Danish National Prescription Registry Research Articles

Prediagnostic use of menopausal hormone therapy and long-term survival of localized epithelial ovarian cancer: The Extreme study.

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC.

Sleep Disorders and Sleep Disturbances in Persons with Multiple Sclerosis: A Population-Based Matched Case-Control Study in Denmark

Introduction: Adverse sleep is common in multiple sclerosis (MS). Population-based studies including adequate control groups are lacking. We hypothesized that the prevalence of sleep disorders and other sleep disturbances would be higher in persons with MS than in controls. Methods: We conducted a population-based study linking individual-level data from the Danish MS Registry (n = 21,943 persons with MS) and the Danish Population Registry (n = 109,715 matched controls) with information on sleep disorders from the Danish National Patient Registry and other sleep disturbances assessed by dispensed prescription drugs from the Danish National Prescription Registry. Results: Prevalence of diagnosed sleep disorders in terms of central hypersomnia (0.15% vs. 0.06%), sleep disturbances (1.05% vs. 0.70%), and sleep movements (0.22% vs. 0.13%) and other sleep disturbances identified by dispensed central acting (10.73% vs. 1.10%) and hypnotic use (30.65% vs. 20.13%) medication was statistically significantly higher among persons with MS when compared to controls. We found no statistically significant difference in the prevalence of sleep apnea and parasomnia between groups. Stratified by sex and age at MS diagnosis, results for differences between persons with MS and controls were similar. Conclusion: In this registry-based study, we found that the prevalence of several diagnosed sleep disorders was higher in persons with MS than in controls, that is, those reflecting insomnia and daytime symptoms including hypersomnia. Other sleep disturbances identified by dispensed prescription medication were markedly higher in persons with MS than in controls.

Paternal Preconceptional Alcohol Use Disorder With the Offspring's Mortality Risk

IntroductionPaternal pre-conceptional alcohol use may contribute to early pregnancy loss. However, the link between paternal pre-conceptional alcohol use disorder(AUD) and long-term offspring's mortality risk remains unclear. This study examined the association of paternal pre-conceptional AUD and recency of diagnosis with offspring's mortality, and further stratified the mortality after the first year of birth by age. MethodsThis is a nationwide cohort study with 1973174 Danish births(1980-2012), with follow-up from birth until death, emigration, or 31-December 2016. Paternal conceptional AUD was identified from Danish National Patient Register and Prescription Registry, categorizing recency of diagnosis into <1 year, 1-<4 years, 4-<8 years, ≥8 years. Logistic regression estimated odds ratios and 95% confidence intervals(CIs) for offspring mortality risk. All data were analyzed in 2023. ResultsPaternal pre-conceptional AUD was associated with a 28% increased mortality after one year of birth(95%CI=1.09-1.51), 23% increased infant mortality(95%CI=1.07-1.42), and 23% increased odds of stillbirth(95%CI=1.06-1.43). Paternal AUD diagnosed <1 year before conception was associated with an 85%-111% increased risk of mortality in offspring aged 15-40 years. More recent AUD diagnosis(i.e.,one year before conception) had a higher risks of death from infectious and circulatory diseases in offpring. ConclusionsOffspring of fathers with AUD before conception had higher mortality risk from birth to early adulthood, especially when AUD diagnosis is close to conception. Current awareness regarding paternal pre-conceptional alcohol dependence use is insufficient. Promoting alcohol dependence avoidance, including educating men on the impact of alcohol on child health during pre-pregnancy examination may help reduce or prevent long-term offspring mortality.

Sedative drug prescription patterns in Danish adults from 2002 through 2021. A register-based cohort study

ObjectivePharmacological treatment strategies for insomnia seem to vary, and there is lack of knowledge about how sedative drugs are used in a real-world setting. We investigated changes in sedative drug prescription patterns in Danish adults who initiated treatment between 2002 and 2016. MethodsAll adults with a first-time purchase of a sedative drug registered in the Danish National Prescription Register from 2002 through 2016 were followed for five years between 2002 and 2021 for subsequent prescriptions of sedative drugs, death, or emigration. Sedative drugs were classified into anxiolytic benzodiazepines (N05BA), hypnotic benzodiazepines (N05CD), Z-drugs (N05CF), melatonin (N05CH01), promethazine (R06AD), and low-dose quetiapine (N05AH04). Analyses were stratified on time: 2002–2006, 2007–2011, and 2012–2016. ResultsA total of 842,880 individuals purchased their first sedative drug between 2002 and 2016. Most of them (40.0%) initiated treatment between 2002 and 2006, whereas 29.2% initiated treatment in 2012–2016. In 2002–2006, anxiolytic benzodiazepines (46.4%), Z-drugs (42.8%), and hypnotic benzodiazepines (5.4%) were the most common first treatment. This pattern changed over time with a gradual increase in the use of melatonin, promethazine, and low-dose quetiapine, which in 2011–2016 accounted for 27% of all first treatments. During the five years from first prescription, around 27% shifted to a different sedative drug. This percentage increased slightly over time, but over time the first shift to another drug class was most often to a Z-drug or anxiolytic benzodiazepine. Few individuals (5.8%) had more than one shift and the third choice seemed randomly distributed across all other drug classes. ConclusionSedative drug prescriptions are distributed on different drug classes, with Z-drugs and anxiolytic benzodiazepines as the most frequent first treatment, and second choice in case of shift.

