Forslag til endring av retningslinje ved konservativ behandling av NSTEMI

Sammendrag Bakgrunn Studier gjort internasjonalt har vist at fondaparinuks gir lavere morbiditet og mortalitet på lang sikt, sammenlignet med det lavmolekylære heparinet enoksaparin, ved konservativ antitrombotisk behandling av NSTEMI. Med bakgrunn i dette har vi sett på nåværende praksis for slik behandling av denne pasientgruppen på hjerteavdelingen på Ullevål Universitetssykehus (UUS). Da det ikke er samsvar mellom praksis på UUS og internasjonale guidelines, ønsket vi å utarbeide en strategi for implementering av en ny retningslinje for antitrombotisk behandling ved NSTEMI, med bytte fra enoksaparin til fondaparinuks. Metode Kunnskapsgrunnlaget ble bekreftet ved søk i medline/pubmed, og det ble gjort en spørreskjemaundersøkelse for å avdekke gjeldende praksis. Videre ble det gjort litteratursøk i Medline/Ovid for å finne dokumenterte implementeringstiltak. Resultater Ved UUS brukes det i hovedsak dalteparin ved konservativ behandling av NSTEMI, hvilket samsvarer med de nasjonale retningslinjer. Flere tiltak for endring av den lokale retningslinjen ble vurdert, og følgende tiltak foreslås: 1. Avdelingsledelsen nedsetter en ansvarlig prosjektgruppe med en prosjektkoordinator. 2. Felles undervisningsmøter med utdeling av spørreskjemaer for tilbakemelding. 3. Muntlig orientering samt informasjonsskriv om det nye tiltaket til personalet. 4. Regelmessige møter i prosjektgruppen med evaluering av resultater samt tilbakemeldinger fra personalet. 5. Kontinuerlig oppdatering om resultatene av prosjektet til personalet både muntlig og via e-post, samt oppfordring til å gi respons på hvordan det fungerer. 6. Evaluering av prosjektet etter ett år. Her benyttes indikatoren ”andelen pasienter med NSTEMI som blir behandlet konservativt i akuttfasen med fondaparinuks ved hjerteavdelingen på UUS.” Konklusjon Kunnskapsgrunnlaget viser at et bytte til fondaparinuks er fordelaktig med tanke på redusert morbiditet og mortalitet på lang sikt, lettere administrasjon og reduserte kostnader. De tiltakene vi har kommet frem til kan være praktisk gjennomførbare i den aktuelle avdelingen, og kan være hensiktsmessige i innføringen av en ny retningslinje

Hepcidin analysis in pneumonia: Comparison of immunoassay and LC-MS/MS

Background The iron-regulatory hormone hepcidin is a promising biomarker to differentiate anaemia of inflammation from iron deficiency. Plasma hepcidin concentrations increase substantially during inflammation, and the amount of smaller, non-biologically active isoforms of hepcidin increase in inflammatory conditions. These smaller isoforms are measured in some, but not all analytical methods. Thus, we evaluated the comparability of two analytical methods with different isoform selectivity during and after acute-phase pneumonia as a highly inflammatory model disease. Methods Blood samples from a cohort of 267 hospitalized community-acquired pneumonia patients collected at admission and a 6-week follow-up were analysed. Hepcidin was measured in plasma by an immunoassay, which recognizes all hepcidin isoforms, and a liquid chromatography tandem mass spectrometry (LC-MS/MS), which selectively measures the bioactive hepcidin-25. Additionally, a subset of serum samples was analysed by LC-MS/MS. Results Hepcidin measurements by immunoassay were higher compared with LC-MS/MS. The relative mean difference of hepcidin plasma concentrations between the two analytical methods was larger in admission samples than in follow-up samples (admission samples 200 ng/mL: 78%, follow-up samples >10 ng/mL: 22%). During acute-phase pneumonia, serum concentrations were on average 22% lower than plasma concentrations when measured by LC-MS/MS. Conclusions Immunoassay measured higher hepcidin concentrations compared with LC-MS/MS, with more pronounced differences in high-concentration samples during acute-phase pneumonia. These findings should be considered in local method validations and in future harmonization and standardization optimization of hepcidin measurements.publishedVersio

