Investigation of a Perspective Urban Tree Species, Ginkgo biloba L., by Scientific Analysis of Historical Old Specimens.

In this study, we examined over 200-year-old Ginkgo biloba L. specimens under different environmental conditions. The overall aim was to explore which factors influence their vitality and general fitness in urban environments and thus their ability to tolerate stressful habitats. In order to determine this, we used a number of different methods, including histological examinations (stomatal density and size) and physiological measurements (peroxidase enzyme activity), as well as assessing the air pollution tolerance index (APTI). The investigation of the genetic relationships between individuals was performed using flow cytometry and miRNA marker methods. The genetic tests revealed that all individuals are diploid, whereas the lus-miR168 and lus-miR408 markers indicated a kinship relation between them. These results show that the effect of different habitat characteristics can be detected through morphological and physiological responses, thus indicating relatively higher stress values for all studied individuals. A significant correlation can be found between the level of adaptability and the relatedness of the examined individuals. These results suggest that Ginkgo biloba L. is well adapted to an environment with increased stress factors and therefore suitable for use in urban areas.

Renal cell carcinoma and risk of second primary cancer: A Danish nationwide cohort study.

AIM: To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC). METHODS: We identified all patients diagnosed with incident RCC during 1995-2019, using population-based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population. RESULTS: The absolute 1- and 20-year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person-years (PY) (SIR, 2.3; 95% CI: 2.1-2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to <5 years of follow-up (SIR, 1.3; 95% CI: 1.2-1.4), and 6 per 1000 PY beyond 5 years of follow-up (SIR, 1.4; 95% CI: 1.3-1.5). The sustained elevated cancer risk beyond 1 year of follow-up was mainly attributed to excess risk of lung and bladder cancer. The risk of second primary cancer was higher in 2006-2019 than in 1995-2005, but only during the first year of follow-up. CONCLUSION: Patients with incident RCC have a sustained 40% elevated long-term risk of second primary cancer, compared with the general population. This increased risk is mainly attributed to lung and bladder cancer.

Developing a Colorimetrically Balanced, Measurement-Based Petal Colour System for Cultivated Rose (Rosa L. Cultivars) and the Resulting Colour Categories.

There is no practical and at the same time objective colour system available for describing cultivated roses (Rosa L. cultivars). For this reason, a new colour classification system was developed which is colorimetrically balanced and appropriate for algorithmic colour identification; however, it is also suitable for field-work. The system is based on the following colorimetric criteria: (A) Each colour category is characterised by a measured petal colour in the CIE L*a*b* standard as the centroid of the category. (B) The CIEDE2000 colour differences between the adjacent centroid colours are limited (5 < ΔE00 < 7). (C) The maximal colour difference between the measured colours in a category is also limited (to 12.12 ΔE00). (D) A measured petal colour can only be classified into an existing category if the colour difference from the centroid colour of the given category is less than 5.81 ΔE00, otherwise a new category is required. (E) A category is only considered non-redundant if it has at least one measured petal colour that cannot be classified elsewhere. (F) The classification of the petal colours is based on the least colour difference from the centroid colours. As a result, 133 colour categories were required for describing all the 8139 petal colours of the rose cultivars of the Budatétény Rose Garden (Hungary). Each colour category has the following parameters: standardised colour name, the colorimetric parameters of the centroid, grouping, RHS colour chart coding, and reference cultivars, which are described in the article.

Social characteristics and social benefit use among premenopausal breast cancer survivors in Denmark: a population-based cohort study.

PURPOSE: In 2020, one million women aged < 55 years were diagnosed with breast cancer globally. The impact of breast cancer and its treatments on these women's ability to work and need for social benefits may differ by social characteristics. We evaluated social benefit use following breast cancer by education and cohabitation. METHODS: We conducted a nationwide population-based cohort study, including women aged 18-55 years diagnosed with stage I-III breast cancer in Denmark during 2002-2011. Statistics Denmark provided information on cohabitation, education, and social benefit use from 1 year pre-diagnosis to 10 years post-diagnosis. We calculated weekly proportions of self-support, unemployment, disability pension, flexi jobs, and sick leave according to education and cohabitation. RESULTS: Of 5345 women, 81.8% were self-supporting, 4.5% received disability pensions, 1.6% had flexi jobs, 3.6% were on sick leave, and 5.5% were unemployed 1 year pre-diagnosis. Ten years post-diagnosis, the proportions were 69.0%, 13.0%, 10.5%, 3.4%, and 2.0% of 3663 survivors. Disability pensions and flexi jobs increased from 12.1 to 26.4% and 2.8 to 13.5% in women with short education, from 4.1 to 12.8% and 1.8 to 12.2% in women with medium education, and from 0.8 to 6.0% and 0.9 to 6.9% in longer educated. Disability pensions increased more in women living alone (7.8 to 19.9%), than in cohabiting women (3.6 to 11.3%). CONCLUSIONS: Use of social benefits reflecting lost ability to work was highest in less educated women and in women living alone. IMPLICATIONS FOR CANCER SURVIVORS: Awareness of these groups is crucial when tailoring efforts to support work participation in cancer survivors.

