Dynamic path analysis – a useful tool to investigate mediation processes in clinical survival trials

When it comes to clinical survival trials, regulatory restrictions usually require the application of methods that solely utilize baseline covariates and the intention‐to‐treat principle. Thereby, much potentially useful information is lost, as collection of time‐to‐event data often goes hand in hand with collection of information on biomarkers and other internal time‐dependent covariates. However, there are tools to incorporate information from repeated measurements in a useful manner that can help to shed more light on the underlying treatment mechanisms. We consider dynamic path analysis, a model for mediation analysis in the presence of a time‐to‐event outcome and time‐dependent covariates to investigate direct and indirect effects in a study of different lipid‐lowering treatments in patients with previous myocardial infarctions. Further, we address the question whether survival in itself may produce associations between the treatment and the mediator in dynamic path analysis and give an argument that because of linearity of the assumed additive hazard model, this is not the case. We further elaborate on our view that, when studying mediation, we are actually dealing with underlying processes rather than single variables measured only once during the study period. This becomes apparent in results from various models applied to the study of lipid‐lowering treatments as well as our additionally conducted simulation study, where we clearly observe that discarding information on repeated measurements can lead to potentially erroneous conclusions. Copyright © 2015 John Wiley & Sons, Ltd.     

Income-related health inequalities in the Nordic countries: examining the role of education, occupational class, and age

Numerous studies have concluded that people's socioeconomic position is related to mortality and morbidity, but that the strength of this association varies considerably both within and between European regions. This has spurred several researchers to more closely examine educational and occupational gradients in health in the Nordic countries to clarify the causes of cross-national differences. However, comparable studies using income as an indicator of socioeconomic position are still lacking. This study uses recent and highly comparable data to fill this gap. The aim of this study is threefold. First, we ask to what extent there is an income gradient in health in the Nordic countries, and to what extent the association differs between these countries. Second and third, we examine whether differences in the attenuation of the income gradient by education and occupational class, and age-specific differences between countries, may act as explanations for differences in the income gradient between the Nordic countries. The data source are three waves of the European Social Survey (ESS, 2002/2004/2006), which included 17,801 people aged 25 and over from Denmark, Finland, Norway, and Sweden. Two subjective health measures (physical/mental self reported health and limiting longstanding illness) were analysed by means of logistic regression. The results show that, in all countries, people reported significantly better health and were less likely to suffer from longstanding illness as they had a higher income. This association is strongest in Norway and Finland and weakest in Denmark. The income gradient in health, but not country differences in this gradient, is partly explained by education and occupational class. Additionally, the strength of the income gradient in health varies between age groups. The relatively high health inequalities between income groups in Norway and Finland are already visible in the youngest age groups. The results imply that the socioeconomic gradient in health will arguably not be strongly reduced in the near future as a result of cohort replacement, as has been suggested in previous studies. Health policy interventions may be particularly important five to ten years prior to retirement and in early adulthood.     

Variations in relative health inequalities: are they a mathematical artefact?

Background

Substantial research has documented variations in the magnitude of relative socioeconomic differences in health across European countries, and within countries, across different age groups. The aim of this paper is to examine to what extent these variations are determined by differences in the overall rate or prevalence of a health outcome across countries and age-groups in the total population.

Methods

Three surveys (European Social Survey, and two different population census-mortality registry linked longitudinal data) were used. We plotted rates of mortality and prevalence of poor self-rated health against ratios of mortality and morbidity prevalence associated with educational level. We calculated Pearson coefficients to examine the magnitude of correlations.

Results

We found a significant negative correlation between total mortality rates and associated rate ratios of mortality by education in the SEDHA study (r = -0.40, p = 0.04), but not in the HUNT study (r = -0.37, p = 0.06). There was a weaker but significant negative correlation between the prevalence of poor health and associated prevalence ratios by education in the European social survey (r = -0.22, p = 0.00). Correlations increased as underlying prevalence and rates increased, while they were weaker or null at low prevalence or rates.

Conclusion

We found some evidence that the magnitude of relative inequalities in mortality and morbidity is negatively correlated with underlying morbidity prevalence and mortality rates. Although correlations are moderate, underlying morbidity prevalence and mortality rates should be taken into account in the interpretation of variations in relative health inequalities among populations.     

Residence near power lines and the risk of birth defects

BACKGROUND: There has been some concern that exposure to electromagnetic fields may cause birth defects. We studied risks of birth defects by residential exposure to 50-Hz magnetic fields from power lines. METHODS: We estimated the distance between residence and power lines for 161,844 Norwegian residences, and their corresponding magnetic fields in the period 1980 to 1997. Risks of 24 categories of birth defects were compared across exposure levels, adjusting for social and demographic variables. RESULTS: Among those living near power lines, the greatest reductions in risk were for cardiac defects (odds ratio = 0.5; 95% confidence interval = 0.3-0.9) and respiratory defects (0.4; 0.2-0.9). The largest increase in risk was for esophageal defects (2.5; 1.0-5.9). Other associations were weaker and had wide confidence intervals. CONCLUSIONS: There was little evidence that residence near power lines affected the risk of birth defects. The observed decreased risks of cardiac and respiratory defects and the increased risk of esophageal defects should be interpreted with caution given the number of endpoints, the imprecision in the calculations of the distance from the residence to the power line, and the limited information on pregnant women's change of residence.     

