A national surveillance program for evaluating new reagent lots in medical laboratories

Objectives Differences between laboratory results attributable to the use of different reagent lots can potentially affect the diagnosis and monitoring of patients. To minimize patient risks, all laboratories should verify that new reagent lots meet agreed analytical performance specifications (APS). We propose a simplified, pragmatic approach for laboratories that involves compilating results into a national surveillance program, and present the first results obtained when applying this approach to troponins, glycated hemoglobin (HbA1c), prostate-specific antigen (PSA) and D-dimer. Methods In the surveillance program we have (i) determined APS for selected analytes, (ii) implemented a simplified procedure for lot evaluation with patient samples used in laboratories across Norway and (iii) performed central processing of the results from the participating laboratories. Results Over a one-year period, 27 Norwegian laboratories returned results from 28 lot changes for troponin I, 11 for troponin T, and 29 for HbA1c, PSA and D-dimer. The mean difference between two reagent lots was 4.5% for troponin I (for a concentration interval of 20–32 ng/L), 5.1% for troponin T (10.7–17.5 ng/L), 2.2% for HbA1c (40–50 mmol/mol), 3.7% for PSA (3–5 μg/L) and 5.5% for D-dimer (0.4–1.0 mg/L FEU). Conclusions A novel procedure for reagent lot evaluation is proposed in which information about multiple lot changes from different medical laboratories can be accumulated nationally. Sharing this information allows simplification of lot evaluations in individual laboratories and provides real-world data about lot-to-lot variations.publishedVersio

Systemiske soppinfeksjoner - En utfordring i fremmarsj : Molekylær identifikasjon og resistensbestemmelse

Invasive fungal infections-a rising challenge Molecular identification and susceptibility testing Abstract: Fungi, both yeast and mouldes are emerging, as important pathogens in immunocompromised patients. Symptoms and signs of invasive fungal infection may be unspesific, and clinical diagnosis is difficult- hence early fungal identification is important for improving outcome. OBJECTIVE: This thesis aims to identify isolates from invasive fungal infection and provide a basis for molecular diagnostics by sequencing ribosomal DNA (rDNA) in clinical isolates. Furthermore the E-test, a novel susceptibility test for yeast was evaluated. METHODS: PCR amplification and sequencing of 18S rDNA were used to analyse clinical samples of yeasts and filamentous fungi from invasive infections in patients at Rikshospitalet. The results were compared to conventional identification. In addition the samples were subjected to susceptibility testing to fluconazole and voriconazole using disc diffusion test and the recently released E-test. RESULTS: Molecular identification showed higher sensitivity than conventional diagnostics. VITEK-2 and CHROMagar performed better than API 20 C AUX. Isolates resistant to fluconazole were sensitive to voriconazole. The results obtained with the E-test were comparable to those obtained by disc diffusion. DISCUSSION: Molecular fungal identification is a promising approach for sensitive and early diagnosis of invasive fungal infection. Time from sampling to identification can be reduced to eight hours and the sensitivity improved. With the emergence of fluconazole resistant fungal pathogens the advent of voriconazole is a welcome one. The E-test can be reliably used to determine susceptibility to antifungal drugs

Medisinsk biokjemi: Oversikt og variasjon i bestilling av analyser i primærhelsetjenesten og på poliklinikker i spesialisthelsetjenesten i Norge i 2018

