Empirical evidence of underutilization of referrals for epilepsy surgery evaluation.

BACKGROUND: Epilepsy surgery is a treatment that can cure patients with intractable epilepsy. This study investigates whether referrals for epilepsy surgery evaluation are underutilized. METHODS: Patients with epilepsy aged 18-60 years were identified in a computerized registry held by public health care providers in a Swedish county using ICD codes. Clinical data and data on referral status for epilepsy surgery were obtained from the patients' medical records. Potential candidates for epilepsy surgery evaluation were identified using pre-specified criteria. Obstacles for referral were analysed by comparing clinical data in patients who were considered for referral and those who were not. Appropriateness of non-referral was evaluated against recommendations from the Swedish Council on Technology in Health Care (SBU). RESULTS: Of 378 patients with epilepsy in the registry, 251 agreed to participate. Of 251, 40 were already referred patients and 48 patients were identified as potential candidates for epilepsy surgery evaluation by study criteria. Referral had been considered but not performed in 15 of the potential candidates. Potential candidates not considered for referral were less likely to have seen a neurologist, to have had an EEG, CT and MRI, and more likely to have cognitive disturbances. Following the recommendations by the SBU, 28 of 48 potential candidates were identified as inappropriately not referred patients. CONCLUSION: The number of missed referrals for epilepsy surgery evaluation was estimated to be 60 per 100,000 inhabitants. Several important obstacles were found for not referring patients for epilepsy surgery evaluation.

Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH).

Chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN) in peripheral blood lymphocytes have for decades been used as cytogenetic biomarkers to survey genotoxic risks in the work environment. The conceptual basis for this application has been the idea that increased cytogenetic damage reflects an enhanced cancer risk. Nordic and Italian cohorts have been established to evaluate this hypothesis, and analyses presented previously have shown a positive trend between CA frequency and increased cancer risk. We now report on a pooled analysis of updated data for 3541 subjects examined for CAs, 2703 for SCEs, and 1496 for MN. To standardize for interlaboratory variation, the results for the various cytogenetic end points were trichotomized on the basis of the absolute value distribution within each laboratory as "low" (1-33 percentile), "medium" (34-66 percentile), or "high" (67-100 percentile). In the Nordic cohort, there was an elevated standardized incidence ratio (SMR) for all cancer among subjects with high CA frequency [1.53; 95% confidence interval (CI), 1.13-2.05] but not for those with medium or low CA frequency. In the Italian cohort, a SMR in cancer of 2.01 (95% CI, 1.35-2.89) was obtained for those with a high CA frequency level, whereas the SMRs for those with medium or low did not noticeably differ from unity. Cox's proportional hazards models gave no evidence that the effect of CAs on total cancer incidence/mortality was modified by gender, age at test, or time since test. No association was seen between the SCEs or the MN frequencies and subsequent cancer incidence/mortality. The present study further supports our previous observation on the cancer predictivity of the CA biomarker, which seems to be independent of age at test, gender, and time since test. The risk patterns were similar within each national cohort. This result suggests that the frequency of CAs in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans, reflecting either early biological effects of genotoxic carcinogens or individual cancer susceptibility.

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs.

It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated cohorts, forming a joint study base of 5271 subjects, will now be performed, allowing a more solid evaluation. The importance of potential effect modifiers, such as gender, age at testing, and time since testing, will be evaluated using Poisson regression models. Two other potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

Socioeconomic context in area of living and risk of myocardial infarction: results from Stockholm Heart Epidemiology Program (SHEEP).

STUDY OBJECTIVE: To analyse if socioeconomic characteristics in area of living affect the risk of myocardial infarction in a Swedish urban population, and to evaluate to what extent the contextual effect is confounded by the individual exposures. DESIGN: A population based case-referent study (SHEEP). SETTING: Cases (n=1631) were all incident first events of myocardial infarction during 1992-1994. The study base included all Swedish citizens aged 45-70 years, living in Stockholm metropolitan area during these years. The social context of all metropolitan parishes (n=89) was determined by routine statistics on 21 socioeconomic indicators. A factor analysis of the socioeconomic indicators resulted in three dimensions of socioeconomic deprivation, which were analysed separately as three different contextual exposures. MAIN RESULTS: The main characteristics of the extracted factors were; class structure, social exclusion and poverty. Among men, there were increased relative risks of similar magnitudes (1.28 to 1.33) in the more deprived areas according to all three dimensions of the socioeconomic context. However, when adjusting for individual exposures, the poverty factor had the strongest contextual impact. The contextual effects among women showed a different pattern. In comparison with women living the most affluent areas according to the class structure index, women in the rest of Stockholm metropolitan area had nearly 70% higher risk of myocardial infarction after adjustment for individual social exposures. CONCLUSIONS: The results suggest that the socioeconomic context in area of living increases the risk of myocardial infarction. The increased risk in only partially explained by individual social factors (the compositional effect).