Validation of the "Indication for Use" (INDO) Variable in the Danish National Prescription Registry.

Despite its potential value in register-based pharmacoepidemiologic research, recorded information on "indication for use" (INDO) in the Danish National Prescription Registry has rarely been used, likely because of questions about the variable's validity, which to our knowledge no study has systematically assessed. We extracted data on 80,814 prescriptions from the software systems (PharmaNet and C2) of five Danish community pharmacies filled between 4 and 16 February 2019 and 2020. Using the indication information recorded in the pharmacy software systems as the gold standard, we evaluated the extent and quality of the corresponding information from the Prescription Registry. Of all prescriptions identified, we captured >99% in the Prescription Registry. The proportion of prescriptions with recorded indication codes in the Prescription Registry was 82% (n = 66,164) but was lower for C2 than PharmaNet. Correcting for the overrepresentation of C2 data in our sample, the estimated proportion of registration was ≈88%. Almost 100% (66,158 of 66,164) of the prescriptions with recorded indication codes in the Prescription Registry had correctly recorded indication codes. Nonspecific indication codes were present in 5.6%-36% of selected drugs and drug classes. Prescriptions filled at Danish community pharmacies are accurately captured by the Danish National Prescription Registry, and the recorded information on indication is generally valid and usable in research. However, minor concerns remain about missingness, nonspecific recorded indication codes, and lower validity, and a higher proportion of missingness of recorded indication codes is expected before 2017.A supplementary digital video by the article's co-author, Hanin Harbi, is available at http://links.lww.com/EDE/C89.

Are self-reported medical conditions and medicine use from middle-aged and older adults credible? A validation study comparing Danish SHARE-data with National Health Register data

Self-reported information on medical conditions and medicine use is widely used in epidemiological research. We investigated the validity of self-reported medical conditions and medicine use from Danish participants in the Survey of Health, Ageing and Retirement in Europe. Self-reported health data were linked at individual level with the National Patient Registry and the Danish National Prescription Registry (n=5572). Agreement was assessed by kappavalue and presented as sensitivity, specificity, predictive values, and odds ratios. The agreement of self-reported medical conditions varied by type (κ=0.23-0.67), lowest for cholesterol-related diseases,highest for diabetes. Self-reported medicine use varied by medication type (κ=0.33-0.90) lowest for painkillers, highest for diabetes. Women had lower odds for self-reporting medicine use correctlybut higher odds for self-reported diseases. Higher age was associated with lower agreement, while higher education with higher agreement. Although Danish data from the Survey of Health, Ageing and Retirement in Europe on medical conditions and medicine vary, the data are valid for epidemiological use for most medicine data, and for diseases associated with hospitalizations or influencing everyday life.Caution is warranted for self-reported data from 70+ year olds and people with lower educational level.

Long-Term Use of Benzodiazepines and Benzodiazepine-Related Drugs: A Register-Based Danish Cohort Study on Determinants and Risk of Dose Escalation.

The authors investigated the frequency and determinants of long-term use and risk of dose escalation of benzodiazepines and benzodiazepine-related drugs (benzodiazepine receptor agonists, or BZRAs). All adults ages 20-80 years living in Denmark on January 1, 2000 (N=4,297,045) were followed for redeemed prescriptions of BZRAs in the Danish National Prescription Registry from January 1, 2000, to December 31, 2020. For each drug class, we calculated long-term use for more than 1 or 7 years, and dose escalation measured as increase in dose to a level above the recommended level. Associations were examined using logistic regression. The authors identified 950,767 incident BZRA users, of whom 15% and 3% became long-term users for more than 1 or 7 years, respectively. These percentages were highest for individuals who initiated Z-drugs (17.8% and 4%). Among the 5% of BZRA users who had at least 3 years of continuous use, there was no indication of dose escalation, as the median dose remained relatively stable. However, 7% (N=3,545) of BZRA users escalated to doses above the recommended level. Psychiatric comorbidity, especially substance use disorder, was associated with higher risk of long-term use and dose escalation. A limited portion of the population that received BZRA prescriptions were classified as continuous users, and only a small proportion of this group escalated to doses higher than those recommended in clinical guidelines. Thus, this study does not, under the current regulations, support the belief that BZRA use frequently results in long-term use or dose escalation.

