Cancer risk in persons with new-onset anaemia:a population-based cohort study in Denmark

Abstract Background The time interval from first symptom and sign until a cancer diagnosis significantly affects the prognosis. Therefore, recognising and acting on signs of cancer, such as anaemia, is essential. Evidence is sparse on the overall risk of cancer and the risk of specific cancer types in persons with new-onset anaemia detected in an unselected general practice population. We aimed to assess the risk of cancer in persons with new-onset anaemia detected in general practice, both overall and for selected cancer types. Methods This observational population-based cohort study used individually linked electronic data from laboratory information systems and nationwide healthcare registries in Denmark. We included persons aged 40–90 years without a prior history of cancer and with new-onset anaemia (no anaemia during the previous 15 months) detected in general practice in 2014–2018. We measured the incidence proportion and standardised incidence ratios of a new cancer diagnosis (all cancers except for non-melanoma skin cancers) during 12 months follow-up. Results A total of 48,925 persons (median [interquartile interval] age, 69 [55–78] years; 55.5% men) were included in the study. In total, 7.9% (95% confidence interval (CI): 7.6 to 8.2) of men and 5.2% (CI: 4.9 to 5.5) of women were diagnosed with cancer during 12 months. Across selected anaemia types, the highest cancer incidence proportion was seen in women with ‘anaemia of inflammation’ (15.3%, CI: 13.1 to 17.5) (ferritin > 100 ng/mL and increased C-reactive protein (CRP)) and in men with ‘combined inflammatory iron deficiency anaemia’ (19.3%, CI: 14.5 to 24.1) (ferritin < 100 ng/mL and increased CRP). For these two anaemia types, the cancer incidence across cancer types was 10- to 30-fold higher compared to the general population. Conclusions Persons with new-onset anaemia detected in general practice have a high cancer risk; and markedly high for ‘combined inflammatory iron deficiency anaemia’ and ‘anaemia of inflammation’. Anaemia is a sign of cancer that calls for increased awareness and action. There is a need for research on how to improve the initial pathway for new-onset anaemia in general practice

Diagnostic workup of cancer in patients with new-onset anaemia:a Danish cohort study in general practice

Background Anaemia is associated with adverse outcomes, including increased morbidity and all-cause mortality. Diagnostic workup of patients with anaemia is essential to detect underlying disease, especially undiagnosed malignancy. Objective To describe the cancer-relevant diagnostic workup in patients with new-onset anaemia detected in general practice. An additional aim was to analyse associations between patient characteristics and the diagnostic workup. Design Observational population-based cohort study using electronic laboratory and register data. Setting Danish general practice. Subjects Patients aged 40–90 years with new-onset anaemia (no anaemia in the preceding 15 months) detected in general practice. Patients were identified in Danish laboratory information systems and nationwide registries in 2014–2018. Main outcome measures We measured the proportion of patients receiving predefined diagnostic investigations, that is, cancer patient pathway, colonoscopy, gastroscopy, computerised tomography (CT) scan, faecal test for haemoglobin, and bone marrow examination within three months of the anaemia index date. Results We included 59,993 patients, and around half of the patients with ‘iron deficiency anaemia’, ‘anaemia of inflammation’, or ‘combined inflammatory iron deficiency anaemia’ had no cancer-relevant diagnostic investigations performed. Patients aged 60–79 years and patients with severe anaemia were more likely to have investigations performed, while patients with comorbidity were less likely to have investigations performed. Conclusion Around half of the patients with anaemia subtypes that may indicate underlying cancer had no cancer-relevant diagnostic investigations performed. This may represent missed diagnostic opportunities. Future interventions are needed to improve the diagnostic workup of cancer in patients with anaemia, for example, laboratory alert systems and clinical decision support.KEY POINTS The general practitioners are often the first to detect anaemia and its underlying disease (e.g. undiagnosed malignancy). Large-scale studies are needed on the diagnostic workup of patients with anaemia in general practice in relation to an underlying malignancy. This study shows that the majority of patients with anaemia had no cancer-relevant diagnostic investigations performed, which may cause diagnostic delay. Interventions seems needed to improve the diagnostic workup of cancer in these patients to ensure timely diagnosis

Insufficient classification of anaemia in general practice:a Danish register-based observational study