Psychosocial work environment and myocardial infarction: improving risk estimation by combining two complementary job stress models in the SHEEP Study.

OBJECTIVES: Associations between two alternative formulations of job stress derived from the effort-reward imbalance and the job strain model and first non-fatal acute myocardial infarction were studied. Whereas the job strain model concentrates on situational (extrinsic) characteristics the effort-reward imbalance model analyses distinct person (intrinsic) characteristics in addition to situational ones. In view of these conceptual differences the hypothesis was tested that combining information from the two models improves the risk estimation of acute myocardial infarction. METHODS: 951 male and female myocardial infarction cases and 1147 referents aged 45-64 years of The Stockholm Heart Epidemiology (SHEEP) case-control study underwent a clinical examination. Information on job stress and health adverse behaviours was derived from standardised questionnaires. RESULTS: Multivariate analysis showed moderately increased odds ratios for either model. Yet, with respect to the effort-reward imbalance model gender specific effects were found: in men the extrinsic component contributed to risk estimation, whereas this was the case with the intrinsic component in women. Controlling each job stress model for the other in order to test the independent effect of either approach did not show systematically increased odds ratios. An improved estimation of acute myocardial infarction risk resulted from combining information from the two models by defining groups characterised by simultaneous exposure to effort-reward imbalance and job strain (men: odds ratio 2.02 (95% confidence intervals (CI) 1.34 to 3.07); women odds ratio 2.19 (95% CI 1.11 to 4.28)). CONCLUSIONS: Findings show an improved risk estimation of acute myocardial infarction by combining information from the two job stress models under study. Moreover, gender specific effects of the two components of the effort-reward imbalance model were observed.

Association between job characteristics and plasma fibrinogen in a normal working population: a cross sectional analysis in referents of the SHEEP Study. Stockholm Heart Epidemiology Program.

STUDY OBJECTIVE: To explore the association between job characteristics and plasma fibrinogen concentrations. DESIGN: Cross sectional design. SETTING: The Greater Stockholm area. SUBJECTS: A total of 1018 men and 490 women aged 45-70 who were randomly selected from the general population during 1992-1994. They were all employed and had no history of myocardial infarction. MAIN RESULTS: The self reported job characteristics were measured by a Swedish version of the Karasek demand-control questionnaire. For inferred scoring of job characteristics, psychosocial exposure categories (job control and psychological demands) were assigned by linking each subject's occupational history with a work organisation exposure matrix. Job strain was defined as the ratio between demands and control. In univariate analyses, expected linear trends were found in three of four tests of association between high plasma fibrinogen and low control (the self reported score for women and the inferred score for both sexes), in one of four tests of association between high plasma fibrinogen and high demands (the inferred score for women) and in two of four tests of association between high plasma fibrinogen and job strain (the inferred score for both sexes). Multiple logistic regression analyses showed that men in the inferred job strain group have an increased risk of falling into the increased plasma fibrinogen concentration group (above median level of the distribution) (odds ratio (OR) 1.2; 95% CI 1.0, 1.5) after adjustment for the variables that were associated with plasma fibrinogen in the univariate analyses. In women, low self reported control, high inferred demand, and inferred job strain were significantly associated with increased plasma fibrinogen concentration (OR 1.3; 95% CI 1.0, 1.8, OR 1.5; 95% CI 1.0, 2.2, OR 1.5; 95% CI 1.1, 2.2, respectively). CONCLUSIONS: These results indicate that adverse job characteristics may be related to plasma fibrinogen concentrations and this relation is more relevant in female workers. The clearest evidence for psychosocial effects on plasma fibrinogen seems to be with job control and the associations are clearer for the objective than for the self report variables.

Is the effect of job strain on myocardial infarction risk due to interaction between high psychological demands and low decision latitude? Results from Stockholm Heart Epidemiology Program (SHEEP).