Clinical factors associated with patterns of endocrine therapy adherence in premenopausal breast cancer patients.

INTRODUCTION: Patients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence. METHODS: We included stage I-III premenopausal breast cancer patients diagnosed during 2002-2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns. RESULTS: We identified three adherence patterns among 4,353 women-high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers. CONCLUSIONS: Women with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.

Mental Health Conditions in Partners and Adult Children of Stroke Survivors.

Importance: Family caregiving after critical illness has been associated with several adverse health outcomes, including various aspects of mental health, but research focusing specifically on family members of stroke survivors is limited. Objectives: To examine the associations of stroke in a partner or parent with the risk of depression, substance use disorders, anxiety disorders, and self-harm or suicide. Design, Setting, and Participants: This nationwide, population-based cohort study used data from Danish nationwide administrative and clinical registries (2004-2021). Participants included partners and adult children of survivors of stroke. Data analysis was performed from March to December 2023. Exposure: Having a partner or parent who survived stroke. Main Outcomes and Measures: The Aalen-Johansen estimator was used to compute propensity score-weighted 3-year absolute risks, risk differences, and risk ratios for depression, substance use disorders, anxiety disorders, and self-harm or suicide among partners or children of survivors of stroke compared with partners or children of survivors of myocardial infarction (MI) and matched individuals from the general population. Results: The study included a total of 1 923 732 individuals: 70 917 partners of stroke survivors (median [IQR] age, 68 [59-76] years; 46 369 women [65%]), 70 664 partners of MI survivors (median [IQR] age, 65 [55-73] years; 51 849 women [73%]), 354 570 partners of individuals from the general population (median [IQR] age, 68 [59-76] years; 231 833 women [65%]), 207 386 adult children of stroke survivors (median [IQR] age, 45 [36-52] years; 99 382 women [48%]), 183 309 adult children of MI survivors (median [IQR] age, 42 [33-49] years; 88 078 women [48%]), and 1 036 886 adult children of individuals from the general population (median [IQR] age, 45 [36-52] years; 496 875 women [48%]). Baseline characteristics were well balanced across cohorts after propensity score weighting. Among partners of stroke survivors, the 3-year absolute risk was 1.0% for depression, 0.7% for substance use disorders, 0.3% for anxiety disorders, and 0.04% for self-harm or suicide. Risk ratio point estimates for the assessed outcomes ranged from 1.14 to 1.42 compared with the general population and from 1.04 to 1.09 compared with partners of MI survivors. The elevated risk of depression in partners of stroke survivors was more pronounced after severe or moderate stroke than after mild stroke. Among adult children of stroke survivors, the 3-year absolute risk was 0.6% for depression, 0.6% for substance use disorders, 0.2% for anxiety disorders, and 0.05% for self-harm or suicide. Both absolute risks and risk ratios for adult children of stroke survivors were smaller than those reported in the partner analyses. Conclusions and Relevance: In this cohort study of partners and adult children of stroke survivors, risks of several mental health conditions and self-harm or suicide were moderately higher compared with the general population and, to a lesser extent, partners and adult children of MI survivors. These findings highlight the potential consequences of stroke among family members, particularly partners, and its findings may possibly serve as a quantitative foundation for the development of future stroke rehabilitation services.

Association between maternal employment status and presence of children with major congenital anomalies in Denmark.

