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A sudden increase in blood sample requisitions from primary care physicians may indicate an incentive to investigate cer-tain symptoms further. Patients with slowly progressing malig-nancies may debut with insidious symptoms and seek medical attention with increasing frequency, which indeed has been demonstrated through different markers of primary care activ-ity in the last 1–2 years prior to a cancer diagnosis [1, 2]. However, within hematological malignancies in particular, early signs of slowly progressing or pre-malignant conditions may in fact be detectable several years before the malignant disease is diagnosed [3–5]. Identifying early signs of malig-nancy or pre-malignancy is important in order to increase chances of successful treatment and lower morbidity and mor-tality [6–8]. Even in asymptomatic and otherwise low-risk hematological patients, it has been demonstrated that early detection may enable risk stratification for follow-up of the (pre-)malignant conditions, help provide relevant care and improve early disease detection in the right patients [9]. In this descriptive study we aimed to describe the pre-diagnostic activity in primary care going back 15 years prior to the malig-nant diagnosis in order to explore if laboratory activity may indicate that early (pre-)malignant conditions register in pri-mary care years before a diagnosis is made. This was done by describing the blood sampling activity patterns in primary care in both cancer patients to-be and controls, looking at both solid tumors and hematological malignancies. The overall aim of the study was to evaluate the potential for earlier diag-nosis of certain malignant diseases

Background: The Copenhagen General Practice Laboratory (CGPL) was founded in 1922 to provide paraclinical analyses to the primary health-care sector in Copenhagen. At the end of 2015, CGPL was closed and the CopLab database was established to make CGPL data available for research. Methods: We isolated tests performed at the CGPL with clinically relevant test results. The database was linked to national registers containing health, social, and demographic information. Results are presented with descriptive statistics showing counts, percentages, medians, and interquartile ranges (IQR). Results: The CopLab database includes 1,373,643 unique individuals from primary care with test results from laboratory analyses of blood/urine/semen as well as cardiac and lung function tests collected by CGPL from greater Copenhagen from 2000 to 2015. The CopLab database holds nearly all test results requested by general practitioners throughout years 2000 to 2015 for residents in the greater Copenhagen area. The median age of the individuals was 51 years and 59.7% were females. Each individual has a median of 4 requisitions. More than 1 million participants are currently alive and living in Denmark and may be followed in national registries such as the Danish National Patient Registry, Laboratory Database, National Prescription Database etc.

ackground Type 2 diabetes (T2D) treatment has changed markedly within the last decades. We aimed to explore whether people with severe mental illness (SMI) have followed the same changes in T2D treatment as those without SMI, as multiple studies suggest that people with SMI receive suboptimal care for somatic disorders. Methods In this registry-based annual cohort study, we explored the T2D treatment from 2001 to 2015 provided in general practices of the Greater Copenhagen area. We stratified the T2D cohorts by their pre-existing SMI status. T2D was defined based on elevated glycated hemoglobin (≥48 mmol/mol) or glucose (≥11 mmol/L) using data from the Copenhagen Primary Care Laboratory Database. Individuals with schizophrenia spectrum disorders (ICD-10 F20–29) or affective disorders (bipolar disorder or unipolar depression, ICD-10 F30–33) were identified based on hospital-acquired diagnoses made within 5 years before January 1 each year for people with prevalent T2D or 5 years before meeting our T2D definition for incident patients. For comparison, we defined a non-SMI group, including people who did not have a hospital-acquired diagnosis of schizophrenia spectrum disorders, affective disorders, or personality disorders. For each calendar year, we assembled cohorts of people with T2D with or without SMI. We used Poisson regression to calculate the rates per 100 person-years of having at least one biochemical test (glycated hemoglobin, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and urine albumin-creatinine ratio), having poor control of these biochemical results, taking glucose-lowering or cardiovascular medications, or experiencing a clinical outcome, including all-cause mortality and cardiovascular mortality. Three outcomes (cardiovascular events, cardiovascular mortality, and all-cause mortality) were additionally examined and adjusted for age and sex in a post hoc analysis. Results From 2001 to 2015, Background: Type 2 diabetes (T2D) treatment has changed markedly within the last decades. We aimed to explore whether people with severe mental illness (SMI) have followed the same changes in T2D treatment as those without SMI, as multiple studies suggest that people with SMI receive suboptimal care for somatic disorders. Methods: In this registry-based annual cohort study, we explored the T2D treatment from 2001 to 2015 provided in general practices of the Greater Copenhagen area. We stratified the T2D cohorts by their pre-existing SMI status. T2D was defined based on elevated glycated hemoglobin (≥48 mmol/mol) or glucose (≥11 mmol/L) using data from the Copenhagen Primary Care Laboratory Database. Individuals with schizophrenia spectrum disorders (ICD-10 F20–29) or affective disorders (bipolar disorder or unipolar depression, ICD-10 F30–33) were identified based on hospital-acquired diagnoses made within 5 years before January 1 each year for people with prevalent T2D or 5 years before meeting our T2D definition for incident patients. For comparison, we defined a non-SMI group, including people who did not have a hospital-acquired diagnosis of schizophrenia spectrum disorders, affective disorders, or personality disorders. For each calendar year, we assembled cohorts of people with T2D with or without SMI. We used Poisson regression to calculate the rates per 100 person-years of having at least one biochemical test (glycated hemoglobin, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and urine albumin-creatinine ratio), having poor control of these biochemical results, taking glucose-lowering or cardiovascular medications, or experiencing a clinical outcome, including all-cause mortality and cardiovascular mortality. Three outcomes (cardiovascular events, cardiovascular mortality, and all-cause mortality) were additionally examined and adjusted for age and sex in a post hoc analysis. Results: From 2001 to 2015, 66,914 individuals were