BACKGROUND: Anaemia can be a pointer of underlying severe disease, including undiagnosed malignancy. Subsequent blood tests are essential to classify the anaemia into subtypes and to facilitate targeted diagnostic investigation to ensure timely diagnosis of underlying disease. OBJECTIVE: We aimed to describe and classify anaemia based on laboratory tests from patients with new-onset anaemia detected in general practice. An additional aim was to analyse associations between patient characteristics and unclassified anaemia (not classifiable according to an algorithm). DESIGN: Population-based cross-sectional study. SETTING: Danish general practice. SUBJECTS: A total of 62,731 patients (age: 40–90 years) with new-onset anaemia were identified in Danish laboratory information systems and nationwide registries, and data were obtained for 2014–2018. MAIN OUTCOME MEASURES: We measured the proportion of patients classified into subtypes of anaemia based on blood tests requested by general practitioners within 31 days of the anaemia index date. RESULTS: Of the 62,731 patients with new-onset anaemia, we identified unclassified anaemia in 78.9% (95% confidence interval (CI): 77.3–80.5) of men and 65.1% (CI: 63.4–66.9) of women. The likelihood of unclassified anaemia increased with age, increasing comorbidity and decreasing severity of anaemia. CONCLUSION: The majority of patients with new-onset anaemia could not be classified through a simple algorithm due to missing blood tests, which highlights a potential missed opportunity for diagnosis. Standardised laboratory testing of patients with anaemia is warranted to ensure adequate follow-up and early detection of underlying severe disease. KEY POINTS: Anaemia can be a sign of malignancy, and anaemia classification is an important step in the diagnosis of underlying disorders. The majority of patients with anaemia could not be classified according to a simple algorithm due to missing blood tests. Some patient characteristics were associated with a high risk of unclassified anaemia: high age, high comorbidity, and severe anaemia. Standardised laboratory testing in patients with anaemia is needed to inform targeted diagnostic investigation to ensure timely diagnosis

The Danish Myelodysplastic Syndromes Database:Patient Characteristics and Validity of Data Records

BACKGROUND: The Danish Myelodysplastic Syndromes Database (DMDSD) comprises nearly all patients diagnosed with myelodysplastic syndromes (MDS) in Denmark since 2010. The DMDSD has not yet been used for epidemiological research and the quality of registered variables remains to be investigated. OBJECTIVE: To describe characteristics of the patients registered in the DMDSD and to calculate predictive values and the proportion of missing values of registered data records. METHODS: We performed a nationwide cross-sectional validation study of recorded disease and treatment data on MDS patients during 2010–2019. Patient characteristics and the proportion of missing values were tabulated. A random sample of 12% was drawn to calculate predictive values with 95% confidence intervals (CIs) of 48 variables using information from medical records as a reference standard. RESULTS: Overall, 2284 patients were identified (median age: 76 years, men 62%). Of these, 10% had therapy-related MDS, and 6% had an antecedent hematological disease. Hemoglobin level was less than 6.2 mmol/L for 59% of patients. Within the first two years of treatment, 59% received transfusions, 35% received erythropoiesis-stimulating agents, and 15% were treated with a hypomethylating agent. For the majority of variables (around 80%), there were no missing data. A total of 260 medical records were available for validation. The positive predictive value of the MDS diagnosis was 92% (95% CI: 88–95). Predictive values ranged from 64% to 100% and exceeded 90% for 36 out of 48 variables. Stratification by year of diagnosis suggested that the positive predictive value of the MDS diagnosis improved from 88% before 2015 to 95% after. CONCLUSION: In this study, there was a high accuracy of recorded data and a low proportion of missing data. Thus, the DMDSD serves as a valuable data source for future epidemiological studies on MDS

The Danish National Acute Leukemia Registry

AIM OF DATABASE: The main aim of the Danish National Acute Leukemia Registry (DNLR) was to obtain information about the epidemiology of the hematologic cancers acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). STUDY POPULATION: The registry was established in January 2000 by the Danish Acute Leukemia Group and has been expanded over the years. It includes adult AML patients diagnosed in Denmark since 2000, ALL patients diagnosed since 2005, and MDS patients diagnosed since 2010. The coverage of leukemia patients exceeds 99%, and the coverage of MDS patients is currently 90%. MAIN VARIABLES AND DESCRIPTIVE DATA: Approximately, 250 AML patients, 25 ALL patients, and 230 MDS patients are registered in the DNLR every year. In January 2015, the registry included detailed patient characteristics, disease characteristics, treatment characteristics, and outcome data on more than 3,500 AML, 300 ALL, and 1,100 MDS patients. Many of the included prognostic variables have been found to be of high quality including positive predictive values and completeness exceeding 90%. These variables have been used in prognostic observational studies in the last few years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. CONCLUSION: The completeness and positive predictive values of the leukemia data have been found to be high. In recent years, the DNLR has shown to be an important high-quality resource for clinical prognostic research

Stringent or nonstringent complete remission and prognosis in acute myeloid leukemia:a Danish population-based study

Key Points sCR and non-sCR in acute myeloid leukemia are associated with different prognoses. Three lineage blood cell recoveries have independent impacts on prognosis.</jats:p