IMPORTANCE: The burden of caring for children with complex medical problems such as major congenital anomalies falls principally on mothers, who in turn suffer a variety of potentially severe economic consequences. As well, health consequences of caregiving often further impact the social and economic prospects of mothers of children with major congenital anomalies (MCMCAs). Evaluating the long-term economic consequences of extensive in-home caregiving among MCMCAs can inform strategies to mitigate these effects. OBJECTIVE: To assess whether MCMCAs face reduced employment and increased need for disability benefits over a 20-year period. DESIGN: A population-based matched cohort study. SETTING: Denmark. PARTICIPANTS: All women who gave birth to a singleton child with a major congenital anomaly in Denmark between January 1, 1997 and December 31, 2017 (n = 23,637) and a comparison cohort of mothers matched by maternal age, parity, and infant's year of birth (n = 234,586). EXPOSURES: Liveborn infant with a major congenital anomaly. MAIN OUTCOMES AND MEASURES: The primary outcome was mothers' employment status, stratified by their child's age. Employment status was categorized as employed, outside the workforce (on temporary leave, holding a flexible job, or pursuing education), or unemployed; the number of weeks in each category was measured over time. The secondary outcome was time to receipt of a disability pension, which in Denmark implies permanent exit from the labor market. We used a negative binomial regression model to estimate the number of weeks in each employment category, stratified by the child's age (i.e., 0-1 year, > 1-6 years, 7-13 years, 14-18 years). A Cox proportional hazards regression model was used to compute hazard ratios as a measure of the relative risk of receiving a disability pension. Rate ratios and hazard ratios were adjusted for maternal demographics, pregnancy history, health, and infant's year of birth. RESULTS: During 1-6 years after delivery, MCMCAs were outside the workforce for a median of 50 weeks (IQR, 6-107 weeks), while members of the comparison cohort were outside the workforce for a median of 48 weeks (IQR, 4-98 weeks), corresponding to an adjusted rate ratio [ARR] of 1.05 (95% confidence interval [CI], 1.04-1.07). During the first year after delivery, MCMCAs were more likely to be employed than mothers in the comparison cohort (ARR, 1.08; 95% CI, 1.06-1.10). At all timepoints thereafter, MCMCAs had a lower rate of workforce participation. The rate of being outside the workforce was 5% higher than mothers in the comparison cohort during 1-6 years after delivery (ARR, 1.05; 95% CI, 1.04-1.07), 9% higher during 7-13 years after delivery (ARR, 1.09; 95% CI, 1.06-1.12), and 12% higher during 14-18 years after delivery (ARR, 1.12; 95% CI, 1.07-1.18). Overall, MCMCAs had a 20% increased risk of receiving a disability pension during follow-up than mothers in the matched comparison cohort [incidence rates 3.10 per 1000 person-years (95% CI, 2.89-3.32) vs. 2.34 per 1000 person-years (95% CI, 2.29-2.40), adjusted hazard ratio, 1.20; 95% CI, 1.11-1.29]. CONCLUSION AND RELEVANCE: MCMCAs were less likely to participate in the Danish workforce, less likely to be employed, and more likely to receive disability pensions than mothers of unaffected children. The rate of leaving the workforce intensified as their affected children grew older. The high demands of caregiving among MCMCAs may have long-term employment consequences even in nations with comprehensive and heavily tax-supported childcare systems, such as Denmark.

Risk of Cancer in Patients With Diverticular Disease: A Population-Based Cohort Study.

BACKGROUND & AIMS: Several studies have investigated the association between diverticular disease (DD) and colorectal cancer. However, whether there is an association between DD and malignancies other than those in the colorectum remains uncertain. METHODS: For the 1978-2019 period, we conducted a nationwide, population-based cohort study using national Danish health care data. We followed patients with DD for up to 20 years, beginning 1 year after the date of DD diagnosis until the first occurrence of incident cancer, emigration, death, 20 years of follow-up, or December 31, 2019. We calculated cumulative incidence proportions of cancer and standardized incidence ratios (SIRs) comparing cancer incidence among patients with DD with that in the general population. RESULTS: We identified 200,639 patients with DD, of whom 20,498 were diagnosed with cancer during the 1-20 years after their DD diagnosis. The SIRs were increased for most cancer sites except for those in the colorectum (SIR, 0.75; 95% confidence interval, 0.72-0.78). The highest SIRs were observed for cancers of the lung, bronchi, and trachea (SIR, 1.20; 95% confidence interval, 1.15-1.24) and kidney (SIR, 1.27; 95% confidence interval, 1.16-1.39). CONCLUSIONS: Our findings show an increased long-term relative risk of cancer following a diagnosis of DD. These findings are likely caused by prevalence of numerous risk factors in patients with DD that confer an increased risk of cancer. The decreased relative risk of colorectal cancer might be explained by an increased likelihood of patients with DD undergoing colonoscopy with polypectomy.