Monocytosis (>= 0.5 x 10(9)/L in peripheral blood) is the hallmark of chronic myelomonocytic leukaemia (CMML) but may be present in a spectrum of diseases including other haematological malignancies. In the primary care sector, monocytosis is a relatively common finding, but its predictive value for haematological malignancy is unknown. We included 663 184 adult primary care patients from the greater Copenhagen area with one or more differential cell counts registered between 2000 and 2016 and followed them in the extensive nationwide Danish health data registers for 3 years after blood sampling. We used logistic regression to model the risk of haematological malignancy and death following monocytosis. Monocytosis was associated with an increased risk of all types of haematological malignancy with the greatest relative risk increase observed in CMML with an OR of 105.22 (95% confidence interval: 38.27-289.30). Sustained monocytosis (at least two requisitions in 3 months) further increased CMML risk, although the diagnosis was still very rare, that is, observed in only 0.1% of these individuals. Outside the haematological setting, the absolute risk of haematological malignancy associated with monocytosis is low and haematological malignancy should mainly be suspected when monocytosis is sustained or the clinical presentation raises suspicion of malignancy., Funding Agencies|Miss Amalie Jorgensen Memorial Grant; Hasselbalch and Lykkegaard Andersen Research Fund; Department of Hematology, University Hospital Copenhagen, Rigshospitalet

Background The prevalence of chronic kidney disease (CKD) is increasing globally. Early diagnosis in primary care may have a role in ensuring proper intervention. We aimed to determine the prevalence and outcome of CKD in primary care. Methods We performed an observational cohort study in primary care in Copenhagen (2001–2015). Outcomes were stroke, myocardial infarction (MI), heart failure (HF), peripheral artery disease (PAD), all-cause- and cardiovascular mortality. We combined individuals with normal kidney function and CKD stage 2 as reference. We conducted cause-specific Cox proportional regressions to calculate the hazard ratios for outcomes according to CKD group. We explored the associations between kidney function and the outcomes examined using eGFR as a continuous variable modelled with penalised splines. All models were adjusted for age, gender, diabetes, hypertension, existing CVD, heart failure, LDL cholesterol and use of antihypertensive treatment. Results We included 171,133 individuals with at least two eGFR measurements of which the majority (n = 157,002) had eGFR > 60 ml/min/1.73m2 at index date, and 0.05% were in CKD stage 5. Event rates were low in eGFR > 60 ml/min/1.73m2 but increased in those with higher stages of CKD. In adjusted analyses we observed an increase in hazard rates for every outcome with every increment in CKD stage. Compared to the reference group, individuals in CKD stage 4 had double the hazard rate of PAD, MI, cardiovascular and all-cause mortality. Conclusions Our data from a large primary care cohort demonstrate an early increase in the risk of adverse outcomes already at CKD stage 3. This underlines the importance of studying early intervention in primary care., Background: The prevalence of chronic kidney disease (CKD) is increasing globally. Early diagnosis in primary care may have a role in ensuring proper intervention. We aimed to determine the prevalence and outcome of CKD in primary care. Methods: We performed an observational cohort study in primary care in Copenhagen (2001–2015). Outcomes were stroke, myocardial infarction (MI), heart failure (HF), peripheral artery disease (PAD), all-cause- and cardiovascular mortality. We combined individuals with normal kidney function and CKD stage 2 as reference. We conducted cause-specific Cox proportional regressions to calculate the hazard ratios for outcomes according to CKD group. We explored the associations between kidney function and the outcomes examined using eGFR as a continuous variable modelled with penalised splines. All models were adjusted for age, gender, diabetes, hypertension, existing CVD, heart failure, LDL cholesterol and use of antihypertensive treatment. Results: We included 171,133 individuals with at least two eGFR measurements of which the majority (n = 157,002) had eGFR > 60 ml/min/1.73m2 at index date, and 0.05% were in CKD stage 5. Event rates were low in eGFR > 60 ml/min/1.73m2 but increased in those with higher stages of CKD. In adjusted analyses we observed an increase in hazard rates for every outcome with every increment in CKD stage. Compared to the reference group, individuals in CKD stage 4 had double the hazard rate of PAD, MI, cardiovascular and all-cause mortality. Conclusions: Our data from a large primary care cohort demonstrate an early increase in the risk of adverse outcomes already at CKD stage 3. This underlines the importance of studying early intervention in primary care.

