Risk and adverse clinical outcomes of thrombocytopenia among patients with solid tumors-a Danish population-based cohort study.

BACKGROUND: Knowledge about thrombocytopenia among patients with solid tumors is scarce. We examined the risk of thrombocytopenia among patients with solid tumors and its association with adverse outcomes. METHODS: Using Danish health registries, we identified all patients with incident solid tumors from 2015-2018 (n = 52,380) and a platelet count measurement within 2 weeks prior to or on their cancer diagnosis date. The risk of thrombocytopenia was categorized as grades 0 (any platelet count × 109/L): <150; 1: <100; 2: <75; 3: <50; 4: <25, and 5: <10. To study the outcomes, each patient with thrombocytopenia was matched with up to five cancer patients without thrombocytopenia by age, sex, cancer type, and stage. Cox regression was used to compute hazard ratios (HRs) of bleeding, transfusion, or death, adjusting for confounding factors. RESULTS: The 1-year risk of thrombocytopenia was 23%, increasing to 30% at 4 years. This risk was higher in patients receiving chemotherapy (43% at 1 year and 49% at 4 years). Overall, patients with thrombocytopenia had higher 30-days rates of bleeding (HR = 1.72 [95% confidence interval, CI: 1.41-2.11]). Thrombocytopenia was also associated with an increased rate of transfusion, and death, but some of the risk estimates were imprecise. CONCLUSIONS: The risk of thrombocytopenia was substantial among patients with solid tumors and associated with adverse outcomes.

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.

Stroke and Risk of Mental Disorders Compared With Matched General Population and Myocardial Infarction Comparators.

BACKGROUND: Accurate estimates of risks of poststroke outcomes from large population-based studies can provide a basis for public health policy decisions. We examined the absolute and relative risks of a spectrum of incident mental disorders following ischemic stroke and intracerebral hemorrhage. METHODS: During 2004 to 2018, we used Danish registries to identify patients (≥18 years and with no hospital history of mental disorders), with a first-time ischemic stroke (n=76 767) or intracerebral hemorrhage (n=9344), as well as age-,sex-, and calendar year-matched general population (n=464 840) and myocardial infarction (n=92 968) comparators. We computed risk differences, considering death a competing event, and hazard ratios adjusted for income, occupation, education, and history of cardiovascular and noncardiovascular comorbidity. RESULTS: Compared with the general population, following ischemic stroke, the 1-year risk difference was 7.3% (95% CI, 7.0-7.5) for mood disorders (driven by depression), 1.4% (95% CI, 1.3-1.5) for organic brain disorders (driven by dementia and delirium), 0.8% (95% CI, 0.7-0.8) for substance abuse disorders (driven by alcohol and tobacco abuse), and 0.5% (95% CI, 0.4-0.5) for neurotic disorders (driven by anxiety and stress disorders). For suicide, risk differences were near null. Hazard ratios were particularly elevated in the first year of follow-up, ranging from a 2- to a 4-fold increased hazard, decreasing thereafter. Compared with myocardial infarction patients, the 1-year risk difference was 4.9% (95% CI, 4.6 to 5.3) for mood disorders, 1.0% (95% CI, 0.8 to 1.1) for organic brain disorders, 0.1% (95% CI, 0.0 to 0.2) for substance abuse disorders, but -0.2% (95% CI, -0.2 to -0.1) for neurotic disorders. Hazard ratios during the first year of follow-up were elevated 1.1- to 1.8-fold for mood, organic brain, and neurotic disorders, while decreased 0.8-fold for neurotic disorders. CONCLUSIONS: The considerably greater risks of mental disorders following a stroke, particularly mood disorders, underline the importance of mental health evaluation after stroke.

Dynamic Hemostasis and Fibrinolysis Assays in Intensive Care COVID-19 Patients and Association with Thrombosis and Bleeding-A Systematic Review and a Cohort Study.

Patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19), the infectious pathology caused by severe acute respiratory syndrome coronavirus 2, have a high risk of thrombosis, though the precise mechanisms behind this remain unclarified. A systematic literature search in PubMed and EMBASE identified 18 prospective studies applying dynamic coagulation assays in ICU COVID-19 patients. Overall, these studies revealed normal or slightly reduced primary hemostasis, prolonged clot initiation, but increased clot firmness. Thrombin generation assay parameters generally were equivalent to the control groups or within reference range. Fibrinolysis assays showed increased clot resistance. Only six studies related their findings to clinical outcome. We also prospectively included 51 COVID-19 patients admitted to the ICU. Blood samples were examined on day 1, 3-4, and 7-8 with platelet function tests, rotational thromboelastometry (ROTEM), in vivo and ex vivo thrombin generation, and clot lysis assay. Data on thrombosis, bleeding, and mortality were recorded during 30 days. Primary hemostasis was comparable to healthy controls, but COVID-19 patients had longer ROTEM-clotting times and higher maximum clot firmness than healthy controls. Ex vivo thrombin generation was similar to that of healthy controls while in vivo thrombin generation markers, thrombin-antithrombin (TAT) complex, and prothrombin fragment 1 + 2 (F1 + 2) were higher in ICU COVID-19 patients than in healthy controls. Impaired fibrinolysis was present at all time points. TAT complex and F1 + 2 levels were significantly higher in patients developing thrombosis (n = 16) than in those without. In conclusion, only few previous studies employed dynamic hemostasis assays in COVID-19 ICU-patients and failed to reveal a clear association with development of thrombosis. In ICU COVID-19 patients, we confirmed normal platelet aggregation, while in vivo thrombin generation was increased and fibrinolysis decreased. Thrombosis may be driven by increased thrombin formation in vivo.

Biotin interference in routine IDS-iSYS immunoassays for aldosterone, renin, insulin-like growth factor 1, growth hormone and bone alkaline phosphatase.

Biotin is increasingly used as dietary supplement. As many immunoassays rely on a binding between biotin and streptavidin, intake of biotin may interfere with laboratory tests, leading to spurious test results. We examined the extent to which levels of aldosterone, renin, insulin-like growth factor 1 (IGF-1), growth hormone (GH) and bone alkaline phosphatase (BAP) were affected by biotin. In an experimental study performed at Aarhus University Hospital, Denmark, patient samples (plasma or serum) were pooled and spiked with biotin in increasing concentrations (0, 20, 50, 100 and 500 ng/mL). All biomarkers were analyzed using Immunodiagnostic Systems (IDS-iSYS) Multi-Discipline Automated System assays. The average bias (%) was calculated, as the difference in concentrations between the sample without biotin (reference) and the samples with increasing concentrations of biotin. Both aldosterone and renin assays showed substantial biotin interference in a dose-dependent manner, with biases up to +3484% for aldosterone and -98% for renin in the highest concentrations of biotin (100-500 ng/mL). IGF-1, GH and BAP results were generally less affected by added biotin and significant bias (>10%) was observed only when the biotin concentration was 100 ng/mL (IGF-1 and GH) or 500 ng/mL (BAP). In conclusion, biotin interfered with the IDS-iSYS immunoassays, particularly for aldosterone and renin. The assays for GH, IGF-1 and BAP were less sensitive and only with high concentrations of biotin.

High-sensitivity troponin T and I in patients suspected of acute myocardial infarction.

Measurement of cardiac troponin (cTn) is the cornerstone in the diagnosis of myocardial infarction (MI). Potential disparities in concentrations of cTn, trajectories and mortality, following initial measurement warrant further investigation. Such data may guide clinicians treating patients suspected of MI. Plasma concentrations of cTnT and cTnI were measured in 503 consecutive patients at Aarhus University Hospital between June 13th and June 27th, 2019. cTnT was measured with the Roche cobas® E602 hs-cTnT assay, while cTnI was measured with the Siemens ADVIA Centaur® XPT hs-cTnI assay. Analytical agreement was determined based on assay-specific 99th percentiles. Medical records were reviewed for adjudication of the MI diagnosis. MI was the final diagnosis in 65 patients (12.9%) and the analytical agreement between cTnT and cTnI assays was 95.2%. For patients diagnosed with MI, cTnI reached higher peak concentrations in shorter time, compared to cTnT. All-cause mortality risk increased with increasing levels of both biomarkers. In this study, the analytical agreement of two cTn assays was high. However, some disparities in troponin trajectories were observed.

Disseminated intravascular coagulation: epidemiology, biomarkers, and management.