Danish Prostate Registry (DanProst) – an Updated Version of the Danish Prostate Cancer Registry, Methodology, and Early Results

In 2016, we introduced the Danish Prostate Cancer Registry (DaPCaR) which was built on the National Pathology Register from 1995 to 2011. DaPCaR was laborious to use as most data had to be manually imputed with no regular updates. In here we present a new comprehensive centralized prostate registry called the Danish Prostate Registry (DanProst), which includes all men having undergone any histological evaluation of prostate tissue merged with laboratory-, treatment-, prescription data as well as vital status. Here the data included and the methodology of DanProst are described. DanProst is built upon all men with a histological assessment of the prostate from the Danish National Registry for Pathology. The primary histology and potential prostate cancer histological diagnosis for each unique individual is extracted and translated by newly made algorithms for topography, procedure, diagnostic conclusion, and pathological staging. Further information is added from DaPCaR, the CPR Registry, the Danish Cause of Death Registry, the Danish Cancer Registry, the National Patient Registry, the Danish Register of Laboratory Results for Research, and the Danish National Prescription Registry. The translation algorithms were validated based on the comparison with DaPCaR in the period 2010–2016. DanProst includes 190,422 men. A total of 95,152 (50%) men are diagnosed with prostate cancer until 2021. Median diagnostic PSA was 11 ng/ml, most men are diagnosed by ultrasound-guided biopsy (N = 63,751; 67%), and most frequently defined primary treatment was radical prostatectomy (N = 14,778; 19%). DanProst to DaPCaR coherency was > 99%, 95%, and 94% for the primary histological procedure, primary histological conclusion, and diagnostic histological conclusion, respectively. DanProst is a continuously updated, centrally kept, validated registry with automatic integration of data from other national registries, allowing for contemporary nationwide analysis in men with histological assessment of the prostate.

Use of hypnotic-sedative medication and risk of falls and fractures in adults: A self-controlled case series study.

To evaluate the risk of falls and fractures in users of benzodiazepines, Z-drugs, or melatonin. We followed 699,335 adults with a purchase of benzodiazepines, Z-drugs, or melatonin in the Danish National Prescription Registry between 2003 and 2016 for falls and fractures in the Danish National Patient Registry between 2000 and 2018. A self-controlled case-series analysis and conditional Poisson regression were used to derive incidence rate ratios (IRR) of falls and fractures during six predefined periods. In total 62,105 and 36,808 adults, respectively, experienced a fall or fracture. For older adults, the risk of falls was highest during the 3-month pre-treatment period (IRRmen+70 , 4.22 (95% confidence interval, 3.53-5.05), IRRwomen + 70 , 3.03 (2.59-3.55)) compared to the baseline (>1 year before initiation). The risk continued to be higher in the later treatment periods. Contrarily, in men and women aged 40-69 years, the risk was only higher in the 3-month pre-treatment period. The incidence of falls among young men and women was slightly lower after initiation of sedating medication (treatment period, IRRmen15-39 , 0.66 (0.50-0.86), IRRwomen15-39 , 0.65 (0.51-0.83)). Analyses with fractures as outcome yielded similar results. Although falls and fractures occur more often in persons using sedative-hypnotic medication, the higher risk of falls and fractures in the pre-treatment period relative to the period directly after treatment, suggests that this association is better explained by other factors that elicited the prescription of this medication rather than the adverse effects of the sedative-hypnotic medication.

