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Sif Gudbrandsdottir,
Henrik Sverre Birgens, Henrik Frederiksen,
Bjarne Anker Jensen,
Morten Krogh Jensen,
Lars Kjeldsen,
Tobias Wirenfeldt Klausen,
Herdis Larsen,
Hans Torben Mourits-Andersen,
Claus Henrik Nielsen,
Ove Juul Nielsen,
Torben Plesner,
Stanislaw Pulczynski,
Inge Helleberg Rasmussen,
Dorthe Rønnov-Jessen,
Hans Carl Hasselbalch
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ABSTRACT: In this study we report the first results from the largest cohort to date of newly diagnosed adult ITP patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤ 25 x10(9)/L or ≤ 50 x10(9)/L with bleeding symptoms. 133 patients were randomly assigned to either dexamethasone monotherapy 40 mg/day for 4 days (n=71) or in combination with rituximab 375 mg/m(2) weekly for 4 weeks (n=62). Patients in both groups were allowed supplemental dexamethasone every 1-4 week for up to 6 cycles. Our primary endpoint, sustained response (i.e., platelets ≥ 50 x10(9)/L) at 6 months follow-up, was reached in 58 % of patients in the rituximab + dexamethasone group vs 37 % in the dexamethasone group (p = 0.02). The median follow-up time was 922 days. We found longer time-to-relapse (p = 0.03) and longer time-to-rescue-treatment (p = 0.007) in the rituximab + dexamethasone group than in the dexamethasone group. There was an increased incidence of grade 3-4 adverse events in the rituximab + dexamethasone group (p = 0.04). In conclusion, rituximab + dexamethasone induced higher response rates and longer time-to-relapse than dexamethasone alone. This study is registered at http://clinicaltrials.gov as NCT00909077.
Blood 01/2013; · 9.90 Impact Factor
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ABSTRACT: Adult immune thrombocytopenia was previously considered a benign disease affecting young people and with a low risk of severe bleeding. This view was challenged by studies published during the past decade, as the median age of adult immune thrombocytopenia patients has been found to be 55-60 years and the incidence increases with age. Recent studies reported that mortality and morbidity are increased compared with the general population. In this review, we describe patient-specific factors associated with the outcome of disease, the clinical course of immune thrombocytopenia including the potential adverse impact of some treatments and finally the overall prognosis.
Expert Review of Hematology 04/2012; 5(2):219-28. · 1.16 Impact Factor
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ABSTRACT: The objective of this study was to investigate the use of thrombopoietin-receptor agonists (TPO-ra) in patients with refractory primary immune thrombocytopenia (ITP) as well as off-label use of TPO-ra in Danish haematology departments. Hospital medical records from 32 of the 39 patients having received TPO-ra from 2009 to 1 May 2011 were available for data collection and included in the study. Of these patients, 15 received TPO-ra for refractory primary ITP, 7 for secondary ITP (chronic lymphatic leukaemia, systemic lupus erythematosus, Evans syndrome, human immunodeficiency virus and celiac disease) and 10 were treated for non-ITP (chemotherapy-induced, acute myeloid leukaemia, myelodysplastic syndrome, hereditary spherocytosis and suspected chemically induced thrombocytopenia). Initial response to TPO-ra defined as platelet counts >30 × 10(9)/l after 4 weeks of treatment was found in 59% of primary ITP patients, 57% of patients with secondary ITP and 40% of patients with non-ITP. There were four deaths in the cohort, three of which were related to pre-existing medical conditions. Otherwise adverse effects were in general mild. This Danish retrospective registration study has demonstrated that in the off-protocol setting, the use of TPO-ra is associated with response rates largely similar to those seen in previous protocol-monitored studies and no new adverse events were reported.
Platelets 12/2011; 23(6):423-9. · 1.85 Impact Factor
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ABSTRACT: Patients with chronic myeloproliferative neoplasms, including essential thrombocythemia (ET), polycythemia vera (PV), and chronic myeloid leukemia (CML), are at increased risk of new hematologic malignancies, but their risk of nonhematologic malignancies remains unknown. In the present study, we assessed the risk of both types of malignancies after an ET, PV, or CML diagnosis. We linked 2 population-based nationwide registries, the Danish National Registry of Patients, covering all Danish hospitals and the Danish Cancer Registry, and assessed subsequent cancer risk in a cohort of all 7229 patients diagnosed with a chronic myeloproliferative neoplasm during 1977-2008. We compared the incidence of subsequent cancer in this cohort with that expected on the basis of cancer incidence in the general population (standardized incidence ratio). Overall, ET, PV, and CML patients were at increased risk of developing both new hematologic and nonhematologic cancers. The standardized incidence ratio for developing a nonhematologic cancer was 1.2 (95% confidence interval [95% CI]): 1.0-1.4) for patients with ET, 1.4 (95% CI: 1.3-1.5) for patients with PV, and 1.6 (95% CI: 1.3-2.0) for patients with CML. We conclude that patients with chronic myeloproliferative neoplasms are at increased risk of developing a new malignant disease.
Blood 12/2011; 118(25):6515-20. · 9.90 Impact Factor
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ABSTRACT: Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved in the pathogenesis of ITP. This article aims to provide an overview of current treatment options, with particular emphasis on new biological therapies: rituximab, a monoclonal anti-CD20 antibody, and the thrombopoietin receptor agonists romiplostim and eltrombopag.
Ugeskrift for laeger 01/2011; 173(4):271-4.
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ABSTRACT: Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune-mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved in the pathogenesis of ITP.This article aims to provide an overview of our knowledge of the pathogenesis of ITP.
Ugeskrift for laeger 01/2011; 173(4):274-7.
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ABSTRACT: Recently, the use of proton pump inhibitors (PPIs) has been associated with an increased risk of pneumonia. We aimed to confirm this association and to identify the risk factors.
We conducted a population-based case-control study using data from the County of Funen, Denmark. Cases (n=7642) were defined as all patients with a first-discharge diagnosis of community-acquired pneumonia from a hospital during 2000 through 2004. We also selected 34 176 control subjects, who were frequency matched to the cases by age and sex. Data on the use of PPIs and other drugs, on microbiological samples, on x-ray examination findings, and on comorbid conditions were extracted from local registries. Confounders were controlled by logistic regression.
The adjusted odds ratio (OR) associating current use of PPIs with community-acquired pneumonia was 1.5 (95% confidence interval [CI], 1.3-1.7). No association was found with histamine(2)-receptor antagonists (OR, 1.10; 95% CI, 0.8-1.3) or with past use of PPIs (OR, 1.2; 95% CI, 0.9-1.6). Recent initiation of treatment with PPIs (0-7 days before index date) showed a particularly strong association with community-acquired pneumonia (OR, 5.0; 95% 2.1-11.7), while the risk decreased with treatment that was started a long time ago (OR, 1.3; 95% CI, 1.2-1.4). Subgroup analyses revealed high ORs for users younger than 40 years (OR, 2.3; 95% CI, 1.3-4.0). No dose-response effect could be demonstrated.
The use of PPIs, especially when recently begun, is associated with an increased risk of community-acquired pneumonia.
Archives of Internal Medicine 06/2007; 167(9):950-5. · 11.46 Impact Factor
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ABSTRACT: The aim of this study was to explore and describe self-rated health in middle-aged and elderly Danes using both a cross-sectional and a longitudinal design. Global and (age) comparative self-rated health are examined and compared.
This study is interview based and comprises data on 11,294 Danes aged 45-102 with more than 1,900 participants aged 90 years and older.
As expected, global self-rated health declines with age in both cross-sectional and longitudinal analyses. In contrast, comparative self-rated health either increases or remains stable with age in cross-sectional analyses while in longitudinal analyses there is a slight decline in comparative self-rated health.
The age-trajectory of global self-rated health is similar in individuals and populations. For comparative self-rated health, however, the individual on average experiences a slight decline, whereas on the population level comparative self-rated health either increases or remains stable. The explanation for this is likely to be higher mortality and higher non-response among the participants with the poorest self-rated health.
Scandinavian Journal of Public Health 02/2007; 35(2):164-71. · 1.39 Impact Factor
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ABSTRACT: The purpose is to study the age trajectory of hand-grip strength after the age of 45 years.
In this study, we use data from three large nationwide population-based surveys of Danes aged 45 to 102 years with a total of 8342 participants with grip-strength measurements and up to 4 years of follow-up. Grip strength was measured by using a portable hand dynamometer.
Grip strength declines throughout life for both males and females, but among the oldest women, the longitudinal curve reaches a horizontal plateau. The course of the decline is estimated by using full information in the longitudinal data and is found to be almost linear in the age span of 50 to 85 years. In this age span, mean annual grip-strength loss is estimated to be 0.59 (0.02) (SE) kg for men and 0.31 (0.01) kg for women.
This study confirms the previously reported grip-strength decline with increasing age. Estimates were obtained by using full-information methods from large population-representative studies. Equations of expected grip strength, as well as tables with sex-, age-, and height-stratified reference data, provide an opportunity to include grip-strength measurement in clinical care in similar populations.
Annals of Epidemiology 08/2006; 16(7):554-62. · 3.21 Impact Factor
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ABSTRACT: Prospective cohort study.
To investigate whether physical performance, grip strength, cognitive function, and depression symptomatology are risk factors for incident low back pain (LBP) over a 2-year period in seniors.
LBP is common in the older age groups, but little is known about predictors of LBP in this age group.
Data from the 2001 and 2003 data collection from the population-based Longitudinal Study of Aging Danish Twins formed the basis of this analysis. Participants free from LBP at baseline (no LBP during the past month, N = 1387) were included and interview data on overall physical function, and assessment of grip strength, overall cognitive function, and depression at baseline were obtained. LBP status at follow-up was assessed using a modified version of the Standardized Nordic Questionnaire. Logistic regression was used to assess the associations between the baseline risk factors and LBP at follow-up.
A total of 1387 persons 70 to 100 years of age at baseline were included in the analyses. Of the initially LBP-free individuals, 7% had experienced LBP more than 30 days out of the past year, 7% had altered or decreased their physical activities due to LBP, and 11% had received treatment for LBP at follow-up. Good overall physical function (being among the top 50%) at baseline was protective for LBP of more than 30 days duration and for diminishing physical activities due to LBP and for care seeking due to LBP. High depression scores (being among the top 25%) were strongly associated with altering or decreasing daily activities because of LBP. Grip strength and overall cognitive performance at baseline were associated with lower incidence of LBP and decreasing activities due to LBP at follow-up; however, these associations were not statistically significant.
Poor overall physical function and depression symptomatology are associated with LBP and consequences of LBP in persons 70 years of age and older.
Spine 07/2006; 31(14):1628-32. · 2.08 Impact Factor
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ABSTRACT: Neck pain (NP) and back pain (BP) are common complaints in seniors yet specific information on these complaints is lacking in the scientific literature. We present cross-sectional interview data from the 2003 data collection within the population based Longitudinal Study of Aging Danish Twins dealing with the 1-month prevalence of NP and BP and the intensity of possible pain. Further, we present the 1-year prevalence of NP and BP, duration of pain, influence of NP and BP on daily activities and care seeking for NP and BP. 84.4% of invited twins aged 70-102 years participated in the study. The 1-month prevalence of NP and BP was similar to previously reported results. 7% of men and 13% of women reported moderate or severe NP and 12% of men and 19% of women reported moderate or severe BP on a monthly basis. 10% of men and 12% of women reported more than 30 days of NP within the past year and 13% of men and 21% of women reported more than 30 days of BP within the past year. 5% of men and 8% of women had altered or diminished their physical activities due to NP and 9% of men and 16% of women had diminished their physical activities due to BP within the past year. 10% of men and 12% of women had had treatment for NP within the past year and 13% of men and 19% of women had had treatment for BP within the past year, most commonly from general medical practitioners and physical therapists. Altering or diminishing physical activities and care seeking were associated with both pain intensity and duration of pain. NP and BP of longer duration were associated with significantly lower physical performance scores when compared to no NP or BP during the past year. NP and BP in seniors are probably associated with difficulty but not inability to perform daily activities.
