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We examined the role of receptor profiles and other prognostic factors in survival outcomes after stereotactic radiosurgery (SRS) for brain metastases in breast cancer patients, to help improve selection of candidates for SRS. We included 149 consecutive patients who received SRS between 2012 and 2019 at the University Hospital of Copenhagen, Rigshospitalet, Denmark. Overall survival (OS) following SRS was determined through the Kaplan–Meier method, while CNS progression-free survival (CNS-PFS) was determined through competing risk analysis. Prognostic factors for both OS and CNS-PFS were evaluated through uni- and multivariate Cox regression and Fine-Gray models, respectively. The proportional hazards assumptions were tested through Schoenfeld residuals, and non-proportionality was accounted for by the inclusion of time-dependent variables. Median OS was 14.8 months for the entire cohort and was as follows for the four receptor profiles: 33.3 months for ER+/HER2+ (ER: estrogen receptor, HER2: human epidermal growth factor receptor 2), 11.0 months for ER+/HER2−, 17.7 months for ER−/HER2+, and 5.3 months for ER−/HER2−. In the multivariate model, the ER−/HER2− receptor profile (hazard ratio (HR): 2.00, 95% confidence interval (CI): 1.09–3.67) and the presence of extracranial visceral metastases (HR: 2.90, 95% CI: 1.53–5.50) were associated with worse OS. The ER+/HER2+ receptor profile (HR: 0.43, 95% CI: 0.19–0.96) and 5+ lines of treatment (HR: 0.40, 95% CI: 0.20–0.82) were both associated with improved OS. For CNS-PFS, 5+ lines of treatment (sub-distributional hazard ratio (SHR): 2.88, 95% CI: 1.06–7.81) was associated with worse CNS-PFS, while extracranial visceral metastases (SHR: 0.54, 95% CI: 0.30–0.97) was associated with reduced risk of CNS progression – which is primarily due to patients with extracranial metastases dying before developing new CNS progression. Extracranial visceral disease and the ER−/HER2− receptor profile were associated with poor survival outcomes following SRS. [ABSTRACT FROM AUTHOR]

Introduction: Recurrence of cancer is not routinely registered in Danish national health registers. This study aimed to develop and validate a register-based algorithm to identify patients diagnosed with recurrent lung cancer and to estimate the accuracy of the identified diagnosis date. Material and Methods: Patients with early-stage lung cancer treated with surgery were included in the study. Recurrence indicators were diagnosis and procedure codes recorded in the Danish National Patient Register and pathology results recorded in the Danish National Pathology Register. Information from CT scans and medical records served as the gold standard to assess the accuracy of the algorithm. Results: The final population consisted of 217 patients; 72 (33%) had recurrence according to the gold standard. The median follow-up time since primary lung cancer diagnosis was 29 months (interquartile interval: 18– 46). The algorithm for identifying a recurrence reached a sensitivity of 83.3% (95% CI: 72.7– 91.1), a specificity of 93.8% (95% CI: 88.5– 97.1), and a positive predictive value of 87.0% (95% CI: 76.7– 93.9). The algorithm identified 70% of the recurrences within 60 days of the recurrence date registered by the gold standard method. The positive predictive value of the algorithm decreased to 70% when the algorithm was simulated in a population with a recurrence rate of 15%. Conclusion: The proposed algorithm demonstrated good performance in a population with 33% recurrences over a median of 29 months. It can be used to identify patients diagnosed with recurrent lung cancer, and it may be a valuable tool for future research in this field. However, a lower positive predictive value is seen when applying the algorithm in populations with low recurrence rates. [ABSTRACT FROM AUTHOR]

Interpretable risk assessment of SARS-CoV-2 positive patients can aid clinicians to implement precision medicine. Here we trained a machine learning model to predict mortality within 12 weeks of a first positive SARS-CoV-2 test. By leveraging data on 33,938 confirmed SARS-CoV-2 cases in eastern Denmark, we considered 2723 variables extracted from electronic health records (EHR) including demographics, diagnoses, medications, laboratory test results and vital parameters. A discrete-time framework for survival modelling enabled us to predict personalized survival curves and explain individual risk factors. Performance on the test set was measured with a weighted concordance index of 0.95 and an area under the curve for precision-recall of 0.71. Age, sex, number of medications, previous hospitalizations and lymphocyte counts were identified as top mortality risk factors. Our explainable survival model developed on EHR data also revealed temporal dynamics of the 22 selected risk factors. Upon further validation, this model may allow direct reporting of personalized survival probabilities in routine care. [ABSTRACT FROM AUTHOR]