Microparticles and multi-unit systems for advanced drug delivery.

Microparticles have unique benefits in the formulation of multiparticulate and multi-unit type pharmaceutical dosage forms allowing improved drug safety and efficacy with favorable pharmacokinetics and patient centricity. On the other hand, the above advantages are served by high and well reproducible quality attributes of the medicinal product where even flexible design and controlled processability offer success as well as possible longer product life-cycle for the manufacturers. Moreover, the specific demands of patients can be taken into account, including simplified dosing regimens, flexible dosage, drug combinations, palatability, and ease of swallowing. In the more than 70 years since the first modified-release formulation appeared on the market, many new formulations have been marketed and many publications have appeared in the literature. More unique and newer pharmaceutical technologies and excipients have become available for producing tailor-made particles with micrometer dimensions and beyond. All these have contributed to the fact that the sub-units (e.g. minitablets, pellets, microspheres) that make up a multiparticulate system can vary widely in composition and properties. Some units have mucoadhesive properties and others can float to contribute to a suitable release profile that can be designed for the multiparticulate formula as a whole. Nowadays, there are some available formulations on the market, which are able to release the active substance even for several months (3 or 6 months depending on the type of treatment). In this review, the latest developments in technologies that have been used for a long time are presented, as well as innovative solutions such as the applicability of 3D printing to produce subunits of multiparticulate systems. Furthermore, the diversity of multiparticulate systems, different routes of administration are also presented, touching the ones which are capable of carrying the active substance as well as the relevant, commercially available multiparticle-based medical devices. The versatility in size from 1 µm and multiplicity of formulation technologies promise a solid foundation for the future applications of dosage form design and development.

Inhalation Dosage Forms: A Focus on Dry Powder Inhalers and Their Advancements.

In this review, an extensive analysis of dry powder inhalers (DPIs) is offered, focusing on their characteristics, formulation, stability, and manufacturing. The advantages of pulmonary delivery were investigated, as well as the significance of the particle size in drug deposition. The preparation of DPI formulations was also comprehensively explored, including physico-chemical characterization of powders, powder processing techniques, and formulation considerations. In addition to manufacturing procedures, testing methods were also discussed, providing insights into the development and evaluation of DPI formulations. This review also explores the design basics and critical attributes specific to DPIs, highlighting the significance of their optimization to achieve an effective inhalation therapy. Additionally, the morphology and stability of 3 DPI capsules (Spiriva, Braltus, and Onbrez) were investigated, offering valuable insights into the properties of these formulations. Altogether, these findings contribute to a deeper understanding of DPIs and their development, performance, and optimization of inhalation dosage forms.

Mental Health Conditions Among Children and Adolescents With Congenital Heart Disease: A Danish Population-Based Cohort Study.

BACKGROUND: Despite the known mental health burden among children with congenital heart disease (CHD), the literature is constrained by a lack of comparison cohorts and population-based follow-up data. We examined the incidence of mental health conditions among children with CHD, relative to 3 comparison cohorts. METHODS: This population-based cohort study identified all children with CHD (<18 years of age; n=16 473) in Denmark from 1996 to 2017, through linkage of individual-level data across national registries. This allowed for complete follow-up of the population. Comparison cohorts included children from the general population (n=162 204), siblings of children with CHD (n=20 079), and children with non-CHD major congenital anomalies (n=47 799). Mental health conditions were identified using inpatient and outpatient hospital discharge codes, prescription data, and data on use of community-based psychology, psychiatry, and psychotherapy services. We computed cumulative incidence by 18 years of age, incidence rates, and adjusted hazard ratios (aHRs) using Cox regression. aHRs accounted for sex, year of CHD diagnosis, parental mental health, and socioeconomic status. All estimates were stratified by age, sex, and CHD complexity. RESULTS: The cumulative incidence of mental health conditions by 18 years of age in the CHD cohort was 35.1% (95% CI, 34.0%-36.1%), corresponding to aHRs of 1.64 (95% CI, 1.58-1.71), 1.41 (95% CI, 1.30-1.52), and 1.02 (95% CI, 0.98-1.07) compared with the general population, sibling, and major congenital anomaly cohorts, respectively. Mental health incidence rates showed prominent peaks in early childhood and adolescence. Males and children with severe or single-ventricle CHD demonstrated higher incidence rates of mental health conditions relative to females and children with mild or moderate CHD, respectively. Compared with the general population and sibling cohorts, incidence rates and aHRs in the CHD cohort were highest for severe stress reactions, attention deficit/hyperactivity disorder, intellectual disability, and autism spectrum disorder. Compared with children in the major congenital anomaly cohort, the aHRs were close to 1. CONCLUSIONS: More than one-third of children with CHD were diagnosed or treated for a mental health condition by 18 years of age. Mental health conditions began early in life and were most prominent among males and children with severe or single-ventricle heart disease.

