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Using three different registers a cohort study was undertaken to describe the relationship between type of occupation and hospitalization. A total of 958 096 subjects aged 20-64 years were followed-up for one year regarding inpatient care. Several significant associations between type of occupation and incidence of hospitalization for different diagnoses were observed. Male subjects employed in occupations where a high proportion reported a combination of hectic work and few possibilities to learn new things were more frequently hospitalized for myocardial infarction than other working men. The relative 'hospitalization' ratio for men 20-54 years of age in these strenuous occupations was estimated as 1.6 with a 95% confidence interval of 1.3-1.9. For women, the relative 'hospitalization' ratio in the ages 20-64 in occupations where a high proportion reported a combination of hectic and monotonous work was estimated as 1.6 with a 95% confidence interval of 1.1-2.3. Both these associations were statistically significant even after controlling for 12 possible confounding factors.

A job-exposure matrix has been developed linking the work tasks in the Swedish National Census of population 1960 to exposure to 50 single agents or groups of substances. All 1,905,660 men, aged 20-64 years in 1960, reporting themselves as gainfully employed in the Census, were observed for the occurrence of urothelial cancer 1961-1979 by linkage to the National Swedish Cancer Registry. Subjects classified as exposed to creosote had a relative risk (with 95% confidence interval) of 2.6 (1.2-5.9) for renal pelvis cancer and 1.3 (1.0-1.8) for urinary bladder cancer; subjects exposed to polychlorinated biphenyls (PCB) had a relative risk of 1.3 (1.0-1.8) for urinary bladder cancer. Adjustment was made for age, socioeconomic group, and degree of urbanization. Exposure to combustion gases from coal gave a relative risk of 1.2 (1.0-1.4) for bladder cancer. The study carries several sources of nondifferential misclassification diluting the estimates of the relative risks toward 1.0. The limitations of exposure classification by job-exposure matrices are discussed.

In Finland, the incidence of coronary heart disease is reported to be about twice as high as in the neighbouring country of Sweden. The aim of this study was to find out what happens to this excess risk among Finnish immigrants to Sweden. A geographically defined population in Stockholm County was followed up in the in-patient care registry and the cause-of-death registry in order to find cases for a case-control study. All episodes of myocardial infarction (ICD numbers 410.00 and 410.99) that had occurred in men born between 1911 and 1935 during the period 1974-76 were recorded. An age-matched control group was randomly selected from the population. By means of the civil registration system it was possible to identify country of birth and length of stay in Sweden. Of the 356 cases, 32 (9%) had been born in Finland compared with 55 (6%) of the 887 controls. The overall relative risk for the Finnish immigrants compared with native Swedes was 1.7. For the group of Finnish immigrants who had been in Sweden for 20 years or more the relative risk was 1.3. It was concluded that since the relative risk decreases during the stay in Sweden the environmental factors dominate the explanation of the difference in the relative risk of developing myocardial infarction between Finland and Sweden.

To study the association between postmenopausal hormone therapy (PMH) use and the risk of rheumatoid arthritis (RA) stratifying the cases by the presence/absence of antibodies against citrullinated peptides (ACPA). A subset of the Epidemiological Investigation of RA (EIRA), a population-based case-control study, comprising postmenopausal women aged 50–70 living in Sweden, between 2006 and 2011 was analysed (523 cases and 1057 controls). All participants answered an extensive questionnaire, including questions regarding PMH use and potential confounders (education, smoking, BMI, oral contraceptives, reproductive factors). We calculated odds ratios (OR) of developing ACPA-positive/-negative RA, with 95 % confidence intervals (CI) and adjusted for age, residential area and smoking. Current users of PMH had a decreased risk of ACPA-positive RA compared with never users (OR 0.6, 95 % CI 0.3–0.9). The decreased risk was observed mainly in the age-group 50–59 years (OR 0.3, 95 % CI 0.1–0.8) but not in the age-group 60–70 years (OR 0.8, 95 % CI 0.4–1.4). Among current users of a combined therapy (estrogen plus progestogens) an OR of 0.3 (95 % CI 0.1–0.7) of ACPA-positive RA was observed, while no significant association was found among women who used estrogen only (OR 0.8, 95 % CI 0.5–1.6). No association between PMH use and ACPA-negative RA was found. PMH use might reduce the risk of ACPA-positive RA in post-menopausal women over 50 years of age, but not of ACPA-negative RA. The negative influence of this treatment on the risk of other chronic conditions cannot be overlooked.

Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 × 10(−36)) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95%CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15:01 carriage, absence of HLA-A*02:01, and high anti-EBNA1 antibody levels (OR = 24.9; 95%CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLA-DRB1*04:01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95%CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.

Background: HLA-DRB1*15:01, absence of HLA-A*02:01, and smoking interact to increase multiple sclerosis (MS) risk. Objective: To analyze whether MS-associated human leukocyte antigen (HLA) alleles, apart from DRB1*15:01 and absence of A*02:01, interact with smoking in MS development, and to explore whether the established HLA-smoking interaction is affected by the DQA1*01:01 allele, which confers a protective effect only in the presence of DRB1*15:01. Methods: In two Swedish population-based case–control studies (5838 cases, 5412 controls), subjects with different genotypes and smoking habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals employing logistic regression. Interaction on the additive scale between different genotypes and smoking was evaluated. Results: The DRB1*08:01 allele interacted with smoking to increase MS risk. The interaction between DRB1*15:01 and both the absence of A*02:01 and smoking was confined to DQA1*01:01 negative subjects, whereas no interactions occurred among DQA1*01:01 positive subjects. Conclusion: Multifaceted interactions take place between different class II alleles and smoking in MS development. The influence of DRB1*15:01 and its interaction with the absence of A*02:01 and smoking is dependent on DQA1*01:01 status which may be due to differences in the responding T-cell repertoires.

Background Several treatments are on the horizon for Duchenne muscular dystrophy (DMD), a terminal orphan disease. In many jurisdictions, decisions regarding pricing and reimbursement of these health technologies comprise evidence of value for money. Objective The objective of this study was to develop a cost-effectiveness model based on the Duchenne muscular dystrophy Functional Ability Self-Assessment Tool (DMDSAT), a new rating scale created specifically to measure disease progression in clinical practice and trials and model DMD in economic evaluations, and compare it with two alternative model structures. Methods We constructed three Markov cohort state-transition models to evaluate the cost-effectiveness of a hypothetical intervention for DMD versus standard of care in a UK setting. Model I was based on the DMDSAT, model II on stages of disease as defined in the DMD clinical care guidelines and model III on patients’ ventilation status. The conceptual model structures were formulated in collaboration with three DMD experts. Results All three models were judged to have good validity with regards to the appropriateness of the choice of modelling technique, conceptual representation of the disease, model input data and model outcomes. Across frameworks, lifetime direct medical costs with standard of care ranged between £217,510 and £284,640, total costs between £624,240 and £713,840, and total number of quality-adjusted life-years between 5.96 and 7.17. Conclusions We present a first version of a model for the economic evaluation of treatments for DMD based on the DMDSAT, as well as two alternative frameworks encompassing conventional staging of disease progression. Our findings should be helpful to inform health technology assessments and health economic programmes of future treatments for DMD. Electronic supplementary material The online version of this article (doi:10.1007/s40273-016-0461-5) contains supplementary material, which is available to authorized users.

To study trends in the incidence of and mortality from stroke in Stockholm during 1974-81 all cases (n = 56566) of stroke in patients aged over 40 were identified from the Swedish Cause of Death Register and the Inpatient Care Register. Information on the population at risk was obtained from the civil registration system. A multiplicative model was used to control for changes in the distribution of age during the study. Mortality from stroke decreased annually throughout the study by a mean of 2.3% for men and 3.5% for women. This favourable development was not accompanied by a similar decrease in the incidence of stroke. In men the total incidence (including recurrent strokes) and incidence of first stroke increased continuously. In women the total incidence showed virtually no change, whereas the incidence of first stroke decreased somewhat. These findings, in addition to an expected shift of age profile in the population towards more elderly people, should be considered in the planning of future health care resources.