Bakgrunn: Riktig rekvirering av laboratorieanalyser er viktig for diagnostikk og behandling av pasienter. Fra tidligere undersøkelser i Norge og utlandet vet man at både overrekvirering og underrekvirering forekommer relativt hyppig. Fra 1. januar 2018 ble det innført et nytt takstsystem for refusjon av laboratorieanalyser i Norge basert på et nasjonalt enhetlig kodeverk (norsk laboratoriekodeverk, NLK). Dermed er det for første gang mulig å benytte data fra refusjoner til offentlige og private laboratorier til å studere rekvirering av enkeltanalyser. Målsetningen med denne oppgaven var å beskrive omfang og variasjon for rekvirering av analyser utført i primærhelsetjenesten og poliklinisk i spesialisthelsetjenesten innenfor medisinsk biokjemi 2018, samt å sammenligne rekvirering av utvalgte analyser opp mot størrelse på den aktuelle pasientgruppen. Metode: Data fra refusjon for analyser innen medisinsk biokjemi utført for pasienter i primærhelsetjenesten, hos avtalespesialister og på poliklinikker i spesialisthelsetjenesten i 2018 ble sammenlignet med befolkningsdata og helseindikatorer i fylker, kommuner og bydeler. Geografisk variasjon i bestilling av analyser ble undersøkt samlet for alle analyser og for utvalgte enkeltanalyser. For noen av analysene med høyest utbetalt refusjon ble antall analyser også sammenlignet med størrelse på den aktuelle pasientgruppen ved hjelp av data fra reseptregisteret, norsk pasientregister eller kommunalt pasientregister. Resultater: Samlet refusjon for analyser utført av offentlige og private laboratorier var ca. 1 milliard kroner og for analyser utført pasientnært i primærhelsetjenesten ca. 375 millioner kroner i 2018. Analysene/analysegruppene det ble utbetalt mest refusjon for var HbA1c, differensialtelling av leukocytter, CRP, TSH/fritt T4, Vitamin B12 og B9 (folsyre), homocystein og MMA, NT-proBNP/BNP og Vitamin D. Refusjon for alle analyser samlet varierte med en faktor på 2,0 fra fylket med lavest til høyest refusjon, en betydelig del av denne variasjonen kan sannsynligvis forklares med ulik befolkningssammensetning. På enkeltanalysenivå var det mindre variasjon mellom fylkene for rekvirering for HbA1c, CRP og TSH (med faktorer på under 2), moderat variasjon for Vitamin B12 og B9 (faktor rundt 2) og større variasjon for NT-proBNP/BNP, homocystein og MMA med faktorer på henholdsvis 4,2, 13 og 22. For differensialtelling og Vitamin D var det ikke mulig å analysere geografisk variasjon grunnet ulik bruk av analysekoder ved laboratoriene. Konklusjon: Innføringen av et nytt takstsystem for refusjon av laboratorieanalyser basert på NLK gir gode muligheter til å undersøke omfang og variasjon i bestilling av laboratorieanalyser innenfor medisinsk biokjemi. Det foreligger relativt stor variasjon mellom fylkene for bestilling av analyser samlet sett og for noen av enkeltanalysene som er undersøkt i oppgavene. Dette kan være av interesse å undersøke videre i fremtidige arbeider

Prognostic Value of Nucleated RBCs for Patients With Suspected Sepsis in the Emergency Department: A Single-Center Prospective Cohort Study

Objectives: Increase of nucleated RBCs in peripheral blood has been shown to be predictive of mortality in ICU patients. The aim of this study was to explore the prognostic value of nucleated RBCs in the first blood sample taken at admission to the emergency department from patients with suspected sepsis. Design: Single-center prospective cohort study. Setting: Emergency department. Patients: One-thousand two-hundred thirty-one consecutive adult patients with suspected sepsis were included in a prospective quality register-based co-hort study. Inclusion criteria were as follows: patients received in rapid response team with blood cultures taken and immediate antibiotics given in the emergency department. Intervention: Not applicable. Measurement and main results: Nucleated RBCs, Sequential Organ Failure Assessment score, Quick Sequential Organ Failure Assessment, Charlson Comorbidity Index, and commonly used laboratory tests measured in the emergency department were compared with 30-day mortality. Nvaucleated RBC counts were divided into five groups, called “Nucleated RBC score,” according to nucleated RBC count levels and analyzed with logistic regression together with the Sequential Organ Failure Assessment score and Charlson Comorbidity Index. Of the 262 patients with nucleated RBCs equal to or higher than the detection limit (0.01 × 109/L), 26% died within 30 days, compared with 12% of the 969 patients with nucleated RBCs below the detection limit (p < 0.0001). Mortality was significantly higher for each increase in Nucleated RBC score, except from score 2 to 3, and was 62% in the highest group. In multivariate logistic regression, odds ratios for 30-day mortality were as follows: Nucleated RBC score: 1.33 (95% CI, 1.13–1.56), Sequential Organ Failure Assessment score: 1.32 (1.29–1.56), and Charlson Comorbidity Index: 1.17 (1.09–1.25). Conclusions: Most patients with suspected sepsis in emergency department had undetectable nucleated RBCs at admission to the emergency department. However, increased nucleated RBCs significantly predicted 30-day mortality. Nucleated RBCs may provide additional prognostic information to Sequential Organ Failure Assessment score and other laboratory tests