Risk and Prognosis of Cancer in Patients With Cerebral Venous Thrombosis Compared With the Danish General Population.

BACKGROUND: Whether cerebral venous thrombosis (CVT) is a marker of cancer in clinical practice remains unknown. Little is known about the prognosis of cancer detected subsequent to CVT. METHODS: We used Danish nationwide registries (1996-2019) to identify patients with a first-time primary inpatient diagnosis of CVT without a history of cancer (N=811, 65% women, median age 42 years). We assessed the risk of an incident cancer diagnosis using standardized incidence ratios (SIRs). This measure contrasts the number of observed cancers among patients with CVT to the number of expected cancers where patients with CVT have the same cancer risk as the general population. We used Kaplan-Meier survival analysis and Cox regression to compare the survival of patients with both cancer and CVT with the survival of patients with cancer but without CVT, matched on cancer site, sex, age, and year of cancer diagnosis. RESULTS: Observing 43 incident cancer cases during follow-up, the overall SIR was unity (SIR, 1.04 [95% CI, 0.75-1.40]). However, the risk was ≈7-fold the expected level in the first 3 months following CVT diagnosis (SIR, 7.00 [95% CI, 3.02-13.80]) and ≈2-fold the expected level from 3 to 12 months following CVT diagnosis (SIR, 2.21 [95% CI, 0.89-4.56]). By 12 months following CVT diagnosis, the risk resembled the expected level (SIR, 0.76 [95% CI, 0.50-1.09]). Survival among cancer patients with prior CVT versus cancer patients without prior CVT was 91% versus 87% after 6 months and 65% versus 70% after 5 years. The adjusted hazard ratio of death was 0.78 (95% CI, 0.44-1.38). CONCLUSIONS: Patients with CVT were not at overall increased risk of a cancer diagnosis, except in the first 3 months after diagnosis during which period the risk was elevated ≈7-fold. The estimate from this early period, however, was based on only a few cancer diagnoses. Unlike other forms of venous thrombosis, a prior diagnosis of CVT did not negatively impact cancer survival.

The Role of the Plant-Soil Relationship in Agricultural Production-With Particular Regard to PGPB Application and Phytoremediation.

Plant growth-promoting bacteria (PGPB) and other living organisms can help with the challenges of modern agriculture. PGPB offer ever-expanding possibilities for science and commerce, and the scientific results have been very advanced in recent years. In our current work, we collected the scientific results of recent years and the opinions of experts on the subject. Opinions and results on soil-plant relations, as well as the importance of PGPB and the latest related experiences, are important topics of our review work, which highlights the scientific results of the last 3-4 years. Overall, it can be concluded from all these observations that the bacteria that promote plant development are becoming more and more important in agriculture almost all over the world, thus, promoting more sustainable and environmentally conscious agricultural production and avoiding the use of artificial fertilizers and chemicals. Since many mechanisms of action, namely biochemical and operational processes, are still under investigation, a new emerging scientific direction is expected in the coming years with regard to PGPB, microbial, and other plant growth-stimulating substances, in which omics and microbial modulation also play a leading role.

Histological and Physiological Effects of Treatment of Rudbeckia hirta with Gamma Radiation.

The breeding of resistant, high-yield, decorative ornamental plant varieties may be impacted by climate change in the future. The use of radiation induces mutations in plants, thereby increasing the genetic variability of plant species. Rudbeckia hirta has long been a very popular species in urban green space management. The goal is to examine whether gamma mutation breeding can be applied to the breeding stock. Specifically, differences were measured between the M1 and M2 generations, as well as the effect of different radiation doses belonging to the same generation. Morphological measurements showed that gamma radiation has an effect on the measured parameters in several cases (larger crop size, faster development, larger number of trichomes). Physiological measurements (examination of chlorophyll and carotenoid content, POD activity, and APTI) also showed a beneficial effect of radiation, especially at higher doses (30 Gy), for both tested generations. The treatment was also effective in the case of 45 Gy, but this radiation dose resulted in lower physiological data. The measurements show that gamma radiation has an effect on the Rudbeckia hirta strain and may play a role in breeding in the future.

