Um stöðu læknisfræðinnar á íslenskum ríkisspítala

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The use of recombinant activated factor VIIa for major bleedings in open heart surgery

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenINTRODUCTION: We evaluated the efficacy of activated recombinant factor VIIa (rFVIIa) administration for critical bleeding during cardiothoracic surgery in Iceland. MATERIALS AND METHODS: Over a 33 month period, 10 consecutive patients with major life-threatening bleeding during or right after open cardiac surgery that received rFVIIa in 11 operations. Clinical information was retrospectively collected from hospital charts. RESULTS: The 10 patients were on average 66 year old, ranging 36-82 yrs. All patients were NYHA-class III or IV, there of three underwent emergency surgery. Complicated AVR+/-CABG was the most common type of operation (n=5), with average operation time 673 min. (range 475-932) and perfusion time 287 min. (range 198-615). After the administration of rFVIIa, haemostasis was acquired in 8 of 11 operations, with a significant improvement in coagulation parameters. Three patiens needed reoperation for bleeding. Transfusion of packed red cell (p=0.002) and plasma (p<0.02) decreased significantly after administration of rFVIIa and prothrombin time was shortened (p<0.004). Five patients succumbed, one of them with a cerebral infarction and pulmonary embolus, the latter confirmed at autopsy. Other causes of death were intractable bleeding, myocardial infarction, multiorgan failure and disseminated intravascular coagulopathy. CONCLUSIONS: rFVIIa can be used effectively to stop intractable bleedings in open heart surgery, with 8 out of 11 patients in this small series achieving hemostasis after its administration. Mortality in this group of patients was high (50%), however, in all cases rFVIIa was used as an end-of-the-line treatment where other therapy had failed. One patient died from pulmonary embolism and cerebral infarct, raising the question of hypercoagulation. Further studies on the side effects and indications of rFVIIa treatment are necessary.Inngangur: Rannsakaður var með aftursæjum hætti árangur meðhöndlunar lífshættulegra blæðinga í opnum hjartaaðgerðum á Landspítala með líftæknigerðum espuðum storkuþætti VII (recombinant factor VIIa, rFVIIa). Efniviður og aðferðir: Frá júní 2003 til mars 2006 fengu 10 sjúklingar rFVIIa vegna meiriháttar blæðinga sem ekki tókst að stöðva með hefðbundinni meðferð í 11 hjartaskurðaðgerðum. Upplýsingar voru fengnar úr sjúkraskrám. Niðurstöður: Meðalaldur var 66 ár (bil 36-82). Allir sjúklingarnir voru í NYHA-flokki III eða IV, þar af gengust þrír undir bráðaaðgerð. Algengustu aðgerðirnar voru ósæðarlokuskipti (n=5), með eða án kransæðahjáveitu. Tímalengd aðgerðanna var að meðaltali 673 mínútur (bil 475-932) og tími í hjarta- og lungnavél 287 mínútur (bil 198-615). Í 8 af 11 aðgerðum stöðvaðist blæðing skömmu eftir gjöf rFVIIa. Þrír sjúklingar þurftu þó enduraðgerð vegna blæðinga. Gjöf rauðkornaþykknis (p=0,002) og blóðvatns (p<0,02) minnkaði marktækt eftir gjöf rFVIIa og próþrombín-tími styttist (p<0,004). Fimm sjúklingar lifðu aðgerðina af en dánarorsakir hinna fimm voru óstöðvandi blæðing í aðgerð, segarek til lungna, hjartadrep, fjölkerfabilun og blóðstorkusótt. Ályktun: rFVIIa er virkt lyf til að stöðva meiriháttar blæðingar í opnum hjartaaðgerðum, en blæðing stöðvaðist í 8 af 11 aðgerðum við gjöf lyfsins. Fimm sjúklingar af tíu lifðu aðgerðirnar af og útskrifuðust heim en hafa verður í huga að lyfið var einungis gefið þegar öll önnur meðferð hafði verið reynd til hlítar og sjúklingarnir hefðu annars dáið úr blæðingu. Í einu tilviki lést sjúklingur úr óstöðvandi blæðingu þrátt fyrir gjöf rFVIIa. Einn sjúklingur lést úr segareki til lungna og annar vegna bráðs hjartadreps, hvort tveggja dauðsföll sem gætu hafa tengst gjöf lyfsins

