Danish Laboratory Research Articles

Paediatric reference intervals for haematology parameters analysed on Sysmex XN-9000: acomparison of methods in the framework of indirect sampling.

To provide age- and sex-specific paediatric reference intervals (RIs) for 13 haematological parameters analysed on Sysmex XN-9000 and compare different methods for estimating RIs after indirect sampling. Via the Danish Laboratory Information System, we conducted a population-based study. We identified samples from children aged 0-18 years analysed at Aarhus University Hospital from 2019 to 2023, including samples from general practitioners only. Information about all parameters were available for all samples via linkage to the local laboratory middleware. Then, we applied two different methods. First, we excluded potential pathological samples by predefined criteria: if the child had other abnormal blood measurements at date of request, or had a blood sample of any type analysed in the period two months before to two months after. We estimated RIs stratified by age- and sex using the non-parametric percentile method. Second, we used refineR (an open source automated algorithm) to exclude pathological samples and for RI estimation. Finally, we compared our data to results from a study using the direct method. We identified 22,786 samples. After exclusion by predefined criteria, the population comprised 10,199 samples from 8,736 children (57 % of samples were from females and median age was 13 years). We estimated RIs for red blood cell, white blood cell and platelet indices. The two different methods showed agreement. Furthermore, our data provided results comparable to direct sampling. Our study provided age- and sex-specific paediatric RIs for 13 haematology parameters useful for laboratories worldwide. RIs were robust using different methods in the framework of indirect sampling. Finally, our data showed agreement with the direct method, indicating that indirect sampling could be useful for establishing RIs on haematology parameters in the future.

Correlation of drug dose estimated from national prescription registers with mean blood level of antiseizure medication in pregnancy.

The purpose was to examine the correlation of antiseizure medication drug dose estimated from prescription fill records from prescription registers with blood levels during pregnancy. We conducted a Nation-wide study of mothers who gave birth in Denmark between 1 January 2014 and 31 December 2018 using data from Danish Prescription and Laboratory Registers. We identified mothers with blood level measurements of antiseizure medication. The main exposure was estimated antiseizure medication dosage estimated from pregnancy-filled prescriptions in the Danish Prescription Register. The main outcome was the correlation of estimated dose with mean blood level of antiseizure medication in pregnancy. For privacy reasons, the number of blood level measurement and prescription fills were rounded to nearest 10, but proportions reported as exact values. Among 298 560 pregnancies, we identified pregnancies with recorded prescription fill from the prescription register for valproate (N = 90), lamotrigine (N = 1360), levetiracetam (N = 340), topiramate (N = 100), and carbamazepine (N = 60). In these pregnancies, blood level measurements were available in 50 (53%) pregnancies for valproate, 850 (62%) pregnancies for lamotrigine, 320 (93%) pregnancies for levetiracetam, 50 (68%) pregnancies for carbamazepine, and 40 (35%) pregnancies for topiramate. Pearsons's correlation coefficients for the correlation of estimated antiseizure medication dose with mean blood levels were 0.67 (p < 0.0001) for valproate, 0.63 (p < 0.0001) for lamotrigine, 0.63 (p < 0.0001) for levetiracetam, 0.76 (<0.0001) for carbamazepine and 0.89 (<0.0001) for topiramate. Dose of antiseizure medication estimated from prescription fills was a good proxy for blood levels and thus for biological exposure in pregnancy, suggesting that administrative prescription fill records may be a valuable resource for estimating exposure to antiseizure medication in pregnancy.