Long-term medical treatment and adherence in patients with left ventricular assist devices: a Danish nationwide cohort study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Grant from Karen Elise Jensen Foundation and Helse Foundation. Introduction An increasing number of patients with advanced heart failure (HF) live with a left ventricular assist device (LVAD). Data regarding medical treatment after LVAD implantation is sparse, including the impact of socioeconomic factors and multimorbidity. Purpose To describe medication use and assess the influence of socioeconomic factors and multimorbidity on medication use in the first two years following LVAD implant. Methods We conducted a nationwide cohort study based on data from the Danish clinical LVAD databases, the Scandiatransplant Database, and Danish nationwide administrative and medical registries. We identified patients with LVAD implantation between January 1, 2008, and December 31, 2018, who were discharged with LVAD therapy. Patients were followed until heart transplantation, LVAD explant, death, or December 31, 2018. Medication use was defined as a redeemed prescription from the Danish National Prescription Registry using ATC codes. Socioeconomic factors included cohabitation status, highest education attained, employment status, and personal income. Multimorbidity was defined as two or more chronic conditions. Medical treatment 90 days before LVAD implant and 720 days post-LVAD were assessed using descriptive statistics in 90 days intervals. Results We identified 119 patients; 88.2% were male, and the mean age (standard deviation) was 52.6 (14.5) years. The median (IQR) follow-up time was 0.8 years (0.4;1.8 years). 44.5% of patients underwent heart transplantation, and 4.2% had the LVAD explanted during follow-up. 27.7% of the patients were living alone, 27.7% had a low educational level, 37.8% were unemployed, 15.1% were in the lowest income (25 percentile), and 16.8% were categorized with multimorbidity (without cardiovascular disease group). The proportion of medication users of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (88.7%), beta-blocker (67%), mineralocorticoid receptor antagonists (62.9%), warfarin (87.6%), and aspirin (55.7%) within 90 days post-LVAD were substantially higher than pre-LVAD and were stable during the follow-up (Figure 1). In contrast, the proportion of diuretic users was lower post-LVAD implant than pre-LVAD, decreased further, and plateaued up to 180 days after hospital discharge. Stratified analyses according to socioeconomic factors and multimorbidity showed no differences in medication use (Figure 2). Conclusions Guideline-derived medical therapies for HF increased after LVAD implantation and were stable during long-term follow-up. As expected, the proportion of warfarin users increased substantially after LVAD implantation. Surprisingly, the percentage of aspirin users was not at the same level as for warfarin users. Socioeconomic factors and comorbidity burden did not influence long-term medication use of guideline-derived HF therapies, warfarin and aspirin in LVAD recipients.

Use of statins and risk of myeloproliferative neoplasms: a Danish nationwide case-control study.

Previous studies have indicated a possible cancer-protective effect of statins in solid cancers; however, this has never been investigated in myeloproliferative neoplasms (MPNs). We aimed to investigate the association between statin use and the risk of MPNs in a nested nationwide case-control study, using Danish national population registries. Information on statin use was obtained from the Danish National Prescription Registry, and patients diagnosed with MPNs between 2010 and 2018 were identified from the Danish National Chronic Myeloid Neoplasia Registry. The association between statin use and MPNs was estimated using age- and sex-adjusted odds ratios (ORs) and fully adjusted ORs (aORs), adjusting for prespecified confounders. The study population included 3816 cases with MPNs and 19 080 population controls (5:1) matched for age and sex using incidence density sampling. Overall, 34.9% of the cases and 33.5% of the controls ever used statins, resulting in an OR for MPN of 1.07 (95% confidence interval [CI], 0.99-1.16) and an aOR of 0.87 (95%CI, 0.80-0.96), respectively. 17.2% were categorized as long-term users (≥5 years) among the cases compared with 19.0% among controls, yielding an OR for MPN of 0.90 (95%CI, 0.81-1.00) and an aOR of 0.72 (95%CI, 0.64-0.81). Analysis of the effect of the cumulative duration of statin use revealed a dose-dependent response, and the association was consistent for sex, age, and MPN subgroups and across different statin types. Statin users were associated with significantly lower odds of being diagnosed with an MPN, indicating a possible cancer-preventive effect of statins. The retrospective of this study precludes causal inferences.

Does attendance in outdoor kindergartens reduce the use of antibiotics in children?

To determine whether children enrolled in rural outdoor kindergartens had a lower risk of redeeming at least one prescription for antibiotics compared to children enrolled in urban conventional kindergartens, and if type of antibiotics prescribed differed according to kindergarten type. Two Danish municipalities provided data including civil registration numbers from children enrolled in a rural outdoor kindergarten in 2011-2019, and a subsample of all children enrolled in urban conventional kindergartens in the same period. Civil registration numbers were linked to individual-level information on redeemed prescriptions for antibiotics from the Danish National Prescription Registry. Regression models were performed on 2,132 children enrolled in outdoor kindergartens, and 2,208 children enrolled in conventional kindergartens. There was no difference between groups in risk of redeeming at least one prescription for all types of antibiotics (Adjusted Risk Ratio: 0.97 (95% Confidence Intervals 0.93,1.02, p=0.26)). Similarly, there were no differences between kindergarten type and risk of redeeming at least one prescription for systemic, narrow-spectrum systemic antibacterial, broad-spectrum systemic antibacterial, or topical antibiotics. Compared to children who were enrolled in conventional kindergartens, children who were enrolled in outdoor kindergartens did not have a lower risk of redeeming prescriptions for any type of antibiotics.