Non-Traumatic Subdural Hematoma and Cancer: A Cohort Study.

Introduction: Cancer may increase the risk of bleeding. However, whether subdural hematoma is a marker of occult cancer remains unknown. We examined the association between non-traumatic subdural hematoma and cancer risk in a cohort study. Materials and Methods: Using Danish nationwide health registries, we identified 2713 patients with non-traumatic subdural hematoma and no previous cancer diagnosis, who were hospitalized between April 1, 1996 and December 31, 2019. We computed age-, sex-, and calendar year-standardized incidence ratios (SIRs) as the ratio of the observed to expected number of patients with cancer by using national incidence rates as reference as a measure of relative risk. Results: We identified 77 cancer cases within the first year of follow-up and 272 cancer cases thereafter. The one-year risk of cancer was 2.8% (95% confidence interval: 2.2-3.5), and the one-year SIR was 1.7 (95% confidence interval: 1.3-2.1). During the subsequent years, the SIR was 1.0 (95% confidence interval: 0.9-1.1). The relative risk was elevated for some hematological and liver cancers. Conclusion: The risk of a new cancer diagnosis was clearly increased in patients with non-traumatic subdural hematoma compared with the general population during the first year of follow-up. However, the absolute risk was low, thus limiting the clinical relevance of pursuing early cancer detection in these patients.

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

BACKGROUND: 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. METHODS: 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. FINDINGS: 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]). INTERPRETATION: 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. FUNDING: None.

Risk of primary haematologic cancers following incident non-metastatic breast cancer: A Danish population-based cohort study.

BACKGROUND: Breast cancer survivors may have increased risk of subsequent haematologic cancer. We compared their risk of haematologic cancers with the general population during 38 years of follow-up. METHODS: Using population-based Danish medical registries, we assembled a nationwide cohort of women diagnosed with incident non-metastatic breast cancer during 1980-2017, with follow-up through 2018. We compared breast cancer survivors with the general population by computing standardised incidence ratios (SIR) and 95% confidence intervals (CI). RESULTS: Among 101,117 breast cancer survivors, we observed 815 incident haematologic cancers (median follow-up: 7.9 years). We observed excess risk of acute myeloid leukaemia (AML) (SIR: 1.65, 95%CI: 1.33-2.01), particularly in women who received chemotherapy (SIR: 3.33, 95%CI: 2.24-4.75) and premenopausal women (SIR: 3.23, 95%CI: 2.41-4.25). The risk of acute lymphoid leukaemia (ALL) was increased (SIR: 2.25, 95%CI: 1.29-3.66), whereas the risk of chronic lymphoid leukaemia (CLL) was decreased (SIR: 0.66, 95%CI: 0.53-0.82). An additional analysis showed elevated risk of CLL 0-6 months after breast cancer diagnosis (SIR: 3.00 95%CI: 1.75-4.80). CONCLUSION: Compared to the general population, breast cancer survivors had elevated risk of AML, particularly when treated with chemotherapy. The risk of ALL was elevated, whereas the risk of CLL was lower. The higher risk of CLL in the first six months after diagnosis likely reflects surveillance bias-due to intensified diagnostic efforts at breast cancer diagnosis and treatment-prompting earlier detection. This has likely reduced the long-term risk of CLL in breast cancer survivors.