Critical test result management at Danish hospital laboratories: a national survey

Critical test results in clinical laboratories are crucial for timely patient care, serving as indicators of potentially life-threatening conditions. Despite their importance, a notable heterogeneity in management practices exists globally. This study investigates the current practices of managing critical results at Danish clinical biochemistry laboratories and identifies areas prone for improvement. A comprehensive online survey was distributed to all 21 Danish clinical biochemistry laboratories regarding their critical result management, including documentation practices, critical limit selection, and quality assurance measures. A total of 17 laboratories (81%) responded. The answers revealed a generally uniform approach to managing critical results, with all laboratories having 24-h reporting, local instructions and using the telephone as communication channel. However, variations were noted in documentation practices and critical limit selection. Notably, 23.5% of the laboratories reported that one out of every ten critical results was not reported, indicating a significant risk of delayed critical results. This is further complicated by the limited use of predefined timeframes for reporting and also, only few laboratories actively monitored response times. The findings emphasize the need for more standardized documentation and evaluation practices to align with international standards and to enhance patient safety. While the laboratories showed a commitment to standardized procedures, the study emphasizes the necessity of a National or Nordic guideline to supplement the ISO 15189:2022. This study is a step towards optimizing critical result management, not only in Danish clinical biochemistry laboratories but also across various laboratory specialties, thereby improving overall laboratory quality, efficiency, and patient safety.

Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation.

Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function. Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding. Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49mL/min/1.73m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49mL/min/1.73m2. Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30mL/min/1.73m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49mL/min/1.73m2.

Fifteen-year temporal changes in rates of acute kidney injury among children in Denmark

BackgroundWe aimed to examine temporal changes in the annual rate of acute kidney injury (AKI) in Danish children and associated changes in patient characteristics including potential underlying risk factors.MethodsIn this population-based cohort study, we used plasma creatinine measurements from Danish laboratory databases to identify AKI episodes in children aged 0–17 years from 2007 to 2021. For each child, the first AKI episode per calendar year was included. We estimated the annual crude and sex- and age-standardized AKI rate as the number of children with an AKI episode divided by the total number of children as reported by census numbers. Using Danish medical databases, we assessed patient characteristics including potential risk factors for AKI, such as use of nephrotoxic medication, surgery, sepsis, and perinatal factors.ResultsIn total, 14,200 children contributed with 16,345 AKI episodes over 15 years. The mean annual AKI rate was 148 (95% CI: 141–155) per 100,000 children. From 2007 to 2021, the annual AKI rate demonstrated minor year-to-year variability without any discernible overall trend. The highest AKI rate was recorded in 2007 at 174 (95% CI: 161–187) per 100,000 children, while the lowest rate occurred in 2012 at 129 (95% CI: 118–140) per 100,000 children. In 2021, the AKI rate was 148 (95% CI: 141–155) per 100,000 children. Characteristics of children with AKI were similar throughout the study period.ConclusionThe rate of AKI among Danish children was stable from 2007 to 2021 with little variation in patient characteristics over time.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

P-087 Expanding the comparison of an AI automated semen analyses for concentration determinations with manual analyses and a cell counting system

Abstract Study question Can comparable results be obtained for sperm concentrations determinations in differing clinical settings when using an AI driven analyser, a cytometer, and WHO manual counts? Summary answer Outcomes suggest that comparable results can be obtained when utilising the differing counting techniques. What is known already Despite robust methods described by WHO, protocol variations exist, creating a lack of reproducible and consistent semen analysis results in standard laboratories, as described by Bjorndahl etal 2016. Human error can influence results where WHO protocols are not utilised in conjunction with rigorous IQA and EQA. A human performing an analysis is considered the gold standard, but it's apparent, as demonstrated by time-lapse embryo evaluation, that human assessments can be enhanced with machine assistance to increase accuracy. To establish the benefit of machine assistance, it is necessary to demonstrate comparable results with the manual operator and reliable machine cell counters. Study design, size, duration To assess whether comparable results could be obtained with a well-trained reproductive scientist and a cell counting system, two reputable IVF clinics were selected to perform their standard analyses and perform a repeat test with an automated analyser. A number of semen analyses were performed over a six-month time-period for patients attending IVF clinics for a pre-treatment evaluation. Participants/materials, setting, methods 107 samples were collected and analysed between June 2022 to December 2023 in laboratories in Copenhagen and London. Participants were selected on a random basis. The semen analyses were performed in a manner described by the WHO6, with an additional assessment with a NucleoCounter™ chemometec in the Danish laboratory. Simultaneously, a concentration determination was performed on a Mojo AISA ™. (Artificial Intelligence Semen Analysis system). Main results and the role of chance Manual concentration assessments, the cytometer data and the AISA concentration results were plotted and examined. Comparable values were obtained when data for the manual assessment v AI machine assessment and the data obtained for fluorescent marked sperm v AI analysis were assessed. A significant Spearman correlation was obtained by the manual analysis team and the team who used the cytometer counting system, values of 0.93 and 0.99, (error average 17.5 and 24.4) respectively. Limitations, reasons for caution Increasing the sample frame of this current study, including more laboratories for a multi-centre trial would increase the power of the findings. Inter and intra operator and repeat machine evaluations are planned to establish the human variations during analysis and establish if this can be mitigated by machine assistance. Wider implications of the findings The results demonstrate that a machine assisted semen analysis is comparable to a gold standard semen analysis performed by a reputable laboratory staff either when compared to a manual operator and to a cell sorting system where sperm are labelled with a fluorescent probe. Trial registration number N/A