The objectives are to examine if the excess risk of myocardial infarction from exposure to job strain is due to interaction between high demands and low control and to analyse what role such an interaction has regarding socioeconomic differences in risk of myocardial infarction. The material is a population-based case-referent study having incident first events of myocardial infarction as outcome (SHEEP: Stockholm Heart Epidemiology Program). The analysis is restricted to males 45-64 yr of age with a more detailed analysis confined to those still working at inclusion. In total, 1047 cases and 1450 referents were included in the analysis. Exposure categories of job strain were formed from self reported questionnaire information. The results show that high demands and low decision latitude interact with a synergy index of 7.5 (95% C.I.: 1.8-30.6) providing empirical support for the core mechanism of the job strain model. Manual workers are more susceptible when exposed to job strain and its components and this increased susceptibility explains about 25-50% of the relative excess risk among manual workers. Low decision latitude may also, as a causal link, explain about 30% of the socioeconomic difference in risk of myocardial infarction. The distinction between the interaction and the causal link mechanisms identifies new etiologic questions and intervention alternatives. The specific causes of the increased susceptibility among manual workers to job strain and its components seem to be an interesting and important research question.

Recent time trends in acute myocardial infarction in Stockholm, Sweden.

AIMS: The purpose of this study was to analyse time trends in first acute myocardial infarction (AMI) incidence in Stockholm County during 1984-1996. METHODS AND RESULTS: The study base consisted of the population of Stockholm County 30-89 years old 1984-1996. New cases of first AMI in the study base were identified by combining information regarding hospital discharges and deaths. The diagnostic quality was evaluated for 2403 First-AMI cases 45-70 years old that occurred during 1992-1994. The evaluation indicated a very high agreement with diagnostic criteria of AMI among hospital treated cases. Among fatal cases outside hospital, the autopsy rate was nearly 70%. The incidence of first AMI declined during the study period for both men and women. In men, the age-adjusted incidence of first AMI was 18% lower in 1994-1996 than in 1984-1987 and in women it was 13% lower. The average yearly decline was 2% for men and 1.4% for women. CONCLUSION: The results of this study suggest a continued decline in AMI incidence in Stockholm. A reduction in the proportion of regular smokers has probably contributed to this decline. Future trends in AMI incidence are difficult to predict in view of diverging trends in risk factors.

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health.

The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

Assessment of genotoxic exposure in Swedish coke-oven work by different methods of biological monitoring.

This study evaluated the results of several biological methods used simultaneously to monitor coke-oven work. Blood samples from 44 male coke-oven workers and 48 male referents, matched for age and smoking/snuff consumption, were examined for cytogenetic damage in lymphocytes. Urinary thioether excretion was determined for 62, and urine mutagenicity for 31, of the subjects, who followed a standardized diet during the urine sampling. Exposure to polycyclic aromatic hydrocarbons varied with work task, the ambient air levels of benzo[a]pyrene sometimes exceeding 5 micrograms/m3. Cytogenetic damage, urine mutagenicity, and thioether excretion did not differ between the groups. The smokers, however, had significantly higher sister chromatid exchange frequencies, urine mutagenicity, and thioether excretion than the nonsmokers. The absence of biological indications of genotoxic exposure was unexpected and indicates that the studied methods are not adequate to assess the carcinogenic risks of Swedish coke-oven workers.

Mortality and incidence of cancer among Swedish gas workers.

The mortality and incidence of cancer was studied among 295 workers at a Swedish gas production company. All men employed for at least one year between 1965 and 1972 were included in the study. The follow up period for mortality was 1966 to 1986, and the incidence of cancer was followed up from 1966 to 1983. Expected numbers of deaths were based on local death rates among occupationally active men, the expected numbers of cancer were based on national statistics. The total mortality was increased, mainly due to an excess of deaths from circulatory diseases. The excess was larger after long follow up and after long employment periods. Two cases of cancer in the nose and nasal sinuses were found; there was no excess of lung cancer. Smoking habits were investigated for a subset of the cohort and did not differ from the average for men in large cities. The findings are discussed in relation to other studies of soot and combustion exposed workers.

How to evaluate interaction between causes: a review of practices in cardiovascular epidemiology.

To increase the knowledge of interaction or synergy between risk factors in an important task in medical research. Still, current literature in cardiovascular epidemiology reflects major misconceptions as how to evaluate interaction. This paper presents Rothman's model of causation from which strict empirical criteria of interaction can be derived. In principle, the method to apply consists of comparing risk differences for one risk factor of interest across strata of the other. Commonly used but incorrect approaches are exemplified and discussed. These include reporting risk of disease among those with combined exposure, comparing relative risks for one exposure after stratification by level of the other, and including an interaction term in the regression model and drawing conclusions from its P-value.

Genetic differentiation in four European subspecies of red deer (Cervus elaphus L.).