The project was designed to test the assumption that certain psychosocial characteristics of occupational groups are associated with elevated myocardial infarction risk. All cases of myocardial infarction below the age of 65 in men living in the region of greater Stockholm during the years 1974-1976 were identified (deaths as well as survivals) in the official registries of hospitalizations and deaths. For each case two controls without infarction (in younger ages four) matched for age, area of residence and sex were selected randomly from the parish registries. For each case and control (n = 334 and 882, respectively) information was available regarding occupation. The psychosocial characteristics of each one of the 118 occupations were recorded by means of a nation wide interview survey (3876 working men) in 1977. Relative age-adjusted risks of developing a myocardial infarction were calculated for occupations in which many vs occupations in which few subjects reported a given characteristic (50% with most vs 50% with least). Shift work and monotony were associated with significant excess risk. Hectic work was not associated with excess risk by itself but in combination with variables associated with low decision latitude and/or few possibilities for growth it was associated with significant excess risk.

This paper reviews a number of studies which have presented results on the association between shift work and cardiovascular disease. It is suggested that many of the early studies suffer from methodological flaws which render them difficult to interpret. In studies in which incidence of disease has been computed and related to exposure to shift work, the results indicate a higher risk for cardiovascular disease among shift workers as compared to day workers. The evidence cannot yet, however, be considered conclusive.

In this paper some previously found associations between psychosocial occupational characteristics and myocardial infarction (MI) risk are scrutinized regarding confounding effects. Standardized occupational characteristics were obtained for 118 occupational groups by means of a nation wide interview survey (3876 men). Possible confounding factors available were smoking, low level of education, high proportion of immigrants (mainly of Finnish origin) and heavy lifting. The standardized characteristics were utilized in a case-control study of 1216 men 40–64 years of age, living in the Stockholm County. It was concluded that occupations characterized by both high demand and at the same time small possibility of control or growth (‘strain’) are associated with an elevated MI risk regardless of the confounding factors. Taking each of the confounding factors into account the risk of developing MI for men aged 40–54 years employed in these strenous occupations is about twice as high as for those employed in other occupations.

In the present thesis methods for utilizing some of the many registers in Sweden for epidemiological purposes were further developed. These purposes include immigrant studies, case-control studies dealing with psychosocial job characteristics, and studies of time trends. A theoretical framework for handling problems of misclassification when using register data was developed. Register data were used to examine several hypotheses concerning the occurrence and etiology of myocardial infarction (MI). The result of these all emphasize the role of environmental factors in the etiology of MI. Further information on the relationship between migration and MI was obtained. Male Finnish immigrants in Sweden tend to adopt the lower risk of native Swedes. This implies that environmental factors are important in explaining the difference in incidence of MI between Finland and Sweden. This also implies that it may be possible to decrease the risk by changing environmental conditions. The relationship between psychosocial work environment and MI risk was studied in a new way by using information on occupation. Occupations characterized by hectic work and at the same time providing little possibility for control or growth were significantly associated with an elevated MI risk. The risk for men aged 40-54 years employed in these strenuous occupations was about twice as high as for those in other occupations. This result remained relatively unaffected when several potential confounding factors were taken into consideration. A study was undertaken to examine trends in the incidence and mortality of MI in Stockholm (1974-80). For men the incidence as well as the mortality was appreciably increased. For women there was an appreciable increase in incidence while the increase in mortality was more uncertain. The observed increases in incidence and mortality are contrary to the trend for most other nations in the Western hemisphere. The reason for the increasing trend in Stockholm is, however, unknown.

