Return to work: does cardiac rehabilitation make a difference? Danish nationwide register-based study.

AIM: to assess whether participation in cardiac rehabilitation affects the probability of returning to work after ischaemic heart disease. METHODS: the study population consisted of 24,509 patients (18-70 years of age) discharged from an inpatient admission at a Danish hospital during 2014-2018 and who were working before their admission. Only patients with a percutaneous coronary intervention or coronary artery bypass grafting surgery procedure and ICD-10 codes I20-I25 as their main diagnosis or ICD-10 codes I21, I240, I248 or I249 as secondary diagnosis during an emergency admission were included. Exposure was defined as participation in cardiac rehabilitation (N = 15,742), and binary indicator of being at work in the last week of a given month were used as primary outcomes. Coarsened exact matching (CEM) of exposed and unexposed patients was used to reduce selection bias. Logistic regression models were applied on the matched population (N = 15,762). RESULTS: Less deprived and less comorbid patients were more likely to receive cardiac rehabilitation. CEM succeeded in arriving at a population where this selection was reduced and in this population we found that patients who received cardiac rehabilitation had a lower probability of returning to work after 3 months (OR 0.81, 95%CI: 0.77-0.84), a higher but insignificant probability after 6 (OR 1.02, 95%CI: 0.97-1.08), and a higher probability after 9 (OR 1.08, 95%CI: 1.02-1.15) and 12 months (OR 1.20, 95%CI: 1.13-1.28). CONCLUSIONS: Deprived and comorbid patients have lower use of cardiac rehabilitation. In a matched population where this bias is reduced, cardiac rehabilitation will increase the probability of returning to work.

Effects of screening for anxiety and depression in patients with ischaemic heart disease - a nationwide Danish register study.

AIM: To investigate the effect of screening for anxiety and depression (AD) in patients with ischaemic heart disease (IHD) on the likelihood of receiving treatment for AD. METHODS: We used a nationwide dataset of all Danish patients with an incident IHD diagnosis in the period 2015-2018 (N = 80,701) of which 20,461 (25%) were exposed to screening for AD as part of cardiac rehabilitation. A binary composite indicator for the use of any AD treatment (prescriptions of AD drugs, general practitioner (GP) counselling or referral to a psychologist), was modelled as the dependent variable. The probability of receiving AD treatment was estimated using linear probability and instrumental variable regression models. RESULTS: Exposure to AD screening was lower for patients with low income (change in probability -0.67, 95% CI -0.76; -0.59), low education (change in probability -0.16, 95% CI -0.20; -0.13), and a high comorbidity burden (change in probability -0.09, 95% CI -0.10; -0.07). Screened patients had a lower conditional probability of AD treatment (change in probability -0.0061, p < 0.001) than non-screened patients. The patient's GP also had an impact on the probability of being referred for AD treatment. Using an instrumental variable approach did not affect the results. CONCLUSIONS: Screening for AD was subject to selection at the patient level; patients at lower risk of AD had a higher probability of being screened. Hence, extending systematic screening to cover a larger population may not achieve a noticeable increase in the uptake of AD treatment if it is not supported by appropriate measures to reduce reverse selection into screening.

Co-payment and adolescents' use of psychologist treatment: Spill over effects on mental health care and on suicide attempts.

The literature around co-payment shows evidence of increasing consumption following reduced co-payment. We apply difference-in-difference methods to assess the effect of abolishing the co-payment on psychologist treatment of anxiety and depression in 18 to 21-year olds. We apply nationwide individual level data with individuals close to this age interval as control group. The population amounts to approximately 1.2 million individuals and a total of 51 million patient months of observations. We show that after removing co-payment, the use of psychologist treatment almost doubles. We find that this increase involves moderately positive spill over effects on outpatient psychiatric care and on prescriptions of antidepressants. In the heterogeneity analysis we find evidence of higher effects on adolescents from families with lower income, indicating that reduced co-payments may increase equality in access. We also see that effects are higher for individuals listed with general practitioners (GPs) with a reluctant referral style; indicating that these GPs' behavior is affected by patient co-payment rates. Interestingly, we find evidence of significant reductions in suicide attempts - primarily among high-income women and low-income men. This indicates that better access to mental health care for adolescents may have a positive impact on their mental health and well-being.

Socioeconomic consequences of traumatic and non-traumatic spinal cord injuries: a Danish nationwide register-based study.

STUDY DESIGN: A nationwide population-based register study. OBJECTIVES: To investigate the socioeconomic consequences of traumatic (tSCI) and non-traumatic (ntSCI) spinal cord injuries (SCI) in relation to health care costs, risk of job loss, and divorce. SETTING: Denmark. METHODS: All survivors admitted for specialized SCI rehabilitation from 2008 to 2018 were included (n = 1751), together with their relatives (n = 3084). Control groups for the SCI group (n = 8139) and their relatives (n = 15,921) were identified. Data on socioeconomics up to 2 years before and up to 4 years after the injury year were included. RESULTS: Survivors of tSCI and ntSCI had significantly increased health care costs 2 years before injury compared to their controls, and increased health care cost was maintained 4 years after the injury (all p values < 0.0001). The SCI group had significantly increased risk of job loss (OR = 9.26; 95% CI: 7.70-11.15) and higher risk of divorce (OR = 1.44; 95% CI: 1.08-1.87) the 3 following years after injury compared to controls, but risk of divorce was only significant for the ntSCI group (OR = 1.58; 95% CI: 1.09-2.29). No significant differences on health care cost and job loss between the group of relatives of SCI survivors and their controls were found, except for the relatives (n = 1604) of SCI survivors <18 years old, where a higher risk of job loss was found (OR = 1.43, 95% CI 0.97-2.1). CONCLUSION: These results emphasize that socioeconomic consequences for survivors of both tSCI and ntSCI are pervasive and long-lasting.

Cost-effectiveness analysis of a supported employment intervention for people with mood and anxiety disorders in Denmark - the IPS-MA intervention.

OBJECTIVES: We aimed to investigate the cost-utility and cost-effectiveness of a modified Individual Placement and Support intervention for people with mood and anxiety disorders (IPS-MA). METHODS: Costs were assessed from a societal perspective. Health care costs were derived from registers and combined with data on use of IPS-MA services, municipal social care, and labour market services. EQ-5D was used to compute QALY. Missing data were imputed in a sensitivity analysis. We also computed the cost per gain in hours worked. Incremental cost-effectiveness ratios (ICER) were computed and bootstrapped to obtain confidence intervals for QALY and gain in hours worked. RESULTS: We found no difference in overall costs between groups. A significant saving was found in use of labour market services in the IPS-MA group. But the IPS-MA group had significantly lower wage earnings compared to the control group. The intervention group had a higher, though statistically in-significant, increase in QALYs than the control group. The ICER did not show statistically significant results, but there was a tendency, that IPS-MA could have a positive effect on health-related quality of life without any additional costs. However, participants in the IPS-MA group had a significantly lower gain in hours worked compared to the control group. CONCLUSIONS: Despite a significant saving in use of labour market services, IPS-MA was not cost-effective. Participants in the IPS-MA group worked significantly fewer hours and earned significantly less than participants in the control group at 1-year follow-up.

Psychiatric and Physical Health Outcomes Associated with Interpersonal Violence: A Propensity Score Matching Approach.

This study examined the association between interpersonal violence and a range of psychiatric and physical health outcomes and assessed whether these associations changed when controlling for a stress-related diagnosis. An observational case-control study was conducted on a sample of 4,059 victims of violence. Using propensity score matching a number of risk factors (assessed five years prior assault) were used. Controls were matched 10:1 using the Danish Central Registry System. Outcomes were ICD-10 diagnoses of a range of psychiatric and physical health outcomes in the 15 years post-injury. Statistically significant associations were found for all psychiatric conditions and a diagnosis of a drug or substance misuse disorder. These findings remained even after controlling for a diagnosis of a stress-related disorder. Large scale case-control studies using the Danish nationwide registers enables a powerful way of assessing the relative impact of exposure to interpersonal violence on the development of psychiatric and physical health problems.

Quality of life, psychological distress and violence among women in close relationships: a population-based study in Finland.

BACKGROUND: The aim of this study was to examine associations between exposure to violence, quality of life, and psychological distress. Women aged 19-54 years who had been exposed to violence by someone in a close relationship were compared with women unexposed to violence in Finland. We also aimed to investigate associations between different forms of violence (physical, sexual, emotional, or any combination of these) with quality of life and psychological distress. METHODS: We selected a sample of 22,398 women who had returned self-completed questionnaires from a Finnish population-based health survey between 2013 and 2016. Exposure to violence during the past year was assessed through specific questions from the survey. The EUROHIS-QOL 8-item index was used to measure quality of life, and ordinary least square regressions were fitted. The mental health inventory (MHI-5) was used to measure psychological distress. We investigated associations with multivariate logistic regression analysis. RESULTS: Among women in Finland, the prevalence of exposure to violence in any type of close relationship during the past year was 7.6%. Women who had been exposed to violence had significantly worse scores of the EUROHIS-QOL 8-item index, and psychological distress was significantly worse (p < 0.001), compared with unexposed women. Strong associations were found between combinations of violence and both quality of life (coefficient - 0.51, p < 0.001) and mental health (odds ratio 4.16, 95% confidence interval 3.44-5.03). Compared with women who had been exposed to violence by a stranger, women who had been exposed to violence by someone in a close relationship had significantly lower quality-of-life scores (p < 0.001). CONCLUSIONS: This study found that experience of close relationship violence had a negative influence on both quality of life and psychological distress among women in the general Finnish population. Comparison with victims of violence by strangers shows that some of the lower quality-of-life scores among victims are driven by the perpetrator and victim being in a close relationship. Preventive policies in primary care settings aimed at screening and educating young people should be considered as an early form of intervention to reduce the negative mental health consequences of violence.

A performance comparison of patient pathways in Nordic capital areas - a pilot study for ischaemic stroke patients.

Aims: This article describes and discusses the extension of performance measurement using an episode-based approach so that the measurement includes primary care, and social and long-term-care services. By using data on incident stroke patients from the capital areas of four Nordic countries, this pilot study: (a) extended the disease-based performance analysis to include new indicators that better describe patient care pathways at different levels of care; (b) described and compared the performance of care given in the four areas; (c) evaluated how additional information changed the rankings of performance between the areas; and (d) described the trends in performance in the capital areas. Methods: The construction of data was based on a common protocol that used routinely collected national registers and statistics linked with local municipal registers. We created new variables describing the timing of discharge to home and institutionalisation, as well as describing the use and cost of primary and social hospital services. Risk adjustment was performed with four different sets of confounders. Results: Differences existed in various performance indicators between the four metropolitan areas. The ranking was sensitive to the risk-adjustment method. The study showed that for stroke patients a performance comparison with data that are only from secondary and tertiary care, and without a valid severity measure, is not sufficient for international comparisons. Conclusions: Extending and deepening international performance analysis in order to cover patient pathways, including primary care and social services, is very useful for benchmarking activities when focusing on diseases affecting older people.

Post-hospital medical respite care for homeless people in Denmark: a randomized controlled trial and cost-utility analysis.

BACKGROUND: Being homeless entails higher mortality, morbidity, and prevalence of psychiatric diseases. This leads to more frequent and expensive use of health care services. Medical respite care enables an opportunity to recuperate after a hospitalization and has shown a positive effect on readmissions, but little is known about the cost-effectiveness of medical respite care for homeless people discharged from acute hospitalization. Therefore, the aim of the present study was to investigate the cost-effectiveness of a 2-week stay in post-hospital medical respite care. METHODS: A randomized controlled trial and cost-utility analysis, from a societal perspective, was conducted between April 2014 and March 2016. Homeless people aged > 18 years with an acute admission were included from 10 different hospitals in the Capital Region of Denmark. The intervention group (n = 53) was offered a 2-week medical respite care stay at a Red Cross facility and the control group (n = 43) was discharged without any extra help (usual care), but with the opportunity to seek help in shelters and from street nurses and doctors in the municipalities. The primary outcome was the difference in health care costs 3 months following inclusion in the study. Secondary outcomes were change in health-related quality of life and health care costs 6 months following inclusion in the study. Data were collected through Danish registries, financial management systems in the municipalities and at the Red Cross, and by using the EQ-5D questionnaire. RESULTS: After 3 and 6 months, the intervention group had €4761 (p = 0.10) and €8515 (p = 0.04) lower costs than the control group, respectively. Crude costs at 3 months were €8448 and €13,553 for the intervention and control group respectively. The higher costs in the control group were mainly related to acute admissions. Both groups had minor quality-adjusted life year gains. CONCLUSIONS: This is the first randomized controlled trial to investigate the cost-effectiveness of a 2-week medical respite care stay for homeless people after hospitalization. The study showed that the intervention is cost-effective. Furthermore, this study illustrates that it is possible to perform research with satisfying follow-up with a target group that is hard to reach. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02649595.

Costs associated with adverse events among acute patients.

BACKGROUND: The aim of this study was to analyse the additional treatment costs of acute patients admitted to a Danish hospital who suffered an adverse event (AE) during in-hospital treatment. METHODS: A matched case-control design was utilised. Using a combination of trigger words and patient record reviews 91 patients exposed to AEs were identified. Controls were identified among patients admitted to the same department during the same 20-month period. The matching was based on age, gender, and main diagnosis. Cost data was extracted from the Danish National Cost Database for four different periods after beginning of the admission. RESULTS: Patients exposed to an AE were associated with higher mean cost of EUR 9505 during their index admission (p = 0.014). For the period of 6 months from the beginning of the admission minus the admission itself they were associated with higher mean cost of EUR 4968 (p = 0.016). For the period from the 7th month until the end of the 12th month there was no statistically significant difference (p = 0.104). For the total period of 12 month, patients exposed to an AE were associated with statistically significant higher mean cost of EUR 13,930 (p = 0.001). CONCLUSIONS: AEs are associated with significant hospital costs. Our findings suggest that a follow-up period of 6 months is necessary when investigating the costs associated with AEs among acute patients. Further research of specific types of AEs and the costs of preventing these types of AEs would improve the understanding of the relationship between adverse events and costs.

Incident users of antipsychotics: who are they and how do they fare?

PURPOSE: In Denmark, as well as in many other countries, consumption of antipsychotics is on the rise, partly due to increasing off-label use. The aim of this study was to analyze and quantify the extent of off-label use and polypharmacy in incident users of antipsychotic medication, and to examine initial antipsychotic prescribing patterns and associated use of mental health care services. METHOD: Population-based cohort study linking the following Danish national registers: the Central Psychiatric Research Register, the Register of Medicinal Product Statistics, and Statistics Denmark. RESULTS: From 2007 to 2012, 154,351 Danish subjects initiated treatment with antipsychotics. Among these, 71,254 (46 %) subjects had a psychiatric diagnosis recorded. The most frequent diagnoses were reaction to severe stress and adjustment disorders (10,106; 14 %), depressive episode (8876; 12 %), and recurrent depressive disorder (6810; 10 %). We found high antipsychotic discontinuation rates during the first few months (45 % in 4 months) and frequent antidepressant co-prescribing from treatment onset (47 %). Significantly greater likelihood of psychiatric hospitalization was observed for antipsychotic polypharmacy (HR 1.38; 95 % CI 1.32-1.45), whereas antipsychotic discontinuation was associated with decreased hospitalization risk in most off-label conditions. CONCLUSIONS: The brief duration of most antipsychotic prescriptions suggests that antipsychotics are prescribed more liberally than recommended. As a consequence of the range of adverse effects associated with antipsychotic drug use, the documented widespread off-label prescribing practices warrant careful monitoring for adverse effects and prompt discontinuation in case of an unfavorable risk-benefit ratio.

Costs and Quality at the Hospital Level in the Nordic Countries.

This article develops and analyzes patient register-based measures of quality for the major Nordic countries. Previous studies show that Finnish hospitals have significantly higher average productivity than hospitals in Sweden, Denmark, and Norway and also a substantial variation within each country. This paper examines whether quality differences can form part of the explanation and attempts to uncover quality-cost trade-offs. Data on costs and discharges in each diagnosis-related group for 160 acute hospitals in 2008-2009 were collected. Patient register-based measures of quality such as readmissions, mortality (in hospital or outside), and patient safety indices were developed and case-mix adjusted. Productivity is estimated using bootstrapped data envelopment analysis. Results indicate that case-mix adjustment is important, and there are significant differences in the case-mix adjusted performance measures as well as in productivity both at the national and hospital levels. For most quality indicators, the performance measures reveal room for improvement. There is a weak but statistical significant trade-off between productivity and inpatient readmissions within 30 days but a tendency that hospitals with high 30-day mortality also have higher costs. Hence, no clear cost-quality trade-off pattern was discovered. Patient registers can be used and developed to improve future quality and cost comparisons.

Costs of traffic injuries.

OBJECTIVE: The aim of this study was to analyse the socioeconomic costs of traffic injuries in Denmark, notably the healthcare costs and the productivity costs related to traffic injuries, in a bottom-up, register-based perspective. METHOD: Traffic injury victims were identified using national emergency room data and police records. Victims were matched with five controls per case by means of propensity score, nearest-neighbour matching. In the cohort, consisting of the 52 526 individuals that experienced a traffic injury in 2000 and 262 630 matched controls, attributable healthcare costs were assessed using Danish national healthcare registers. Productivity costs were computed using duration analysis (Cox regression models). In a subanalysis, cost per severe traffic injury was computed for the 12 995 individuals that experienced a severe injury. RESULTS: The socioeconomic cost of a traffic injury was €1406 (2009 price level) in the first year, and €8950 over a 10-year period. Per 100 000 population, the 10-year cost was €6 565 668. A severe traffic injury costs €4969 per person in the first year, and €4 006 685 per 100 000 population over a 10-year period. Victims of traffic injuries are younger and generally worse off, compared to the general population. CONCLUSIONS: Prevention of traffic injuries could result in societal savings. The bottom-up, register-based approach renders more precise figures for these savings. The socioeconomic profile of injury victims differs from that of the general population on most parameters.

The DOMUS study protocol: a randomized clinical trial of accelerated transition from oncological treatment to specialized palliative care at home.

BACKGROUND: The focus of Specialized Palliative Care (SPC) is to improve care for patients with incurable diseases and their families, which includes the opportunity to make their own choice of place of care and ultimately place of death. The Danish Palliative Care Trial (DOMUS) aims to investigate whether an accelerated transition process from oncological treatment to continuing SPC at home for patients with incurable cancer results in more patients reaching their preferred place of care and death. The SPC in this trial is enriched with a manualized psychological intervention. METHODS/DESIGN: DOMUS is a controlled randomized clinical trial with a balanced parallel-group randomization (1:1). The planned sample size is 340 in- and outpatients treated at the Department of Oncology at Copenhagen University Hospital. Patients are randomly assigned either to: a) standard care plus SPC enriched with a standardized psychological intervention for patients and caregivers at home or b) standard care alone. Inclusion criteria are incurable cancer with no or limited antineoplastic treatment options. DISCUSSION: Programs that facilitate transition from hospital treatment to SPC at home for patients with incurable cancer can be a powerful tool to improve patients' quality of life and support family/caregivers during the disease trajectory. The present study offers a model for achieving optimal delivery of palliative care in the patient's preferred place of care and attempt to clarify challenges. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01885637.

Health-Related Costs of Intimate Partner Violence: Using Linked Police and Health Registers.

This study aims to estimate direct health-related costs for victims of intimate partner violence (IPV) using nationwide linked data based on police reports and two healthcare registers in Finland from 2015 to 2020 (N = 21,073). We used a unique register dataset to identify IPV victims from the data based on police reports and estimated the attributable costs by applying econometric models to individual-level data. We used exact matching to create a reference group who had not been exposed to IPV. The mean, unadjusted, attributable healthcare cost for victims of IPV was €6,910 per individual over the 5-year period after being first identified as a victim. When adjusting for gender, age, education, occupation, and mental-health- and pregnancy-related diagnoses, the mean attributable health-related cost for the 5 years was €3,280. The annual attributable costs of the victims were consistently higher than those for nonvictims during the entire study period. Thus, our results suggest that the adverse health consequences of IPV persist and are associated with excess health service use for 5 years after exposure to IPV. Most victims of IPV were women, but men were also exposed to IPV, although the estimates were statistically significant only for female victims. Victims of IPV were over-represented among individuals outside the labor force and lower among those who were educated. The total healthcare costs of victims of IPV varied according to the socioeconomic factors. This study highlights the need for using linked register data to understand the characteristics of IPV and to assess its healthcare costs. The study results suggest that there is a significant socioeconomic gradient in victimization, which could also be useful to address future IPV prevention and resource allocation.

Magnesium sulphate for fetal neuroprotection: a cost-effectiveness analysis.

BACKGROUND: The aim of this study was to assess the cost-effectiveness of administering magnesium sulphate to patients in whom preterm birth at < 32+0 weeks gestation is either imminent or threatened for the purpose of fetal neuroprotection. METHODS: Multiple decision tree models and probabilistic sensitivity analyses were used to compare the administration of magnesium sulphate with the alternative of no treatment. Two separate cost perspectives were utilized in this series of analyses: a health system and a societal perspective. In addition, two separate measures of effectiveness were utilized: cases of cerebral palsy (CP) averted and quality-adjusted life years (QALYs). RESULTS: From a health system and a societal perspective, respectively, a savings of $2,242 and $112,602 is obtained for each QALY gained and a savings of $30,942 and $1,554,198 is obtained for each case of CP averted when magnesium sulphate is administered to patients in whom preterm birth is imminent. From a health system perspective and a societal perspective, respectively, a cost of $2,083 is incurred and a savings of $108,277 is obtained for each QALY gained and a cost of $28,755 is incurred and a savings of $1,494,500 is obtained for each case of CP averted when magnesium sulphate is administered to patients in whom preterm birth is threatened. CONCLUSIONS: Administration of magnesium sulphate to patients in whom preterm birth is imminent is a dominant (i.e. cost-effective) strategy, no matter what cost perspective or measure of effectiveness is used. Administration of magnesium sulphate to patients in whom preterm birth is threatened is a dominant strategy from a societal perspective and is very likely to be cost-effective from a health system perspective.

Characterisation of FAP-1 expression and CD95 mediated apoptosis in the A818-6 pancreatic adenocarcinoma differentiation system.

The present study investigated the expression and localisation of FAP-1 (Fas associated phosphatase-1) and CD95 in a 3D differentiation model in comparison to 2D monolayers of the pancreatic adenocarcinoma cell line A818-6. Under non-adherent growth conditions, A818-6 cells differentiate into 3D highly organised polarised epithelial hollow spheres, resembling duct-like structures. A818-6 cells showed a differentiation-dependent FAP-1 localisation. Cells grown as 2D monolayers revealed FAP-1 staining in a juxtanuclear cisternal position, as well as localisation in the nucleus. After differentiation into hollow spheres, FAP-1 was relocated towards the actin cytoskeleton beneath the outer plasma membrane of polarised cells and no further nuclear localisation was observed. CD95 surface staining was found only in a subset of A818-6 monolayer cells, while differentiated hollow spheres appeared to express CD95 in all cells of a given sphere. We rarely observed co-localisation of CD95 and FAP-1 in A818-6 monolayer cells, but strong co-localisation beneath the outer plasma membrane in polarised cells. Analysis of surface expression by flow cytometry revealed that only a subset (36%) of monolayer cells showed CD95 surface expression, and after induction of hollow spheres, CD95 presentation at the outer plasma membrane was reduced to 13% of hollow spheres. Induction of apoptosis by stimulation with agonistic anti-CD95 antibodies, resulted in increased caspase activity in both, monolayer cells and hollow spheres. Knock down of FAP-1 mRNA in A818-6 monolayer cells did not alter resposiveness to CD95 agonistic antibodies. These data suggested that CD95 signal transduction was not affected by FAP-1 expression in A818-6 monolayer cells. In differentiated 3D hollow spheres, we found a polarisation-induced co-localisation of CD95 and FAP-1. A tight control of receptor surface representation and signalling induced apoptosis ensures controlled removal of individual cells instead of a "snowball effect" of apoptotic events.

Inflammatory macrophages induce Nrf2 transcription factor-dependent proteasome activity in colonic NCM460 cells and thereby confer anti-apoptotic protection.

Adaptation of epithelial cells to persistent oxidative stress plays an important role in inflammation-associated carcinogenesis. This adaptation process involves activation of Nrf2 (nuclear factor-E2-related factor-2), which has been recently shown to contribute to carcinogenesis through the induction of proteasomal gene expression and proteasome activity. To verify this possible link between inflammation, oxidative stress, and Nrf2-dependent proteasome activation, we explored the impact of inflammatory (M1) macrophages on the human colon epithelial cell line NCM460. Transwell cocultures with macrophages differentiated from granulocyte monocyte-colony-stimulating factor-treated monocytes led to an increased activity of Nrf2 in NCM460 cells along with an elevated proteasome activity. This higher proteasome activity resulted from Nrf2-dependent induction of proteasomal gene expression, as shown for the 19 and 20 S subunit proteins S5a and α5, respectively. These effects of macrophage coculture were preceded by an increase of reactive oxygen species in cocultured NCM460 cells and could be blocked by catalase or by the reactive oxygen species scavenger Tiron, whereas transient treatment of NCM460 cells with H(2)O(2) similarly led to Nrf2-dependent proteasome activation. Through the Nrf2-dependent increase of proteasomal gene expression and proteasome activity, the sensitivity of NCM460 cells to tumor necrosis factor-related apoptosis-inducing ligand- or irinotecan-induced apoptosis declined. These findings indicate that inflammatory conditions such as the presence of M1 macrophages and the resulting oxidative stress are involved in the Nrf2-dependent gain of proteasome activity in epithelial cells, e.g. colonocytes, giving rise of greater resistance to apoptosis. This mechanism might contribute to inflammation-associated carcinogenesis, e.g. of the colon.

Physical violence and health-related quality of life: Danish cross-sectional analyses.

BACKGROUND: The aim of this study was to evaluate the association between experienced physical violence and health-related quality of life (HRQoL) by comparing self-reported health status for individuals with and without experience of physical violence. Our hypothesis was that individuals exposed to violence would experience worse HRQoL than non-exposed individuals. We tested whether men and women and different age groups experience similar reductions in HRQoL, and the extent to which such differences might be associated with social circumstances and lifestyle conditions. Finally, we explored the HRQoL consequences of exposure to violence in a longer time perspective. METHODS: We used data from self-completed questionnaires in two Danish nationally representative, cross-sectional health interview surveys. Exposure to violence was indicated through specific survey questions (Straus' conflict tactics scale) enquiring about different types of violence during the last 12 months. Health status of respondents was elicited by the EQ-5D and SF-36 questionnaires. The health status profiles were converted to health score indexes using the Danish algorithm for EQ-5D and the revised Brazier algorithm for SF-6D. Differences in score indexes between the exposed and non-exposed individuals were explored separately for men and women using ordinary least square regression with four age categories as explanatory variables. RESULTS: In the 2000 and 2005 surveys, respectively, 4.9% and 5.7% of respondents indicated that they had been exposed to physical violence within the last 12 months. Exposure to violence was more prevalent in the younger age groups and more prevalent for men than women. Respondents exposed to violence had lower score indexes on both the EQ-5D and the SF-6D compared with the non-exposed. Respondents who reported exposure to violence in both 2000 and 2005 reported lower HRQoL than individuals who only reported exposure in one of the surveys. CONCLUSIONS: The results of this study provide evidence for an association between exposure to physical violence and reduction in health-related quality of life.

Specific regulation of low-abundance transcript variants encoding human Acyl-CoA binding protein (ACBP) isoforms.

Despite intensive efforts on annotation of eukaryotic transcriptoms, little is known about the regulation of low-abundance transcripts. To address this question, we analysed the regulation of novel low-abundance transcript variants of human acyl-CoA binding protein (ACBP), an important multifunctional housekeeping protein, which we have identified by screening of human expressed sequence tags in combination with ab initio gene prediction. By using RT-, real-time RT- and rapid amplification of cDNA ends-PCR in five human tissues, we find these transcripts, which are generated by a consequent use of alternative promoters and alternate first or first two exons, to be authentic ones. They show a tissue-specific distribution and intrinsic responsiveness to glucose and insulin. Promoter analyses of the corresponding transcripts revealed a differential regulation mediated by sterol regulatory element-binding protein-2, hepatocyte nuclear factor-4α and nuclear factor κB (NF-κB), central transcription factors of fat and glucose metabolism and inflammation. Subcellular localization studies of deduced isoforms in liver HepG2 cells showed that they are distributed in different compartments. By demonstrating that ACBP is a target of NF-κB, our findings link fatty acid metabolism with inflammation. Furthermore, our findings show that low-abundance transcripts are regulated in a similar mode than their high-abundance counterparts.