Aims This study investigated left atrial (LA) parameters as measured on transthoracic echocardiography as predictors of incident heart failure (HF) in a community cohort. Methods and results In a large general population study (n = 2221), participants underwent a health examination with echocardiography. The maximum and minimum LA volumes indexed to body surface area (LAVImax and LAVImin) were measured and the LA emptying fraction (LAEF) and LA expansion index (LAEI) were calculated. Among 1951 participants without atrial fibrillation or significant valve disease, the mean age was 59±16 years and 58% were women. At baseline, 1% (n = 16) had a left ventricular ejection fraction of <50%, 44% had hypertension, and 10% had diabetes. During follow-up (median 15.8 years, interquartile range: 11.3-16.2 years), 187 (10%) participants were diagnosed with incident HF. Participants who were diagnosed with HF during follow-up had a larger LAVImax and LAVImin and a lower LAEF and LAEI compared to participants without HF. In unadjusted analysis, LAVImax, LAVImin, LAEF and LAEI were predictors of incident HF. After multivariable adjustment for clinical and echocardiographic parameters, only LAVImin remained an independent predictor of incident HF (hazard ratio per 1 standard deviation increase: 1.22 [95% confidence interval 1.01-1.47], p = 0.038). Conclusion In the general population, LAVImin is an independent predictor of incident HF. LAVImax, currently the only LA measure in a routine echocardiographic examination, was not an independent predictor of incident HF. [ABSTRACT FROM AUTHOR]

Recurrence of endometrial cancer is not routinely registered in the Danish national health registers. The aim of this study was to develop and validate a register-based algorithm to identify women diagnosed with endometrial cancer recurrence in Denmark to facilitate register-based research in this field. We conducted a cohort study based on data from Danish health registers. The algorithm was designed to identify women with recurrence and estimate the accompanying diagnosis date, which was based on information from the Danish National Patient Registry and the Danish National Pathology Registry. Indicators of recurrence were pathology registrations and procedure or diagnosis codes suggesting recurrence and related treatment. The gold standard for endometrial cancer recurrence originated from a Danish nationwide study of 2612 women diagnosed with endometrial cancer, FIGO stage I–II during 2005–2009. Recurrence was suspected in 308 women based on pathology reports, and recurrence suspicion was confirmed or rejected in the 308 women based on reviews of the medical records. The algorithm was validated by comparing the recurrence status identified by the algorithm and the recurrence status in the gold standard. After relevant exclusions, the final study population consisted of 268 women, hereof 160 (60%) with recurrence according to the gold standard. The algorithm displayed a sensitivity of 91.3% (95% confidence interval (CI): 85.8–95.1), a specificity of 91.7% (95% CI: 84.8–96.1) and a positive predictive value of 94.2% (95% CI: 89.3–97.3). The algorithm estimated the recurrence date within 30 days of the gold standard in 86% and within 60 days of the gold standard in 94% of the identified patients. The algorithm demonstrated good performance; it could be a valuable tool for future research in endometrial cancer recurrence and may facilitate studies with potential impact on clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Information on cancer recurrence is rarely available outside clinical trials. Wide exclusion criteria used in clinical trials tend to limit the generalizability of findings to the entire population of people living beyond a cancer disease. Therefore, population-level evidence is needed. The aim of this study was to develop and validate a register-based algorithm to identify patients diagnosed with recurrence after curative treatment of malignant melanoma. Patients and Methods: Indicators of recurrence were diagnosis and procedure codes recorded in the Danish National Patient Register and pathology results recorded in the Danish National Pathology Register. Medical records on recurrence status and recurrence date in the Danish Melanoma Database served as the gold standard to assess the accuracy of the algorithm. Results: The study included 1747 patients diagnosed with malignant melanoma; 95 (5.4%) were diagnosed with recurrence of malignant melanoma according to the gold standard. The algorithm reached a sensitivity of 93.7% (95% confidence interval (CI) 86.8– 97.6), a specificity of 99.2% (95% CI: 98.6– 99.5), a positive predictive value of 86.4% (95% CI: 78.2– 92.4), and negative predictive value of 99.6% (95% CI: 99.2– 99.9). Lin's concordance correlation coefficient was 0.992 (95% CI: 0.989– 0.996) for the agreement between the recurrence dates generated by the algorithm and by the gold standard. Conclusion: The algorithm can be used to identify patients diagnosed with recurrence of malignant melanoma and to establish the timing of recurrence. This can generate population-level evidence on disease-free survival and diagnostic pathways for recurrence of malignant melanoma. [ABSTRACT FROM AUTHOR]