This article summarizes some of the major findings in research on associations between psychosocial factors and cardiovascular illness. Methodological difficulties are discussed. Findings from some of the authors' own studies serve as illustrations. It is emphasized that an interplay between environmental and individual factors is of great importance. Personality factors relevant to the risk of cardiovascular illness may distort individual descriptions of the work environment. Cardiovascular risk factors such as cigarette smoking and repeated blood pressure elevations may be influenced by psychosocial factors. Lack of intellectual discretion at work, particularly if combined with excessive demands, may increase the risk of cardiovascular illness.

It is unclear whether smoking interacts with different aspects of Epstein–Barr virus (EBV) infection with regard to multiple sclerosis (MS) risk. We aimed to investigate whether smoking acts synergistically with elevated EBNA-1 antibody levels or infectious mononucleosis (IM) history regarding MS risk. Two Swedish population-based case–control studies were used (6,340 cases and 6,219 matched controls). Subjects with different smoking, EBNA-1 and IM status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Current and past smokers had higher EBNA-1 antibody levels than never smokers (p

Neuropsychiatric effects were examined among 206 men, of whom 135 had been house painters and 71 had been house carpenters, affiliated with their respective trade unions for at least 10 years before 1970. Their lifetime organic solvent exposure was evaluated through the aid of an interview. Relevant potential confounding factors were accounted for in the statistical analysis. Neuropsychiatric symptoms compatible with chronic toxic encephalopathy were more common among the painters than among the carpenters, and these symptoms became increasingly prevalent with increasing cumulative solvent exposure. On only one of 12 psychometric tests, block design, did the painters perform worse than the carpenters, and in this test the painters' performance deteriorated with increasing cumulative exposure. For the majority of the psychometric tests, and for the coordination tests, there were no differences between the painters and carpenters, but the painters with "low" exposure tended to show better, and "heavily" exposed painters worse, results than the carpenters. The 52 painters with the heaviest cumulative exposures and 45 carpenters were examined for psychiatric diagnosis according to DSM-III, with electroencephalography and auditory evoked potential, P-300. Three painters and two carpenters had diagnoses compatible with an organic mental disorder. There were no overall differences between the painters and carpenters, either for the visually examined electroencephalograms or the P-300 latencies. The excess of neuropsychiatric symptoms among the painters was probably causally linked to solvent exposure. However, these symptoms seemed only rarely, if ever, serious enough to entail a psychiatric diagnosis. Concerning other outcomes, the investigation may not lead to a determination of whether the exposure-response relationship among the painters, with no difference between the entire group of painters and carpenters, is caused by solvent exposure or by selection factors within the group of painters.

Background To prevent debilitating and irreversible joint damage, rheumatoid arthritis (RA) is often treated with tumor necrosis factor inhibitor (TNFi), but many patients do not respond to this costly therapy. Few predictors for response are known, and it has been proposed that genetic factors which influence the development of RA may also influence disease severity and response to therapy. Several previous studies have attempted to confirm this but results remain inconclusive. We expand on previous studies by including more RA risk alleles, and maximize power by combining them into a genetic risk score. Method We linked genotyped RA patients from the Epidemiological Investigation of Rheumatoid Arthritis study to the Swedish Rheumatology Quality Register, identifying patients who started a TNFi as their first biological disease-modifying anti-rheumatic drug, with a return visit within 2–8 months after treatment start (N = 867). We calculated risk scores from 76 established RA risk SNPs, and four HLA-DRB1 amino acid positions, and tested whether risk scores or individual genetic risk factors could predict the European League Against Rheumatism (EULAR) response. Results We found no association between any of the risk scores or HLA-DRB1 haplotypes and EULAR response, neither overall nor stratified by anti-citrullinated protein/peptide antibody (ACPA) status. When evaluating each of the 76 SNPs, we found that the number of SNPs presenting significant associations was not higher than expected by chance (5/76 SNPs had p