#2976 CHRONIC KIDNEY DISEASE WITH COMORBIDITY IN PRIMARY CARE: CARDIORENAL TREATMENT, QUALITY OF CARE AND PROGNOSIS

Abstract Background and Aims Diabetes, heart failure, hypertension and cardiovascular disease are common in primary care, and frequently coexist with impaired kidney function (CKD), further increasing risk of cardiovascular- and renal events as well as premature death. These comorbidities therefore call for more complex treatment regimens and monitoring. Our aim was to describe the prevalence, management, and prognosis of individuals with CKD and additional comorbidity in a large primary care cohort. Method Individuals were included from the Copenhagen Primary Care Laboratory (CopLab) Database, which contains 112 million biochemistry results from persons followed in primary care between 2000 and 2015 and divided into three groups based on (CKD-EPI) eGFR (&amp;gt;60 ml/min, 30-59 ml/min and &amp;lt;30 ml/min) with or without comorbidity in the form of diabetes or heart failure. We included all individuals with at least two measurements of creatinine. The date of the second measurement of creatinine was considered index date (baseline). The database has been combined with pharmacological data (The Danish National Prescription Registry), outpatient clinic visits and hospitalizations (The Danish National Patient Registry - NPR), and mortality information (The Danish Civil Registration System). Heart Failure was defined by ICD-codes in NPR from outpatient clinic visits and hospitalizations and we calculated crude event rates for a range of outcomes according to comorbidity. Diabetes was defined as at least one measurement of plasma or serum glucose ≥11 mmol/l or HbA1c ≥48 mmol/mol in CopLab. We evaluated monitoring of eGFR, albuminuria (UACR) and use of guideline-recommended pharmacological therapy (i.e. RAS-blockers and statins) in each group. Results In the total primary care population of 171,134 individuals of which 63.8% were female, 8.3% had impaired kidney function (eGFR&amp;lt;60ml/min). The median follow-up for the three eGFR groups was 8.4, 4.7 and 2.0 years, respectively. Overall, event rates were higher in individuals with impaired kidney function and comorbidity, i.e. mortality in the group with eGFR&amp;lt;30 ml/min with concurrent heart failure; 42.8 per 100 patient-years (PY). Event rates for ESKD were low in general (0.03 to 0.51 per 100 PY) except for individuals with eGFR&amp;lt;30 ml/min (2.1 to 3.5 per 100 PY). Annual monitoring of eGFR was high in all groups (&amp;gt;90%) with increasing frequency in individuals with impaired kidney function, and measurement of UACR was low in groups with non-diabetic CKD (10-30%). Antihypertensive treatment was frequently prescribed in eGFR &amp;lt;30 ml/min; overall 87.6% and 94.8% with coexisting diabetes and 92.8% with coexisting heart failure. The use of RAS inhibition was more used in diabetes and in heart failure (&amp;gt;50%) but less with low eGFR. Statin therapy was used in approximately 50% of individuals with diabetes, regardless of CKD group, but was used to a much less extent in non-diabetic CKD (20-24%). Conclusion Our data from a large primary care cohort demonstrate a high prevalence of coexisting diabetes and/or heart failure with CKD, increasing the risk for adverse outcomes. The quality of CKD care in general practice may be improved, especially in the non-diabetic population.

Preconception use of antibiotics and fecundability: a Danish prospective cohort study

To assess the association between preconception antibiotic use and fecundability, the per menstrual cycle probability of conception. SnartForaeldre.dk, a Danish prospective cohort study of women trying to conceive (2007-2020). Not applicable. 9462 female participants, median age 29 years at enrollment. Antibiotic use was defined by filled prescriptions retrieved from the Danish National Prescription Registry, using Anatomical Therapeutic Chemical codes, and modeled as time-varying (menstrual cycle-varying) exposure. Pregnancy status was reported on female follow-up questionnaires every 8 weeks for up to 12 months or until conception. Fecundability ratios (FR) and 95% confidence intervals (CI) were computed using proportional probabilities regression models, with adjustment for age, partner age, education, smoking, folic acid supplementation, body mass index, parity, cycle regularity, timing of intercourse, and sexually transmitted infections. During all cycles of observation, the percentage of participants filing at least 1 antibiotic prescription was 11.9%; 8.6% had a prescription for penicillins, 2.1% for sulfonamides, and 1.8% for macrolides. Based on life-table methods, 86.5% of participants conceived within 12 cycles of follow-up. Recent preconception antibiotic use was associated with reduced fecundability (≥1 prescription vs. none: adjusted FR = 0.86; 95% CI, 0.76-0.99). For participants using penicillins, sulfonamides, or macrolides, the adjusted FRs were 0.97 (95% CI, 0.83-1.12), 0.68 (95% CI, 0.47-0.98), and 0.59 (95% CI, 0.37-0.93), respectively. Preconception use of antibiotics, specifically sulfonamides and macrolides, was associated with decreased fecundability compared with no use. The observed associations may be explained plausibly by confounding by indication, as we lacked data on indications for the prescribed antibiotics. Consequently, we cannot separate the effect of the medication from the effect of the underlying infection.