It has been argued that persons with severe mental illness (SMI) receive poorer treatment for somatic comorbidities. This study assesses the treatment rates of glucose-lowering and cardiovascular medications among persons with incident type 2 diabetes (T2D) and SMI compared to persons with T2D without SMI. We identified persons ≥30 years old with incident diabetes (HbA1c ≥ 48 mmol/mol and/or glucose ≥ 11.0 mmol/L) from 2001 through 2015 in the Copenhagen Primary Care Laboratory (CopLab) Database. The SMI group included persons with psychotic, affective, or personality disorders within five years preceding the T2D diagnosis. Using a Poisson regression model, we calculated the adjusted rate ratios (aRR) for the redemption of various glucose-lowering and cardiovascular medications up to ten years after T2D diagnosis. We identified 1,316 persons with T2D and SMI and 41,538 persons with T2D but no SMI. Despite similar glycemic control at diagnosis, persons with SMI redeemed a glucose-lowering medication more often than persons without SMI in the period 0.5-2 years after the T2D diagnosis; for example, the aRR was 1.05 (95% CI 1.00-1.11) in the period 1.5-2 years after the T2D diagnosis. This difference was mainly driven by metformin. In contrast, persons with SMI were less often treated with cardiovascular medications during the first 3 years after T2D diagnosis, e.g., in the period 1.5-2 years after T2D diagnosis, the aRR was 0.96 (95% CI 0.92-0.99). For people with SMI in addition to T2D, metformin is more likely to be used in the initial years after T2D diagnosis, while our results suggest potential room for improvement regarding the use of cardiovascular medications.

To examine whether education level influences screening, monitoring, and treatment of hypercholesterolemia., Objective: To examine whether education level influences screening, monitoring, and treatment of hypercholesterolemia. Design: Epidemiological cohort study. Setting: Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre. Subjects: Cholesterol blood test results ordered by general practitioners in Greater Copenhagen were retrieved from 2000-2018. Using the International Standard Classification of Education classification, the population was categorized by length of education in three groups (basic education; up to 10 years, intermediate education; 11-12 years, advanced education; 13 years or more). The database comprised 13,019,486 blood sample results from 653,903 patients. Main Outcome Measures: Frequency of lipid measurement, prevalence of statin treatment, age and comorbidity at treatment initiation, total cholesterol threshold for statin treatment initiation, and achievement of treatment goal. Results: The basic education group was measured more frequently (1.46% absolute percentage difference of total population measured [95% CI 0.86%–2.05%] in 2000 and 9.67% [95% CI 9.20%–10.15%] in 2018) over the period compared to the intermediate education group. The advanced education group was younger when receiving first statin prescription (1.87 years younger [95% CI 1.02–2.72] in 2000 and 1.06 years younger [95% CI 0.54–1.58 in 2018) compared to the intermediate education group. All education groups reached the treatment goals equally well when statin treatment was initiated. Conclusion: Higher education was associated with earlier statin prescription, although the higher educated group was monitored less frequently. There was no difference in reaching treatment goal between the three education groups. These findings suggest patients with higher education level achieve an earlier dyslipidemia prevention intervention with an equally satisfying result compared to lower education patients.Key Points Little is known about the role of social inequa