Hemochromatosis : Clinical Penetration of the C282Y Mutation

ABSTRACT Title: Hemochromatosis: Clinical Penetration of the C282Y Mutation Background: Hemochromatosis is a disease in which iron accumulates in the body. Its most common form is caused by a homozygous gene mutation at the HFE gene called C282Y. The gene pattern is autosomal-recessive. The accumulation of iron is achieved over many years, and the clinical symptoms are often vague. It has been proposed that the clinical penetrance of the mutation is not complete, and the aim of this literature research is to establish the penetrance rate of the disease and how this relates to the possibility of starting screening programmes. Methods: Searches performed using PubMed/Medline. 33 articles were considered, including 7 reviews. Results: The tendency among the articles reviewed, especially the ones including a large population, is that the clinical penetrance is low. More research is needed to establish a more exact rate of penetrance, but at this moment, screening is not to be recommended considering this aspect

Hepcidin and ferritin predict microbial etiology in community-acquired pneumonia

Background Iron is crucial for survival and growth of microbes. Consequently, limiting iron availability is a human antimicrobial defense mechanism. We explored iron and iron-related proteins as potential biomarkers in community-acquired pneumonia and hypothesized that infection-induced changes in these potential biomarkers differ between groups of pathogens and could predict microbial etiology. Methods Blood samples from a prospective cohort of 267 patients with community-acquired pneumonia were analyzed for hepcidin, ferritin, iron, transferrin, and soluble transferrin receptor at admission, clinical stabilization, and a 6-week follow-up. A total of 111 patients with an established microbiological diagnosis confined to 1 microbial group (atypical bacterial, typical bacterial, or viral) were included in predictive analyses. Results High admission levels of ferritin predicted atypical bacterial versus typical bacterial etiology (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.18–4.32; P = .014). Furthermore, hepcidin and ferritin predicted atypical bacterial versus viral etiology (hepcidin: OR = 3.12, 95% CI = 1.34–7.28, P = .008; ferritin: OR = 2.38, 95% CI = 1.28–4.45, P = .006). The findings were independent of C-reactive protein and procalcitonin. Conclusions Hepcidin and ferritin are potential biomarkers of microbial etiology in community-acquired pneumonia.publishedVersio

Hepcidin predicts 5-year mortality after community-acquired pneumonia

Background Virtually all living organisms, including microbes and humans, depend on iron to survive and grow. During an infection, the plasma level of iron and several iron-related proteins change substantially. We hypothesized that iron and iron-related proteins could predict short- and long-term outcomes in community-acquired pneumonia. Methods Blood samples from a prospective cohort of 267 in-patients with community-acquired pneumonia were analysed for hepcidin, ferritin, iron, transferrin, transferrin saturation, and soluble transferrin receptor at admission and 6-weeks post-discharge. Adverse short-term outcome was defined as admission to intensive care unit or death within 30 days, and long-term outcome was assessed as 5-year overall mortality. Logistic regression, Kaplan Meier survival curves, and Cox regression models with cut-offs at median for the potential biomarkers were used for statistical evaluation. Results Low admission levels of hepcidin predicted 5-year overall mortality, independently of age, sex, comorbid conditions, and anaemia. Low levels of ferritin at admission as well as low levels of iron and transferrin saturation and high levels of soluble transferrin receptor at the 6-week follow-up were predictors of 5-year overall mortality in univariable, but not in multivariable analyses. Neither of these potential biomarkers predicted adverse short-term outcomes. Conclusions In hospitalized patients with community-acquired pneumonia, low levels of hepcidin at admission predicted 5-year overall mortality, but not short-term adverse outcome