Valsartan, Losartan and Irbesartan use in the USA, UK, Canada and Denmark after the nitrosamine recalls: a descriptive cohort study

ObjectivesTo examine valsartan, losartan and irbesartan usage and switching patterns in the USA, UK, Canada and Denmark before and after July 2018, when the first Angiotensin-Receptor-Blocker (ARB) (valsartan) was recalled.DesignRetrospective...

Incidence and prognosis of superficial vein thrombosis during pregnancy and the post-partum period: a Danish nationwide cohort study

The incidence of superficial vein thrombosis (SVT) of the legs and the subsequent risk of venous thromboembolism during pregnancy and the post-partum period is unknown. To better understand the clinical course of SVT during these times, we aimed to estimate the incidence rate of SVT during pregnancy and in the post-partum period, as well as the risk of subsequent venous thromboembolism. In this nationwide cohort study, we collected data on all pregnant women who delivered between Jan 1, 1997, and Dec 31, 2017, in Denmark were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, and the Danish National Prescription Registry. Data on ethnicity were not available. Incidence rates per 1000 person-years were calculated for each trimester and the antepartum and post-partum period. Among women with a pregnancy-related SVT, risk of subsequent venous thromboembolism within the same pregnancy or post-partum period were calculated and compared with a matched cohort of pregnant women without SVT using Cox proportional hazards analysis. During 1 276 046 deliveries, 710 diagnoses of lower extremity SVT occurred from conception up to 12 weeks postpartum (0·6 per 1000 person-years [95% CI 0·5-0·6]). The incidence rates of SVT per 1000 person-years were 0·1 (95% CI 0·1-0·2) during the during the first trimester, 0·2 (0·2-0·3) during the second trimester, and 0·5 (0·5-0·6) during the third trimester. The incidence rate was 1·6 per 1000 person-years (95% CI 1·4-1·7) during the post-partum period. Of the 211 women with antepartum SVT included in the analysis, 22 (10·4%) were diagnosed with venous thromboembolism, compared with 25 (0·1%) in women without SVT (hazard ratio 83·3 [95% CI 46·3-149·7]). The incidence rate of SVT during pregnancy and the post-partum period was low. However, if SVT during pregnancy was diagnosed, the risk of developing venous thromboembolism during the same pregnancy was high. These results might help physicians and patients to make decisions about anticoagulant management of pregnancy-related SVT. None.

Abstract P4-03-02: Low-dose aspirin prescriptions and breast cancer recurrence: a Danish nationwide cohort study with up to 23 years of follow-up

