[Show abstract][Hide abstract] ABSTRACT: Few data exist on the long-term prognosis of patients with chronic primary chronic immune thrombocytopenia (ITP). We examined the risk of infections, hemorrhage resulting in hospitalization, hematologic malignancies, and total and cause-specific mortality among patients with ITP compared with the general population. We used population-based medical databases to identify 407 patients with primary chronic ITP diagnosed during 1996 to 2007 and 4069 general population members individually matched on age, sex, and comorbidity level. We used Cox regression analysis to estimate rate ratios (RRs) adjusted for age (≤ 60 or > 60 years), sex, calendar year, and level of comorbidity. The adjusted 1-year RR of infection was 4.5 (95% confidence interval [CI], 3.3-6.1) for patients with chronic ITP compared with the general population cohort. The adjusted RR decreased to 1.8 (95% CI, 1.3-2.5) for the second to fifth year of follow-up. The adjusted 5-year RR was 3.2 (95% CI, 1.2-9.0) for hospitalized intracranial hemorrhage, 4.4 (95% CI, 2.3-8.3) for other hospitalized hemorrhages, and 4.7 (95% CI, 1.7-12.7) for hematologic malignancy. The 5-year all-cause mortality RR was 2.3 (95% CI, 1.8-3.0). In summary, primary chronic ITP was associated with substantially increased long-term risk of infections, hemorrhagic episodes requiring hospitalization, hematologic malignancies, and mortality.
[Show abstract][Hide abstract] ABSTRACT: We conducted a nationwide cohort study of adult Danish patients with primary chronic immune thrombocytopenia (cITP) to examine selected patient and clinical characteristics as predictors for splenectomy. We analyzed data from the Danish National Patient Registry and patient medical records from 1996 to 2007. Using Cox regression analyses, we calculated incidence rate ratios (IRRs) and associated 95% confidence intervals (CI) for splenectomy. We included 371 adult cITP patients. Of these, 87 patients (23%) underwent a splenectomy during a median of 3.6 years of follow-up. The majority (84%) of cITP patients who underwent splenectomy had splenectomy within the first year after cITP diagnosis. Predictors for splenectomy included age ≤ 75 years (adjusted 1-year IRR = 6.79 (95% CI, 2.10-21.90)) at least one platelet count ≤ 30 × 10(9)/L (i.e., high disease activity; adjusted 1-year IRR = 2.67 (95% CI, 1.37-5.22)) during follow-up and year of cITP diagnosis in early period (1996-2001; adjusted 1 year IRR = 2.37 (95% CI, 1.46-3.85)). Presence of chronic comorbidity was associated with lower rates of splenectomy (adjusted 1 year IRR = 0.58 (95% CI, 0.33-1.05)). Our findings suggest that high disease activity and absence of chronic comorbidity may be associated with higher rates of splenectomy, and that contraindications for splenectomy (i.e., patients' perceived frailty) cause the physicians to use the procedure cautiously.
Annals of Hematology 02/2011; 90(2):207-12. DOI:10.1007/s00277-010-1047-5 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Few population-based studies exist on incidence, risk of infection and mortality in hairy cell leukaemia (HCL).
We used population-based medical databases to identify 209 patients who were diagnosed with HCL in the period from January 1997 to August 2007 in Denmark. An age- and sex-matched comparison cohort of 2,090 persons was selected from the general population. We computed the incidence of HCL using demographic data. Hospitalizations with pneumonia and bacteraemia were determined from the Danish National Patient Registry. Cox regression analysis was used to estimate the relative risk (RR) of infection and mortality ratios (MRR) adjusting for age, sex and comorbidity.
The HCL incidence rates were 1.97 (95% confidence interval 1.51-2.53) and 5.37 (4.57-6.28) per million person-years for women and men, respectively. During a median follow-up of 4.5 years, 48 HCL patients were hospitalized with pneumonia or bacteraemia. The adjusted RR of infection was 8.04 (4.99-12.95) the first year after diagnosis and 1.17 (0.71-1.94) for the remaining follow-up period. The adjusted MRRs were 4.26 (2.61-6.96) and 1.12 (0.75-1.65) the first year after diagnosis and the remaining follow-up period, respectively.
In the second and subsequent years after HCL diagnosis, the risk of infection and mortality was similar to that of the general population.
Danish medical bulletin 12/2010; 57(12):A4216. · 1.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is unknown whether a prior diagnosis of monoclonal gammopathy of undetermined significance (MGUS) affects cancer survival.