Hepcidin predicts 5-year mortality after community-acquired pneumonia

Background Virtually all living organisms, including microbes and humans, depend on iron to survive and grow. During an infection, the plasma level of iron and several iron-related proteins change substantially. We hypothesized that iron and iron-related proteins could predict short- and long-term outcomes in community-acquired pneumonia. Methods Blood samples from a prospective cohort of 267 in-patients with community-acquired pneumonia were analysed for hepcidin, ferritin, iron, transferrin, transferrin saturation, and soluble transferrin receptor at admission and 6-weeks post-discharge. Adverse short-term outcome was defined as admission to intensive care unit or death within 30 days, and long-term outcome was assessed as 5-year overall mortality. Logistic regression, Kaplan Meier survival curves, and Cox regression models with cut-offs at median for the potential biomarkers were used for statistical evaluation. Results Low admission levels of hepcidin predicted 5-year overall mortality, independently of age, sex, comorbid conditions, and anaemia. Low levels of ferritin at admission as well as low levels of iron and transferrin saturation and high levels of soluble transferrin receptor at the 6-week follow-up were predictors of 5-year overall mortality in univariable, but not in multivariable analyses. Neither of these potential biomarkers predicted adverse short-term outcomes. Conclusions In hospitalized patients with community-acquired pneumonia, low levels of hepcidin at admission predicted 5-year overall mortality, but not short-term adverse outcome

Inflammatory biomarkers are associated with aetiology and predict outcomes in community-acquired pneumonia: Results of a 5-year follow-up cohort study

Background Biomarkers may facilitate clinical decisions in order to guide antimicrobial treatment and prediction of prognosis in community-acquired pneumonia (CAP). We measured serum C-reactive protein, procalcitonin (PCT) and calprotectin levels, and plasma pentraxin 3 (PTX3) and presepsin levels, along with whole-blood white cell counts, at three time-points, and examined their association with microbial aetiology and adverse clinical outcomes in CAP. Methods Blood samples were obtained at hospital admission, clinical stabilisation and 6-week follow-up from 267 hospitalised adults with CAP. Adverse short-term outcome was defined as intensive care unit admission and 30-day mortality. Long-term outcome was evaluated as 5-year all-cause mortality. Results Peak levels of all biomarkers were seen at hospital admission. Increased admission levels of C-reactive protein, PCT and calprotectin were associated with bacterial aetiology of CAP, while increased admission levels of PCT, PTX3 and presepsin were associated with adverse short-term outcome. In univariate and multivariate regression models, white blood cells and calprotectin at 6-week follow-up were predictors of 5-year all-cause mortality. Conclusions Calprotectin emerges as both a potential early marker of bacterial aetiology and a predictor for 5-year all-cause mortality in CAP, whereas PCT, PTX3 and presepsin may predict short-term outcome

Inflammatory biomarkers are associated with aetiology and predict outcomes in community-acquired pneumonia: results of a 5-year follow-up cohort study

Background Biomarkers may facilitate clinical decisions in order to guide antimicrobial treatment and prediction of prognosis in community-acquired pneumonia (CAP). We measured serum C-reactive protein, procalcitonin (PCT) and calprotectin levels, and plasma pentraxin 3 (PTX3) and presepsin levels, along with whole-blood white cell counts, at three time-points, and examined their association with microbial aetiology and adverse clinical outcomes in CAP. Methods Blood samples were obtained at hospital admission, clinical stabilisation and 6-week follow-up from 267 hospitalised adults with CAP. Adverse short-term outcome was defined as intensive care unit admission and 30-day mortality. Long-term outcome was evaluated as 5-year all-cause mortality. Results Peak levels of all biomarkers were seen at hospital admission. Increased admission levels of C-reactive protein, PCT and calprotectin were associated with bacterial aetiology of CAP, while increased admission levels of PCT, PTX3 and presepsin were associated with adverse short-term outcome. In univariate and multivariate regression models, white blood cells and calprotectin at 6-week follow-up were predictors of 5-year all-cause mortality. Conclusions Calprotectin emerges as both a potential early marker of bacterial aetiology and a predictor for 5-year all-cause mortality in CAP, whereas PCT, PTX3 and presepsin may predict short-term outcome