Background In addition to anti-citrullinated protein antibodies (ACPAs), antibodies targeting carbamylated (i.e., homocitrullinated) proteins (anti-CarP antibodies) have been described in rheumatoid arthritis (RA). However, the extent to which anti-CarP antibodies are truly distinct from ACPA remains unclear, and few studies have focused on specific autoantigens. Here, we examine cross-reactivity between ACPA and anti-CarP antibodies, in the context of the candidate autoantigen α-enolase. Methods Cross-reactivity was examined by immunoblotting of citrullinated and carbamylated proteins using purified ACPA; and by peptide absorption experiments, using the citrullinated α-enolase peptide CEP-1 and a homocitrulline-containing version (carb-CEP-1) in ELISA. The population-based case-control cohort EIRA (n = 2836 RA; 373 controls) was screened for reactivity with CEP-1 and carb-CEP-1, using the ISAC multiplex array. Associations between anti-CarP antibodies, smoking and genetic risk factors were analysed using unconditional logistic regression models. Differences in antibody levels were investigated using the Mann-Whitney U test. Results Affinity-purified ACPA was found to bind carbamylated proteins and homocitrulline-containing peptides, demonstrating definitive cross-reactivity between ACPA and anti-CarP antibodies. Anti-carb-CEP-1 reactivity in EIRA was almost exclusively confined to the CEP-1-positive subset, and this group of RA patients (21 %) displayed a particularly strong ACPA response with marked epitope spreading. The small RA subset (3 %) with homocitrulline reactivity in the absence of citrulline reactivity did not associate with smoking or risk genes, and importantly had significantly lower anti-carb-CEP-1 antibody levels. Conclusion Our data presented herein cast doubt on the specificity of anti-CarP antibodies in RA, which we posit may be a subset of cross-reactive ACPA. Electronic supplementary material The online version of this article (doi:10.1186/s13075-016-1001-6) contains supplementary material, which is available to authorized users.

The main objective of the study was to evaluate the ability of workers to reproduce simulated manual work forces correctly and to quantify these forces in Newtons (N) by means of self-reports. Fourteen male and 14 female workers participated in the study. Three experiments were carried out. In the first experiment, the ability to reproduce the magnitudes of simulated manual forces occurring in daily work and to estimate these forces in Newtons was tested. A specially designed force-measuring device was used for this purpose. In the second experiment, the subjects estimated the weights of five boxes ranging from 1 to 30 kg. In the third experiment, the subjects were asked to produce five predetermined push and pull forces ranging in magnitude from 10 to 300 N on to the handle of the force-measuring device. The ability to reproduce the magnitudes of manual forces when simulating four familiar work tasks was good (the intraclass correlation coefficients ranged from 0.75 to 0.95). The ability to quantify these forces in Newtons was not as good (the product moment correlation coefficients ranged from 0.21 to 0.69). When the subjects estimated the weights of boxes they underestimated the weights. When they produced predetermined push and pull forces they exerted higher forces than expected when low force levels were requested and lower forces when high force levels were requested. However, the forces were correctly ranked. In summary, simulation of the manual push/pull forces used in familiar work tasks seemed to offer sufficient reproducibility to be worth testing for validity. Self-reports, used without previous training or without known 'reference forces', seemed to be very rough when the aim was to estimate in kg or Newtons. However, the fact that individuals could rank the forces correctly opens a potential for refinement of self-reports as a method for quantifying manual forces in objective terms, e.g. kg or Newtons.

During the last decades substantial temporal changes, as well as population differences, in coronary heart disease mortality have occurred in Sweden. There is little information to what extent these changes and differences also apply to myocardial infarction incidence, The aim of this paper was to describe the methods used to identify cases in a recently developed National Acute Myocardial Infarction Register in Sweden, and to present estimates of incidence and case fatality in Sweden. I Incident cases of acute myocardial infarction (AMI) were identified by record linkage of routinely collected data on hospital discharges and deaths. Case fatality within 28 days was ascertained by linkage of incident cases to the National Cause of Death Register. About 40 000 new cases of AMI per year were recorded in Sweden during 1987-1995. Well-known differences in incidence with regard to age and gender were observed, as well as a decline in incidence between 1987 and 1995. A similar case fatality was seen in men and women aged 30-89 among hospitalized cases. When fatal cases outside hospital were also considered the case fatality was somewhat higher in men. Examination of medical records for a national sample of ischaemic heart disease patients suggested a high sensitivity (94%) and a high positive predictive value (86%) for ICD-9 code 410 in hospital discharge data with regard to definite AMI. The National Acute Myocardial Infarction Register offers a new possibility to study the incidence of AMI, as well as case fatality, in Sweden.