We linked data on 1652 cases of MGUS diagnosed during 1978-2006 in North Jutland County, Denmark with the Danish Cancer Registry and the National Patient Registry to obtain information on survival of cancer patients with a previous MGUS compared with that of cancer patients without MGUS, matched on cancer type, age, sex and year of diagnosis. Stratified Cox regression analysis was used to compute mortality rate ratios controlling for the matching factors and comorbidity.
We included 323 cancer patients with previously detected MGUS and 3154 comparison cancer patients without MGUS. The 5-year survival probability was 26.2% (95% CI, 21.2%-31.5%) in cancer patients with MGUS and 30.5% (28.8%-32.1%) in cancer patients without MGUS. The adjusted mortality rate ratio (MRR) was=0.94 (95% CI, 0.82-1.09). Survival following a diagnosis of multiple myeloma, the cancer site of main interest, did not differ according to a preceding MGUS diagnosis. Among patients with immune-related cancers (liver, cervix, malignant melanoma and non-melanoma skin cancers), a preceding MGUS diagnosis was associated with reduced survival (adjusted MRR=1.49 (95% CI: 0.96-2.31)). In contrast, for other non-haematological cancers a prior MGUS diagnosis was associated with a lower MRR (0.78 (95% CI, 0.63-0.96)).
Our study does not indicate that previously detected MGUS is a prognostic factor for cancer survival in general.
European Journal of Internal Medicine 12/2010; 21(6):564-8. DOI:10.1016/j.ejim.2010.08.010 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We quantified and differentiated reticulin and collagen content in bone marrow specimens from chronic immune thrombocytopenic (ITP) patients and examined the correlation between some clinical characteristics and the fibrosis grading. Through the Danish National Patient Registry, we identified 378 patients with chronic ITP from 1997 until 2007. Of these, 253 (67%) had undergone at least one bone marrow biopsy, and we retrieved the bone marrow specimens from 187 (74%). We graded the bone marrow content of reticulin and collagen according to the Thiele scale (Grade 0-3). We also retrieved information on patients' clinical characteristics. We examined the prevalence of bone marrow fibrosis grading > 0 by patients' age (≤ 75 years and > 75 years), sex, platelet count at baseline (< 30 × 10⁹/L, and ≥ 30 × 10⁹/L), splenomegaly, hepatomegaly, and medications. In total 75 chronic ITP patients (40%) had a bone marrow grading >0. Of these, 72 (39%) had Grade 1 reticulin fibers present. Only three patients (< 2%) had collagen fibers present: two had Grade 2 and one had Grade 3. The prevalence of bone marrow grading > 0 was lower in patients aged > 75 years than ≤ 75 years (prevalence ratio = 0.64, 95% CI: 0.36-1.15) and lower in men than women (prevalence ratio = 0.70, 95% CI: 0.45-1.09), while a baseline platelet count ≥ 30 × 10⁹/L was associated with a higher prevalence of grading > 0 (prevalence ratio = 1.24, 95% CI: 0.81-1.86). Thus, bone marrow reticulin and collagen content in chronic ITP patients may be associated with some clinical characteristics.
American Journal of Hematology 12/2010; 85(12):930-4. DOI:10.1002/ajh.21885 · 3.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with multiple myeloma are at increased risk of venous thromboembolism (VTE), but little information is available on VTE risk in patients with the precursor condition monoclonal gammopathy of undetermined significance (MGUS).
To evaluate the risk of VTE and its impact on mortality in patients with MGUS.
We identified 1610 patients with MGUS and no prior diagnosis of VTE during the 1978-2005 period in North Jutland County, Denmark. We used the Danish Central Population Registry to select 16,100 general population comparison cohort members with no prior VTE diagnosis, matched with the MGUS patients by age, sex, and comorbidity. Follow-up data on VTE incidence in the two groups were obtained from the Danish National Patient Registry covering all Danish hospitals. Time-varying Cox regression analysis was used to compute the incidence rate ratio (IRR) of VTE and the mortality rate ratio (MRR) for MGUS patients who developed VTE compared to MGUS patients without VTE.
In the MGUS cohort, 50 VTE events were identified during 12,594 person-years (PY) of follow-up, corresponding to an incidence rate of 4.0 VTEs/1000 PY. The IRR for VTE among MGUS patients compared to the comparison cohort was 1.37 (95% confidence interval (CI): 1.00-1.88). Of the 50 MGUS patients with VTE, one was later diagnosed with malignant transformation. The adjusted MRR for MGUS patients with VTE compared to MGUS patients without VTE was 1.94 (95% CI: 1.36-2.77).
MGUS is a risk factor for VTE, and VTE is a marker for increased mortality among MGUS patients.
European Journal Of Haematology 10/2010; 86(2):129-34. DOI:10.1111/j.1600-0609.2010.01539.x · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bias analysis methods are developed for application to 2 x 2 tables, which may be crude or stratified data. Methods for application to associations adjusted for multiple covariates, such as associations from regression modeling, are rarely seen. We have developed probabilistic methods to evaluate bias from disease misclassification or an unmeasured confounder that can be applied to adjusted estimates of association.
Rather than applying bias correction methods that rearrange data within 2 x 2 tables, we have applied them to bias factors directly. We illustrate the methods by application to two pharmacoepidemiology problems.
In example one, the adjusted odds ratio associating glucocorticoid use with the rate of basal cell carcinoma was 1.15 (95%CI 1.07, 1.25). With bias analysis to account for differential disease misclassification, the median odds ratio was 1.32 and the 95% simulation limits were 1.16 and 1.56. In example two, the adjusted odds ratio associating concomitant use of clopidogrel and proton pump inhibitors with recurrent myocardial infarction was 1.21 (95%CI 0.90, 1.61). With bias analysis to account for confounding by smoking, which was unmeasured, the median odds ratio was 1.15 with 95% simulation interval 0.85 to 1.55.
Methods to apply probabilistic bias analysis to adjusted estimates of association can be implemented if a bias factor can be calculated directly from the bias model. This strategy requires that the bias is independent of confounding by measured variables, or requires that the dependence be incorporated into the bias model, as illustrated in an extension of the second example.
Pharmacoepidemiology and Drug Safety 06/2010; 19(6):638-44. DOI:10.1002/pds.1938 · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen. We performed a population-based study in the county of North Jutland, Denmark, including 120 women aged <60 years who received adjuvant chemotherapy with seven cycles of cyclophosphamide, epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006. They were compared with an aged-matched group of 208 women without previous cancer selected randomly from the same population. Data were collected before start of adjuvant treatment and after 6 months by neuropsychological tests and questionnaires to evaluate cognitive function, quality of life and psychological distress. Neuropsychological tests did not reveal any differences in cognitive function between breast cancer patients after chemotherapy and healthy controls. Patients rated their own cognitive functions as improved after 6 months, and patients, who did not receive adjuvant medical treatment, reached the same level as controls within 6 months. Patients receiving chemotherapy or tamoxifen were up to three times more likely than controls to rate themselves as impaired at 6 months. Our results do not support that adjuvant chemotherapy is associated with cognitive side effects in breast cancer patients.
Breast Cancer Research and Treatment 03/2010; 121(1):91-100. DOI:10.1007/s10549-010-0756-8 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypospadias is a relatively common congenital malformation. Data on temporal trends in prevalence of hypospadias are conflicting. It is unclear whether changes of maternal age distribution over time are associated with changes in hypospadias prevalence.
To study changes in prevalence of hypospadias in Denmark during a 29-yr period and to investigate whether maternal age was associated with the prevalence of hypospadias.
Through Denmark's National Patient Registry, covering all Danish hospitals, we identified all boys diagnosed with hypospadias in Denmark. From the Danish Medical Birth Registry, we obtained information on maternal age and on the annual total number of live-born boys from 1977 to 2005.
Prevalence of hypospadias at birth.
Among 921745 boys born alive from 1977 to 2005, we identified 3490 boys with hypospadias. The prevalence increased from 0.24% in 1977 to 0.52% in 2005, corresponding with an annual increase in prevalence of 2.40% (95% confidence interval: 1.94-2.86). The prevalence of hypospadias did not differ according to maternal age. The mean annual prevalence was 0.38% in sons of mothers aged <or=25 yr, 0.37% in sons of mothers aged 26-30 yr, 0.39% in sons of mothers aged 31-35 yr, and 0.39% in sons of mothers >35 yr.
The hypospadias prevalence was increasing in Denmark from 1977 to 2005. Increased maternal age did not explain this trend.
European Urology 05/2009; 55(5):1022-6. DOI:10.1016/j.eururo.2009.01.005 · 13.94 Impact Factor