#2686 15-YEAR TEMPORAL CHANGES IN RATES OF ACUTE KIDNEY INJURY AMONG CHILDREN: A POPULATION-BASED COHORT STUDY

Abstract Background and Aims Acute kidney injury (AKI) is defined as a sudden decrease in kidney function and is associated with increased morbidity and mortality. The reported prevalence of AKI among hospitalized children is approximately 30% but varies widely depending on population characteristics and method used to define AKI. Little is known about the incidence of community-acquired AKI and potential temporal changes in AKI incidence among children. Such information is important for AKI prevention, resource allocation and future research. In this study, we aimed to examine overall temporal changes in the rate of hospital- and community-acquired pediatric AKI and to describe associated changes in potential underlying risk markers. Method In this population-based cohort study, we included children aged 0-17 years from 1 January 2007 to 31 December 2021 in Denmark. In 2021, the Danish population consisted of 1,168,222 children. We obtained clinical plasma creatinine measurements from the Danish laboratory databases to identify all KDIGO-defined AKI episodes within the study period. For each child, only the first AKI episode per year was included and we defined an AKI episode as a period of 30 days. AKI was defined as community-acquired if the plasma creatinine at time of AKI was taken in the outpatient clinic or the first day of admission/acute setting. We estimated the annual AKI rate as first AKI episodes in a year among children residing in an area covered by the laboratory databases divided by the number of children residing in this area in the same year. Unadjusted rates as well as sex- and age-standardized rates was reported. Using Danish medical databases, we identified potential risk markers for AKI, such as use of nephrotoxic medication, surgery, sepsis, and perinatal factors including low birth weight and preterm birth. Results In total, 14,262 children contributed with 16,492 AKI episodes. The average annual rate of AKI was 149 per 100,000 children and was stable throughout the study period (figure). Of the AKI episodes, 10,921 (66.2%) were community-acquired and 12,714 (77.1 %) were stage 1 AKI. No major changes were seen in the prevalence of risk makers among AKI episodes. Conclusion The rate of AKI among Danish children was stable from year 2007 to 2021 and potential risk markers were largely similar over time.

Caring for Organoids: Patient Personhood and the Ethics of Avoidance in Translational Cancer Research

This article explores the daily practices in a Danish cancer laboratory, where researchers use “personal organoids” as new translational models in the development of personalized medicine. Grown from metastatic cancer tissue of life-threateningly ill patients, personal organoids enable patient-specific drug screenings that may directly shape clinical decision-making and individual patient lives. Hereby, laboratory researchers are confronted with the patient as a person urgently dependent on their research results. We follow how the development of these potentially lifesaving personal models are enabled by “avoidance practices,” through which researchers actively sever models’ connections to the patients as biographical persons. Yet, this separation does not completely disentangle the organoids from the patients. To highlight how alterity and distance can be constitutive of valued social relations, we bring feminist science and technology studies critiques of care into conversation with anthropological accounts of kinship and personhood in South Pacific societies. Our analysis builds on these literatures, unfolding opportunities for laboratory researchers to practice patient personhood through disconnection or an “ethic of avoidance.” Our researcher interlocutors care about cancer patients by caring for organoids and thus exceed the dichotomy between person and thing and enact the patients as biological–biographical persons.

