Severity of liver disease among chronic hepatitis C patients: an observational study of 4594 patients in five European countries.

BACKGROUND AND AIM: Assessment of the severity of liver disease following infection with hepatitis C virus (HCV) is important in treatment selection and prognosis. As invasive liver biopsy procedures are regarded as the reference method to assess the stage of fibrosis, it is important to identify patient characteristics that are predictive of liver fibrosis severity. The aim of the study was to describe the distribution of liver severity scores, clinical characteristics, and physicians' assessment of fibrosis among HCV patients in five European countries. METHODS: This cross-sectional study retrospectively reviewed the medical records of patients who were chronically infected with HCV in 2006. Patients managed for HCV at any of 60 sites in France, Germany, Italy, Spain, and the UK were included. Data collected included patient demographics and clinical characteristics. A combination of univariate and multivariate regression analyses were used to identify predictors of fibrosis severity and factors associated with undergoing biopsy. RESULTS: Four thousand five hundred and ninety-four chronically infected HCV patients were included in this analysis. Management approaches differed between countries, with variations in biopsy use (59.3-18.4%) and preferred fibrosis scoring systems. Where histology results were available, 43.4%, 23.8%, and 32.9% had mild, moderate, and severe fibrosis, respectively. Factors associated with undergoing a biopsy included male gender and co-infection with hepatitis B virus. Chronic alcoholism, a lower first platelet count, and older age were predictors of increased liver fibrosis severity. CONCLUSIONS: These data suggest that there are major differences in how specialists manage their HCV patients across five major European countries.

Thromboembolic events among patients with hepatitis C virus infection and cirrhosis: a matched-cohort study.

INTRODUCTION: Portal vein thrombosis is a known risk among patients with cirrhosis, but the incidence of other thromboembolic events among patients with liver disease is inadequately delineated. This study examined the incidence of venous and arterial thromboembolic events in patients with cirrhosis and hepatitis C virus (HCV) infection and matched comparators. METHODS: Patients diagnosed with HCV or cirrhosis of various etiologies were identified from a large medical claims database and matched by age and sex to comparator cohorts. New-onset diagnoses of venous and arterial thromboembolic events were determined. The incidence rate of each event was calculated and rate ratios computed using Poisson regression models, adjusting for baseline factors. RESULTS: The study included 22,733 HCV-infected patients and 68,198 comparators, and 15,158 cirrhosis patients and 45,473 comparators. The incidence of any thromboembolic event was 233.4 events per 10,000 person-years for the HCV cohort and 138.5 per 10,000 person-years for the comparators; the adjusted incidence rate ratio for any thromboembolic event was 1.62 (95% confidence interval [CI]: 1.48-1.77). For the cirrhosis patients and comparators, the crude rates of any thromboembolic event were 561.1 and 249.7 per 10,000 person-years, respectively. The adjusted incidence rate ratio was 2.28 (95% CI: 2.11-2.47). Arterial events, especially unstable angina and transient ischemic attack, were the most frequent events seen in both the HCV and cirrhosis cohorts, but venous events, especially portal vein thrombosis, showed a more pronounced elevation in patients with liver disease. CONCLUSIONS: Patients with HCV and cirrhosis of various etiologies are at increased risk of several types of thromboembolic events. Physicians should consider this increased risk when managing patients with liver disease.

The high comorbidity burden of the hepatitis C virus infected population in the United States.

BACKGROUND: Chronic hepatitis C (HCV) disease can be complicated with comorbid conditions that may impact treatment eligibility and outcomes. The aim of the study was to systematically review comorbidities and symptoms in an HCV infected population, specifically assessing comorbidities associated with HCV anti-viral treatment and disease, as well as comparing comorbidities between an HCV infected and uninfected control population. METHODS: This was a retrospective cohort study within a United States medical claims database among patients with chronic HCV designed to estimate the two-year period prevalence of comorbidities. Patients with two HCV diagnosis codes, 24 months of continuous health insurance coverage, and full medical and pharmacy benefits were included. RESULTS: Among a chronic HCV cohort of 7411 patients, at least one comorbid condition was seen in almost all patients (> 99%) during the study period. HCV-infected patients reported almost double the number of comorbidities compared to uninfected controls. Of the 25 most common comorbidities, the majority of the comorbidities (n = 22) were known to be associated with either HCV antiviral treatment or disease. The five most frequent comorbidities were liver disease [other] (37.5%), connective tissue disease (37.5%), abdominal pain (36.1%), upper respiratory infections (35.6%), and lower respiratory disease (33.7%). Three notable comorbidities not known to be associated with antiviral treatment or disease were benign neoplasms (24.3%), genitourinary symptoms & ill-defined conditions (14.8%), and viral infections (13.8%). CONCLUSIONS: This US medically insured HCV population is highly comorbid. Effective strategies to manage these comorbidities are necessary to allow wider access to HCV treatment and reduce the future burden of HCV disease and its manifestations.

Parental autoimmune diseases associated with autism spectrum disorders in offspring.

BACKGROUND: Autism spectrum disorders are often idiopathic. Studies have suggested associations between immune response and these disorders. We explored associations between parental autoimmune disorders and children's diagnosis of autism by linking Swedish registries. METHODS: Data for each participant were linked across 3 Swedish registries. The study includes 1227 cases and 25 matched controls for each case (30,693 controls with parental linkage). Parental diagnoses comprised 19 autoimmune disorders. We estimated odds ratios (ORs) using multivariable conditional logistic regression. RESULTS: Parental autoimmune disorder was weakly associated with autism spectrum disorders in offspring (maternal OR = 1.6 [95% confidence interval = 1.1-2.2]; paternal OR = 1.4 [1.0-2.0]). Several maternal autoimmune diseases were correlated with autism. For both parents, rheumatic fever was associated with autism spectrum disorders. CONCLUSIONS: These data support previously reported associations between parental autoimmune disorders and autism spectrum disorders. Parental autoimmune disorders may represent a critical pathway that warrants more detailed investigation.

Comorbidities in patients with persistent or chronic immune thrombocytopenia.

There is a paucity of epidemiological data on the risk of comorbidities in adults with persistent or chronic immune thrombocytopenia (ITP). In this study, we compared the rates of cataracts, diabetes, renal failure, vascular events, lymphoma, and leukemia among patients with and without persistent or chronic ITP. Using administrative data, adult patients with medical claims for ITP from January, 2000 through September, 2006 were identified. An age- and gender-matched comparison cohort without evidence of ITP was randomly selected. The incidence rate ratio (IRR) of each comorbidity among ITP patients relative to the comparison group was estimated using Poisson regression, adjusting for baseline covariates. A total of 3,131 patients with persistent or chronic ITP were identified, and 9,392 were selected for the comparison cohort. The adjusted IRRs were as follows: diabetes 1.73 (95% CI 1.36-2.20), renal failure 2.05 (95% CI 1.67-2.51), any vascular event 1.70 (95% CI 1.41-2.05), lymphoma 5.91 (95% CI 2.61-13.37), leukemia 19.83 (95% CI 5.84-67.34), and mortality 4.21 (95% CI 3.06-5.79). There was no increased risk for cataract or myocardial infarction in the ITP cohort. Patients with persistent or chronic ITP are at increased risk for several comorbidities including hematologic malignancies, relative to a matched comparison cohort.

Occupational exposures and risk of acoustic neuroma.

OBJECTIVES: Acoustic neuroma is a benign tumour accounting for approximately 6-10% of all intracranial tumours and occurs mainly in patients aged ≥50 years. Our aim was to investigate a wide range of occupational exposures, individual occupational titles and socioeconomic status (SES) as potential risk factors for acoustic neuroma. METHODS: We conducted a population-based case-control study of 793 acoustic neuroma cases identified through the Swedish Cancer Registry and 101,762 randomly selected controls. Information on SES and occupation was obtained from censuses and linked to job-exposure matrices. Logistic regression was used to estimate ORs and calculate 95% CIs. RESULTS: An increased OR was seen for mercury exposure <10 years before the reference year (OR 2.9; 95% CI 1.2 to 6.8), and a more modest association for benzene exposure (OR 1.8; 95% CI: 1.0 to 3.2) ≥10 years before the reference year. We observed a threefold increased risk for females working as tailors and dressmakers ≥10 years before the reference year, and a more than threefold significantly elevated OR for those working as truck and conveyor operators <10 years before the reference year. We found no convincing evidence that SES is related to disease development. CONCLUSION: We observed an increased risk of acoustic neuroma associated with occupational exposure to mercury, benzene and textile dust. Men working as truck and conveyor operators <10 years before the reference year had the highest increased risk of acoustic neuroma, but it is unclear what in those occupations might contribute to disease development. Our study also suggested an association between acoustic neuroma and being a class teacher or policeman. However, these findings should be further investigated to exclude the possibility of detection bias.

Variability and predictors of changes in water use during pregnancy.