European Spine Journal 07/2006; 15(6):802-6. · 1.97 Impact Factor
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ABSTRACT: Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by mutations in the Werner (WRN) gene leading to the early onset of many (but not all) aspects of normal aging. To investigate whether the WRN gene affects the course of aging in non-Werner syndrome individuals, we performed association studies analyzing several single nucleotide polymorphisms (SNPs) in the WRN locus. We found certain close-set SNPs in the 5' flanking region and 5' UTR to be significantly associated with the cognitive functioning level in old age.
Annals of the New York Academy of Sciences 06/2006; 1067:309-10. · 3.15 Impact Factor
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ABSTRACT: The microarray technique is an important tool in gene expression analysis to study the activities of thousands of genes measured by their transcript levels under disease or laboratory controlled experimental conditions. Recent studies have suggested a genetic component in the variations of gene expression thus indicating the important role of genetic control over gene activities. In this study, we analyze and report the twin correlation on gene expression in whole blood samples of six female Danish twin pairs aged from 81 to 85 years. We studied the expression phenotype by treating the measured gene expression as a quantitative trait and introducing analytical approaches including the traditional twin methods in population genetics and the multivariate statistical methods. Using this combinatory approach, we were able to estimate and compare the twin correlation on the expression phenotype while accounting for systematic influence in microarray experiments. Analyses on our twin data detected a significant correlation on the expression levels of the actively regulated genes in both monozygotic and dizygotic twins, which is more pronounced in monozygotic twins. Gene ontology analysis has shown that these actively regulated genes are predominantly involved in defense and immune responses against antigenic stimulus. In conclusion, the correlation patterns revealed in our twin data provide evidence of the existence of a heritable mechanism in gene expression regulation persistently functioning even in aged subjects.
Human Genetics 08/2005; 117(2-3):267-74. · 5.07 Impact Factor
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ABSTRACT: Classic twin study.
To determine the heritability of neck pain in persons 70 years of age and older.
Previous studies have shown a moderate effect of genetic factors on back pain in the elderly. Genetic influence on neck pain in old age is unknown.
Data on the 1-month prevalence of neck pain from twin pairs participating in the population based Longitudinal Study of Aging Danish Twins formed the basis of this analysis. To assess twin similarity, probandwise concordance rates, odds ratios, and tetrachoric correlations were calculated and compared for monozygotic and dizygotic twins. Further, heritability estimates were calculated using bivariate probit estimation.
A total of 2,108 twin individuals, including 1,054 complete twin pairs, answered the question related to neck pain at intake into the Longitudinal Study of Aging Danish Twins study. Low and nonsignificant probandwise concordance rates, odds ratios, and tetrachoric correlations were found for both men and women in monozygotic and dizygotic twin pairs, indicating small or negligible genetic effects. Heritability estimates adjusted for age and significant environmental risk factors (rheumatoid arthritis, osteoarthritis, disc prolapse, and coronary heart disease) showed no significant additive genetic, dominant genetic, or common environmental effects.
Genetic factors do not play an important role in the liability to neck pain in persons 70 years of age or older.
Spine 02/2005; 30(2):206-8. · 2.08 Impact Factor
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ABSTRACT: A low level of the central antioxidant enzyme catalase has been suggested to be a risk factor for diseases influenced by oxidative stress. In this study, we investigated the possible association of the catalase -262C/T polymorphism with survival, physical and cognitive functioning, and a number of oxidative stress-mediated disorders. The study population was 2223 Danish individuals, aged 45-93 years, drawn from three population-based surveys. The results suggest that the catalase -262C/T polymorphism is not associated with either survival, or the majority of the age-related phenotypes investigated. However, our data indicate a statistical significant association of TT homozygosity with improved physical functioning as well as a trend of the T allele conferring an improved general cognitive functioning, although these results did not remain significant after correcting for multiple testing. The results raise the hypothesis that the catalase -262T allele serves as protection against neurodegenerative and physical decline, although replication in other studies is warranted for confirmation of these findings.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 10/2004; 59(9):B886-9. · 4.60 Impact Factor
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Ugeskrift for laeger 10/2004; 166(40):3500-1.