Abstract Background Low-dose aspirin irreversibly inhibits the cyclooxygenase enzymes COX-1 and COX-2, which catalyze the formation of prostaglandins and thromboxanes, inhibiting platelet aggregation. Platelets are thought to play a role in tumorigenesis. As such, aspirin may have a beneficial effect on breast cancer prognosis, but results to date are conflicting. Objectives To evaluate the association between aspirin use and breast cancer recurrence up to 23 years after primary diagnosis. Methods We included all women diagnosed with non-metastatic breast cancer during 1996-2004 registered in the Danish Breast Cancer Group (DBCG) clinical database. We obtained information on aspirin prescriptions (&amp;gt;= 2 prescriptions filled between cancer diagnosis and the landmark) from the Danish National Prescription Registry. Information on early and late (&amp;gt;10 years after primary diagnosis) recurrence was obtained using the DBCG database (for recurrence within the first 10 years after diagnosis) and for late recurrence via a previously described and validated algorithm, drawing on data from the Danish National Patient Registry, the Danish Pathology Registry, the Danish Cancer Registry and a contralateral breast cancer database. We used Cox regression to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CI) employing landmark analyses starting follow-up at years 5, 10, 15, and 20 after primary diagnosis. We adjusted for potential confounders including calendar year of diagnosis, menopausal status, comorbidities, estrogen receptor status, clinical stage, grade, surgery type, chemo- and endocrine therapy, diagnostic codes for alcoholism and obesity, as well as co-medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, bisphosphonates, metformin, digoxin, hormone replacement therapy, non-steroidal anti-inflammatory drugs, and vitamin K antagonists). We followed patients until recurrence, death, second cancer, loss to follow-up, or 31 December 2018. Results Among 21,684 women with non-metastatic breast cancer, 4,902 experienced recurrence during 242,427 person-years of follow-up. Our landmark analyses showed a reduced hazard of recurrence in the 5-, 10-, and 15-year landmark cohorts (5-year landmark adjusted HR = 0.80, 95% CI = 0.68, 0.94; 10-year landmark adjusted HR = 0.84, 95% CI = 0.71, 1.00, 15-year landmark adjusted HR = 0.83, 95% CI = 0.61, 1.14). The 20-year landmark analysis revealed an adjusted HR of 1.09 (95% CI = 0.49, 2.46). Conclusions The potential anti-cancer effect of aspirin appears most pronounced in the first 15 years after breast cancer diagnosis. Funding Elisabeth Solmunde is funded by the Danish Cancer Society (R320-A18464-B5768) and the Independent Research Fund Denmark (1149-00013B). This work was supported by grants to Deirdre Cronin-Fenton from the Danish Cancer Society (“Knæk Cancer” R147-A10100). Citation Format: Elisabeth Solmunde, Rikke N Pedersen, Mette Nørgaard, Lene Mellemkjær, Søren Friis, Bent Ejlertsen, Thomas P. Ahern, Deirdre Cronin-Fenton. Low-dose aspirin prescriptions and breast cancer recurrence: a Danish nationwide cohort study with up to 23 years of follow-up [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-02.

DOP21 Disease activity patterns of paediatric Inflammatory Bowel Disease – A Danish nationwide cohort study 1996-2018

Abstract Background Inflammatory bowel diseases (IBD) are heterogenous diseases in terms of their clinical presentation including frequency and severity of flares. We aimed to describe disease activity (DA) patterns in a Danish nationwide cohort including all IBD patients diagnosed &amp;lt; 18 years of age between 1996 and 2018. Methods Paediatric patients diagnosed with Crohn’s disease (pCD) or ulcerative colitis (pUC) were identified from national registers (Danish Civil Registration System, National Patient Registry, Danish National Prescription Registry and Danish Pathology Data Bank). DA was assessed in both incident and prevalent pIBD patients and categorised as mild-moderate in case of a course of topical corticosteroids, oral budesonide, or topical 5-ASA. Episodes were categorised as severe if they involved hospitalization, surgery, oral corticosteroids or biological therapy. DA patterns in incident patients were assessed for 5- and 10-year periods from diagnosis as follows: The 5-year DA pattern: A) No years with DA. B) 1 or 2 years with at least one episode of DA in each year. C) 3 or 4 years with at least one episode of DA in each year. D) All 5 years with at least one yearly episode of DA. The 10-year DA pattern: A) Decreasing: First 5 years with 2 or more years with DA; following 5 years with 2 years or less with DA. B) Increasing: First 5 years with less than 2 years with DA; following 5 years with 2 or more years with DA. C) Chronic continuous: First 10 years with at least 8 years with DA. D) Quiescent: First 10 years with one year or less with DA. E) Chronic intermittent: DA pattern that does not meet the criteria above. Results 1,965 pCD and 1,838 pUC incident patients were included. At diagnosis severe DA was found in 87% in pCD and 80% in pUC, in addition to 6.1% of pUC patients who had a colectomy the first year. After 5 years of disease the annual proportion of pCD and pUC with no DA 70% and 61%. This remained constant after 10 years (pCD:72% and pUC: 64%). In pUC, 12% and 16% required colectomy 5 and 10 years after diagnosis. In prevalent pCD (N=2,515) and pUC (N=2,428) the proportion with no DA each calendar year was stable (pCD: 59%-73% and pUC: 50%-60%, prior to 2010). The majority of both pCD and pUC patients experienced one or two years with at least one episode of DA within the first five years (pCD: 51%, pUC: 53%). During the first 10 years from diagnosis, the decreasing DA pattern was the most common in both pCD and pUC (43% and 47%, respectively) (Figure). Conclusion DA patterns in pIBD are characterised by a high proportion of severe activity initially with a decreasing pattern after 5 and 10 years follow-up. No change in the proportion of patients with no DA was seen despite the introduction of biologic therapy in the period.