Background: This study investigates the accuracy of the reporting of medication use by proxy- and self-respondents, and it compares the prognostic value of the number of medications from survey and registry data for predicting mortality across self- and proxy-respondents.Methods: The study is based on the linkage of the Longitudinal Study of Aging Danish Twins and the Danish 1905-Cohort Study with the Danish National Prescription Registry. We investigated the concordance between survey and registry data, and the prognostic value of medication use when assessed using survey and registry data, to predict mortality for self- and proxy-respondents at intake surveys.Results: Among self-respondents, the agreement was moderate (κ = 0.52-0.58) for most therapeutic groups, whereas among proxy-respondents, the agreement was low to moderate (κ = 0.36-0.60). The magnitude of the relative differences was, generally, greater among proxies than among self-respondents. Each additional increase in the total number of medications was associated with 7%-8% mortality increase among self- and 4%-6% mortality increase among proxy-respondents in both the survey and registry data. The predictive value of the total number of medications estimated from either data source was lower among proxies (c-statistic = 0.56-0.58) than among self-respondents (c-statistic = 0.74).Conclusions: The concordance between survey and registry data regarding medication use and the predictive value of the number of medications for mortality were lower among proxy- than among self-respondents. [ABSTRACT FROM AUTHOR]

Objective: Specialised follow-up care after cancer treatment is changing towards increased involvement of general practice. To ensure timely detection of new cancer events, knowledge is warranted on the timing of cancer recurrence (CR) and second primary cancer (SPC), including risk factors for CR., Methods: This population-based register study included 67,092 patients diagnosed with malignant melanoma, bladder, lung, ovarian, endometrial, colorectal and breast cancer in Denmark in 2008-2016. The time from primary cancer to CR or SPC and risk factors for prolonged time to CR were analysed and stratified on sex and primary cancer type., Results: Cancer recurrence proportions ranged from 6% to 35%. The risk of CR increased profoundly within the first 3 years and then levelled off, except for breast cancer. A total of 3%-6% of patients had SPC, with monotonously increasing cumulative incidence proportions. Besides primary tumour characteristics, lower educational level, living alone and comorbidity were associated with earlier CR. For example, in female malignant melanoma, HRs and 95% confidence intervals were 0.47 (0.37-0.61) for high educational level, 1.40 (1.16-1.68) for living alone and 2.38 (1.53-3.70) for high comorbidity., Conclusion: The results may inform stratified risk assessment in decision of frequency, location and duration of post-cancer follow-up care., (© 2019 John Wiley & Sons Ltd.)

Aims To investigate the relative importance of individual tissue Doppler imaging variables to predict adverse events in a high-risk population with diabetes, ischaemic heart disease, and/or systolic dysfunction. Methods and results Transthoracic echocardiograms were analysed in 388 diabetic patients without significant valve disease, bundle branch block, and atrial fibrillation who underwent coronary angiography. Multivariable Cox's regression analyses were used to establish the association between peak systolic (s′), early diastolic (e′), and late diastolic (a′) tissue velocities and outcomes (hospitalization for heart failure or death). The mean age and left ventricular ejection fraction (LVEF) was 66 ± 10 years and 45 ± 12%, respectively. During 2.3 (±1.0) years of follow-up, 91 patients (24%) met the combined endpoint. After adjustment for LVEF, coronary artery pathology, heart failure at baseline, age, and gender, each 1 cm/s decrease in s′, e′, and a′ was associated with a hazard ratio (HR) of 1.18 (0.89–1.57), 1.03 (0.86–1.22), and 1.20 (1.05–1.37), respectively. A significant interaction was found between s′ and a′, P < 0.01. In patients with lower than mean s′, 1 cm/s decrease in a′ was associated with HR 1.31 (1.10–1.55, P < 0.01), whereas a′ was without prognostic importance in patients with higher than mean s′ [HR 0.99 (0.78–1.25, P = 0.6)]. Patients having lower than mean values of both s′ and a′ had a poorer prognosis than patients having at least one of s′ and a′ high. Conclusion Peak systolic and late diastolic tissue velocities add prognostic information beyond LVEF in high-risk patients. Variables should be considered together as they interact on prognosis. [ABSTRACT FROM PUBLISHER]

- Maribo is a new Danish CM chondrite, which fell on January 17, 2009, at 19:08:28 CET. The fall was observed by many eye witnesses and recorded by a surveillance camera, an all sky camera, a few seismic stations, and by meteor radar observatories in Germany. A single fragment of Maribo with a dry weight of 25.8 g was found on March 4, 2009. The coarse-grained components in Maribo include chondrules, fine-grained olivine aggregates, large isolated lithic clasts, metals, and mineral fragments (often olivine), and rare Ca,Al-rich inclusions. The components are typically rimmed by fine-grained dust mantles. The matrix includes abundant dust rimmed fragments of tochilinite with a layered, fishbone-like texture, tochilinite-cronstedtite intergrowths, sulfides, metals, and carbonates often intergrown with tochilinite. The oxygen isotopic composition: (δ17O = −1.27‰; δ18O = 4.96‰; Δ17O = −3.85‰) plots at the edge of the CM field, close to the CCAM line. The very low Δ17O and the presence of unaltered components suggest that Maribo is among the least altered CM chondrites. The bulk chemistry of Maribo is typical of CM chondrites. Trapped noble gases are similar in abundance and isotopic composition to other CM chondrites, stepwise heating data indicating the presence of gas components hosted by presolar diamond and silicon carbide. The organics in Maribo include components also seen in Murchison as well as nitrogen-rich components unique to Maribo. [ABSTRACT FROM AUTHOR]