Kidney function before and after acute kidney injury: a nationwide population-based cohort study.

Acute kidney injury (AKI) is a common and serious condition defined by a rapid decline in kidney function. Data on changes in long-term kidney function following AKI are sparse and conflicting. Therefore, we examined the changes in estimated glomerular filtration rate (eGFR) from before to after AKI in a nationwide population-based setting. Using Danish laboratory databases, we identified individuals with first-time AKI defined by an acute increase in plasma creatinine (pCr) during 2010 to 2017. Individuals with three or more outpatient pCr measurements before and after AKI were included and cohorts were stratified by baseline eGFR (≥/<60mL/min/1.73 m2). Linear regression models were used to estimate and compare individual eGFR slopes and eGFR levels before and after AKI. Among individuals with a baseline eGFR ≥60mL/min/1.73 m2 (n=64805), first-time AKI was associated with a median difference in eGFR level of -5.6mL/min/1.73 m2 [interquartile range (IQR) -16.1 to 1.8] and a median difference in eGFR slope of -0.4mL/min/1.73 m2/year (IQR -5.5 to 4.4). Correspondingly, among individuals with a baseline eGFR <60mL/min/1.73 m2 (n=33267), first-time AKI was associated with a median difference in eGFR level of -2.2mL/min/1.73 m2 (IQR -9.2 to 4.3) and a median difference in eGFR slope of 1.5mL/min/1.73 m2/year (IQR -2.9 to 6.5). Among individuals with first-time AKI surviving to have repeated outpatient pCr measurements, AKI was associated with changes in eGFR level and eGFR slope for which the magnitude and direction depended on baseline eGFR.

Changing Epidemiology: Outbreak of Monkey Pox

Monkeypox is a viral illness endemic to African countries. 20 May 2022, W.H.O alarmed all countries on the outbreak of the monkeypox virus1. Symptoms include headache fever swollen lymph nodes lethargy and the development of rash. Two types of clades (strains) are found that is central and West African clades. A central clade is more infectious than a western clade. A western clade is self-limiting within 2-3 weeks with a case fatality rate of 1% while the central clade is a 10% fatality rate. Monkeypox virus causes monkeypox a zoonotic disease which belongs to the poxviridae family2 which is closely related to the smallpox virus. Indicated from historical data smallpox vaccination with vaccinia virus (orthopoxviral) was 85% protective against monkey pox3. Danish laboratory in 1958 discover the virus in monkeys from where its name monkey pox originates4. The first case was discovered in a 9-month baby for the first time in Congo in 19705. A previous systematic review of the summer of 2018 described the epidemiological outbreak of the monkeypox virus6. United Kingdom’s first case was presented on 16 May 24, 2022, after laboratory confirmation7. The incubation period of monkeypox ranges from 6-13 days with possible extension to 5-21 days. The illness consistently ends by 2-4 weeks. Smallpox vaccines provide adequate protection against the monkeypox virus. World health organization suggests that health workers who are treating or exposed to monkeypox patients or their laboratory samples be immunized against smallpox. Effective laboratory investigation is a significant measure for identification and management. PCR on multiple lesions from various sites can be utilized to diagnose the potential condition. It should be sent to the government public lab and the control &amp; command center must be notified. Refrigerated (2-8c) samples should be sent within 5 days of collection. Sample of swab should be of nylon, polyester, or Dacron swab with plastic, wood, or thin aluminum shaft. International support for increased surveillance and detection is important for monkeypox cases for understanding the changing epidemiology of the resurging disease. In the current environment of pandemic threats, the public health importance should not be underestimated. Outside of African countries appearances of cases highlights the risk of geographical spread. Discontinuation of the smallpox vaccine has created a landscape for monkeypox. Government guidelines for emergency diseases should be used with proper notification of case reports to the directorate. Personal protection equipment with equipped labs should be provided. All children less than 12 should be vaccinated with smallpox vaccines. A combination of standard, contact, droplet and airborne precaution should be used. Place the patient in a single room with a portable HEPA filter or airborne infection isolation room. Staff from equipped laboratories should obtain samples from suspected/confirmed monkeypox virus infection. Appropriate personal protective equipment (PPE) should be provided and disposed of properly before leaving the room. Monitoring and tracing contact must be maintained and recorded. World health organization effective hand hygiene five moments should be performed by healthcare workers frequently. Use guidelines for correct containment and disposal of contaminated waste. Be care full always with the soiled laundry to avoid contact with lesion material and used PPE materials. Ensure procedures are in place for cleaning and disinfecting environmental surfaces in patient care zones. Always use the government of Pakistan’s national health guidelines for emergencies.