Prevalence of atrial fibrillation and use of warfarin among patients with ischemic stroke

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenObjective: Atrial fibrillation (AF) is the most common sustained cardiac arrythmia and a significant cause of morbidity. Stroke and transient ischemic attack (TIA) are well known serious complications of AF. In the last decade, a number of studies have shown that the risk of stroke in patients with AF is reduced by anticoagulation therapy with warfarin. The aim of this study was to assess the prevalence of AF in patients with acute ischemic stroke or TIA and to look at the use of anticoagulation therapy in patients who either had a previously known AF or were diagnosed to have AF during hospitalisation for ischemic stroke or TIA. Methods: Medical records of 918 patients admitted to Landspitali University Hospital in Iceland in 1997-2000 with the diagnosis of TIA or ischemic stroke were reviewed to detect a subgroup with AF. In addition to demographic data and cardiac function studies, information was collected about other possible coexisting stroke risk factors. Results: A total of 159 patients (17%) had AF in 124 (78%) of whom the AF was previously known. In 35 patients AF was diagnosed during the hospitalisation.The majority of those patients also had at least one other risk factor for stroke. On admission, 27 patients (22%) of those with previously known AF were being treated with warfarin. In eleven (41%) the anticoagulation was subtherapeutic as the INR was found to be lower than 2,0. At discharge, 74 patients of those 131 (56%) who were alive were receiving warfarin anticoagulation. Conclusion: The prevalence of AF in patients with TIA or ischemic stroke was somewhat high in this study. AF and other risk factors for stroke were found to commonly coexist. Despite the well documented effect of warfarin in such patients, this therapy was underused for both primary and secondary stroke prevention.Tilgangur: Gáttatif er algengasta viðvarandi hjartsláttartruflunin og getur haft afgerandi áhrif á lífs­gæði. Heiladrep er einn alvarlegasti fylgikvilli gáttatifs og fjölmargar rannsóknir á síðasta áratug sýna að draga má úr tíðni þessa fylgikvilla með warfarín blóðþynningarmeðferð. Tilgangur þessarar rannsóknar var að kanna algengi gáttatifs hjá sjúklingum með heiladrep og skammvinnt blóðþurrðarkast í heila og hvernig staðið var að blóðþynningu hjá þeim sem höfðu áður þekkt gáttatif. Efniviður og aðferðir: Upplýsinga var aflað á aftur­skyggnan hátt um alla sjúklinga sem komu á Land­spítala vegna heiladreps eða skammvinnrar blóðþurrðar í heila á fjögurra ára tímabili (1997-2000). Þessar upplýsingar höfðu verið skráðar á framvirkan kerfisbundinn hátt í Heilablóðfallsskrá. Í þessari rannsókn var litið sérstaklega á gögn sjúklinga sem jafnframt voru greindir með gáttatif, ýmist áður eða í sjúkrahúslegunni eftir heilablóðfallið. Niðurstöður: Á meðal 918 sjúklinga með heiladrep eða skammvinnna blóðþurrð í heila sem gögn voru til um reyndust 124 (13,5%) hafa þekkt gáttatif fyrir greiningu heilaáfallsins. Þrjátíu og fimm til viðbótar greindust með gáttatif í legunni og hjartsláttartruflun því til staðar hjá 159 (17%) þeirra sem greindust með heiladrep eða blóðþurrðarkast. Af þeim sem voru með þekkt gáttatif fyrir voru aðeins 27 (22%) á blóðþynningarmeðferð með warfaríni við greiningu heilaáfallsins og aðeins 16 af 27 (59%) höfðu INR gildi (International Normalized Ratio) yfir 2,0 við innlögn. Tuttugu og átta sjúklingar létust í legunni. Alls útskrifuðust 74 af 131 (56%) sjúklingi á warfarínmeðferð. Velflestir sjúklinganna höfðu að minnsta kosti einn viðbótaráhættuþátt fyrir blóðþurrðarsjúkdómi í heila auk gáttatifs. Ályktun: Gáttatif er algengt meðal sjúklinga sem fá heiladrep eða skammvinna heilablóðþurrð en margir þeirra hafa aðra áhættuþætti heila­blóð­þurrð­ar­sjúk­dóms að auki. Erfitt er því að átta sig á beinu orsakasamhengi gáttatifs og heilaáfalls hjá stórum hluta þessara sjúklinga. Niðurstöður þessarar rann­sókn­ar benda til þess að notkun warfaríns hafi ver­ið ábótavant bæði fyrir og eftir heilablóðþurrð á rann­sóknartímabilin

Comparison of the effectiveness and safety of direct oral anticoagulants: nationwide propensity score-weighted study

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Comparison of medication adherence to different oral anticoagulants : population-based cohort study

Publisher Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE: Previous observational studies have yielded conflicting results on whether medication adherence differs between patients receiving warfarin and direct oral anticoagulants (DOACs). Importantly, no study has adequately accounted for warfarin dosing being continuously modified based on INR values while dosing of DOACs is fixed. We aimed to compare non-adherence between new users of apixaban, dabigatran, rivaroxaban and warfarin in a population-based cohort. METHODS: New users of apixaban, dabigatran, rivaroxaban and warfarin from 2014 to 2019 living in the Icelandic capital area were included. Non-adherence was defined as proportion of days covered below 80%. Inverse probability weighting was used to yield balanced study groups and non-adherence was compared using logistic regression. Factors associated with non-adherence were estimated using multivariable logistic regression. RESULTS: Overall, 1266 patients received apixaban, 247 dabigatran, 1566 rivaroxaban and 768 warfarin. The proportion of patients with non-adherence ranged from 10.5% to 16.7%. Dabigatran was associated with significantly higher odds of non-adherence compared with apixaban (OR 1.57, 95% CI 1.21 to 2.04, p<0.001), rivaroxaban (OR 1.45, 95% CI 1.12 to 1.89, p=0.005) and warfarin (OR 1.63, 95% CI 1.23 to 2.15, p<0.001). The odds of non-adherence were similar for apixaban, rivaroxaban and warfarin. Apart from the type of oral anticoagulants (OACs) used, female sex, hypertension, history of cerebrovascular accident and concomitant statin use were all independently associated with lower odds of non-adherence. CONCLUSION: Dabigatran was associated with higher odds of non-adherence compared with other OACs. Non-adherence was similar between apixaban, rivaroxaban and warfarin users. Female sex and higher comorbidity were associated with better medication adherence.Peer reviewe

Disease associations with monoclonal gammopathy of undetermined significance can only be evaluated using screened cohorts : results from the population-based iStopMM study

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been associated with other medical conditions. Since systematic screening is not recommended, MGUS is typically diagnosed due to underlying diseases and most cases are not diagnosed. Most previous studies on MGUS disease associations have been based on clinical cohorts, possibly resulting in selection bias. Here we estimate this selection bias by comparing clinically diagnosed and screened individuals with MGUS with regards to demographics, laboratory features, and comorbidities. A total of 75,422 participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study were screened for MGUS by serum protein electrophoresis, immunofixation and free light chain assay (clinicaltrials gov. Identifier: NCT03327597). We identified 3,352 individuals with MGUS, whereof 240 had previously been clinically diagnosed (clinical MGUS), and crosslinked our data with large, nationwide registries for information on comorbidities. Those with clinical MGUS were more likely to have at least one comorbidity (odds ratio=2.24; 95% confidence interval: 1.30-4.19), and on average had more comorbidities than the screened MGUS group (3.23 vs. 2.36, mean difference 0.68; 95% confidence interval: 0.46-0.90). They were also more likely to have rheumatological disease, neurological disease, chronic kidney disease, liver disease, heart failure, or endocrine disorders. These findings indicate that individuals with clinical MGUS have more comorbidities than the general MGUS population and that previous studies have been affected by significant selection bias. Our findings highlight the importance of screening data when studying biological and epidemiological implications of MGUS.Peer reviewe

Defining new reference intervals for serum free light chains in individuals with chronic kidney disease : Results of the iStopMM study

Publisher Copyright: © 2022. The Author(s). © 2022. The Author(s).Serum free light chain (FLC) concentration is greatly affected by kidney function. Using a large prospective population-based cohort, we aimed to establish a reference interval for FLCs in persons with chronic kidney disease (CKD). A total of 75422 participants of the iStopMM study were screened with serum FLC, serum protein electrophoresis and immunofixation. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Central 99% reference intervals were determined, and 95% confidence intervals calculated. Included were 6461 (12%) participants with measured FLCs, eGFR < 60 mL/min/1.73 m2, not receiving renal replacement therapy, and without evidence of monoclonality. Using current reference intervals, 60% and 21% had kappa and lambda FLC values outside the normal range. The FLC ratio was outside standard reference interval (0.26-1.65) in 9% of participants and outside current kidney reference interval (0.37-3.10) in 0.7%. New reference intervals for FLC and FLC ratio were established. New reference intervals for the FLC ratio were 0.46-2.62, 0.48-3.38, and 0.54-3.30 for eGFR 45-59, 30-44, and < 30 mL/min/1.73 m2 groups, respectively. The crude prevalence of LC-MGUS in CKD patients was 0.5%. We conclude that current reference intervals for FLC and FLC ratio are inaccurate in CKD patients and propose new eGFR based reference intervals to be implemented.Peer reviewe

Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.Black Swan Research Initiative by the International Myeloma Foundation Icelandic Centre for Research European Research Council (ERC) University of Iceland Landspitali University Hospita

Sequence variant affects GCSAML splicing, mast cell specific proteins, and risk of urticaria

Funding Information: The authors thank the individuals who participated in this study and whose contributions made this work possible. We also thank our valued colleagues who contributed to the data collection and phenotypic characterization of clinical samples as well as to the genotyping and analysis of the whole-genome association data. This research has been conducted using the UK Biobank Resource under application numbers 24711 and 24898. Publisher Copyright: © 2023, The Author(s).Urticaria is a skin disorder characterized by outbreaks of raised pruritic wheals. In order to identify sequence variants associated with urticaria, we performed a meta-analysis of genome-wide association studies for urticaria with a total of 40,694 cases and 1,230,001 controls from Iceland, the UK, Finland, and Japan. We also performed transcriptome- and proteome-wide analyses in Iceland and the UK. We found nine sequence variants at nine loci associating with urticaria. The variants are at genes participating in type 2 immune responses and/or mast cell biology (CBLB, FCER1A, GCSAML, STAT6, TPSD1, ZFPM1), the innate immunity (C4), and NF-κB signaling. The most significant association was observed for the splice-donor variant rs56043070[A] (hg38: chr1:247556467) in GCSAML (MAF = 6.6%, OR = 1.24 (95%CI: 1.20–1.28), P-value = 3.6 × 10-44). We assessed the effects of the variants on transcripts, and levels of proteins relevant to urticaria pathophysiology. Our results emphasize the role of type 2 immune response and mast cell activation in the pathogenesis of urticaria. Our findings may point to an IgE-independent urticaria pathway that could help address unmet clinical need.Peer reviewe

A new hemostatic agent for the treatment of intractable bleeding [editorial]

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenEðlileg blóðstorknun er sjálfsvörn blóðrásarinnar sem sér til þess að blóðið renni um æðar líkamans en ekki út úr þeim. Eðlileg blóðstorknun hefst þegar náttúrulegur storkuþáttur VIIa (sem berst með blóðinu) tengist vefjaþætti (tissue factor, áður kallað thromboplastin) í særðum æðavegg. Samtímis loða blóðflögur við von Willebrand prótein í sárinu. VIIa/ vefjaþáttar-komplexinn veldur myndun þrombíns sem breytir meðal annars fíbrínógeni í fíbrín og espar blóðflögur þannig að þær kekkjast saman. Storkuþættir tengjast samtímis yfirborði kekkjaðra blóðflagna í sárum. Blóðstorknunin verður því aðeins í sárinu en ekki í ósködduðum hlutum æðakerfisins. Að auki er hinn ósári hluti æðakerfisins varinn af náttúrulegum blóðþynningar- og storkuleysandi efnum gegn blóðstorknun