An epidemiological investigation has been initiated from Sweden with the aim to study and compare dental health, dental treatment needs and attitudes to dental care in two well-defined age-groups, children of 5 and 12 years of age, in eight EU countries. To ensure comparability of the clinical registrations, data collection was preceded by clinical calibrations of the examiners from the participating countries. All the examiners participated in a workshop with initial calibration exercises. Agreement, expressed as sensitivity, was measured between the Swedish examiner acting as the reference examiner and each of the other examiners in turn, and assessed separately for the two age-groups. For DMFS/dmfs, agreement ranged from 44.3% to 82.2%. These results were discussed and where necessary the criteria were modified and/or made more stringent, so that they were clearcut and could be adhered to consistently. In a second calibration between the Swedish and the national examiner undertaken in each of the seven countries, the inter-examiner agreement (sensitivity) varied between 85.4% and 100%. The mean sensitivity for DMFS/dmfs after the total calibration procedures was 89.5% for the 12-year olds and 91.7 for the 5-year olds. The mean sensitivity for both age-groups together was 90.6% and the corresponding value for specificity was 98.9%.

The principal aim of the present study was to evaluate questionnaire-based information on past physical work loads (6-year recall).Effects of memory difficulties on reproducibility were evaluated for 82 subjects by comparing previously reported results on current work loads (test-retest procedure) with the same items recalled 6 years later. Validity was assessed by comparing self-reports in 1995, regarding work loads in 1989, with worksite measurements performed in 1989.Six-year reproducibility, calculated as weighted kappa coefficients (k(w)), varied between 0.36 and 0.86, with the highest values for proportion of the workday spent sitting and for perceived general exertion and the lowest values for trunk and neck flexion. The six-year reproducibility results were similar to previously reported test-retest results for these items; this finding indicates that memory difficulties was a minor problem. The validity of the questionnaire responses, expressed as rank correlations (r(s)) between the questionnaire responses and workplace measurements, varied between -0.16 and 0.78. The highest values were obtained for the items sitting and repetitive work, and the lowest and "unacceptable" values were for head rotation and neck flexion. Misclassification of exposure did not appear to be differential with regard to musculoskeletal symptom status, as judged by the calculated risk estimates.The validity of some of these self-administered questionnaire items appears sufficient for a crude assessment of physical work loads in the past in epidemiologic studies of the general population with predominantly low levels of exposure.

A study was undertaken to examine trends in the incidence and mortality of myocardial infarction in Sweden. All cases (n = 19908) of myocardial infarction diagnosed in the population of Stockholm county during 1974-80 were identified by means of the cause of death register and the inpatient care register. Information on patients at risk was obtained from the civil registration system. The relative risk of developing, or dying of, myocardial infarction in one specific year, compared with the average for the whole period, was taken as the basis for describing the trends. For men in Stockholm the incidence as well as the mortality was appreciably increased; the annual increase in incidence was 3% and in mortality 4%. There were no signs of decreasing lethality. For women there was an appreciable increase in incidence; for mortality the result was less specific but was compatible with an increase. The observed increases in incidence and mortality appeared to be real and were probably not due to an increasing tendency for patients to seek hospital treatment or for doctors to make the diagnosis. The reason for the increase is unknown.

