case-Control Study

P-160 Abstract: In order to study the potential consequences of the Chernobyl nuclear power plant accident in April 1986 and to specify the risk factors of differentiated thyroid cancer for children and young adults, we are carrying out, in close collaboration with cancer registries, a population-based case-control study in the East regions of France, that were most contaminated by fallout from the Chernobyl accident. The study will include a total of more than 700 cases and 700 controls. The thyroid case patients must have been born from January 1, 1971 and been diagnosed with histologically verified differentiated thyroid carcinoma between 2002 and 2006 in one of the 8 areas concerned with the study (Alsace, Burgundy, Champagne-Ardennes, Franche Comté, Lorraine, Rhône-Alpes, Provence-Alpes-Côte d'Azur and Corsica). General population control subjects will be randomly drawn from telephone lists, and will be matched to case patients by age, sex, and regions of residence at the time of the cancer diagnosis. Information will be collected on study subjects by use of a detailed questionnaire that will be administered by a trained interviewer during an in-person interview. The interview includes questions about known or suspected risk factors for thyroid cancer together with selected lifestyle factors and accurate places of residence in the days and first 2 months after the accident. For each study subject, total individual radiation doses to the thyroid will be reconstructed by taking into account external radiation doses received during radiodiagnostic examinations, radiotherapeutic treatment or from occupational exposure, the whereabouts and dietary habits of the subjects and information on environmental contamination. This project will also include a study of gene-environment interactions. Buccal cell DNA will be collected during interviews of cases and controls. Interviews started in June 2005. The complete data and DNA collection should be completed at the beginning of 2008. First results are awaited for 2009. Once finished, this project will be pooled with 3 other case-control studies, including a similar project carried out on the adult population in France, one in New Caledonia, and one in French Polynesia. These 4 studies, whose questionnaires were initially designed to be compatible, will offer the possibility to study a population of approximately 2000 cases and 2000 controls, of various ethnic origins and with variable lifestyles, and thus, to investigate the main suspected risk factors of thyroid cancer. The presentation will point out the objectives, design and methods of the study, as well as an assessment after 12 months of implementation.

Obtaining a driver’s license and seizure relapse in patients with childhood-onset epilepsy

To examine factors influencing obtaining a driver's license and subsequent prognosis among people with epilepsy vs control subjects. Eighty-one patients from a population-based cohort with childhood-onset epilepsy, followed prospectively for 45 years, and 96 general population control subjects were compared with regard to driving licensing, seizure relapses, and accidents. By the end of the follow-up period, all 81 subjects had achieved at least one 2-year seizure-free interval in adulthood and were eligible for a driver's license. Of these, 64 vs 90% of control subjects had obtained a license (p < 0.0001). On multivariable analysis, factors associated with not obtaining a driver's license among subjects were female gender (relative risk [RR] 2.4, 95% CI 1.0 to 5.5, p = 0.02), nonidiopathic etiology (RR 2.0, 95% CI 1.1 to 3.8, p = 0.02), and presence of learning disabilities (RR 2.0, 95% CI 1.2 to 3.2, p = 0.02). Having a driver's license was associated with a higher rate of employment (RR 1.9, 95% CI 1.2 to 3.0, p = 0.0002). Relapses of seizures had occurred in 37% of the 81 patients theoretically eligible for a license but only in 25% of the 52 subjects who actually obtained one (p = 0.003). Shortening the eligibility period from 2 to 1 year would not significantly alter the relapse rate in this population. The accident rate was not increased among patients vs control subjects. During a long-term follow-up, differences in driving licensing between patients with uncomplicated epilepsy and healthy control subjects persist despite legal eligibility. The lower actual relapse rates among those with epilepsy who obtain a license than in those who are eligible suggest that those at higher risk of relapse are less likely to obtain a license.

The Use of Health-Care Resources in Obesity-Hypoventilation Syndrome

To document health-care utilization (ie, physician claims and hospitalizations) in patients with obesity-hypoventilation syndrome (OHS), for 5 years prior to the diagnosis and for 2 years after the diagnosis and initiation of treatment. Retrospective observational cohort study. University-based sleep disorders center in Manitoba, Canada. Twenty OHS patients (mean [+/- SD] age, 52.7 +/- 9.5 years; body mass index [BMI], 47.3 +/- 11.0 kg/m(2); PaCO(2), 59.7 +/- 13.8 mm Hg; PaO(2), 51.6 +/- 12.4 mm Hg) were matched to two sets of control subjects. First, each case was matched to 15 general population control subjects (GPCs) by age, gender, and geographic location, and, second, each case was matched to a single obese control subject (OBC) who was matched using the same criteria as for the GPCs, plus the measurement of BMI. In the 5 years before diagnosis, the 20 OHS patients had (mean +/- SE) 11.2 +/- 1.8 physician visits per patient per year vs 5.7 +/- 0.8 (p < 0.01) visits for OBCs and 4.5 +/- 0.4 (p < 0.001) visits for GPCs. OHS patients generated higher fees, $623 +/- 96 per patient per year for the 5 years prior to diagnosis compared to $252 +/- 34 (p < 0.001) for OBCs and $236 +/- 25 (p < 0.001) for GPCs. OHS patients were much more likely to be hospitalized than were subjects in either control group in the 5 years prior to diagnosis (odds ratio [OR] vs GPCs, 8.6) (95% confidence interval [CI], 5.9 to 12.7); OR vs OBCs, 4.9 (95% CI, 2.3 to 10.1). In the 2 years after diagnosis and the initiation of treatment (usually continuous positive airway pressure or bilevel positive airway pressure), there was a significant linear reduction in physician fees. In the 2 years after the initiation of treatment, there was a 68.4% decrease in days hospitalized per year (5 years before treatment, 7.9 days per patient per year; after 2 years of treatment, 2.5 days per patient per year [p = 0.01]). OHS patients are heavy users of health care for several years prior to evaluation and treatment of their sleep breathing disorder; there is a substantial reduction in days hospitalized once the diagnosis is made and treatment is instituted.