Disseminated intravascular coagulation (DIC) is a systemic activation of the coagulation system, which results in microvascular thrombosis and, simultaneously, potentially life-threatening haemorrhage attributed to consumption of platelets and coagulation factors. Underlying conditions, e.g. infection, cancer, or obstetrical complications are responsible for the initiation and propagation of the DIC process. This review provides insights into the epidemiology of DIC and the current understanding of its pathophysiology. It details the use of diagnostic biomarkers, current diagnostic recommendations from international medical societies, and it provides an overview of emerging diagnostic and prognostic biomarkers. Last, it provides guidance on management. It is concluded that timely and accurate diagnosis of DIC and its underlying condition is essential for the prognosis. Treatment should primarily focus on the underlying cause of DIC and supportive treatment should be individualised according to the underlying aetiology, patient's symptoms and laboratory records.

Syncope as a sign of occult cancers: a population-based cohort study.

BACKGROUND: We examined if syncope was a marker of an occult cancer by comparing the risk in patients with a syncope episode with that of the general population. METHODS: Using Danish population-based medical registries, we identified all patients diagnosed with syncope during 1994-2013 and followed them until a cancer diagnosis, emigration, death or end of follow-up, whichever came first. We computed cumulative risks and standardised incidence ratios (SIR) with 95% confidence intervals (CI). RESULTS: Among 208,361 patients with syncope, 20,278 subsequent cancers were observed. The 6-month cumulative risk of any cancer was 1.2%, increasing to 17.9 % for 1-20 years of follow-up. The highest cumulative risks after 6 months of follow-up were lung cancer (0.2%), colorectal cancer (0.2%), prostate cancer (0.1%) and brain cancer (0.1%). The 6-month SIR were 2.7 (95% CI: 2.4-3.0) for lung cancer, 2.0 (95% CI: 1.8-2.2) for colorectal cancer, 1.7 (95% CI: 1.5-1.9) for prostate cancer and 10.0 (95% CI: 8.6-11.4) for brain cancer. CONCLUSIONS: Syncope was a weak marker of an occult cancer. In short-term the highest cumulative risks were observed for lung, colorectal, prostate and brain cancers. An aggressive search for occult cancer in a patient with syncope is probably not warranted.

Risk of primary urological and genital cancers following incident breast cancer: a Danish population-based cohort study.

PURPOSE: The prevalence of breast cancer survivors has increased due to dissemination of population-based mammographic screening and improved treatments. Recent changes in anti-hormonal therapies for breast cancer may have modified the risks of subsequent urological and genital cancers. We examine the risk of subsequent primary urological and genital cancers in patients with incident breast cancer compared with risks in the general population. METHODS: Using population-based Danish medical registries, we identified a cohort of women with primary breast cancer (1990-2017). We followed them from one year after their breast cancer diagnosis until any subsequent urological or genital cancer diagnosis. We computed incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as the observed number of cancers relative to the expected number based on national incidence rates (by sex, age, and calendar year). RESULTS: Among 84,972 patients with breast cancer (median age 61 years), we observed 623 urological cancers and 1397 genital cancers during a median follow-up of 7.4 years. The incidence rate per 100,000 person-years was stable during follow-up (83 for urological cancers and 176 for genital cancers). The SIR was increased for ovarian cancer (1.37, 95% CI 1.23-1.52) and uterine cancer (1.37, 95% CI 1.25-1.50), but only during the pre-aromatase inhibitor era (before 2007). Moreover, the SIR of kidney cancer was increased (1.52, 95% CI 1.15-1.97), but only during 2007-2017. The SIR for urinary bladder cancer was marginally increased (1.15, 95% CI 1.04-1.28) with no temporal effects. No associations were observed for cervical cancer. CONCLUSION: Breast cancer survivors had higher risks of uterine and ovarian cancer than expected, but only before 2007, and of kidney cancer, but only after 2007. The risk of urinary bladder cancer was moderately increased without temporal effects, and we observed no association with cervical cancer.

Association between lipid fractions and age of first myocardial infarction.