Objectives The aim of this study was to analyze the relationship of job strain (high psychological job demands and low decision latitude) to hypertension, serum lipids, and plasma fibrinogen. Methods The study population consisted of employed persons between the ages of 15 and 64 years in the counties of Stockholm, Vasternorrland, and Jamtland, Sweden. The data collection was carried out during 1992-1998. A total of 10 382 subjects participated in a medical examination and completed a questionnaire. Results No strong associations were found between job strain and plasma fibrinogen. The males reporting job strain had lower levels of total cholesterol and high-density lipoprotein cholesterol than the other males. Similar tendencies were found for the females. The females, but not the males, with job strain had an increased prevalence of hypertension when compared with the subjects with relaxed psychosocial work characteristics. In the subgroups of younger males and females an adverse association between job strain and the ratio between low-density and high-density lipoprotein cholesterol was noted. Conclusions The results do not support the hypothesis that job strain has an adverse impact on serum total cholesterol and plasma fibrinogen levels. They suggest that an increased risk of coronary heart disease in association with job strain, if causal, is mediated by other factors, possibly partly by hypertension and low levels of high-density lipoprotein cholesterol.

Introduction Whether low socioeconomic status (SES) is associated with worse rheumatoid arthritis (RA) outcomes in countries with general tax-financed healthcare systems (such as Sweden) remains to be elucidated. Our aim was to investigate the influence of educational background (achieving university/college degree (high) or not (low)) on the outcomes of early RA, in terms of disease activity (DAS28), pain (VAS-pain), and functional impairment (HAQ). Methods We evaluated DMARD-naïve RA patients recruited in the Epidemiological Investigation of RA (EIRA) study with outcomes followed in the Swedish Rheumatology Quality (SRQ) register (N = 3021). Outcomes were categorized in three ways: 1) scores equal to/above median vs. below median; 2) DAS28-based low disease activity, good response, remission; 3) scores decreased over the median vs. less than median. Associations between educational background and outcomes were calculated by modified Poisson regressions, at diagnosis and at each of the three standard (3, 6, 12 months) follow-up visits. Results Patients with different educational background had similar symptom durations (195 days) and anti-rheumatic therapies at baseline, and comparable treatment patterns during follow-up. Patients with a high education level had significantly less pain and less functional disability at baseline and throughout the whole follow-up period (VAS-pain: baseline: 49 (28-67) vs. 53 (33-71), p

We asked patients "At what times of the day do you usually take your medicine?" In contrast to compliance interviews dealing with missed doses, this question was previously shown to give valid information. Here we present results from 126 patients on theophyllines three times daily, the most common dosage schedule for these drugs in Sweden in 1978. Only 2% of the patients stated the ideal 8-h intervals between all doses, while 72% had confined all their doses within 12 h. The first and second intervals ranged from 0 to 11 h with a mean of 5.5 and 6.1 h respectively. The third interval varied from 7 to 18 h with a mean of 12.4 h. Patients might benefit more from their therapy by even-spacing of their intake of theophylline.

The purpose of this study was to develop methods to evaluate treatment needs (TNEED) and previous treatment (TDONE) in different populations. In the collaborative study, 'Children's Dental Health in Europe', the methods were used in connection with a clinical examination to document and compare treatment needs in 200 5-year-olds and 200 12-year-olds from each of the 8 participating countries. The study comprised a total of 3200 children from Belgium, Germany, Greece, Ireland, Italy, Scotland, Spain, and Sweden. The method for calculating TNEED was validated by estimation of required time to meet the treatment needs (TNTIME). The calculated TNEED shows a clear relationship with the evaluated TNTIME, and the method is applicable to different population subgroups. The results revealed large differences in both TNEED and TDONE among the different countries and between the two age groups.

Objectives In many epidemiologic studies the subjects rate both the exposure and the outcome, assigning numerical values to the variables according to their perceptions and judgments. Hypothetically, subjects who tend to overestimate, exaggerate, or use high numerical values in rating tasks would rate both exposure and outcome higher than subjects who tend to underestimate, dissimulate, or use low numerical values. A range of such rating behaviors among the subjects would introduce uncontrollable bias to relative risk estimates, in most cases an overestimation. The aim of this study was to assess the possible presence of and effects on relative risk estimates of such high and low rating behavior among subjects in an epidemiologic study of musculoskeletal disorders. Methods Rating behavior was analyzed by intercorrelating the ratings of 19 different stimuli. High positive correlations would indicate the presence of high and low rating behavior. Results The correlations were, however, both positive and negative and close to zero. Adjusting for rating behavior did not affect relative risk estimates, based on subjective ratings of both exposure and outcome. Conclusion There is no support in this study for the existence of a range of high and low rating behavior among subjects who rate neutral and nonaffective stimuli, such as time, weight, number and physical exposure, as well as pain and other symptoms. There is therefore no support for the idea of a bias to relative risk estimates from such rating behavior in studies where subjects rate both exposure and outcome variables of this kind.