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ABSTRACT: Werner's syndrome is a premature aging syndrome with many features common to normal aging. The possible association between phenotypic markers for normal aging and SNP's in the WRN gene was investigated in 426 dizygotic, Danish twins age 70-90 years. All participants were scored every second year using a number of physical and cognitive tests. In addition their self-rated health was registered as well as self reported status with regards to nine diseases. Blood was drawn from all participants and purified DNA was typed for four SNP's in the WRN gene. The four SNP's were located in intron 1, exon 6, exon 9 and exon 34. In an unpaired analysis of this material a significant association between the intron 1 SNP and cognitive function was demonstrated. Our finding, which will need corroboration in independent samples, therefore may suggest that the t-allele of the intron 1 SNP is beneficial to cognitive function. However, since the t-allele of this SNP is very rare, we did not encounter any tt-homozygous individuals for this allele.
Experimental Gerontology 08/2004; 39(7):1101-7. · 3.74 Impact Factor
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ABSTRACT: Self-reported 1-month prevalence of back pain in older twins assessed at intake in a population-based longitudinal survey.
To determine the relative contribution of genetic and environmental factors to back pain in old age.
To date, genetic contributions to back pain in old age have not been assessed, to the authors' best knowledge.
Interview data given at entry into a nationwide cohort-sequential population-based survey of Danish twins aged 70 years and older in 1995, 1997, 1999, and 2001 form the basis of this analysis. Analysis of twin similarity was estimated using probandwise concordance rates, odds ratios, and tetrachoric correlations for back pain. Heritability (proportion of the population variance attributable to genetic variation) was estimated by bivariate probit estimation and adjusted for known significant environmental factors. Odds ratios for known environmental effects were estimated after controlling for age, sex, and genetic effects.
Modest and nonsignificant differences between monozygotic and dizygotic twin pairs were found for probandwise concordance rates, odds ratios, and tet-rachoric correlations for both men and women. In the bivariate probit estimation, a current or previous diagnosis of osteoporosis, degenerative joint disease, or lumbar disc prolapse was found to significantly affect the risk of back pain. Additive genetic effects explained approximately one fourth of the liability to report back pain in men and none of the occurrence in women. Individual environmental effects were found to explain roughly 75% of the occurrence of back pain in men and 100% in women.
Additive genetic effects are modest contributors to back pain in older men but not in women. A current or previous medical diagnosis of osteoporosis, degenerative joint disease, or lumbar disc prolapse is-strongly associated with back pain, also when genetic factors are controlled for. Because of inherent methodologic issues, this estimate of the genetic influence on back pain in old age is probably conservative.
Spine 05/2004; 29(8):897-901; discussion 902. · 2.08 Impact Factor
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Epidemiology 04/2004; 15(2):251-2. · 5.57 Impact Factor
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ABSTRACT: Cross-sectional and longitudinal analysis of data comprising 4486 Danish twins 70-102 years of age.
To describe the 1-month prevalence of back pain, neck pain, and concurrent back and neck pain and the development of these over time, associations with other health problems, education, smoking, and physical, and mental functioning.
Back pain and neck pain are prevalent symptoms in the population; however, there is little research addressing these conditions in older age groups.
Extensive interview data on health, lifestyle, social, and educational factors were collected in a nationwide cohort-sequential study of 70+-year-old Danish twins. Data for back pain, neck pain, lifetime prevalence of a comprehensive list of diseases, education, and self-rated health were based on self-report. Physical and mental functioning were measured using validated performance tests. Data including associated factors were analyzed in a cross-sectional analysis for answers given at entry into the study, and longitudinal analysis was performed for participants in all four surveys.
The overall 1-month prevalence for back pain only was 15%, for neck pain only 11%, and for concurrent back and neck pain 11%. The prevalence varied negligibly over time and between the age groups, and 63% of participants in all surveys had no episodes or only one episode of back or neck pain. Back pain and neck pain were associated with a number of other diseases and with poorer self-rated health. Back and neck pain sufferers had significantly lower scores on physical but not cognitive functioning.
Back pain and neck pain are common, intermittent symptoms in old age. Back pain and neck pain are associated with general poor physical health in old age.
Spine 04/2004; 29(5):576-80. · 2.08 Impact Factor