OBJECTIVE: Dyslipidemia is a major cause of early coronary heart disease (CHD). Low-density-lipoprotein cholesterol (LDL-C), remnant cholesterol (remnant-C) and high-density lipoprotein cholesterol (HDL-C) have all been shown to be associated with risk of CHD. We aimed to compare the association of these lipid fractions with age at first myocardial infarction(MI). Design. Multicenter study of consecutive patients hospitalized with a first MI. Linear regression models were used to assess the independent association of LDL-C, remnant-C and HDL-C with age at first MI. Results. The study included 1744 patients. In univariate analyses, LDL-C, remnant-C, and HDL-C were all significantly associated with age at first MI. However, in multivariate analyses only LDL-C [-2.5 years (95%CI: -3.1 to -1.8) per 1 SD increase] and to a lesser extent remnant-C [-0.9 years (95% CI: -1.5 to -0.3)] continued to be associated with age of MI, while HDL-C [0.5 years (95%CI: -0.2 to 1.2)] was not. Conclusions. LDL-C is the lipid fraction strongest associated with younger age of presentation of first MI. These results support the importance of controlling and treating LDL-C in prevention of premature MI.

Risk and Prognosis of Cancer After Lower Limb Arterial Thrombosis.

BACKGROUND: Venous thromboembolism can be a presenting symptom of cancer, but the association between lower limb arterial thrombosis and cancer is unknown. We therefore examined cancer risk and prognosis of cancer in patients with lower limb arterial thrombosis. METHODS: Using nationwide population-based Danish medical registries, we identified all patients diagnosed with first-time lower limb arterial thrombosis (1994-2013) and followed them until the occurrence of any subsequent cancer diagnosis, emigration, death, or November 30, 2013, whichever came first. We computed standardized incidence ratios with 95% confidence intervals as the observed number of cancers relative to the expected number based on national incidence rates by sex, age, and calendar year. To examine the prognostic impact of lower limb arterial thrombosis on all-cause mortality after cancer, we constructed a matched comparison cohort of patients who had cancer without lower limb arterial thrombosis. RESULTS: Among 6600 patients with lower limb arterial thrombosis, we observed 772 subsequent cancers. The risk of any cancer was 2.5% after 6 months of follow-up, increasing to 17.9% after 20 years. During the first 6 months of follow-up, the standardized incidence ratio of any cancer was 3.28 (95% confidence interval, 2.79-3.82). The standardized incidence ratio remained elevated during 7 to 12 months (1.42; 95% confidence interval, 1.09-1.83) and beyond 12 months (1.14; 95% confidence interval, 1.05-1.24). The strongest associations were found for lung cancer and other smoking-related cancers. Lower limb arterial thrombosis also was associated with increased all-cause mortality after colon, lung, urinary bladder, and breast cancer, but not after prostate cancer. CONCLUSIONS: Lower limb arterial thrombosis was a marker of occult cancer, especially lung cancer, and was an adverse prognostic factor for mortality in common cancers.

Risk of Dementia in Adults With Congenital Heart Disease: Population-Based Cohort Study.

BACKGROUND: More children with congenital heart disease (CHD) are surviving to adulthood, and CHD is associated with risk factors for dementia. We compared the risk of dementia in CHD adults to that of the general population. METHODS: In this cohort study, we used medical registries and a medical record review covering all Danish hospitals to identify adults with CHD diagnosed between 1963 and 2012. These individuals with CHD were followed from January 1, 1981, 30 years of age, or date of first CHD registration (index date for matched members of the general population cohort) until hospital diagnosis of dementia, death, emigration, or end of study (December 31, 2012). For each individual with CHD, we identified 10 members of the general population utilizing the Danish Civil Registration System matched on sex and birth year. We computed cumulative incidences and hazard ratios (HRs) of dementia, adjusting for sex and birth year. RESULTS: The cumulative incidence of dementia was 4% by 80 years of age in 10 632 adults with CHD (46% male). The overall HR comparing adults with CHD with the general population cohort was 1.6 (95% confidence interval [CI], 1.3-2.0). The HR among individuals with CHD without extracardiac defects was 1.4 (95% CI, 1.1-1.8). Adults with mild-to-moderate CHD had an HR of 1.5 (95% CI, 1.1-2.0), whereas the HR was 2.0 (95% CI, 1.2-3.3) for severe CHD, including univentricular hearts. The HR for early onset dementia (<65 years of age) was 2.6 (95% CI, 1.8-3.8), whereas the late-onset HR was 1.3 (95% CI, 1.0-1.8). CONCLUSIONS: CHD was associated with an increased risk of dementia compared with the general population, in particular for early onset dementia. Further understanding of dementia risk in the population with CHD is a potential target for future investigation.

