Decreasing incidence of registered hydatidiform moles in Denmark 1999-2014.

Incidences of hydatidiform mole (HM) registered in European countries varies from 0.98/1000 to 2.17/1000 deliveries, while higher incidences have been reported in other parts of the world. We calculated the incidence by selecting data on HMs classified as "first", "second" and "third" from 01.01.1999 to 31.12.2014 registered in the Danish Pathology Registry, which we previously showed to be the most complete data source on the number of HMs in Denmark. In the study period, 1976 first HMs were registered; 1080 (55%) were classified as PHMs (partial HMs) and 896 (45%) as NPHMs (HMs not registered as PHMs). The average incidence of HM was 1.98/1000 deliveries. The incidence of PHM was 1.08/1000 deliveries and the incidence of NPHM was 0.90/1000 deliveries. Forty HMs were registered as second HMs; 85% (34/40) were of the same histopathological type as the first HM. The registered incidence of HM decreased from 2.55/1000 deliveries in 1999 to 1.61/1000 deliveries in 2014 (p < 0.005). The decrease in the incidence of HM was identical with a decrease in the incidence of PHM. New medical practices such as medical abortion and only forwarding selected pregnancy products for histopathologic examination may cause a declining number of HMs registered.

Hydatidiform mole: validity of the registration in the Danish National Patient Registry, the Danish Cancer Registry, and the Danish Pathology Registry 1999-2009.

PURPOSE: To examine the validity of registration of hydatidiform mole (HM) in the Danish National Patient Registry (NPR), the Danish Cancer Registry (DCR), and the Danish Pathology Registry (DPR). PATIENTS AND METHODS: We selected women registered with a first-time HM code in NPR, DCR, and DPR from 1999 to 2009. We found most women registered in DPR. For a random sample of women registered in DPR, the coding was validated by comparing with the pathology report. Completeness and positive predictive value (PPV) of registration with an HM code in NPR and DCR were calculated using DPR as the reference. Details of women registered in NPR or DCR, but not in DPR, were scrutinized. RESULTS: In NPR and DPR, 1,520 women were identified in total; 1,057 (70%) were found in both registries, 65 (4%) only in NPR, and 398 (26%) only in DPR. In DCR and DPR, 1,498 women were identified in total; 1,174 (78%) in both registries, 47 (3%) only in DCR, and 277 (19%) only in DPR. For 149/150 randomly selected women registered with an HM code in DPR (99%), the pathology report was consistent with the diagnosis of HM. Completeness of NPR was 73% (95% CI: 70%-75%) and PPV was 94% (95% CI: 93%-95%). Completeness of DCR was 72% (95% CI: 69%-75%) in 1999-2003 and 90% (95% CI: 87%-92%) in 2004-2009. PPV of DCR was 96% (95% CI: 95%-97%) throughout the period. CONCLUSION: Validation of registry data is important before using these. For research on the number of HMs in Denmark, DPR is the most valid data source. NPR and DCR appear to be equally valid before 2004. However, for research after 2004, DCR should be preferred rather than NPR.

Mortality in cancer patients with a history of cutaneous squamous cell carcinoma--a nationwide population-based cohort study.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is associated with underlying immunosuppression, so it may be a prognostic marker in patients with subsequent cancer. We therefore conducted a nationwide population-based Danish cohort study to evaluate whether a history of cutaneuos SCC has prognostic impact in patients with one of the following index cancers: non-Hodgkin's lymphoma (NHL), or cancer of the lung, colon, rectum, breast, or prostate. METHODS: We used Danish medical databases, which cover the entire Danish population of 5.6 million inhabitants and linked them using the unique personal identification number assigned to all Danish residents. From 1982 through 2003, we identified 745 index cancer patients with and 79,143 without previous cutaneous SCC. Using Cox proportional hazards regression, we calculated adjusted mortality rate ratios (MRRs) with 95% confidence intervals (CIs). RESULTS: Overall, previous SCC was associated with an increased mortality of cancer (MRR 1.13, 95% CI: 1.04-1.23). When examining index cancers separately, increased MRRs were found for cancer of the lung (MRR 1.23, 95% CI: 1.05-1.43), colon (MRR 1.13, 95% CI: 0.92-1.40), rectum (MRR 1.29, 95% CI: 1.00-1.67), breast (MRR 1.09, 95% CI: 0.82-1.43), and NHL (MRR 1.09, 95% CI: 0.81-1.47), but not for prostate cancer (MRR 0.99, 95% CI: 0.83-1.18). CONCLUSIONS: Our results suggest that previous cutaneous SCC is associated with poor prognosis of some cancers. This finding stresses the importance of adherence to the existing recommendations of screening, diagnosis, and treatment of cancer in patients with a history of SCC.