Preventing the Next Pandemic: Is Live Vaccine Efficacious against Monkeypox, or Is There a Need for Killed Virus and mRNA Vaccines?

(1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods and Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses—ACAM2000, JYNNEOS, and LC16—with the first being a replicating vaccine and the latter being non- or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental immunity to MPV. ACAM2000 (a live-attenuated replicating vaccine) and JYNNEOS (a live-attenuated, nonreplicating vaccine) are two US FDA-approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer complications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or developed into a mRNA vaccine before monkeypox is declared a pandemic.

New Technologies to Change Work: The Creation of Professional Identity and Legitimacy

Studies of professionals in organizations have highlighted the importance of building and maintaining a mandate, and have proposed that many professionals face difficulties defining their differentiating skills and knowledge in the context of new technologies. In this paper, we examine how the influx of new technology and robots in particular, influence the professionalization struggles and strategies by the Danish medical laboratory scientists (lab scientists), which we term a marginalized professions due to its weak professional status in the healthcare field. We examine how the professional project and professional capital is constructed and put to work by the association of the lab scientists as we underscore the important yet overlooked role played by associations in shaping how new technology may be coupled to the professional project. Using a theorization inspired by Bourdieu in particular, we show how robots may pose both an opportunity and a ‘wicked’ problem for professionalization. We conclude by discussion these contributions and outlines options for future research.

P-174 OPTIMISE: Optimization of treatment selection and follow-up in oligometastatic colorectal cancer – a ctDNA-guided phase II randomized approach with a run-in feasibility part

Patients with detectable circulating tumor DNA (ctDNA) after surgery for colorectal cancer are considered to have microscopic residual disease and consequently a high risk of recurrence. The same applies to patients after local ablative treatment (LAT) for metastatic colorectal cancer (mCRC). We observed a temporal clearance of ctDNA during adjuvant chemotherapy, but ctDNA recurrence after therapy termination. This indicate that patients with ctDNA positive status may need more intensified adjuvant chemotherapy than standard of care (SOC). In OPTIMISE we investigate the use of ctDNA for treatment decisions on adjuvant chemotherapy after LAT for mCRC. We hypothesis that recurrence can be prevented with intensified adjuvant chemotherapy in patients with ctDNA positive blood samples post ablations, and that patients without detectable ctDNA have undergone successful radical treatment and will not need adjuvant chemotherapy. OPTIMISE is an open label 1:1 randomized multicentre, phase II study, comparing ctDNA guided adjuvant chemotherapy against standard of care (SOC) approach, with a run-in phase investigating feasibility measures. Eligibility criteria comprise, Radical intended treatment for metastatic spread from CRC (resection, radiofrequency ablation, stereotactic body radiation therapy, or other experimental local treatment), No evidence of further disease according to SOC, Age ≥ 18 years, ECOG performance status 0-2, Clinically eligible for adjuvant triple chemotherapy at investigators decision, Adequate bone marrow function allowing systemic chemotherapy, Anticonception for fertile women and for the male patients with a fertile partner, Written and verbally informed consent. Exclusion criteria are, Neuropathy CTCAE grade > 1, Other malignant tumour within 5 year except non-melanoma skin cancer or carcinoma in situ cervicis uteri, Pregnant or breastfeeding women, Intolerance or allergy to 5-FU, leucovorin, oxaliplatin, irinotecan or capecitabin Before randomization participants undergo a PET-CT scan to exclude metabolically detectable lesions. In ARM A patients are treated according to SOC, and blood samples collected for later retrospective ctDNA analysis. In ARM B, patients follow a ctDNA-guided strategy; ctDNA positivity lead to escalation strategy with 4 months of FOLFOXIRI followed by 2 months of 5-FU, ctDNA negative status to de-escalation strategy by shared decision-making. Endpoints Primary endpoint; fraction of patients alive without recurrence 2 years after inclusion. Secondary endpoints; CTCAE grade 3-5 toxicity, ctDNA negativity (6 months + 1 year), Time to molecular -biological and radiological recurrence, Rate of local and distant relapse, Overall survival, QoL and Cost-effectiveness. Laboratory methods. Blood samples are collected in streck-tubes and analysed for tumor specific mutations and methylations by multiplex ddPCRs in two Danish laboratories (with tumor-agnostic approach). Sample size is 350 but will be revised based on findings in the run-in phase. Feasibility measures for the run-in phase are: Inclusion of 30 patients over 12 months in two Danish Hospitals, Compliance with randomization > 80%, Rate of unexpected PET-CT positive cases 20%, Eligibility for triple chemotherapy > 80%. The study is including. NCT04680260. Sponsors.