Higher Risk of Vascular Dementia in Myocardial Infarction Survivors.

BACKGROUND: Increased risk of dementia after myocardial infarction (MI) may be mediated by shared risk factors (eg, atherosclerosis) and post-MI stroke. We examined risk of dementia in 1-year survivors of MI. METHODS: Using Danish medical registries, we conducted a nationwide population-based cohort study of all patients with first-time MI and a sex-, birth year-, and calendar year-matched general population comparison cohort without MI (1980-2012). Cox regression analysis was used to compute 1- to 35-year adjusted hazard ratios (aHRs) for dementia, controlled for matching factors and adjusted for comorbidities and socioeconomic status. RESULTS: We identified 314 911 patients with MI and 1 573 193 matched comparison cohort members randomly sampled from the general population (median age, 70 years; 63% male). After 35 years of follow-up, the cumulative incidence of all-cause dementia in the MI cohort was 9% (2.8% for Alzheimer disease, 1.6% for vascular dementia, and 4.5% for other dementias). Compared with the general population cohort, MI was not associated with all-cause dementia (aHR, 1.01; 95% confidence interval [CI], 0.98-1.03). Risk of Alzheimer disease (aHR, 0.92; 95% CI, 0.88-0.95) and other dementias (aHR, 0.98; 95% CI, 0.95-1.01) also approximated unity. However, MI was associated with higher risk of vascular dementia (aHR, 1.35; 95% CI, 1.28-1.43), which was substantially strengthened for patients experiencing stroke after MI (aHR, 4.48; 95% CI, 3.29-6.12). CONCLUSIONS: MI was associated with higher risk of vascular dementia throughout follow-up, and this association was stronger in patients with stroke. The risk of Alzheimer disease and other dementias was not higher in patients with MI.

Levels of and Changes in Childhood Body Mass Index in Relation to Risk of Atrial Fibrillation and Atrial Flutter in Adulthood.

Children with obesity have a cardiometabolic risk profile that may predispose them to cardiovascular diseases. We examined the associations of childhood body mass index (BMI) and changes in BMI with the risk of atrial fibrillation and flutter (AFF) in adulthood. We conducted a population-based cohort study of Danish schoolchildren aged 7-13 years born from 1930 to 1989. Among 314,140 children, 17,594 were diagnosed with AFF as adults (1977-2014). In both men and women, above-average BMIs in childhood were associated with increased risks of AFF. Children who were persistently heavy at ages 7 and 13 years and children whose BMIs increased from the internal 25.0th-75.0th percentiles or from the internal 75.1th-90.0th percentiles between ages 7 and 13 years had higher risks of AFF in adulthood than children whose BMIs remained in the internal 25.0th-75.0th percentiles at both ages. A decrease in BMI percentile categories between 7 and 13 years of age reduced risks of AFF in adulthood, with risks of AFF reverting to levels similar to those in the reference group for women but not for men. In conclusion, risks of AFF in adulthood increased with higher childhood BMIs. Remission from overweight by age 13 years reduced AFF risks, especially in women.

Pregnancy, Birth, Neonatal, and Postnatal Neurological Outcomes After Pregnancy With Migraine.