Hip fracture history and risk of nonmelanoma skin cancer: a Danish population-based study.

BACKGROUND: Vitamin D deficiency is associated with osteoporotic fractures, such as hip fracture. Sun exposure, the natural source of vitamin D, is the main risk factor for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In this study, we examined the association between a history of hip fracture and risk of BCC and SCC. METHODS: We conducted a population-based case-controlled study using data on BCC and SCC cases registered in the Danish Cancer Registry from 1990-2005. For each case, we selected five population controls matched by age and gender. We used conditional logistic regression to compute odds ratios (OR) and 95% confidence intervals (CI), while adjusting for chronic diseases and socioeconomic status. RESULTS: A history of hip fracture was associated with a decreased risk of BCC (OR 0.90, 95% CI 0.85-0.94), which was most pronounced in cases of tumors on the trunk, extremities, or at multiple sites. We found no association for SCC (OR 1.07, 95% CI 0.98-1.17). CONCLUSION: Our study showed an inverse association between history of hip fracture and risk of BCC, but not of SCC. Sun exposure, resulting in vitamin D synthesis, may explain the link between the two diseases.

Survival in breast cancer patients with bone metastases and skeletal-related events: a population-based cohort study in Denmark (1999-2007).

Bone lesions as a consequence of bone metastases in breast cancer patients can increase risk for skeletal-related events (SREs) (i.e., radiation to the bone, a pathological or osteoporotic fracture event, hypercalcemia, spinal cord compression, or surgery to the bone). The mortality risk for breast cancer patients with SREs subsequent to bone metastases is unclear. We assessed this relationship in a large, population-based cohort of breast cancer patients in Denmark. We identified 35,912 newly diagnosed breast cancer patients from January 1, 1999 to December 31, 2007 in the Danish National Patient Registry (DNPR) and followed them through April 1, 2008. Information on stage and treatment was obtained from the Danish Cancer Registry. We used the Kaplan-Meier method to estimate survival, and Cox's regression analysis to estimate the mortality rate ratio (MRR) by the presence of bone metastases with and without SREs, adjusting for age and comorbidity. The 5-year survival was 75.8% for breast cancer patients without bone metastases, 8.3% for patients with bone metastases, and 2.5% for those with both bone metastases and SREs. The adjusted MRR was 10.5 [95% confidence interval (CI) 9.5-11.6] for breast cancer patients with bone metastases, and 14.4 (95% CI 13.1-15.8) for those with bone metastases and SREs, compared with breast cancer patients with no bone metastases but possibly other sites of metastases. A similar pattern persisted when analyses were stratified by stage or treatment. Breast cancer patients with bone metastases and SREs have a poor prognosis compared to those with and without bone metastases regardless of cancer treatment or stage of disease at diagnosis.

Predictors for splenectomy among patients with primary chronic immune thrombocytopenia: a population-based cohort study from Denmark.

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.

Bone marrow reticulin and collagen content in patients with adult chronic immune thrombocytopenic purpura: a Danish nationwide study.

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.

Validity of asthma diagnoses in the Danish National Registry of Patients, including an assessment of impact of misclassification on risk estimates in an actual dataset.

OBJECTIVE: Asthma diagnoses recorded in the Danish National Registry of Patients (DNRP) are a misclassified measure of the actual asthma status. We quantified this misclassification and examined its impact on the results of an epidemiologic study on asthma. STUDY DESIGN AND SETTING: We validated the DNRP asthma diagnoses against records of asthma diagnosed at medical examinations conducted during mandatory conscription evaluation. We had data on 22,177 male conscripts who were born from January 1st, 1977 to December 31st, 1983, in a conscription district in northern Denmark. We obtained asthma diagnoses recorded among the conscripts in the DNRP from January 1st, 1977 through December 31st, 2003. We estimated sensitivity, specificity, and positive predictive value (PPV) of the DNRP asthma diagnoses. We then conducted sensitivity analysis to quantify the impact of nondifferential misclassification on the rate ratios measuring the association between asthma and risks of different skin cancers. RESULTS: The sensitivity of the DNRP for detecting an asthma diagnosis was 0.44 (95% confidence interval [CI]: 0.42-0.47), the specificity was 0.98 (95% CI: 0.98-0.99) and the PPV was 0.65 (95% CI: 0.62-0.68). Both direct and inverse associations between asthma and the different types of skin cancers became more pronounced after correcting for the misclassification. CONCLUSION: The DNRP registered asthma diagnosis may be used to measure asthma status in epidemiologic studies seeking to estimate relative effects of asthma. Even at low values of DNRP sensitivity of asthma diagnoses were not sufficient to nullify observed relative associations in an actual dataset. The specificity of DNRP asthma diagnosis is high.