Red deer representing the four different European subspecies Cervus elaphus atlanticus, C. e. elaphus, C. e. germanicus, and C. e. scoticus were examined for allozyme variability at 35 enzyme loci. The proportion of polymorphic loci within populations (P) ranged from 0 to 13.8 per cent and the average heterozygosity (H) from 0 to 3.6 per cent. These estimates are within the range previously observed among mammalian species. Significant allele frequency differences were found both within and between subspecies. The mean genetic distance between subspecies (D = 0.0164) was smaller than the differentiation at similar taxonomic levels among other ungulates, probably because of a shorter time since divergence. Within subspecies the genetic differences between populations were similar to those reported between populations within closely related species in the same geographic region. Cluster analysis based on genetic distances indicated a major genetic dichotomy between the British C. e. scoticus and the Norwegian C. e. atlanticus on one hand and the Swedish C. e. elaphus and the continental C. e. germanicus on the other. Populations of pure C. e. elaphus were not found to differ genetically in any substantial way from Swedish populations of possible heterogeneous subspecific origin. An allele unique to C. e. scoticus was found in a Swedish enclosed population where imports of British deer are known to have taken place. A population established to preserve the genetic characteristics of the C. e. elaphus subspecies appeared to have lost 36 per cent of the electrophoretically measurable heterozygosity.

Myocardial infarction in male and female dominated occupations.

The aim of the study was to investigate whether workers in jobs dominated by the opposite sex have an increased risk of myocardial infarction (MI). A case-referent study was carried out to estimate the relative risk of first MI in different occupational groups. The study base comprised all men and women in five counties in the middle of Sweden during 1976-84. Cases of MI were identified from both hospital discharge records and death records. Information on occupation was obtained from two consecutive censuses. Primary health related selection was analysed for men with data from the physical examination of conscripts to compulsory military service in 1969-70 combined with data from the censuses of 1970-90 and data on early retirement in 1971-92. Increased risk of MI was found among both women (relative risk (RR) 1.41, 95% confidence interval (95% CI) 1.15 to 1.73) and men (1.21, 1.10 to 1.32) in blue collar jobs where men predominate, and among men with white collar jobs (1.26, 1.09 to 1.45) where women predominate. However, the increased risk among men in white collar jobs was probably due to negative health selection into these occupations. These results do not support the notion that being of the sexual minority in an occupation is in itself an important risk factor for MI.

Mortality and cancer incidence among laboratory technicians in medical research and routine laboratories (Sweden).

OBJECTIVES: To investigate cancer incidence and mortality among laboratory employees. METHODS: Mortality and cancer incidence were investigated among 2553 female and male laboratory workers employed at the Karolinska Institute and Karolinska Hospital in Stockholm between 1950 and 1989. Mortality was followed from 1952-1993 and cancer incidence from 1958-1992. Expected numbers were based on the general population in Stockholm, standardizing for age, gender, and calendar period. RESULTS: The overall mortality and cancer incidence in the cohort was lower than expected. There were in all 10 cases of hemato-lymphatic malignancies (three acute myeloid leukemias, four non-Hodgkin lymphomas, two Hodgkin's lymphomas, and one multiple myeloma) in the cohort. The standardized incidence ratio (SIR) for hematolymphatic tumors was increased among workers who had ever been employed in laboratories with a high probability for chemical exposure, SIR 224 (95% CI 108-412). The risk of breast cancer among women was increased after more than 10 years of work in high-exposure laboratories, SIR 225 (128-365). The number of malignant melanomas exceeded those expected. CONCLUSIONS: The findings support earlier observations of an increased risk of hematolymphatic cancer among laboratory workers. The routine for handling chemicals and functionality of ventilatory equipment must be under continuous supervision.

Does heavy physical exertion trigger myocardial infarction? A case-crossover analysis nested in a population-based case-referent study.

To study possible triggering of first events of acute myocardial infarction by heavy physical exertion, the authors conducted a case-crossover analysis (1993-1994) within a population-based case-referent study in Stockholm County, Sweden (the Stockholm Heart Epidemiology Program). Interviews were carried out with 699 myocardial infarction patients after onset of the disease. These cases represented 47 percent of all cases in the study base, and 70 percent of all nonfatal cases. The relative risk from vigorous exertion was 6.1 (95% confidence interval: 4.2, 9.0). The rate difference was 1.5 per million person-hours, and the attributable proportion was 5.7 percent. The risk was modified by physical fitness, with an increased risk being seen among sedentary subjects as in earlier studies, but the data also suggested a U-shaped association. In addition, the trigger effect was modified by socioeconomic status. Premonitory symptoms were common, and this implies risks of reverse causation bias and misclassification of case exposure information that require methodological consideration. Different techniques (the use of the usual-frequency type of control information, a pair-matched analysis, and a standard case-referent analysis) were applied to overcome the threat of misclassification of control exposure information. A case-crossover analysis in a random sample of healthy subjects resulted in a relative risk close to unity, as expected.