BACKGROUND: Prevalence of migraine is high during the reproductive age. Although migraine often improves during pregnancy, the risk of adverse pregnancy, birth, neonatal, and neurological outcomes in mother and offspring remains poorly understood. OBJECTIVE: To investigate the associations between maternal migraine and risks of adverse pregnancy outcomes in the mother, and birth, neonatal and postnatal outcomes in the offspring. METHODS: We used Danish population registries to assemble a cohort of pregnancies among women with migraine and an age- and conception year-matched comparison cohort of pregnancies among women without migraine. The study period was 2005-2012. We computed adjusted prevalence ratios (aPRs) for pregnancy and birth outcomes and adjusted risk ratios (aRRs) for neonatal and postnatal outcomes, adjusting for age, preconception medical history, and preconception reproductive history. RESULTS: We identified 22,841 pregnancies among women with migraine and 228,324 matched pregnancies among women without migraine. Migraine was associated with an increased risk of pregnancy-associated hypertension disorders (aPR: 1.50 [95% confidence interval (CI): 1.39-1.61]) and miscarriage (aPR: 1.10 [95% CI: 1.05-1.15]). Migraine was associated with an increased prevalence of low birth weight (aPR: 1.14 [95% CI: 1.06-1.23]), preterm birth (aPR: 1.21 [95% CI: 1.13-1.30]) and cesarean delivery (aPR: 1.20 [95% CI: 1.15-1.25]), but not of small for gestational age offspring (aPR: 0.94 [95% CI: 0.88-0.99]) and birth defects (aPR: 1.01 [95% CI: 0.93-1.09]). Offspring prenatally exposed to maternal migraine had elevated risks of several outcomes in the neonatal and postnatal period, including intensive care unit admission (aRR: 1.22 [95% CI: 1.03-1.45]), hospitalization (aRR: 1.12 [95% CI: 1.06-1.18]), dispensed prescriptions (aRR: 1.34 [95% CI: 1.24-1.45]), respiratory distress syndrome (aRR: 1.20 [95% CI: 1.02-1.42]), and febrile seizures (aRR: 1.27 [95% CI: 1.03-1.57), but not of death (aRR: 0.67 [95% CI: 0.43-1.04]) and cerebral palsy (aRR: 1.00 [95% CI: 0.51-1.94]). CONCLUSIONS: Women with migraine and their offspring have greater risks of several adverse pregnancy outcomes than women without migraine.

Risk of cancer in patients with epistaxis and haemoptysis.

This corrects the article DOI: 10.1038/bjc.2017.85.

Effects of hyperoxia on myocardial injury following cardioversion-A randomized clinical trial.

Oxygen has long been assumed beneficial for all ill and injured patients. However, hyperoxia may be harmful and aggravate myocardial injury such as that caused by myocardial infarction. We aimed to investigate if hyperoxia increases myocardial injury following direct current cardioversion compared with room air. METHODS: Patients undergoing elective biphasic cardioversion for atrial fibrillation or atrial flutter were randomized to receive room air or oxygen (10-15 L/min) during the procedure. The primary endpoint was the difference in high-sensitive Troponin I (hs-cTnI) and -T (hs-cTnT) measured 2 hours before and 4 hours after cardioversion. Secondary endpoints were differences in Copeptin and NT-pro-BNP. RESULTS: A total of 65 patients were randomized to high-flow oxygen (male: 71%, mean age 66.9 years) and 59 patients to room air (male: 80%, mean age 65.5 years). There was no difference in hs-cTnI between patients treated with oxygen compared to patients treated with room air (P=.09) and no significant difference for hs-cTnT, ratio 1.08 (95% CI: 0.99-1.18) (P=.09). Median hs-cTnI difference before and after cardioversion was 0.1 (interquartile range (IQR): -0.5 to 0.5) ng/L for the high-flow oxygen group and -0.3 (IQR: -1.1 to 0.4) ng/L for the room air group. There was no difference in Copeptin between patients treated with oxygen compared to room air (ratio 1.06 (95% CI: 0.89-1.27) (P=.51) or NT-pro-BNP (difference-6.0 ng/L (95% CI: -78.5 to 66.6) P=.87). CONCLUSION: Direct current cardioversion of atrial fibrillation/flutter with and without high-flow oxygen supplement was not associated with myocardial injury evaluated by high sensitive myocardial biomarkers.

Forty-year Seasonality Trends in Occurrence of Myocardial Infarction, Ischemic Stroke, and Hemorrhagic Stroke.

BACKGROUND: The occurrence of myocardial infarction (MI), ischemic stroke, and hemorrhagic stroke has decreased in recent years, but trends in seasonal occurrence remain unclear. METHODS: Using Danish healthcare databases, we identified all patients with a first-time MI, ischemic stroke, or hemorrhagic stroke during the study period (1977-2016). We summarized monthly cases for each disease separately and computed the peak-to-trough ratio as a measure of seasonal occurrence of one cycle. To examine trends over time in seasonal occurrence, we computed the peak-to-trough ratio for each of the 40 years. We also quantified the amount of bias arising from random error in peak-to-trough ratios. RESULTS: Before consideration of bias, the peak-to-trough ratio of summarized monthly cases was 1.11 (95% confidence interval [CI] = 1.10, 1.12) for MI, 1.08 (95% CI = 1.07, 1.09) for ischemic stroke, and 1.12 (95% CI = 1.10, 1.14) for hemorrhagic stroke. The peak-to-trough ratio of MI occurrence increased from 1.09 (95% CI = 1.04, 1.15) in 1977 to 1.16 (95% CI = 1.09, 1.23) in 1999. The trend then remained stable. The peak-to-trough ratio of ischemic stroke occurrence declined continuously during the study period, dropping from 1.12 (95% CI = 1.02, 1.24) in 1977 to 1.06 (95% CI = 1.00, 1.12) in 2016. The peak-to-trough ratio of hemorrhagic stroke occurrence remained stable over time. However, after adjusting for potential bias, time trends in peak-to-trough ratios were almost flat. CONCLUSIONS: We found no substantial seasonality for MI, ischemic stroke, or hemorrhagic stroke occurrence during 1977-2016. Modest peak-to-trough ratios should be interpreted after considering bias induced by random variation.