OBJECTIVE--We evaluated the impact on diabetes-related intermediary traits of common novel type 2 diabetes-associated variants in the JAZF1 (rs864745), CDC123/CAMKID (rs12779790), TSPAN8 (rs7961581), THADA (rs7578597), AD AMTS9 (rs4607103), and NOTCH2 (rs10923931) loci, which were recently identified by meta-analysis of genome-wide association data. RESEARCH DESIGN AND METHODS--We genotyped the six variants in 4,516 middle-aged glucose-tolerant individuals of the population-based Inter99 cohort who were all characterized by an oral glucose tolerance test (OGTT). RESULTS--Homozygous carriers of the minor diabetes risk G-allele of the CDC123/CAMKID rs12779790 showed an 18% decrease in insulinogenic index (95% CI 10-27%; P = 4 x 10[sup -5]), an 18% decrease in corrected insulin response (CIR) (8.1-29%; P = 4 x 10[sup -4]), and a 13% decrease in the ratio of area under the serum-insulin and plasma-glucose curves during an OGTT (AUC-insulin/AUC-glucose) (5.8-20%; P = 4 x 10[sup -4]). Carriers of the diabetes-associated T-allele of JAZF1 rs864745 had an alleledependent 3% decrease in BIGTT-AIR (0.9-4.3%; P = 0.003). Furthermore, the diabetes-associated C-allele of TSPAN8 rs7961581 associated with decreased levels of CIR (4.5% [0.58.4]; P = 0.03), of AUC-insulin/AUC-glucose ratio (3.9% [1.2-6.7]; P = 0.005), and of the insulinogenic index (5.2% [1.9-8.6]; P = 0.002). No association with traits of insulin release or insulin action was observed for the THADA, ADAMTS9, or NOTCH2 variants. CONCLUSIONS--If replicated, our data suggest that type 2 diabetes at-risk alleles in the JAZF1, CDC123/CAMKID, and TSPAN8 loci associate with various OGTT-based surrogate measures of insulin release, emphasizing the contribution of abnormal pancreatic p-cell function in the pathogenesis of type 2 diabetes. Diabetes 57:2534-2540, 2008 [ABSTRACT FROM AUTHOR]

Background: The organisation of cancer follow-up is under scrutiny in many countries, and general practice is suggested to become more involved. A central focus is timely detection of recurring previous cancer and new second primary cancer. More knowledge on the patient pathway before cancer recurrence and second primary cancer is warranted to ensure the best possible organisation of follow-up. We aimed to describe the healthcare utilisation in the year preceding a diagnosis of cancer recurrence or second primary cancer.Methods: This nationwide register study comprises patients diagnosed with bladder, breast, colorectal, endometrial, lung, malignant melanoma and ovarian cancer in Denmark in 2008-2016. The frequency of healthcare contacts during the 12 months preceding a cancer recurrence or second primary cancer was estimated and compared to the frequency of cancer survivors in cancer remission. The main analyses were stratified on sex and healthcare setting. Furthermore, two sub-analyses were stratified on 1) sex, healthcare setting and age group and on 2) sex, healthcare setting and comorbidity status.Results: The study population consisted of 7832 patients with recurrence and 2703 patients with second primary cancer. On average, the patients were in contact with general practice one time per month in the 12th month preceding a new cancer diagnosis (recurrence or second primary cancer). Increasing contact rates were seen from 7 months before diagnosis in general practice and from 12 months before diagnosis in hospitals. This pattern was more pronounced in patients with cancer recurrence, younger patients and patients with no comorbidity. For instance, the contact rate ratios for hospital contacts in non-comorbid women with recurrence demonstrated 30% more contacts in the 12th month before recurrence and 127% more contacts in the 2nd month before recurrence.Conclusions: The results show that cancer survivors are already seen in general practice on a regular basis. The increasing contact rates before a diagnosis of cancer recurrence or second primary cancer indicate that a window of opportunity exists for more timely diagnosis; this is seen in both general practice and in hospitals. Thus, cancer survivors may benefit from improvements in the organisation of cancer follow-up. [ABSTRACT FROM AUTHOR]