Intensive Quality Assurance of Therapist Adherence to Behavioral Interventions for Adolescent Substance Use Problems

This study was a cross-cultural replication of a study that investigated therapist adherence to behavioral interventions as a result of an intensive quality assurance system which was integrated into Multisystemic Therapy (MST). Thirty-three therapists and eight supervisors were block randomized to either an Intensive Quality Assurance or a Workshop Only condition. Twenty-one of these therapists treated 41 cannabis-abusing adolescents and their families. Therapist adherence and youth drug screens were collected during a 5-month baseline period prior to the workshop on contingency management and during 12 months post workshop. The results replicated the previous finding that intensive quality assurance enhanced therapist adherence over workshop, to cognitive-behavioral techniques, but not to contingency management. While the clinical impact of such quality assurance remains to be demonstrated, cannabis abstinence increased as a function of time in therapy, and was more likely with stronger adherence to contingency management, but did not differ across quality assurance interventions.     

Variations in labor supply between female and male hospital physicians: Results from a modern welfare state

In industrialized countries, female physicians have up to 10h lower labor supply a week than male physicians. At the same time, the number of female physicians is increasing. The question analyzed in this article is whether these differences in labor supply for female and male hospital physicians persist in a modern welfare society, such as Norway, where comprehensive welfare reforms aim to reduce gender inequality are implemented. Information on weekly working hours from all hospital physicians in Norway during the period 2001-2007 was merged with economic variables (wages, income from other sources, net personal dept), demographic variables (age, sex, marital status, children born in the year, number of children), managerial positions and variables describing the hospital, specialty and time (year). The estimation method employed both random and fixed-effects models. Labor supply for women was 10-11 percent or 4-4.5h per week lower than among men. The effects of children diverged strongly between the sexes. For instance, childbirth in a given year reduced the supply of working hours by women by approximately 80% but had no effects for men. After controlling for children and other factors, female physicians worked some 3-4% or 1-1.5 fewer hours than comparable male physicians. Although significant, variation in labor supply between female and male physicians is much lower in Norway then in other advanced industrialized countries.     

Pig herds free from human pathogenic Yersinia enterocolitica

Pork products are a substantial source of human yersiniosis, a foodborne disease caused by Yersinia enterocolitica. Thus, the ability to eliminate this agent from pig herds would be an important step in producing human pathogen-free pork. Pig herds free from Y. enterocolitica O:3/biovar 4 have been established and maintained. According to serologic and cultural testing results, 15 of 16 specific pathogen-free herds were free from Y. enterocolitica O:3/biovar 4; this closed breeding pyramid has remained free from this organism since 1996. Pig herds free from human pathogenic Y. enterocolitica suggest that human pathogen-free herds could be attained to provide pork free from zoonotic agents.     

Osteotomy for femoral anteversion: A prospective 9-year study of 52 children

Fifty-two children with increased femoral anteversion had bilateral derotational subtrochanteric osteotomies at a mean age of 7 years. They were followed prospectively until at least 15 years of age; the mean observation time was 9 years. They were a subset of 95 children whose 2-year results were reported in 1989. The mean increase of femoral anteversion after the osteotomy was 6° (0.7° per year) and of the neck-shaft angle 5°. The CE angle did not increase. Although we at present practice a more restrictive attitude towards operation of increased femoral anteversion, our study showed that a derotational osteotomy is effective in eliminating the intoeing gait and associated complaints, and the hip angles change only moderately during the remaining period of growth.     

Sublingual Nitroglycerin Delays Arterial Wave Reflections Despite Increased Aortic “Stiffness” in Patients with Hypertension: A Doppler Echocardiography Study

Venodilatation with consequent reduction in left ventricular filling and end-diastolic wall stress is an important mechanism for the beneficial effects of nitroglycerin in ischemic heart disease and in left ventricular failure. The effects of sublingual nitroglycerin on arterial pulsatile hemodynamics are less well defined. Doppler echocardiography and the calibrated subclavian artery pulse tracing were used to assess hemodynamics in subjects with sustained arterial hypertension (n = 25) before and 5 to 10 minutes after sublingual deposition of 0.5 mg glyceryl trinitrate. Aortic characteristic impedance was calculated by averaging the modulus of the input impedance (ratio of pressure to flow) at high frequencies and by calculating the ratio of pressure and flow increments during upstroke. The pressure wave was split into forward and backward components, and the reflection coefficient (the ratio of backward to forward pressures) was calculated. Parameters of the arterial bed were estimated by using 2- and 3-element Windkessel models. Nitroglycerin delayed the return of arterial wave reflections by 17% (P =.02) and increased aortic characteristic impedance by 20% (P =. 01), but it did not influence total arterial compliance. Mean arterial pressure decreased 7% (P =.0001), but pulse pressure did not change. Stroke volume and the acceleration time of aortic root flow decreased by 13% (P =.0001) and 8% (P =.01), respectively. Cardiac output decreased 7% (P =.01), despite an increase in heart rate of 10% (P =.0001). Peripheral resistance tended to decrease (4%, P =.06). Thus, in subjects with sustained hypertension, sublingual nitroglycerin dilates peripheral, predominantly muscular arteries with a subsequent delayed return of reflected pressure waves. Reflex activation of the sympathetic nervous system with consequent increased acceleration of left ventricular ejection seems to counteract the effect of reduced mean arterial pressure (distending pressure) with respect to the "stiffness" of the aorta.