Introduction: The aim was to investigate whether common pregnancy-related symptoms—nausea, vomiting, back pain, pelvic girdle pain, pelvic cavity pain, vaginal bleeding, itching of vulva, pregnancy itching, leg cramps, uterine contractions and varicose veins—in the first trimester of pregnancy add to the identification of women at high risk of future pregnancy and birth complications. Material and methods: Survey data linked to national register data. All women booking an appointment for a first prenatal visit in one of 192 randomly selected General Practices in East Denmark in the period April 2015–August 2016. The General Practices included 1491 women to this prospective study. Two outcomes, pregnancy complications and birth complications, were collected from the Danish Medical Birth Register. Results: Among the 1413 included women, 199 (14%) experienced complications in later pregnancy. The most serious complication, miscarriage, was experienced by 65 women (4.6%). Other common pregnancy complications were gestational diabetes mellitus (n = 11, 0.8%), gestational hypertension without proteinuria (n = 34, 2.4%), mild to moderate preeclampsia (n = 34, 2.4%) and gestational itching with effect on liver (n = 17, 1.2%). Women who experienced pelvic girdle pain, pelvic cavity pain or vaginal bleeding in the first trimester of pregnancy had a higher risk of pregnancy complications later on in later pregnancy. None of the other examined symptoms showed associations to pregnancy complications. No associations were found between pregnancy-related physical symptoms in first trimester and birth complications. Conclusions: Symptoms in early pregnancy do not add much information about the risk of pregnancy or birth complications, although pain and bleeding may give reason for some concern. This is an important message to women experiencing these common symptoms and to their caregivers.

The association between ferritin and transferrin saturation (TS), respectively, and all-cause mortality is unclear. Furthermore, the influence of concurrent inflammation has not been sufficiently elucidated. We investigated these associations and the effect of concurrently elevated C-reactive protein (CRP), and accordingly report the levels associated with lowest all-cause mortality for females and males with and without inflammation. Blood test results from 161,921 individuals were included. Statistical analyses were performed in sex-stratified subpopulations, with ferritin or TS level as continuous exposure variables, and were adjusted for age, co-morbidity and inflammation status using CRP. An interaction was used to investigate whether the effect of ferritin or TS on all-cause mortality was modified by inflammation status (CRP >= 10 mg/L or CRP < 10 mg/L). Low and high ferritin and TS levels were respectively associated with increased all-cause mortality in females and in males. These associations persisted with concurrent CRP >= 10 mg/L. The ferritin level associated with lowest mortality was 60 mu g/L for females and 125 mu g/L for males with CRP < 10 mg/L. It was 52 mu g/L for females and 118 mu g/L for males with CRP >= 10 mg/L. The TS level associated with lowest mortality was 33.9% for females and 32.3% for males with CRP < 10 mg/L. It was 28.7% for females and 30.6% for males with CRP >= 10 mg/L. Our findings can nuance clinical interpretation and further aid in defining recommended ranges for ferritin and TS.

For patients with cancer, prevalent type 2 diabetes at the date of cancer diagnosis is associated with increased cancerspecific and all-cause mortality (1,2). Yet, despite potential health implications, there is limited knowledge on whether cancer is also a risk factor for type 2 diabetes. Moreover, the impact of new-onset type 2 diabetes after cancer diagnosis on survival among cancer patients is unknown. We investigated the incidence of type 2 diabetes following a cancer diagnosis and evaluated the influence of new-onset type 2 diabetes in patients with cancer on overall survival.

Background Partnership breakups and living alone are associated with several adverse health outcomes. The aim of this study, carried out in Denmark, is to investigate whether accumulated numbers of divorces/partnership breakups or years lived alone across 26 years of adult life are associated with levels of inflammation, and if vulnerability with regards to gender or educational level can be identified. Methods 4835 participants from the Copenhagen Aging and Midlife Biobank (CAMB) aged 48-62 years were included. Data on accumulated numbers of partnership breakups and years living alone were retrieved from a national standardised annual register. Inflammatory markers interleukin 6 (IL-6) and high sensitivity C-reactive protein (hsCRP) were measured in blood samples. Multivariate linear regression analyses were adjusted for age, educational level, early major life events, body mass index, chronic diseases, medicinal intake affecting inflammation, acute inflammation and personality scores. Results For men, an association was found between an increasing number of partnership breakups or number of years living alone and higher levels of inflammatory markers. No such association was found for women, and no evidence of partnership breakups and educational level having a joint effect was found for either gender. Conclusion The findings suggest a strong association between years lived alone or accumulated number of partnership breakups and low-grade inflammation for middle-aged men, but not for women. Among those of either sex with a lower level of education, no specific vulnerability to accumulated years lived alone or number of breakups was identified.