Disinfection by-products in tap water have been found in some studies to be associated with adverse pregnancy outcomes, but little is known about how water use and consumption might change during early pregnancy. Estimating water-related activities only at one time during pregnancy could easily lead to exposure misclassification. To evaluate changes in water use among pregnant women, we used data from a large epidemiologic study in which 1990 women were interviewed around 9 and 20 weeks' gestation. The water variables that were examined included ingestion of cold and hot tap water as well as of bottled water, showering and bathing. Changes were detected between early and mid-pregnancy for ingested cold tap water and showering. Thirty-three percent of the subjects changed cold-water ingestion by > or =1.0 liters/day and 44% changed their time showering by > or =35 min per week during this period. Increases in cold tap water intake were associated with age >35 years, income < $40,000, and non-Hispanic white ethnicity. We also found that the proportion of the total variation due to within-subject variability was 62% for hot tap water ingestion but only 35% for showering and approximately 50% for cold tap water, bottled water and bathing. Limited resources in epidemiologic studies often require a decision between collecting data for a large number of people or collecting multiple measurements for a smaller number of people. The results in this study will be useful to researchers who need to determine where to invest their effort when assessing water-related exposures and should help in evaluation of previously performed studies.

Parental psychiatric disorders associated with autism spectrum disorders in the offspring.

OBJECTIVE: Autism is a developmental disorder defined by impaired social interaction, communication, and behavior. Causes and correlates of autism are largely unknown, but elevated frequencies of psychiatric disorders and distinct personality traits have been reported among the family members of individuals with autism. Linkage of data from Swedish registries was used to investigate whether hospitalization for psychiatric conditions was higher among parents of children with autism compared with control subjects. METHODS: Data sources included the Swedish Medical Birth Register (child's birth), the Swedish Multi-Generation Register (linking parents to children), and Swedish Hospital Discharge Register (hospitalization records). Children born between 1977 and 2003 who had a hospitalization record indicating autism before 10 years of age (n = 1227) were matched with 30,693 control subjects from the Swedish Medical Birth Register by gender, year of birth, and hospital. Parent diagnoses were based on an inpatient hospital diagnostic evaluation and included schizophrenia, other nonaffective psychoses, affective disorders, neurotic and personality disorders and other nonpsychotic disorders, alcohol and drug addiction and abuse, and autism. Odds ratios and 95% confidence intervals were estimated by using conditional logistic regression, adjusted for child's age, gender, hospital of birth, parents' age, country of birth and socioeconomic status, and diagnosis of a mental disorder in the other parent. RESULTS: Parents of children with autism were more likely to have been hospitalized for a mental disorder than parents of control subjects. Schizophrenia was more common among case mothers and fathers compared with respective control parents. Depression and personality disorders were more common among case mothers but not fathers. CONCLUSIONS; This large population study supports the potential for familial aggregation of psychiatric conditions that may provide leads for future investigations of heritable forms of autism.

Occupational noise exposure and risk of acoustic neuroma.

A small number of prior epidemiologic studies of occupational noise exposure based on self-report have suggested an association with acoustic neuroma. The goal of the present study was to further examine the association between noise exposure and acoustic neuroma by using an objective measure of exposure in the form of a job exposure matrix. A total of 793 acoustic neuroma cases aged 21-84 years were identified between 1987 and 1999 from the Swedish Cancer Registry. The 101,756 controls randomly selected from the study base were frequency matched to cases on age, sex, and calendar year of diagnosis. Occupational information, available for 599 of the cases and 73,432 of the controls, was obtained from censuses and was linked to a job exposure matrix based on actual noise measurements. All risk estimates were close to unity, regardless of noise exposure level or parameter. The overall odds ratio for exposure to > or = 85 dB of noise was 0.89 (95% confidence interval: 0.64, 1.23). Contrary to previous study results, the present findings did not demonstrate an increased acoustic neuroma risk related to occupational noise exposure even after allowing for a long latency period. The effect of nondifferential misclassification of exposure must be considered a potential cause of the negative findings.

Predictors of use and consumption of public drinking water among pregnant women.

Disinfection by-products (DBPs) in drinking water may be associated with adverse pregnancy outcomes. However, the results from previous epidemiological studies are not consistent, perhaps in part due to individual variation in water use and consumption. This study was performed to evaluate and describe demographic and behavioral characteristics as predictors of ingested water, showering, bathing, and swimming among pregnant women. Water use and consumption data were collected through telephone interviews with 2297 pregnant women from three geographical sites in the southern United States. The data were analyzed according to demographic, health, and behavioral variables expected to be predictors of water use and thus potential confounding factors relating water use to pregnancy outcome. The candidate predictors were evaluated using backward elimination in regression models. Demographic variables tended to be more strongly predictive of the use and consumption of water than health and behavior-related factors. Non-Hispanic white women drank 0.4 (95% confidence interval (CI) 0.2; 0.7) liters more cold tap water per day than Hispanic women and 0.3 (95% CI 0.1; 0.4) liters more than non-Hispanic black women. Non-Hispanic white women also reported drinking a higher proportion of filtered tap water, whereas Hispanic women replaced more of their tap water with bottled water. Lower socioeconomic groups reported spending a longer time showering and bathing, but were less likely to use swimming pools. The results of this study should help researchers to anticipate and better control for confounding and misclassification in studies of exposure to DBPs and pregnancy outcomes.

