An editorial in this issue explains that the degree of biological interaction between risk factors is measured as the deviation from additivity by the corresponding disease rates and not for example as deviation from multiplicativity. It is the purpose of this article to describe how a logistic regression model, or a Cox regression model, can be defined in order to produce the output that is needed for assessment of biological interaction. We will also demonstrate how common software can be programmed to deliver this output. Finally, we show how this output can be used as input in an Excel sheet that is set up to calculate the measures of biological interaction to be used for the assessment.

OBJECTIVE -The risk of type 2 diabetes is suggested to be increased for individuals exposed to stress. We analyzed the association of work stress by high demands, low decision latitude, and job strain (combination of high demands and low decision latitude) with type 2 diabetes. We also studied low sense of coherence (SOC) (a factor for successful coping with stressors) in association with type 2 diabetes. Finally, we investigated the combination of SOC and demands or SOC and decision latitude in association with the disease. RESEARCH DESIGN AND METHODS-This cross-sectional study recruited 4,821 healthy Swedish women (aged 35-56 years) residing in five municipalities in the Stockholm area. An oral glucose tolerance test identified 52 women with type 2 diabetes. Relative risks (RRs) with 95% CIs were estimated in a logistic multiple regression analysis.RESULTS -No association was found between high demands and type 2 diabetes (RR 1.1 [CI 0.5-2.2]). Low decision latitude was associated with type 2 diabetes with a RR of 2.2 (1.0 -4.8). The RR of type 2 diabetes with low SOC was 3.7 (1.2-11.2). The combination of low SOC and low decision latitude was associated with type 2 diabetes with a RR of 2.6 (1.2-5.7). Homeostasis model assessment revealed an association of 4.2 (1.2-15.0) between low SOC and insulin resistance.CONCLUSIONS -This study provided new evidence that stress factors such as low decision latitude at work and low SOC were associated with type 2 diabetes in middle-aged Swedish women. Diabetes Care 26:719 -724, 2003A n activation of the hypothalamopituitary-adrenal (HPA) axis and the central sympathetic system has been proposed to be responsible for the development of endocrine perturbations, leading to obesity and type 2 diabetes. Hence, psychosocial stress causes insulin resistance via psychoendocrine pathways (1,2). In addition, increased levels of stress hormones, e.g., catecholamines and glucocorticoids, may impair insulin secretion (3). The risk is specifically evident in genetically susceptible individuals exposed to perceived environmental psychological stress (2). A job stress model, the psychological demand-decision latitude model, introduced by Karasek and colleagues (4,5), has been developed for measuring the impact of work stress on the risk of illness. The combination of high demands and low decision latitude, referred to as job strain, increases the risk of coronary heart disease (5-7). Another parameter, sense of coherence (SOC), developed by Antonovsky (8), is suggested to be an important factor in successful coping with stressors and also for maintenance of health. A person with low SOC is more likely to deal unsuccessfully with stressors (8,9). However, to our knowledge there is no published study on the significance of work stress or SOC in association with type 2 diabetes. The aim of our study was to examine the association of self-reported high demands, low decision latitude, job strain, and low SOC with type 2 diabetes in middle-aged Swedish women. Furthermore, the combination of SO...

Abstract-An impaired fibrinolytic function due to elevated plasma levels of plasminogen activator inhibitor (PAI)-1 activity or tissue plasminogen activator (tPA) antigen is correlated with the development of myocardial infarction (MI) in patients with manifest coronary heart disease. Recently, methods for determining the specific tPA/inhibitor complexes constituting tPA antigen in plasma have become available. In the Stockholm Heart Epidemiology Program (SHEEP) study, 86 of 1212 MI patients, subjected to blood sampling in a metabolically stable period, suffered reinfarction before the end of 1996. These individuals have been compared with an approximately equal number of matched MI patients without recurrence and a group of matched healthy control subjects regarding the plasma concentrations of some hemostatic factors. The hemostatic compounds studied (fibrinogen, von Willebrand factor, tPA antigen, PAI-1, and the tPA/PAI-1 complex) were typically higher in the groups (men and women) with recurrence of MI compared with those without. The plasma concentrations were also typically higher in the pooled groups of patients compared with the groups of healthy control subjects. The largest between-group differences were found for the plasma tPA/PAI-1 complex. The crude odds ratio for reinfarction associated with higher concentration (Ն75th percentile among the control subjects) of tPA/PAI-1 was 1.8 (95% CI 1.1 to 3.1); the corresponding crude odds ratio for von Willebrand factor was 2.3 (1.3 to 4.0). The tPA/PAI-1 complex correlated strongly with PAI-1 and tPA antigen in all groups and with serum triglycerides and body mass index in all groups except for women with reinfarction. An increased plasma level of tPA/PAI-1 complex is a novel risk marker for recurrent MI in men and women. Most likely, increased plasma levels of tPA/PAI-1 complex reflect impaired fibrinolysis, because the correlation with PAI-1 is strong. Further support is obtained indicating that the plasma concentration of von Willebrand factor is also an important risk marker for recurrent MI. Key Words: fibrinolysis Ⅲ hemostasis Ⅲ myocardial infarction Ⅲ risk markers A decreased fibrinolytic activity, which is either due to an increased plasma concentration of plasminogen activator inhibitor (PAI)-1 1-4 or an impaired function to release tissue plasminogen activator (tPA) on exercise, 3 has been demonstrated to be connected to an increased risk of myocardial infarction in studies with prospective designs. The plasma concentration of tPA antigen, which typically correlates well with PAI-1 activity rather than with tPA activity, has turned out to be an even stronger predictor of myocardial infarction. 3,5,6 Only a minor portion of the tPA in plasma is functionally active. The major portion involves tPA in complex with various inhibitors, such as PAI-1, anti-plasmin, and C1 inhibitor. We have recently developed 2-site ELISA methods to specifically measure these complexes in plasma. 7 It was found that tPA antigen correlated strongly with the tPA/PAI-1 compl...

ObjectiveWe conducted a nationwide case-control study in Sweden to test the hypothesis that specific clinical characteristics are associated with increased risk of sudden unexpected death in epilepsy (SUDEP).MethodsThe study included 255 SUDEP cases (definite and probable) and 1,148 matched controls. Clinical information was obtained from medical records and the National Patient Register. The association between SUDEP and potential risk factors was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) and interaction assessed by attributable proportion due to interaction (AP).ResultsExperiencing generalized tonic-clonic seizures (GTCS) during the preceding year was associated with a 27-fold increased risk (OR 26.81, 95% CI 14.86–48.38), whereas no excess risk was seen in those with exclusively non-GTCS seizures (OR 1.15, 95% CI 0.54–48.38). The presence of nocturnal GTCS during the last year of observation was associated with a 15-fold risk (OR 15.31, 95% CI 9.57–24.47). Living alone was associated with a 5-fold increased risk of SUDEP (OR 5.01, 95% CI 2.93–8.57) and interaction analysis showed that the combination of not sharing a bedroom and having GTCS conferred an OR of 67.10 (95% CI 29.66–151.88), with AP estimated at 0.69 (CI 0.53–0.85). Among comorbid diseases, a previous diagnosis of substance abuse or alcohol dependence was associated with excess risk of SUDEP.ConclusionsIndividuals with GTCS who sleep alone have a dramatically increased SUDEP risk. Our results indicate that 69% of SUDEP cases in patients who have GTCS and live alone could be prevented if the patients were not unattended at night or were free from GTCS.