In a study in the United States, Sweden, and Hungary, 335 cases of gastric bleeding without predisposing factors were compared with 670 control subjects, and 239 cases of duodenal bleeding were compared with 489 control subjects. For aspirin taken at least every other day during the week before the onset of bleeding (regular use), the relative risk of gastric bleeding was 4.4 (95% confidence interval [CI], 2.9 to 6.7); for occasional use, it was 3.3 (95% CI, 2.1 to 5.0). For ibuprofen, the corresponding estimates were 1.0 (95% CI, 0.4 to 2.6) and 1.1 (95% CI, 0.5 to 2.4). For naproxen, the estimate for regular use was 4.0 (95% CI, 1.5 to 11). The estimates for any use of piroxicam (crude estimate), indomethacin, and diclofenac during the week before onset were 18 (95% CI, 4.1 to 83), 1.6 (95% CI, 0.4 to 5.9), and 0.9 (95% CI, 0.2 to 4.2), respectively. The corresponding relative risks of duodenal bleeding were 7.1 (95% CI, 4.2 to 12) and 2.2 (95% CI, 1.3 to 3.7) for the regular and occasional use of aspirin, 2.4 (95% CI, 0.5 to 11) and 0.8 (95% CI, 0.3 to 2.0) for ibuprofen, 12 (95% CI, 2.8 to 54) and 9.9 (95% CI, 2.3 to 44) for naproxen, 17 (95% CI, 3.6 to 79) for any use of piroxicam (crude estimate), and 1.7 (95% CI, 0.2 to 14) for any use of indomethacin. There was a significant trend in the risk of gastric bleeding with increasing dose of regular aspirin use (p = 0.002). The relative risk estimates for the regular use of 325 mg or less were significantly elevated for both gastric and duodenal bleeding at 3.1 and 6.4, respectively.

Cancer invasion and metastasis occur in a complex three-dimensional (3D) environment, with reciprocal feedback from the surrounding host tissue and vasculature-governing behavior. In this study, we used a novel intravital method that revealed spatiotemporal regulation of Src activity in response to the anti-invasive Src inhibitor dasatinib. A fluorescence lifetime imaging microscopy–fluorescence resonance energy transfer (FLIM-FRET) Src biosensor was used to monitor drug-targeting efficacy in a transgenic p53-mutant mouse model of pancreatic cancer. In contrast to conventional techniques, FLIM-FRET analysis allowed for accurate, time-dependent, live monitoring of drug efficacy and clearance in live tumors. In 3D organotypic cultures, we showed that a spatially distinct gradient of Src activity exists within invading tumor cells, governed by the depth of penetration into complex matrices. In parallel, this gradient was also found to exist within live tumors, where Src activity is enhanced at the invasive border relative to the tumor cortex. Upon treatment with dasatinib, we observed a switch in activity at the invasive borders, correlating with impaired metastatic capacity in vivo. Src regulation was governed by the proximity of cells to the host vasculature, as cells distal to the vasculature were regulated differentially in response to drug treatment compared with cells proximal to the vasculature. Overall, our results in live tumors revealed that a threshold of drug penetrance exists in vivo and that this can be used to map areas of poor drug-targeting efficiency within specific tumor microenvironments. We propose that using FLIM-FRET in this capacity could provide a useful preclinical tool in animal models before clinical translation. Cancer Res; 73(15); 4674–86. ©2013 AACR.