Elevated potassium levels in patients with chronic kidney disease: occurrence, risk factors and clinical outcomes-a Danish population-based cohort study.

Background: Data on the true burden of hyperkalemia (HK) in patients with chronic kidney disease (CKD) in a real-world setting are scarce. Methods: The incidence rate of HK [first blood test with an elevated blood potassium level level >5.0 mmol/L] in primary or hospital care was assessed in a population-based cohort of all newly diagnosed CKD patients [second estimated glomerular filtration rate (eGFR) measurement <60 mL/min/1.73 m2 or hospital diagnosis] in northern Denmark. Risk factors and clinical outcomes were compared for CKD patients with HK and matched CKD patients without HK. Results: Of 157 766 patients with CKD, 28% experienced HK, for an overall HK incidence rate of 70/1000 person-years. Among patients with Stage 3A, 3B, 4 or 5 CKD, 9, 18, 31 and 42%, respectively, experienced HK within the first year. Important HK risk factors included diabetes {prevalence ratio [PR] 1.74 [95% confidence interval (CI) 1.69-1.79]}, heart failure [PR 2.31 (95% CI 2.23-2.40)] and use of angiotensin-converting enzyme inhibitors [PR 1.45 (95% CI 1.42-1.48)], potassium supplements [PR 1.59 (95% CI 1.55-1.62)] or spironolactone [PR 2.53 (95% CI 2.44-2.63)]. In CKD patients who developed HK, 34% had any acute hospitalization 6 months before the HK event, increasing to 57% 6 months after HK [before-after risk ratio 1.72 (95% CI 1.69-1.74)]. The 6-month mortality following HK was 26%, versus 6% in matched non-HK patients. Compared with non-HK patients, 6-month hazard ratios for any acute hospitalization in HK patients were 2.11-fold higher, including hazard ratios of 2.07 for cardiac diagnoses, 2.29 for ventricular arrhythmias, 3.26 for cardiac arrest, 4.77 for intensive care and 4.85 for death. Conclusions: More than one in four CKD patients develops HK. Patients with severe CKD, diabetes, heart failure or use of spironolactone are at high risk. HK is associated with severe clinical outcomes.

Positive predictive value of infective endocarditis in the Danish National Patient Registry: a validation study.

The positive predictive value of an infective endocarditis diagnosis is approximately 80% in the Danish National Patient Registry. However, since infective endocarditis is a heterogeneous disease implying long-term intravenous treatment, we hypothesiszed that the positive predictive value varies by length of hospital stay. A total of 100 patients with first-time infective endocarditis in the Danish National Patient Registry were identified from January 2010 - December 2012 at the University hospital of Aarhus and regional hospitals of Herning and Randers. Medical records were reviewed. We calculated the positive predictive value according to admission length, and separately for patients with a cardiac implantable electronic device and a prosthetic heart valve using the Wilson score method. Among the 92 medical records available for review, the majority of the patients had admission length ⩾2 weeks. The positive predictive value increased with length of admission. In patients with admission length <2 weeks the positive predictive value was 65% while it was 90% for admission length ⩾2 weeks. The positive predictive value was 81% for patients with a cardiac implantable electronic device and 87% for patients with a prosthetic valve. The positive predictive value of the infective endocarditis diagnosis in the Danish National Patient Registry is high for patients with admission length ⩾2 weeks. Using this algorithm, the Danish National Patient Registry provides a valid source for identifying infective endocarditis for research.