Peter B. Mortensen

Impact of acute biventricular pacing on left ventricular performance and volumes in patients with severe heart failure. A tissue doppler and three-dimensional echocardiographic study.

Objectives: We used tissue velocity imaging (TVI) and three-dimensional echocardiography to evaluate the effect of acute biventricular pacing on left ventricular (LV) performance and volumes in patients with severe heart failure and bundle branch block. Background: Biventricular pacing causes acute hemodynamic improvement in patients with severe heart failure, and QRS duration has been used as a predictor of improved resynchronization. Tissue velocity has the potential of demonstrating the degree of LV resynchronization and three-dimensional echocardiography enables accurate quantitation of LV volumes and function. Methods: TVI and three-dimensional echocardiography were performed during sinus rhythm and biventricular pacing in 25 consecutive patients with severe heart failure. Results: Biventricular pacing significantly improved the extent of contracting myocardium in synchrony by 15.4% and the duration of contraction synchrony by 17% (p < 0.05 for both). Furthermore, end-diastolic and end-systolic volumes decreased by 7 ± 4.5% and 13 ± 6% (p < 0.01) and ejection fraction increased by 22.8 ± 9% (p < 0.01). Baseline duration of QRS and the preejection period as well as the extent of myocardium with asynchronous contraction measured by TVI predicted pacing efficacy. In multivariate analysis, only the extent of myocardium with asynchronous contraction at the LV base predicted biventricular pacing efficacy. Conclusion: Biventricular pacing improves LV systolic performance and reduces LV volumes during short-term treatment. TVI provides important pathophysiological information on the degree of LV resynchronization and may contribute to improved patient selection.

Psychiatric family history and schizophrenia risk in Denmark: which mental disorders are relevant?

BACKGROUND A family history of schizophrenia is the strongest single indicator of individual schizophrenia risk. Bipolar affective disorder and schizo-affective disorders have been documented to occur more frequently in parents and siblings of schizophrenia patients, but the familial occurrence of the broader range of mental illnesses and their role as confounders have not been studied in large population-based samples. METHOD All people born in Denmark between 1955 and 1991 (1.74 million) were followed for the development of schizophrenia (9324 cases) during 28 million person-years at risk. Information of schizophrenia in cohort members and psychiatric history in parents and siblings was established through linkage with the Danish Psychiatric Central Register. Data were analysed using log-linear Poisson regression. RESULTS Schizophrenia was, as expected, strongly associated with schizophrenia and related disorders among first-degree relatives. However, almost any other psychiatric disorder among first-degree relatives increased the individuals risk of schizophrenia. The population attributable risk associated with psychiatric family history in general was 27.1% whereas family histories including schizophrenia only accounted for 6.0%. The general psychiatric family history was a confounder of the association between schizophrenia and urbanization of place of birth. CONCLUSIONS Clinically diagnosed schizophrenia is associated with a much broader range of mental disorders in first-degree relatives than previously reported. This may suggest risk haplotypes shared across many disorders and/or shared environmental factors clustering in families. Failure to take the broad range of psychiatric family history into account may bias results of all risk-factor studies of schizophrenia.

Risk of affective and stress related disorders among employees in human service professions

Objectives: To examine the risk of affective and stress related disorders among men and women employed in human service professions. Methods: Population based case-control study using data from national registers. Cases (n = 28 971) were identified in the Danish Psychiatric Central Research Register among all hospitalised patients and outpatients aged 18–65 who received a first time ever diagnosis of affective (ICD-10, F30–39) or stress related (ICD-10, F40–48) disorder from 1 January 1995 to 31 December 1998. Each case was assigned five never admitted referents (n = 144 855) of the same gender and age, randomly drawn from a 5% sample of the Danish population obtained from Statistics Denmark’s Integrated Database for Labour Market Research. Occupation held the year before matching was classified according to the Danish version of the International Classification of Occupation. Health care, education, social work, and customer services were defined as human service professions and constituted 21% of all employed in the study. Adjusted risks (hazard ratios) relative to all other occupations were calculated for 24 human service occupations. Results: The relative risk of depression in human service professions was 1.35 (95% CI 1.24 to 1.47) for women and 1.49 (95% CI 1.29 to 1.73) for men. The risk of stress was 1.18 (95% CI 1.11 to 1.26) for women and 1.49 (95% CI 1.32 to 1.67) for men. Specific professions contributed differentially to the magnitude of risk, with education and social services displaying the highest risks. No increase in risks was found in customer service occupations. Gender was a significant modifying factor with the highest risk levels in men. Conclusions: There was a consistent association between employment in human service occupations and the risk of affective and stress related disorders. Risks were highest for men working in these typically female professions. More work is needed to distinguish work hazards from effects attributable to selection mechanisms and personality characteristics.

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10−6) and rs8057927 in CDH13 (P=1.39 × 10−5). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10−7). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10−7). This signal was replicated in the follow-up analysis (P=2.3 × 10−2). Significant interaction with maternal CMV infection was found for rs7902091 (PSNP × CMV=7.3 × 10−7) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies.

Rates of preterm birth following antenatal maternal exposure to severe life events: a population-based cohort study

BACKGROUND Preterm birth and other pregnancy complications have been linked to maternal stress during pregnancy. We investigated the association between maternal exposure to severe life events and risk of preterm birth. METHODS Mothers of all singleton live births (n = 1.35 million births) in Denmark between 1 January 1979 and 31 December 2002 were linked to data on their children, parents, siblings and partners. We defined exposure as death or serious illness in close relatives in the first or second trimesters or in the 6 months before conception. Log-linear binomial regression was used to estimate the effect of exposure on preterm birth, very preterm birth and extremely preterm birth. RESULTS There were 58 626 (4.34%) preterm births (<37 weeks), 11 732 (0.87%) very preterm births and 3288 (0.24%) extremely preterm births in the study cohort. Severe life events in close relatives in the 6 months before conception increased the risk of preterm birth by 16% (relative risk, RR = 1.16, [95% CI: 1.08-1.23]). Severe life events in older children in the 6 months before conception increased the risk of preterm birth by 23% (RR = 1.23, [95% CI: 1.02-1.49]) and the risk of very preterm birth by 59% (RR = 1.59, [95% CI: 1.08-2.35]). CONCLUSIONS Our population-based cohort study suggests that maternal exposure to severe life events, particularly in the 6 months before pregnancy, may increase the risk of preterm and very preterm birth.

Cancer risk among users of neuroleptic medication: a population-based cohort study.

It has been suggested that neuroleptic medication may decrease cancer risk. We compared cancer risks in a population-based cohort study of 25 264 users (⩾2 prescriptions) of neuroleptic medications in the county of North Jutland, Denmark, during 1989–2002, with that of county residents who did not receive such prescriptions. Statistical analyses were based on age-standardisation and Poisson regression analysis, adjusting for age, calendar period, COPD, liver cirrhosis or alcoholism, use of NSAID, and, for breast cancer, additionally for use of hormone therapy, age at first birth, and number of children. Use of neuroleptic medications was associated with a decreased risk for rectal cancer in both women and men (adjusted IRRs of 0.61 (95% confidence interval, 0.41–0.91) and 0.82 (0.56–1.19), respectively) and for colon cancer in female users (0.78; 0.62–0.98). Some risk reduction was seen for prostate cancer (0.87; 0.69–1.08), but breast cancer risk was close to unity (0.93; 0.74–1.17). Overall, treatment with neuroleptic medications was not related to a reduced risk of cancer, but for cancers of the rectum, colon and prostate there were suggestive decreases in risk.

The relation between socioeconomic and demographic factors and tumour stage in women diagnosed with breast cancer in Denmark, 1983–1999

The authors investigated the association between socioeconomic position and stage of breast cancer at the time of diagnosis in a nationwide Danish study. All 28 765 women with a primary invasive breast cancer diagnosed between 1983 and 1999 were identified in a nationwide clinical database and information on socioeconomic variables was obtained from Statistics Denmark. The risk of being diagnosed with a high-risk breast cancer, that is size >20 mm, lymph-node positive, ductal histology/high histologic grade and hormone receptor negative, was analysed by multivariate logistic regression. The adjusted odds ratio (OR) for high-risk breast cancer was reduced with longer education with a 12% reduced risk (95% confidence interval (CI), 0.80,0.96) in women with higher education and increased with reduced disposable income (low income group: OR, 1.22; 95% CI, 1.10,1.34). There was an urban–rural gradient, with higher risk among rural women (OR 1.10; 95 % CI, 1.02, 1.18) and lower risk among women in the capital suburbs (OR, 0.85; 95% CI, 0.78, 0.93) and capital area (OR, 0.93; 95% CI, 0.84–1.02). These factors were significant only for postmenopausal women, although similar patterns were observed among the premenopausal women, suggesting a subgroup of aggressive premenopausal breast cancers less influenced by socioeconomic factors.

Increased rates of schizophrenia among immigrants: some methodological concerns raised by Danish findings.

BACKGROUND Several studies during recent years have reported an increased occurrence of schizophrenia in selected immigrant groups. However, difficulties in establishing the population denominator for immigrant rates of mental disorder, selective referral for treatment, and other problems may have influenced such results. The current study aims at testing empirically the influence of some of these methodological problems. METHODS Using nationwide case register data from Denmark, the diagnosis specific first-admission rates were compared between persons born in Denmark and other countries respectively. A case-control design was used to compare schizophrenia risk between different immigrant groups. RESULTS Incidence rates of mental disorders among non-Danish residents calculated from admission data showed increased rates of schizophrenia (RR 1.7) and non-affective functional psychoses (RR 1.9). A case-control analysis utilizing non-psychotic admissions as control for schizophrenic admissions yielded essentially the same result, thus excluding selective referral as the sole explanation of the increased schizophrenia rate. However, this was almost exclusively due to increased rates in individuals born in countries neighbouring on Denmark. CONCLUSIONS While selective risk factors may be operating in various groups of immigrants, caution should be warranted in the interpretation of immigrant studies as large portions of transient visitors may obscure actual rates of mental disorders.

Effects of the Core Functions of Government on the Diversity of Executive Agendas

The distribution of attention across issues is of fundamental importance to the political agenda and outputs of government. This article presents an issue-based theory of the diversity of governing agendas where the core functions of government—defense, international affairs, the economy, government operations, and the rule of law—are prioritized ahead of all other issues. It undertakes comparative analysis of issue diversity of the executive agenda of several European countries and the United States over the postwar period. The results offer strong evidence of the limiting effect of core issues—the economy, government operations, defense, and international affairs—on agenda diversity. This suggests not only that some issues receive more attention than others but also that some issues are attended to only at times when the agenda is more diverse. When core functions of government are high on the agenda, executives pursue a less diverse agenda—focusing the majority of their attention on fewer issues. Some issues are more equal than others in executive agenda setting.

The impact of maternal celiac disease on birthweight and preterm birth: a Danish population-based cohort study

BACKGROUND Adverse pregnancy outcomes have been associated with maternal celiac disease (CD). In this study, we investigate the effect of treated and untreated maternal CD on infant birthweight and preterm birth. METHODS A population-based cohort study consisted of all singleton live births in Denmark between 1 January 1979 and 31 December 2004 was used. A total of 1,504,342 babies were born to 836,241 mothers during the study period. Of those, 1105 babies were born to women with diagnosed CD and 346 were born to women with undiagnosed CD. Women with diagnosed CD were considered as treated with a gluten free diet while women with undiagnosed CD were considered as untreated. The outcome measures were: birthweight, small for gestational age (SGA: birthweight <10th centile), very small for gestational age (VSGA: birthweight <5th centile) and preterm birth. We compared these measures in treated and untreated women with those of a reference group (no history of CD). RESULTS Women with untreated CD delivered smaller babies [difference = -98 g (95% CI: -130, -67)], with a higher risk of SGA infants [OR = 1.31 (95% CI: 1.06, 1.63)], VSGA infants [OR = 1.54 (95% CI: 1.17, 2.03)] and preterm birth [OR = 1.33 (95% CI: 1.02, 1.72)] compared with women without CD. Women with treated CD had no increased risk of reduced mean birthweight, risk of delivering SGA and VSGA infants or preterm birth compared with women without CD. CONCLUSION Untreated maternal CD increases the risk of reduced birthweight, the risk of delivering SGA and VSGA infants and preterm birth. Diagnosis and presumed treatment of maternal CD with a gluten-free diet appeared to result in a birthweight and preterm birth rate similar to those in women without CD.