Increased Cancer Risk in Patients with Kidney Disease and Venous Thromboembolism: A Population-Based Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) may be a harbinger of cancer in the general population. Patients with kidney disease have an a priori increased VTE risk. However, it remains unknown how a VTE affects subsequent cancer risk in these patients. OBJECTIVES: To examine the cancer risk in patients with kidney disease following a VTE. METHODS: We conducted a nationwide population-based cohort study in Denmark (1996-2017), including all VTE patients with a diagnosis of kidney disease. We calculated absolute risks of cancer (accounting for competing risk of death) and age-, sex-, and calendar-period standardized incidence ratios (SIRs) comparing the observed cancer incidence with national cancer incidence rates and cancer incidence rates of VTE patients without kidney disease. RESULTS: We followed 3,362 VTE patients with kidney disease (45.9% females) for a median follow-up time of 2.4 years (interquartile range: 0.6-5.4). During follow-up, 464 patients were diagnosed with cancer, of whom 169 (36.4%) were diagnosed within the first year. The 1-year absolute risk of any cancer was 5.0% (95% confidence interval [CI]: 4.3-5.8), with a SIR of 2.9 (95% CI: 2.5-3.4) when compared with the general population, and 2.0 (95% CI: 1.8-2.4) when compared with VTE patients without kidney disease. During subsequent years of follow-up, the SIRs declined to 1.5 (95% CI: 1.3-1.6) when compared with the general population, and 1.1 (95% CI: 0.9-1.2) compared with VTE patients without kidney disease. CONCLUSION: Patients with hospital-diagnosed kidney disease have increased cancer risk after VTE, especially within the first year following the VTE diagnosis.

Fever of Unknown Origin: A Validation Study of Danish ICD-10 Diagnosis Codes.

Background: Real-world data in form of routinely collected clinical data are a valuable resource for epidemiological research in infectious disease. We examined the validity of a discharge diagnosis of fever of unknown origin from hospital discharge registries. Methods: We identified patients with a first in- or outpatient diagnosis (primary or secondary) of fever of unknown origin (ICD-10 code R50.0; R50.8, R50.9) recorded in the Danish National Patient Registry (DNPR) between 2010 and 2017 in the North Denmark Region. We based the validation cohort on a mix of patients diagnosed at a highly specialized university department of infectious diseases (n=100), other internal medicine departments (n=50), and patients diagnosed at a regional non-university hospital (n=50). We estimate positive predictive value (PPV) of diagnosis for fever of unknown origin using medical records as reference. Results: The PPV of a diagnosis of fever of unknown origin for patients diagnosed at the infectious disease department was 61% (95% CI: 51-71%). For other internal medicine departments, it was 14% (95% CI: 6-27%), and for the non-university hospital it was 16% (95% CI: 7-29%). To achieve higher PPVs, we excluded immunocompromised patients, patients who were diagnosed with infection, cancer or rheumatic disease within 7 days after admission, and/or patients with a short hospital stay (maximum 3 days) and no subsequent hospital contact within 1 month. The PPV for diagnoses from the Department of Infectious Diseases improved to 82% (95% CI: 68-91%) for other internal medicine departments it improved to 31% (95% CI: 11-59%), and for the non-university hospital it improved to 36% (95% CI: 13-65%). Conclusion: We found that only diagnoses made in the Department of Infectious Diseases accurately identified fever of unknown origin, whereas diagnoses made in other units mainly covered infection-related fever, cancer-related fever, or short unspecific fever without further diagnostic work-up.

Venous Thromboembolism and Risk of Cancer in Users of Low-Dose Aspirin: A Danish Population-Based Cohort Study.

Background Aspirin may reduce the risk of cancer, particularly gastrointestinal cancer, and venous thromboembolism (VTE). VTE can be the first symptom of occult cancer, but whether it is also a marker of occult cancer in aspirin users remains unknown. Therefore, we investigated the risk of cancer subsequent to VTE among users of low-dose aspirin. Methods We conducted a population-based cohort study using data from Danish health registries for the years 2001 to 2018. We identified all patients with a first-time diagnosis of VTE who also redeemed a prescription for low-dose aspirin (75-150mg) within 90 days prior to the first-time VTE. We categorized aspirin users by the number of prescriptions filled as new users (<5 prescriptions), short-term users (5-19 prescriptions), and long-term users (>19 prescriptions). We computed the absolute cancer risks and standardized incidence ratios (SIRs) for cancer using national cancer incidence rates. Results We followed-up 11,759 users of low-dose aspirin with VTE. Long-term users comprised 50% of aspirin users. The 1-year absolute risk of cancer was 6.0% for new users and 6.7% for short-term and long-term users, with corresponding SIRs of 3.3 (95% confidence interval [CI]: 2.8-4.0), 3.2 (95% CI: 2.9-3.7), and 2.8 (95% CI: 2.6-3.2), respectively. After the first year of follow-up, the SIR decreased to 1.2 (95% CI: 1.1-1.4) for new users, 1.1 (95% CI: 1.1-1.3) for short-term users, and 1.1 (95% CI: 1.0-1.2) for long-term users. Conclusion VTE may be a harbinger of cancer, even in users of low-dose aspirin, regardless of duration of use.