Monkeypox: a visual guide

Monkeypox is caused by the monkeypox virus, an enveloped double-stranded DNA virus that is part of the orthopoxvirus genus, which also includes smallpox. Despite its name, which came from its initial discovery in monkeys in a Danish laboratory in 1958, monkeypox can infect various animals, including rope squirrels, tree squirrels, Gambian pouched rats and dormice. […]

Monkeypox-Trending Mutating &amp; Out Bursting Disease

Monkey pox is a trending as well as mutating viral disease condition spreading all over the world especially the African countries. Monkeypox is a transmittable disease caused by the monkeypox virus that can occur in certain animals as well as humans. The name monkeypox initiates from the preliminary discovery of the virus in monkeys in a Danish laboratory in 1958. The first human case was identified in a child in the Democratic Republic of the Congo in 1970.The time from acquaintance to onset of symptoms is usually 7 to 14 days. The West African clade, which has so far been distinguished in the cases reported in Europe, has been observed to have a case casualty rate of about 3.3% in Nigeria. Till now there is no official confirmed cases of Monkeypox have been reported in India. Monkeypox commences with fever, headache, muscle aches and ends with exhaustion. Some other clinical manifestations are swollen lymph nodes, chills, fever, headache, muscle aches, backache, exhaustion etc. Vaccination in contrast to smallpox was verified through several observational studies to be about 85% effective in avoiding monkeypox.

Disseminated intravascular coagulation diagnosis: Positive predictive value of the ISTH score in a Danish population

BackgroundThe diagnostic accuracy of the ISTH’s disseminated intravascular coagulation (DIC) score remains to be investigated in contemporary patient populations. ObjectiveTo examine the positive predictive value (PPV) of an ISTH DIC score ≥5 for identifying patients with overt DIC in a Danish hospital laboratory information system database. Materials and MethodsA population‐based cross‐sectional validation study in the Central Denmark Region (2015‐2018). Patients with a DIC score ≥5 were identified from the hospital laboratory information system database. Only patients with a potential underlying cause of DIC were included in the analyses. Cases were adjudicated by the authors as the gold standard for DIC diagnosis. The diagnosis of overt DIC was assigned on the basis of clinical signs of microthrombosis and/or bleeding and available laboratory records. PPVs with 95% confidence intervals (CIs) were computed. ResultsMedical records of 225 patients were included. The overall PPV for overt DIC was 68% (95% CI, 61‐74) and for overt + subclinical DIC, 83% (95% CI, 77%‐88%) and increased with higher scores from 47% (95% CI, 35‐59) for DIC score 5 to 88 (95% CI, 79‐94) for DIC score ≥7. PPV was higher among intensive care patients and patient with sepsis, low antithrombin activity, prolonged activated partial thromboplastin time, or high Sequential Organ Failure Assessment score. ConclusionThe accuracy of ISTH DIC score ≥5 was moderate for overt DIC but increased with increasing scores and depended on the underlying cause of DIC. This new knowledge provides guidance to physicians and enables DIC research using laboratory‐based data.