Skin cancer risk among solid organ recipients: a nationwide cohort study in Denmark.

This study assessed the risk of skin cancer following transplantation of 4 types of solid organs, and the risk of skin cancer in patients with chronic diseases that lead to organ transplantations. A population-based cohort of 5279 Danish patients who underwent heart, lung, renal and liver transplantation, and 77,782 patients with chronic heart, lung, renal and liver diseases during 1977-2006 were included in the study. Linkage to the Danish Cancer Registry allowed complete follow-up for basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated. The SIR for squamous cell carcinoma was highest among heart (SIR = 113; 95% CI: 74-166), then renal (SIR = 81; 95% CI: 68-96), lung (SIR = 65; 95% CI: 28-128) and liver (SIR = 60; 95% CI: 27-113) recipients. SIR for squamous cell carcinoma was 4.8 (95% CI: 2.2-9.0) among renal failure patients, but not greatly elevated among patients with the other chronic diseases studied. Organ transplantation is a risk factor for squamous cell carcinoma, with immunosuppressive treatments being the most likely explanation for the association.

Methods to apply probabilistic bias analysis to summary estimates of association.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Non-melanoma skin cancer and ten-year all-cause mortality: a population-based cohort study.

Confounding from comorbidity and socioeconomic status may have biased earlier findings of all-cause mortality among patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We therefore examined all-cause mortality among 72,295 Danish patients with BCC, 11,601 with SCC, and 383,714 age- and gender-matched population control cohort subjects with extensive control for comorbidity and socioeconomic status. Data on cancer, death, and socioeconomic status were obtained from medical databases and Statistics Denmark. We analysed data using Cox regression analysis, with estimation of 10-year mortality rate ratios (MRRs) and 95% confidence intervals (CI). Mortality was reduced among patients with BCC (10-year MRR = 0.91 (95% CI: 0.89-0.92) and did not vary by age, comorbidity, or socioeconomic status. Mortality among patients with SCC was increased and varied by age, selected chronic diseases, but not socioeconomic status. The reduced mortality observed among patients with BCC and the increased mortality among patients with SCC persisted even after extensive control for comorbidity and socioeconomic status.

Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007).

PURPOSE: We describe mortality in patients with prostate cancer with and without bone metastasis further characterized by skeletal related events. MATERIALS AND METHODS: We performed a cohort study of 23,087 incident patients with prostate cancer with a median 2.2-year followup identified through the Danish National Patient Registry from 1999 to 2007. We estimated the cumulative incidence of bone metastasis and skeletal related events, and described survival using the Kaplan-Meier method. Based on a Cox proportional hazard model we estimated mortality rate ratios and associated 95% CIs comparing mortality rates between patients by bone metastasis with and without skeletal related events, adjusting for age and comorbidity. RESULTS: Of the patients 569 (almost 3%) presented with bone metastasis at prostate cancer diagnosis, of whom 248 (43.6%) experienced a skeletal related event during followup. Of the 22,404 men (97% overall) without bone metastasis at diagnosis 2,578 (11.5%) were diagnosed with bone metastasis and 1,329 (5.9%) also experienced a skeletal related event during followup. One and 5-year survival was 87% and 56% in patients with prostate cancer without bone metastasis, 47% and 3% in those with bone metastasis, and 40% and less than 1% in those with bone metastasis and skeletal related events, respectively. Compared with men with prostate cancer without bone metastasis the adjusted 1-year mortality rate ratio was 4.7 (95% CI 4.3-5.2) in those with bone metastasis and no skeletal related events, and 6.6 (95% CI 5.9-7.5) in those with bone metastasis and a skeletal related event. CONCLUSIONS: Bone metastasis and skeletal related events predict poor prognosis in men with prostate cancer.

Validity of a procedure to identify patients with chronic idiopathic thrombocytopenic purpura in the Danish National Registry of Patients.

BACKGROUND: Administrative data may be useful for epidemiological studies of chronic idiopathic thrombocytopenic purpura (ITP). However, the quality of the recorded diagnoses needs evaluation. AIM: We evaluated the validity in predicting chronic ITP of the International Classification of Diseases (ICD)-10 diagnoses of ITP in the Danish National Registry of Patients (NRP). METHODS: We used the NRP to identify patients with ITP, according to code D69.3, from January 1, 1996 to December 31, 2007. We defined chronic ITP as lasting longer than 6 months by including only patients with 2 or more hospital ITP diagnoses over longer than 6 months. We confirmed diagnoses by evaluating each candidate chronic ITP patient's medical chart and estimating the positive predictive value (PPV) and 95% confidence interval (CI) of the recorded NRP diagnostic code. RESULTS: We identified 513 patients with chronic ITP in the NRP. We were able to retrieve the charts of 439. After evaluation of the charts, 410 patients were deemed to have a valid diagnosis of chronic ITP, yielding a PPV of 0.93 (95% CI: 0.91-0.96). CONCLUSION: The validity of this procedure to identify chronic ITP patients was high. The NRP is valid for epidemiological studies of patients with chronic ITP.

Validity of the recorded International Classification of Diseases, 10th edition diagnoses codes of bone metastases and skeletal-related events in breast and prostate cancer patients in the Danish National Registry of Patients.

OBJECTIVE: The clinical history of bone metastases and skeletal-related events (SREs) secondary to cancers is not well understood. In support of studies of the natural history of bone metastases and SREs in Danish prostate and breast cancer patients, we estimated the sensitivity and specificity of hospital diagnoses for bone metastases and SREs (ie, radiation therapy to the bone, pathological or osteoporotic fractures, spinal cord compression and surgery to the bone) in a nationwide medical registry in Denmark. STUDY DESIGN AND SETTING: In North Jutland County, Denmark, we randomly sampled 100 patients with primary prostate cancer and 100 patients with primary breast cancer diagnoses from the National Registry of Patients (NRP), during the period January 1st, 2000 to December 31st, 2000 and followed them for up to five years after their cancer diagnosis. We used information from medical chart reviews as the reference for estimating sensitivity, and specificity of the NRP International Classification of Diseases, 10th edition (ICD-10) coding for bone metastases and SRE diagnoses. RESULTS: For prostate cancer, the overall sensitivity of bone metastases or SRE coding in the NRP was 0.54 (95% confidence interval [CI]: 0.39-0.69), and the specificity was 0.96 (95% CI: 0.87-1.00). For breast cancer, the overall sensitivity of bone metastases or SRE coding in the NRP was 0.58 (95% CI: 0.34-0.80), and the specificity was 0.95 (95% CI: 0.88-0.99). CONCLUSION: We measured the validity of ICD-10 coding in the Danish NRP for bone metastases and SREs in prostate and breast cancer patients and found it has adequate sensitivity and high specificity. The NRP remains a valuable tool for clinical epidemiological studies of bone metastases and SREs.

Do incident and new subsequent cases of non-melanoma skin cancer registered in a Danish prospective cohort study have different 10-year mortality?

BACKGROUND: The Danish Gerda Frentz Cohort (GFC) was created for registering all incident and new subsequent cases of non-melanoma skin cancer (NMSC) among patients seen by Danish dermatologists in 1995. We have recently found, in this cohort, a lower 10-year mortality than in the general population in patients with basal cell carcinoma (BCC). Differences in mortality between incident and new subsequent cases, incomplete registration or selection bias may be responsible for this finding. METHODS: We aimed to quantify differences in mortality between incident and new subsequent cases of NMSC in the GFC and to compare mortality among incident cases recorded in the GFC and those recorded in the Danish Cancer Registry (DCR). We followed 10,830 skin cancer patients and 106,696 age-, gender- and residence-matched population controls through 2006 and computed their cumulative mortality and mortality rate ratio (MRR). RESULTS: One-, 5-, and 10-year cumulative mortality of incident and new subsequent cases of BCC and SCC in the GFC were similar. Likewise, MRR for incident BCC (MRR=0.91; 95% CI 0.84-0.98) and incident SCC (MRR=1.29; 95% CI 1.05-1.56) among patients registered in the GFC were similar to their counterparts in the DCR (MRR=0.96; 95% CI 0.91-1.00 and MRR=1.36; 95% CI 1.22-1.52). CONCLUSION: Mortality of incident and new subsequent cases of NMSC was similar and thus did not explain the reduced mortality of BCC patients.