P850 Co-medication before and after onset of inflammatory bowel disease in adults or elderly

Abstract Background The incidence of Inflammatory Bowel Disease (IBD) is increasing. Co-medication is clinically important in addition to the treatment of IBD. However, real-world data on co-medication is sparse. Thus, we aimed to describe whether a diagnosis of IBD affects the prescription pattern of co-medication used to treat other diseases in adult-onset and elderly-onset IBD. Methods This nationwide cohort study utilized data from Danish Health Registers. We included patients with adult-onset of IBD (18-59 years of age) and elderly-onset of IBD (+60 years of age) from 1998-2018 with three years of follow-up after the diagnosis for all patients. We identified patients who had at least two diagnoses of IBD in The National Patient Register. We described redeemed prescriptions of 11 common groups for medication used to treat conditions other than IBD using data from The Danish National Prescription Registry. Results We identified 36,165 incident patients. We created two cohorts; 27,386 (75%) had adult-onset IBD, and 8,779 (25%) patients had elderly-onset IBD, Table 1. The proportion of patients with redeemed prescriptions in both cohorts was statistically significantly increased one and three years after onset of IBD for antidepressants, antipsychotics, sedatives/hypnotics, opioids, non-opioid analgesics, antidiabetics, and proton pump inhibitors, compared to one and three years before diagnosis, Figure 1 &amp; Figure 2. Conclusion The proportion of patients with redeemed prescriptions for antidepressants, antipsychotics, sedatives/hypnotics, opioids, non-opioid analgesics, antidiabetics, and proton pump inhibitors was significantly increased one and three years after a diagnosis of IBD compared to one and three years before diagnosis.

Heavy prenatal alcohol exposure and overall morbidities: a Danish nationwide cohort study from 1996 to 2018

Heavy prenatal alcohol exposure is harmful and can lead to fetal alcohol spectrum disorders. A systematic review and meta-analysis identified 428 comorbidities in individuals with fetal alcohol spectrum disorders, and reported pooled prevalence estimates. We aimed to investigate overall risk of morbidities in heavy prenatal alcohol-exposed children by estimating risk of the identified comorbidities, and previously unidentified diseases and health-related problems. Our Danish nationwide register-based cohort study included all singleton births. Individuals were followed up to age 18 years, between 1996 and 2018. Stillbirths and children of immigrants were not included in the study, and births of women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data on health and education were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. We estimated crude and standardised risk differences of hospital diagnoses. Heavy prenatal alcohol exposure was defined by hospital contacts with alcohol-attributable diagnoses given to the mother or her child, or by maternal redeemed prescriptions for drugs to treat alcohol dependence 1 year before or during pregnancy. Of 1 407 689 identified singleton births, 219 186 were excluded for reasons including they were born to immigrants, lost to follow-up, or were stillbirths. Of the remaining 1 188 503 children, 4799 (0·4%) had heavy prenatal alcohol exposure and 1 183 704 (99·6%) were classified as non-alcohol-exposed births. 578 179 (48·6%) babies were female and 610 324 (51·4%) were male. We found 234 of 428 previously identified comorbidities in individuals with fetal alcohol spectrum disorder, of which 29 conditions had a standardised risk difference of at least 0·5%, predominantly related to brain function, behavioural disorders, infections, and neonatal conditions. The four highest standardised risk differences were found for low birthweight (4·70% [95% CI 3·70-5·71]), small for gestational age (4·63% [3·72-5·55]), delayed milestone (3·81% [2·99-4·64]), and other preterm infants (2·69% [1·71-3·68]). Of previously unidentified diseases and health-related problems, 32 of 719 had a standardised risk difference of at least 1·0%, mainly related to brain function, some injuries, substance-related conditions, and childhood adversities. Heavy prenatal alcohol exposure is associated with an overall increased risk of child morbidities and previously unrecognised alcohol-related health problems. Prenatal alcohol exposure is a key public health issue with a potential negative impact on child and adolescent health. This study urges for renewed efforts and substantiates the profound degree to which pre-conceptional care is mandatory. The Obel Family Foundation, The Health Foundation, TrygFonden, Aase and Ejnar Danielsens Foundation, The North Denmark Region Health Science and Research Foundation, Holms Memorial Foundation, Dagmar Marshalls Foundation, the A.P. Møller Foundation, King Christian X Foundation, Torben and Alice Frimodts Foundation, the Axel and Eva Kastrup-Nielsens Foundation, and the A.V. Lykfeldts Foundation.