Environmental tobacco smoke and myocardial infarction among never-smokers in the Stockholm Heart Epidemiology Program (SHEEP).

An increased risk for myocardial infarction (MI) related to environmental tobacco smoke (ETS) exposure has previously been reported, but several aspects of the association are still uncertain. We studied the MI risk associated with ETS exposure among 334 nonfatal never-smoking MI cases and 677 population controls, 45-70 years of age, in Stockholm County. A postal questionnaire with a telephone follow-up provided information on ETS exposure and other potential risk factors for MI. After adjustment for age, gender, hospital catchment area, body mass index, socioeconomic status, job strain, hypertension, diet, and diabetes mellitus, the odds ratio for MI was 1.58 (95% confidence interval = 0.97-2.56) for an average daily exposure of 20 cigarettes or more from the spouse. Combined exposure from spouse and work showed an increasing odds ratio for MI, up to 1.55 (95% confidence interval = 1.02-2.34) in the highest category of weighted duration, that is, more than 90 "hour-years" of exposure (1 "hour-year" = 365 hours, or 1 hour per day for 1 year). In addition, more recent exposure appeared to convey a higher risk. Our data confirm an increased risk of MI from exposure to ETS and suggest that intensity of spousal exposure, combined exposure from spouse and work, and time since last exposure are important.

Family history of coronary heart disease, a strong risk factor for myocardial infarction interacting with other cardiovascular risk factors: results from the Stockholm Heart Epidemiology Program (SHEEP).

We explored the relation between family history of coronary heart disease and the risk of myocardial infarction in a case-control study of subjects, 45 to 70 years of age, living in Stockholm, Sweden. Our cases comprised 1091 male and 531 female first-time acute myocardial infarction patients who had survived at least 28 days after their infarction. Referents were randomly selected from the population from which the cases were derived. The adjusted odds ratio (OR) of myocardial infarction was 2.0 (95% confidence interval [CI] = 1.6-2.6) for men reporting > or = 1 affected parent or sibling, compared with men with no family history of coronary heart disease, and 3.4 (95% CI = 2.1-5.9) for those reporting > or = 2 affected parents or siblings. The corresponding OR for women were 2.1 (95% CI = 1.5-3.0) and 4.4 (95% CI = 2.4-8.1). We found evidence for synergistic interactions in women exposed to family history of coronary heart disease in combination with current smoking and with a high quotient between low-density lipoprotein and high-density lipoprotein cholesterol (>4.0), respectively, which yielded adjusted synergy index scores of 2.9 (95% CI = 1.2-7.2) and 3.8 (95% CI = 1.5-9.7), respectively. Similarly, in men we found evidence for interaction for the co-exposure of family history of coronary heart disease and diabetes mellitus. Our study shows that family history of coronary heart disease is not only a strong risk factor for myocardial infarction in both sexes, but that its effect is synergistic with other cardiovascular risk factors as well.

A population-based case-referent study of myocardial infarction and occupational exposure to motor exhaust, other combustion products, organic solvents, lead, and dynamite. Stockholm Heart Epidemiology Program (SHEEP) Study Group.

This case-referent study investigated the risk of myocardial infarction from occupational exposure to motor exhaust, other combustion products, organic solvents, lead, and dynamite. We identified first-time, nonfatal myocardial infarctions among men and women 45-70 years of age in Stockholm County from 1992 through 1994. We selected referent subjects from the population to match the demographic characteristics of the cases. A lifetime history of occupations was obtained by questionnaire. The response rate was 81% for the cases and 74% for the referents, with 1,335 cases and 1,658 referents included in the study. An occupational hygienist assessed occupational exposures, coding the intensity and probability of exposure for each subject. We adjusted relative risk estimates for tobacco smoking, alcohol drinking, hypertension, diabetes mellitus, overweight, and physical inactivity at leisure time. The relative risk of myocardial infarction was 2.11 (95% confidence interval = 1.23-3.60) among those who were highly exposed and 1.42 (95% confidence interval = 1.05-1.92) among those who were intermediately exposed to combustion products from organic material. We observed an exposure-response pattern, in terms of both maximum exposure intensity and cumulative dose. Exposure to dynamite and organic solvents was possibly associated with an increased risk. The other exposures were not consistently associated with myocardial infarction.