Prognostic Value of Nucleated RBCs for Patients With Suspected Sepsis in the Emergency Department: A Single-Center Prospective Cohort Study

OBJECTIVES: Increase of nucleated RBCs in peripheral blood has been shown to be predictive of mortality in ICU patients. The aim of this study was to explore the prognostic value of nucleated RBCs in the first blood sample taken at admission to the emergency department from patients with suspected sepsis. DESIGN: Single-center prospective cohort study. SETTING: Emergency department. PATIENTS: One-thousand two-hundred thirty-one consecutive adult patients with suspected sepsis were included in a prospective quality register-based cohort study. Inclusion criteria were as follows: patients received in rapid response team with blood cultures taken and immediate antibiotics given in the emergency department. Intervention: Not applicable. MEASUREMENT AND MAIN RESULTS: Nucleated RBCs, Sequential Organ Failure Assessment score, Quick Sequential Organ Failure Assessment, Charlson Comorbidity Index, and commonly used laboratory tests measured in the emergency department were compared with 30-day mortality. Nvaucleated RBC counts were divided into five groups, called “Nucleated RBC score,” according to nucleated RBC count levels and analyzed with logistic regression together with the Sequential Organ Failure Assessment score and Charlson Comorbidity Index. Of the 262 patients with nucleated RBCs equal to or higher than the detection limit (0.01 × 109/L), 26% died within 30 days, compared with 12% of the 969 patients with nucleated RBCs below the detection limit (p < 0.0001). Mortality was significantly higher for each increase in Nucleated RBC score, except from score 2 to 3, and was 62% in the highest group. In multivariate logistic regression, odds ratios for 30-day mortality were as follows: Nucleated RBC score: 1.33 (95% CI, 1.13–1.56), Sequential Organ Failure Assessment score: 1.32 (1.29–1.56), and Charlson Comorbidity Index: 1.17 (1.09–1.25). CONCLUSIONS: Most patients with suspected sepsis in emergency department had undetectable nucleated RBCs at admission to the emergency department. However, increased nucleated RBCs significantly predicted 30-day mortality. Nucleated RBCs may provide additional prognostic information to Sequential Organ Failure Assessment score and other laboratory tests

Serum ACE as a prognostic biomarker in COVID-19: A Case series

We have earlier proposed that serum ACE (s‐ACE) could be used as a biomarker for severity in COVID‐19 due to an assumed inverse relationship between ACE and ACE2. High s‐ACE could indicate lower ACE2 activity and therefore more widespread and severe SARS‐CoV2 infection, owing to virally mediated downregulation of ACE2 (1). Dysregulation of the Renin‐Angiotensin‐Aldosterone system (RAAS) are found in comorbidities known as risk factors for increased morbidity and mortality, such as hypertension and cardiovascular disease (2)

Serum ACE as a prognostic biomarker in COVID-19: A Case series

We have earlier proposed that serum ACE (s‐ACE) could be used as a biomarker for severity in COVID‐19 due to an assumed inverse relationship between ACE and ACE2. High s‐ACE could indicate lower ACE2 activity and therefore more widespread and severe SARS‐CoV2 infection, owing to virally mediated downregulation of ACE2 (1). Dysregulation of the Renin‐Angiotensin‐Aldosterone system (RAAS) are found in comorbidities known as risk factors for increased morbidity and mortality, such as hypertension and cardiovascular disease (2)

Reversering av antikoagulerende legemidler ved hjerneblødning

Antikoagulerende legemidler kan effektivt forebygge og behandle blodpropper, men gir samtidig økt risiko for hjerneblødning. Ved hjerneblødning anbefales rask reversering av den antikoagulerende effekten. Reverserende behandling må imidlertid velges ut ifra antikoagulasjonsmidlenes ulike virkningsmekanismer, og spesifikk antidot foretrekkes hvis tilgjengelig

Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study.

BACKGROUND The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification. METHODS Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models. RESULTS A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites. CONCLUSIONS NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID