Fenytoiinin, karbamatsepiinin ja valproiinihapon farmakokinetiikan ongelmakohtia : Kättä pidempää epilepsiapotilaita hoitavalle kliinikolle

English summaryPeer reviewe

Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients

Background Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. Objectives To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. Methods In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. Results Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. Conclusions SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.Peer reviewe

Development of Project Portfolio Cost Monitoring and Forecasting

Projektisalkun kustannusseuranta ja -ennuste ovat yrityksen toiminnan kannalta oleellisia: jos projektit eivät valmistu aikataulussa ja budjetin rajoissa, yrityksen toiminta ei ole kannattavaa. Kannattamattoman yrityksen toiminta tulee ennen pitkään loppumaan. Tutkimuksen tavoitteena oli kehittää kohdeyrityksen projektisalkun kustannusten seurantaa ja ennustamista tarkentamalla nykyistä prosessia ja hyödyntämällä olemassa olevaa projektiohjelmistoa paremmin. Työssä tutkittiin myös tulevaisuuden kehitysnäkymiä tekoälyn hyödyntämiseksi projektisalkun kustannusten seurannan ja kustannusennusteen tekemisessä. Tutkimusmenetelmänä käytettiin yhden yrityksen tapaustutkimusta. Tutkimus keskittyi projektisalkun kustannusseurannan ja -ennusteen kehittämiseen, johon lähtötietoja saadaan yksittäisistä projekteista. Tämän vuoksi tutkimuksen taustan tutkiminen aloitettiin kustannusseurannan ja -ennusteen periaatteiden selvittämisestä yksittäisen projektin näkökulmasta. Siitä siirryttiin tutkimaan aihetta projektisalkun näkökulmasta ja lopuksi tutkittiin tekoälyn mahdollisuuksia kustannusseurannan ja -ennusteen tekemisessä. Tuloksena saatiin yksinkertaistettu kustannushallinnan prosessikuva, jonka pohjalta on mahdollista tehdä yksityiskohtaisempi prosessi- ja tehtäväkuvaus. Sen avulla kustannushallinnan prosessi saadaan selkeämmäksi. Lisäksi projektiohjelmiston käytön tehostamiseen löydettiin viisi kohtaa: tuotantolaskelman tekeminen riittävällä tarkkuudella, tehtävien osoittaminen tekijöille, kustannusten kirjaaminen, ennusteen päivittäminen ja riskien huomiointi kustannusarviossa ja -ennusteessa. Tekoälyn käyttämisellä olisi selkeästi nähtävissä oleva hyöty kustannushallinnan lähtödatan puutteiden identifioinnissa. Lisäksi kustannusennusteen tekeminen tekoälyn avulla voisi periaatteessa olla mahdollista. Tekoälyn hyödyntäminen olisikin saatujen tulosten valossa periaatteessa mahdollista ilman muutoksia nykyisiin järjestelmiin, ja tulokset rohkaisevatkin tutkimaan mahdollisuuksia tarkemmin

Left atrial appendage volume increased in more than half of patients with cryptogenic stroke.

BACKGROUND: Ischemic strokes without a well-defined etiology are labeled as cryptogenic, and account for 30-40% of strokes in stroke registries. The left atrial appendage (LAA) is the most typical origin for intracardiac thrombus formation when associated with atrial fibrillation. Here, we examined whether increased LAA volume detected with cardiac computed tomography (cCT) constitutes a risk factor in cryptogenic stroke patients. METHODS: This study included 82 stroke/TIA patients (57 males; mean age, 58 years) with a diagnosis of cryptogenic stroke after extensive radiological and cardiological investigations. Cases were classified using the TOAST criteria modified by European Association of Echocardiography recommendations for defining cardiac sources of embolism. Forty age- and gender-matched control subjects without cardiovascular diseases were selected for pair-wise comparisons (21 males; mean age, 54 years). LAA volume adjusted for body surface area was measured three dimensionally by tracing the LAA borders on electrocardiogram-gated CT slices. RESULTS: In control subjects, mean LAA volume was 3.4±1.1 mL/m(2). Mean+2SD, which was considered the upper limit for normal LAA volume was 5.6 mL/m(2). In paired Student t-test between the patient group and matched controls, LAA volume was 67% larger in cryptogenic stroke/TIA patients (5.7±2.0 mL/m(2) vs. 3.4±1.1 mL/m(2); P<0.001). Forty-five (55%) patients with cryptogenic stroke/TIA had enlarged LAA. CONCLUSION: LAA is significantly enlarged in more than half of patients with cryptogenic stroke/TIA. LAA thrombosis may contribute to the pathogenesis of stroke in patients considered to have cryptogenic stroke after conventional evaluation

Left atrial appendage (LAA) volumes (mL/m²) in 40 cryptogenic stroke/TIA patients (squares/circles) and 40 age- and gender-matched control subjects (triangles), with 95% confidence interval.

<p>Mean LAA volume (5.7±2.0 mL/m²) was 67% higher in matched patients with stroke/TIA than in control subjects (3.4±1.1 mL/m²). Volume enlargement was similar between stroke patients (squares) and TIA patients (circles), and between hypertensive (black) and normotensive (white) patients.</p

Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients

Abstract Background:Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. Objectives:To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. Methods:In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. Results:Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1–3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. Conclusions:SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised