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Biomedical subjects

Mette Madsen

Publications and source records attributed to Mette Madsen.

At least 19 recordsLinked to original sources

Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction.

BACKGROUND: The selective cyclooxygenase-2 (COX-2) inhibitors and other nonselective nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk, but the risk in patients with established cardiovascular disease is unknown. We analyzed the risk of rehospitalization for acute myocardial infarction (MI) and death related to the use of NSAIDs including selective COX-2 inhibitors in patients with prior MI. METHODS AND RESULTS: All patients with first-time MI between 1995 and 2002 as well as all prescription claims for NSAIDs after discharge were identified from nationwide Danish administrative registers. The risk of death and rehospitalization for MI associated with the use of selective COX-2 inhibitors and nonselective NSAIDs was studied with the use of multivariable proportional hazards models and case-crossover analysis. A total of 58 432 patients were discharged alive and included in the study; 9773 experienced rehospitalization for MI, and 16 573 died. A total of 5.2% of patients received rofecoxib, 4.3% celecoxib, 17.5% ibuprofen, 10.6% diclofenac, and 12.7% other NSAIDs. For any use of rofecoxib, celecoxib, ibuprofen, diclofenac, and other NSAIDs, the hazard ratios and 95% confidence intervals for death were 2.80 (2.41 to 3.25; for rofecoxib), 2.57 (2.15 to 3.08; for celecoxib), 1.50 (1.36 to 1.67; for ibuprofen), 2.40 (2.09 to 2.80; for diclofenac), and 1.29 (1.16 to 1.43; for other NSAIDS); there were dose-related increases in risk of death for all of the drugs. There were trends for increased risk of rehospitalization for MI associated with the use of both the selective COX-2 inhibitors and the nonselective NSAIDs. CONCLUSIONS: Selective COX-2 inhibitors in all dosages and nonselective NSAIDs in high dosages increase mortality in patients with previous MI and should therefore be used with particular caution in these patients.

Aged↗

The macrophage scavenger receptor CD163: endocytic properties of cytoplasmic tail variants.

CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are substantially expressed in blood, liver, and spleen, and the short tail variant is the predominant mRNA species. Using cell transfectants in which cDNA encoding the CD163 variants was inserted at the same site in the genome, we evaluated the expression and endocytic properties of the tail variants. Ligand uptake analysis showed that cells expressing the CD163 short tail variant exhibited a higher capacity for ligand endocytosis than cells expressing the CD163 long tail variants. The difference in endocytic activity was explained by confocal microscopic analysis, showing marked deviations in subcellular distribution. Surface expression was far most pronounced for the CD163 short tail variant, whereas the long tail variants were most abundant in the Golgi region/endosomes. Mutational change of a putative signal for endocytosis (Tyr-Arg-Glu-Met), present in a common part of the cytoplasmic tail of the variants, almost completely inactivated the endocytic activity of the short tail variant. In conclusion, the three physiological tail variants of CD163 may contribute to Hp-Hb endocytosis by means of the common ligand-binding region and endocytic signal. However, the high mRNA expression level and relatively high endocytic capacity of the short tail variant suggest that it accounts for the majority of Hp-Hb uptake from the circulation, whereas the long tail variants may have yet-unknown intracellular roles.

Amino Acid Sequence↗

Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction.

AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995 and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials, and dosages did not increase during the observation period. Patients who did not start treatment shortly after discharge had a low probability of starting treatment later. CONCLUSION: The main problem with underuse of recommended treatment after AMI is that treatment is not initiated at an appropriate dosage shortly after AMI. A focused effort in the immediate post-infarction period would appear to provide long-term benefit.

Adrenergic beta-Antagonists↗

Social integration of adults with cerebral palsy.

Social integration and independence is the ultimate goal of habilitation and social support for patients with cerebral palsy (CP). Having a partner and having children provide support for social integration of adults with or without a disability. We studied 416 participants with CP born between 1965 and 1970 (243 males, 173 females; mean age 32 y 2 mo [SD 2 y]; age range 29-35 y) and compared them with 2247 age-matched comparison individuals. Diagnostic subtypes of the 416 participants were: 31% hemiplegia, 49% diplegia, 11% tetraplegia, and 9% other types. The level of motor impairment, estimated in childhood, with regard to walking ability was 65% able to walk without assistance, 22% with assistance, and 12% not able to walk (for 1% of the participants their walking ability was not known). We found no sign of increased social integration over the past two or three decades in Denmark. Sixty-eight per cent lived independently, 13% lived with their parents, and 16% lived at an accommodation facility arranged by the county (institution). Twenty-eight per cent of the participants were cohabiting and 19% had children. The presence of epilepsy and the severity of physical or cognitive impairment as assessed in childhood predicted independent living and physical and cognitive impairment predicted cohabitation, but parents' socioeconomic position and region of living did not. Fifty-five percent of the participants, compared with 4% of the comparison group, had no competitive employment, cohabiting partner, or biological children. The remaining participants had at least one of these types of social contact, but this more optimally socially integrated half of the participants only combined all three types of social contact half as often as the comparison group. This could be due to cognitive difficulties or premature ageing.

Activities of Daily Living↗

Health behaviour among adolescents in Denmark: influence of school class and individual risk factors.

AIMS: The aim of this study was to assess the relative influence of school class on health behaviour among adolescents versus that of the family's socioeconomic status and individual factors among adolescents. METHODS: The material comprised 3,458 students in grades 8 and 9 in 244 school classes. Data were collected through questionnaires completed by the students and by their class teacher and information from the school physician. Multilevel analysis was used to indicate the relative significance of individual and school class characteristics. RESULTS: We find no consistent pattern between the mother's socioeconomic status and the included health behaviour measurements; however, adolescents from the lower socioeconomic groups had a higher risk of unhealthy dietary habits and adolescents whose mothers were unemployed had a significantly lower risk of drinking alcohol weekly versus all other adolescents. Not living with both biological parents, focusing on friends, and not being very academically proficient were associated with an increased risk of harmful health behaviour. Health behaviour varied substantially between school classes, especially for daily smoking, weekly alcohol consumption, and use of hashish and other euphoriants. Circumstances in the school class more profoundly influenced risk behaviour among adolescents (smoking, alcohol consumption, and use of hashish or other euphoriants) than their dietary habits (eating breakfast, frequent intake of fruit and vegetables, and frequent intake of soft drinks). CONCLUSIONS: The school class had the relatively strongest influence on adolescents' risk behaviour (smoking, alcohol intake, and use of hashish or other euphoriants), whereas family circumstances comprised the strongest influence on dietary habits.

Adolescent↗

Prevalence and characteristics of impaired glucose metabolism in patients referred to comprehensive cardiac rehabilitation: the DANSUK study.

BACKGROUND: Lifestyle and pharmacological interventions can delay the progression of impaired glucose tolerance (IGT) to type 2 diabetes (T2DM), and there is growing evidence that earlier detection of T2DM and intensified risk factor management may result in improved cardiovascular morbidity and mortality. We studied the prevalence of impaired glucose metabolism (T2DM, IGT and impaired fasting glucose; IFG) in patients referred to cardiac rehabilitation, and further studied whether we could identify groups in which an oral glucose tolerance test (OGTT) need not be performed. METHODS: As part of a cardiac rehabilitation trial, 201 patients participated. Patients without a diagnosis of T2DM (N=159) underwent an OGTT 3 months after inclusion. RESULTS: Forty-two patients (21%) had known T2DM at enrolment. Based on the OGTT, 26 patients (13%) had unrecognized T2DM, 36 (18%) had IGT and 19 (9%) were diagnosed with isolated IFG according to the World Health Organization definition. Using fasting plasma glucose alone, 19% of the patients with unrecognized T2DM and two-thirds of patients with IGT would be misclassified. Using IFG as a means to detect IGT showed a sensitivity of only 33% and a positive predictive value of 39%. CONCLUSION: More than 60% of the patients (123/201) referred to cardiac rehabilitation had impaired glucose metabolism and 18% of the screened patients (29/159) would be misclassified if an OGTT was omitted. IFG and IGT did not identify the same patients or the same cardiovascular risk profile. An OGTT test should therefore be considered a constituent part of routine care management in cardiac rehabilitation settings.

Aged↗

Mortality after acute myocardial infarction according to income and education.

OBJECTIVE: To study how income and educational level influence mortality after acute myocardial infarction (AMI). DESIGN AND SETTING: Prospective analysis using individual level linkage of registries in Denmark. PARTICIPANTS: All patients 30-74 years old hospitalised for the first time with AMI in Denmark in 1995-2002. MAIN OUTCOME MEASURES: Relative risk (RR) of 30 day mortality and long term mortality (31 days until 31 December 2003) associated with income (adjusted for education) or educational level (adjusted for income) and further adjusted for sex, age, civil status, and comorbidity. RESULTS: The study identified 21 391 patients 30-64 years old and 16 169 patients 65-74 years old. The 30 day mortality was 7.0% among patients 30-64 years old and 15.9% among those 65-74 years old. Among patients surviving the first 30 days, the long term mortality was 9.9% and 28.3%, respectively. The adjusted RR of 30 day mortality and long term mortality among younger patients with low compared with high income was 1.54 (95% confidence interval 1.36 to 1.79) and 1.65 (1.45 to 1.85), respectively. The RR of 30 day and long term mortality among younger patients with low compared with high education was 1.24 (1.03 to 1.50) and 1.33 (1.11 to 1.59), respectively. The RR of 30 day and long term mortality among older patients with low compared with high income was 1.27 (1.15 to 1.41) and 1.38 (1.27 to 1.50), respectively. Older high and low education patients did not differ in mortality. CONCLUSION: This study shows that both educational level and income substantially and independently affect mortality after AMI, indicating that each indicator has specific effects on mortality and that these indicators are not interchangeable.

Acute Disease↗

Contribution of cubilin and amnionless to processing and membrane targeting of cubilin-amnionless complex.

Cubilin is a peripheral apical membrane receptor for multiple ligands that are taken up in several absorptive epithelia. Recently, amnionless (AMN) was identified to form a functional receptor complex with cubilin. By expression in transfected polarized MDCK cells of AMN and several cubilin fragments, including a functional "mini" version of cubilin, the processing, sorting, and membrane anchoring of the complex to the apical membrane were investigated. The results show that truncation mutants, including the N-terminal domain of cubilin, did not appear at the plasma membrane but instead were retained in the endoplasmic reticulum or partially secreted into the medium. Coexpression with AMN led to efficient transport to the apical cell surface of the cubilin constructs, which included the EGF domains, and prevented release into the medium. AMN co-precipitated with cubilin and co-localized with cubilin at the apical cell surface. Apical sorting was observed for a broad set of nonoverlapping cubilin fragments without the N-terminal region, in the absence of AMN. The preference for apical sorting disappeared when glycosylation was inhibited by tunicamycin. In conclusion, it is shown that both units contribute to the processing of the cubilin-AMN complex to the apical membrane: AMN interacts with the EGF domains of cubilin and is responsible for membrane attachment and export of the complex from the endoplasmic reticulum, whereas the extracellular cubilin molecule is responsible for apical sorting of the complex in a carbohydrate-dependent manner.

Animals↗

Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo.

Amnionless (AMN) and cubilin gene products appear to be essential functional subunits of an endocytic receptor called cubam. Mutation of either gene causes autosomal recessive Imerslund-Gräsbeck syndrome (I-GS, OMIM no. 261100) in humans, a disorder characterized by selective intestinal malabsorption of cobalamin (vitamin B12) and urinary loss of several specific low-molecular-weight proteins. Vital insight into the molecular pathology of I-GS has been obtained from studies of dogs with a similar syndrome. In this work, we show that I-GS segregates in a large canine kindred due to an in-frame deletion of 33 nucleotides in exon 10 of AMN. In a second, unrelated I-GS kindred, affected dogs exhibit a homozygous substitution in the AMN translation initiation codon. Studies in vivo demonstrated that both mutations abrogate AMN expression and block cubilin processing and targeting to the apical membrane. The essential features of AMN dysfunction observed in vivo are recapitulated in a heterologous cell-transfection system, thus validating the system for analysis of AMN-cubilin interactions. Characterization of canine AMN mutations that cause I-GS establishes the canine model as an ortholog of the human disorder well suited to studies of AMN function and coevolution with cubilin.

Animals↗

A randomized clinical trial of hospital-based, comprehensive cardiac rehabilitation versus usual care for patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease (the DANREHAB trial)--design, intervention, and population.

BACKGROUND: Current guidelines broadly recommend comprehensive cardiac rehabilitation (CR), although evidence for this is still limited. It is not known whether evidence from before 1995 is still valid. STUDY DESIGN: The DANish Cardiac ReHABilitation (DANREHAB) trial was designed as a centrally randomized clinical trial to clarify whether hospital-based comprehensive CR is superior to usual care for patients with congestive heart failure, ischemic heart disease, or high risk for ischemic heart disease. A combined primary outcome measure included total mortality, myocardial infarction, or readmissions due to heart disease based on linkage to public registries. The CR was an individually tailored, multidisciplinary program (6 weeks of intensive CR and 12 months of follow-up) including patient education, exercise training, dietary counseling, smoking cessation, psychosocial support, risk factor management, and clinical assessment. STUDY POPULATION: Of 5060 discharged patients, 1614 (32%) were eligible for the trial and 770 patients were randomized (47% of those eligible). Participants were younger (P < .001) and had less comorbidity than nonparticipants (P < .03). CONCLUSION: Our trial shows that a large-scale, centrally randomized clinical trial on comprehensive CR can be conducted among a broadly defined patient group, but reaching the stipulated number of 1800 patients was difficult. Although the study included relatively many women and older people, elderly patients and patients with high comorbidity were underrepresented, which may influence the external validity.

Adult↗

Education and employment prospects in cerebral palsy.

Parents and paediatric neurologists need information on the long-term social prognosis of children with cerebral palsy (CP). No large population-based study has been performed on this topic. On 31 December 1999, to find predictors in childhood of subsequent education and employment, 819 participants with CP born between 1965 and 1978 (471 males; mean age 28y 10 mo, SD 4y, range 21 to 35y) in the Danish Cerebral Palsy Registry were compared with 4406 controls without CP born between 1965 and 1978 (2546 males; mean age 28y 10 mo, SD 4y, range 21 to 35y). Diagnostic subtypes of the 819 participants with CP were: 31% hemiplegia, 43% diplegia, 18% tetraplegia, and 8% other types. Level of motor impairment with respect to walking ability was: 62% able to walk without assistance, 21% with assistance, and 16% not able to walk (for 1% of study children walking ability was not known). Relevant information was obtained from Denmark's unique registries. Of the participants with CP, 33% vs 77% of controls, had education beyond lower secondary school (i.e. after age 15-16y), 29% were competitively employed (vs 82% of controls), 5% were studying, and 5% had specially created jobs. Excluding participants with CP with an estimated developmental quotient (DQ) of less than 50 or inability to walk at age 5 to 6 years, the odds ratios (multivariate analysis) for not being competitively employed were 1.9 for diplegia versus hemiplegia, 22.5 for DQ 50 to 85 versus DQ greater than 85, and 3.7 for those with epilepsy versus those without epilepsy. The severity of motor impairment among participants with CP able to walk had just a minor influence. Only half the participants with CP who had attended mainstream schooling were employed. In conclusion several childhood characteristics seemed to predict long-term social prognosis.

Adult↗

Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995-2002.

OBJECTIVES: To study the use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to 2002. DESIGN: Information about patients with first AMI aged > or = 30 years and the dispensing of beta-blockers and ACE inhibitors from pharmacies within 30 d from discharge was obtained from the National Patient Registry and the Danish Registry of Medicinal Product Statistics. RESULTS: Beta-blocker use increased from 38.1% of patients in 1995 to 67.9% in 2002 (OR = 3.85, CI: 3.58-4.13). Women, elderly patients and patients taking loop-diuretics and antidiabetic drugs received beta-blockers less frequently, but patients taking loop-diuretics or antidiabetic drugs had the greatest increase. ACE inhibitor use increased from 24.5 to 35.5% (OR = 1.86, CI: 1.72-2.01). Women, patients aged < 60 years or > or = 80 years and patients not taking loop-diuretics received ACE inhibitors less frequently, but patients not taking loop-diuretics had the greatest increase. CONCLUSIONS: Beta-blocker use increased markedly post-AMI from 1995 to 2002, whereas ACE inhibitor use increased modestly. The results suggested undertreatment of women, elderly patients and people with diabetes.

Adrenergic beta-Antagonists↗

Hospital variation in mortality after first acute myocardial infarction in Denmark from 1995 to 2002: lower short-term and 1-year mortality in high-volume and specialized hospitals.

BACKGROUND: This study used linked data from the National Hospital Registry to determine the factors that contribute to differences between hospitals in all-cause mortality after first acute myocardial infarction (AMI) between 1995 and 2002. METHODS: The study included 64,321 patients with their first admission for AMI between 1995 and 2002 and surviving the day of admission. Multilevel logistic regression was used to determine the relationships between regional and hospital characteristics and 28-day and 365-day mortality after adjusting for individual characteristics, period, and medical history. RESULTS: Tertiary cardiac care centers (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.67-0.96) and main regional hospitals (OR, 0.90; 95% CI, 0.80-0.99) had improved 28-day mortality compared with local hospitals. A 2-fold increase in annual total MI volume decreased 28-day mortality (OR, 0.91; 95% CI, 0.87-0.94) and 365-day mortality (OR, 0.95; 95% CI, 0.91-0.98). Differences between hospitals were more substantial for short-term mortality, such that patients were about twice as likely to die within 28 days in hospitals with the worst performance versus those with the best performance. Higher regional AMI incidence was associated with lower mortality before 2000; this disappeared after 2000. Other regional contextual characteristics had very modest effects on mortality. CONCLUSIONS: Type of hospital, and especially total MI volume at the hospital level, were significantly associated with mortality after AMI. Individual hospitals varied substantially in both short- and long-term mortality.

Adult↗

Statin use after acute myocardial infarction: a nationwide study in Denmark.

AIMS: To study outpatient statin use after first acute myocardial infarction (AMI) in Denmark between 1995 and 2002 and to determine the predictors of statin use. METHODS: This is a nationwide population-based study using administrative registries. Patients with first AMI between 1995 and 2002 older than 30 years of age and alive 6 months after discharge (n = 45 219) were identified through the National Patient Registry. The statins purchased by these patients within 6 months after discharge were determined using the Registry of Medicinal Product Statistics, a nationwide prescription database. RESULTS: Statin use following AMI increased from 13% in 1995 to 61% in 2002. In 2002, 81% of patients aged 30-64 years used statins. Older patients used fewer statins, but use increased more among patients aged 75-84 years: from 1.3% to 43%. Use in elderly patients did not differ according to gender in 2000-02, but young men used more than younger women. In 2000-02, patients with diabetes (odds ratio (OR): 0.84; 95% confidence interval (CI): 0.74-0.95) and with heart failure (OR: 0.70; 95% CI: 0.64-0.76) were undertreated; this trend was present throughout the period. CONCLUSIONS: In this nationwide study, younger patients after AMI had high statin use in 2002, but high-risk patients such as those with diabetes and heart failure were still being undertreated.

Adult↗

Does financial strain explain the association between children's morbidity and parental non-employment?

OBJECTIVES: To investigate whether family financial resources explain the association between parental labour market participation and children's health in families in Denmark and Sweden. DESIGN: Parent reported questionnaire data from the survey of health and welfare among children and adolescents in the Nordic countries, 1996. PARTICIPANTS: 4299 children aged 2-17 years. MEASURES: Three indicators measured children's health: recurrent psychosomatic symptoms, chronic illness, and prescribed medicine. Four variables and a composite index were used to measure family financial resources. The variable on family labour market participation consisted of five groups according to family type and parents' labour market participation. RESULTS: Children in families with one or both parents without paid work had an increased prevalence of recurrent psychosomatic symptoms (odds ratio from 1.52 to 3.20) and chronic illnesses (odds ratio from 1.43 to 2.25), whereas the use of prescribed medicine did not differ (odds ratio from 0.67 to 1.15). The five indicators on family financial resources only slightly reduced the odds ratios for recurrent psychosomatic symptoms (odds ratio from 1.12 to 2.75) and chronic illnesses (odds ratio from 1.34 to 2.22), and the odds ratios for children's use of prescribed medicine remained unchanged and non-significant (odds ratio from 0.62 to 1.18). CONCLUSIONS: Financial strain associated with non-employment does not explain the increased prevalence of health problems among children in families affected by non-employment in Denmark and Sweden. However, the associations between family labour market participation and children's health differ according to family financial status.

Adolescent↗

Changes in hospitalization rate and mortality after acute myocardial infarction in Denmark after diagnostic criteria and methods changed.

AIMS: To analyse the effect of the change in diagnostic criteria for acute myocardial infarction (AMI) and the use of troponin as a diagnostic marker on the hospitalization rate and mortality of hospitalized AMI patients from 1994 to 2001. METHODS AND RESULTS: Patients (> or =30 years) admitted for their first AMI were identified using the National Patient Registry in Denmark. We registered when each hospital introduced troponin as a diagnostic marker. The reported hospitalization rate decreased until 1998 and then increased substantially from 1999 to 2001 from 3472 to 4163 per million inhabitants (19.9%) for men and from 1648 to 2020 per million inhabitants (22.6%) for women. Troponin use was associated with a significant 14% increase in hospitalization rate in this period [rate ratio 1.14, 95% confidence interval (CI) 1.11-1.18]. The effect of troponin was greatest among patients 70 years and older (rate ratio 1.19, 95% CI 1.14-1.23). The 28 day mortality decreased steadily from 25.9% in 1994 to 17.5% in 2002 (32.4%) and was not affected by troponin use. CONCLUSION: The reported hospitalization rate for AMI increased significantly after the new diagnostic criteria for AMI were introduced. The measurement of cardiac troponins further increased the hospitalization rate. The mortality among hospitalized patients with AMI declined steadily and was not affected by the use of troponins.

Adult↗