Electromagnetic fields and female breast cancer.

The possibility that long term exposure to relatively weak power frequency electromagnetic fields (EMF) could increase the risk of breast cancer has been investigated during the past decade. The hypothesis is based on the assumption that magnetic field exposures suppress melatonin production and that melatonin is protective against breast cancer. Most epidemiological studies have indicated little or no overall effect of EMF exposure, but some early studies suggested effects among premenopausal women, particularly for estrogen receptor positive breast tumors. The early studies were often limited by small numbers, crude exposure information and lack of information on confounding factors. In more recent occupational studies, again no overall risk increases were reported, but some studies found increased risks in certain subgroups, although with no consistent pattern across studies. A recent very large occupational study with improved exposure assessment and enough statistical power also for subgroup analyses found no indications of increased risks in any subgroups. Most of the recent well-designed residential studies report no increased risks, and similar findings are reported in the majority of studies of bed heating devices. Overall, the weight of the evidence available today does not suggest an increased risk of breast cancer related to EMF exposure.

Occupational magnetic field exposure and the risk of acoustic neuroma.

BACKGROUND: Acoustic neuroma is the intracranial tumor subtype showing the highest relative risk in relation to ionizing radiation but other environmental risk factors are largely unknown. This study was performed to investigate the effect of power frequency magnetic fields. METHOD: A total of 793 cases between 1987 and 1999 were identified through the Swedish cancer registry and 101,762 controls were randomly selected from the total population. Information about occupation was obtained from censuses and linked to gender specific job-exposure matrices based on actual measurements of 50 Hz magnetic field exposure. RESULT: We investigated time-weighted average, peak values, and rate of change of magnetic field exposure considering several different time windows in relation to cancer diagnosis. We found no increases in risks regardless of exposure metric or time window of exposure. CONCLUSION: This study is the largest ever on acoustic neuroma and the first study to evaluate this tumor subtype specifically in relation to extremely low frequency magnetic fields. The results do not support the hypothesis that 50 Hz magnetic fields increase the risk of acoustic neuroma.

Occupational magnetic fields and female breast cancer: a case-control study using Swedish population registers and new exposure data.

Several recent epidemiologic studies on occupational magnetic field exposure have suggested an association with female breast cancer. The purpose of this study was to test this hypothesis by using the extensive Swedish population registers in combination with improved exposure assessment. The study base consisted of all women between 1976 and 1999 gainfully employed in Stockholm or Gotland County in Sweden. A total of 20,400 cases of breast cancer were identified from the cancer registry, and 116,227 controls were selected randomly from the study base. Information was available on estrogen receptor status, occupation, socioeconomic status, and age. Parity was available for a subset. The exposure was assessed by linkage to a newly developed job-exposure matrix based on personal magnetic field measurements on women. All risk estimates were close to unity regardless of exposure cutpoint or choice of exposure parameter. The overall odds ratio for women exposed to 0.30 microT or more was 1.01 (95% confidence interval: 0.93, 1.10). The size of the study allowed for estimates with good precision also in subgroups where previous studies have suggested increased risk, but the findings do not support the hypothesis that magnetic fields influence the risk of female breast cancer.

Relative contribution of residential and occupational magnetic field exposure over twenty-four hours among people living close to and far from a power line.

This study sought to estimate the relative contribution of exposure to 50 Hz magnetic fields experienced at home, at work/school, or elsewhere to the total exposure over 24 hr. Personal exposure meters were carried by 97 adults and children in the Stockholm area. About half of the subjects lived close (<50 m) to a transmission line and half far (>100 m) away. Spot measurements and calculations for the residential exposure were also made. For subjects living<50 m from the line, the exposure at home contributed about 80% of the total magnetic field exposure, measured in mT-hours. Adults living far away experienced only 38% of the total exposure at home, but children still received 55%. Subjects with low time-weighted average (TWA) exposure both at home and at work spent 84% of their time in fields <0.1 microT, and those with high TWA at both locations spent 69% of their time in fields > or = 0.2 microT. This contrast was diluted if only exposure at one location was considered. For spot measurements and calculations of the residential exposure, both sensitivity and specificity was good. However, the intermediate field exposure category (0.1-0.19 microT) showed poor correlation to the 24 hr personal measurements.