Comparison of Patients with Hospital-Recorded Nephrotic Syndrome and Patients with Nephrotic Proteinuria and Hypoalbuminemia: A Nationwide Study in Denmark.

Registry-based studies of nephrotic syndrome (NS) may only include a subset of patients with biochemical features of NS. To address this, we compared patients with laboratory-recorded nephrotic proteinuria and hypoalbuminemia to patients with hospital-recorded NS. We identified adult patients with first-time hospital-recorded NS (inpatients, outpatients, or emergency-room visitors) in the Danish National Patient Registry and compared them with adults with first-time recorded nephrotic proteinuria and hypoalbuminemia in Danish laboratory databases during 2004-2018, defining the date of admission or laboratory findings as the index date. We characterized these cohorts by demographics, comorbidity, medication use, and laboratory and histopathologic findings. We identified 1139 patients with hospital-recorded NS and 5268 patients with nephrotic proteinuria and hypoalbuminemia; of these, 760 patients were identified in both cohorts. Within 1 year of the first record of nephrotic proteinuria and hypoalbuminemia, 18% had recorded hospital diagnoses indicating the presence of NS, and 87% had diagnoses reflecting any kind of nephropathy. Among patients identified with nephrotic proteinuria and hypoalbuminemia, their most recent eGFR was substantially lower (median of 35 versus 61 ml/min per 1.73 m2), fewer underwent kidney biopsies around the index date (34% versus 61%), and the prevalence of thromboembolic disease (25% versus 17%) and diabetes (39% versus 18%) was higher when compared with patients with hospital-recorded NS. Patients with nephrotic proteinuria and hypoalbuminemia are five-fold more common than patients with hospital-recorded NS, and they have a lower eGFR and more comorbidities. Selective and incomplete recording of NS may be an important issue when designing and interpreting studies of risks and prognosis of NS.

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.

Characteristics of patients with familial Mediterranean fever in Denmark: a retrospective nationwide register-based cohort study

Objectives: To investigate epidemiology, demography, and genetic and clinical characteristics of patients with familial Mediterranean fever (FMF) in Denmark. Method: In this population-based, cross-sectional cohort study, we identified FMF patients from discharge diagnoses using ICD-10 codes in the Danish National Patient Register, and linked data from the Danish Civil Registration System and laboratory databases for results of MEFV gene variant screening. Results: We identified 495 FMF patients (prevalence 1:11 680) with a median age of 29 years and a female ratio of 51%. The median age at diagnosis of FMF was 13 (IQR 7–22) years, with an estimated median diagnostic delay of 3 (IQR 0.7–6.9) years. The predominant ethnicities were Turkish (41.8%), Lebanese (15.8%), Syrian (6.5%), South-West Asian (7.9%), and South-East Asian (3.0%). The MEFV genotype distribution was 18.7% homozygous, 21.2% compound heterozygous, 32.0% heterozygous, 11.0% with complex alleles or unresolved zygosity, and 17.1% with no detected variants. M694V was the most prevalent variant in the overall cohort (32.5%). Homozygous or compound heterozygous MEFV exon 10 variants were associated with younger age at diagnosis (p < 0.001) and reduced number of hospital contacts before diagnosis (p = 0.008). The Charlson Comorbidity Index was ≥ 2 in 8.1% of patients. The prevalence of amyloidosis was 1.0%. Conclusions: FMF in Denmark is rare and patients are mainly of Eastern Mediterranean ethnicity. Diagnostic delay was long but patients with exon 10 MEFV variants were diagnosed at a younger age. Prolonged diagnostic delay is probably caused by lack of FMF awareness in the Danish healthcare system.