Geenitestit ja lääkehoito

Lääkeinfo.Lääkehoitoihin vaikuttavien geenien tutkiminen voi auttaa suunnittelemaan potilaalle sopivan lääkehoidon ja ehkäisemään lääkehoitojen haittavaikutuksia tai parantamaan hoidon tehoa

Effect of a multi-domain lifestyle intervention on cardiovascular risk in older people : the FINGER trial

Aims Joint prevention of cardiovascular disease (CVD) and dementia could reduce the burden of both conditions. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated a beneficial effect on cognition (primary outcome) and we assessed the effect of this lifestyle intervention on incident CVD (pre-specified secondary outcome). Methods and results FINGER enrolled 1259 individuals aged 60-77 years (ClinicalTrials.gov NCT01041989). They were randomized (1:1) to a 2-year multi-domain intervention with diet, physical and cognitive activity, and vascular monitoring (n = 631), or general health advice (n = 628). National registries provided data on CVD including stroke, transient ischaemic attack (TIA), or coronary heart event. During an average of 7.4 years, 229 participants (18%) had at least one CVD diagnosis: 107 in the intervention group and 122 in the control group. The incidence of cerebrovascular events was lower in the intervention than the control group: hazard ratio (HR) for combined stroke/TIA was 0.71 [95% confidence interval (CI): 0.51-0.99] after adjusting for background characteristics. Hazard ratio for coronary events was 0.84 (CI: 0.56-1.26) and total CVD events 0.80 (95% CI: 0.61-1.04). Among those with history of CVD (n = 145), the incidence of both total CVD events (HR: 0.50, 95% CI: 0.28-0.90) and stroke/TIA (HR: 0.40, 95% CI: 0.20-0.81) was lower in the intervention than the control group. Conclusion A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those who had history of CVD. Key question Can a 2-year multi-domain lifestyle intervention, primarily designed for prevention of cognitive impairment, prevent new cardiovascular events among older adults over an extended follow-up? Key finding Among the 1259 participants aged 60-77 years, the intervention resulted in 13-20% lower cardiovascular disease (CVD) event rates (unadjusted and adjusted analyses), but with large degree of uncertainty. Cerebrovascular event rates were lower but for total CVD only among those with earlier CVD events. Take-home message A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those with a history of CVD.Peer reviewe

Febuxostat, But Not Allopurinol, Markedly Raises the Plasma Concentrations of the Breast Cancer Resistance Protein Substrate Rosuvastatin

Xanthine oxidase inhibitors febuxostat and allopurinol are commonly used in the treatment of gout. Febuxostat inhibits the breast cancer resistance protein (BCRP) in vitro. Rosuvastatin is a BCRP substrate and genetic variability in BCRP markedly affects rosuvastatin pharmacokinetics. In this study, we investigated possible effects of febuxostat and allopurinol on rosuvastatin pharmacokinetics. In a randomized crossover study with 3 phases, 10 healthy volunteers ingested once daily placebo for 7 days, 300 mg allopurinol for 7 days, or placebo for 3 days, followed by 120 mg febuxostat for 4 days, and a single 10 mg dose of rosuvastatin on day 6. Febuxostat increased the peak plasma concentration and area under the plasma concentration-time curve of rosuvastatin 2.1-fold (90% confidence interval 1.8-2.6; P = 5 x 10(-5)) and 1.9-fold (1.5-2.5; P = 0.001), but had no effect on rosuvastatin half-life or renal clearance. Allopurinol, on the other hand, did not affect rosuvastatin pharmacokinetics. In vitro, febuxostat inhibited the ATP-dependent uptake of rosuvastatin into BCRP-overexpressing membrane vesicles with a half-maximal inhibitory concentration of 0.35 mu M, whereas allopurinol showed no inhibition with concentrations up to 200 mu M. Taken together, the results suggest that febuxostat increases rosuvastatin exposure by inhibiting its BCRP-mediated efflux in the small intestine. Febuxostat may, therefore, serve as a useful index inhibitor of BCRP in drug-drug interaction studies in humans. Moreover, concomitant use of febuxostat may increase the exposure to BCRP substrate drugs and, thus, the risk of dose-dependent adverse effects.Peer reviewe

Third follow-up of the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) cohort investigating determinants of cognitive, physical, and psychosocial wellbeing among the oldest old : the CAIDE85+study protocol

Background: The oldest old is the fastest growing age group worldwide and the most prone to severe disability, especially in relation to loss of cognitive function. Improving our understanding of the predictors of cognitive, physical and psychosocial wellbeing among the oldest old can result in substantial benefits for the individuals and for the society as a whole. The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study investigated risk factors and determinants of cognitive impairment in a population-based longitudinal cohort, which was first examined between 1972 and 1992, when individuals were in their midlife, and re-assessed in 1998 and 2005-2009. Most of the study participants are currently aged 85 years or older. We aim to re-examine the cohort's survivors and gain further insights on the mechanisms underlying both cognitive and overall healthy ageing at old age. Methods: CAIDE85+ is the third follow-up of the CAIDE study participants. All individuals still alive and living in the Kuopio and Joensuu areas of Eastern Finland, from the original CAIDE cohort (two random samples,N = 2000 + similar to 900), will be invited to a re-examination. The assessment includes self-reported data related to basic demographics and lifestyle, as well as psychosocial and physical health status. Cognitive and physical evaluations are also conducted. Blood biomarkers relevant for dementia and ageing are assessed. Primary outcomes are the measurements related to cognition and daily life functioning (CERAD, Trail Making Test-A, Letter-Digit Substitution Test, Clinical Dementia Rating and Activities of Daily Living). Secondary endpoints of the study are outcomes related to physical health status, psychosocial wellbeing, as well as age-related health indicators. Discussion: Through a follow-up of more than 40 years, CAIDE85+ will provide invaluable information on the risk and protective factors that contribute to cognitive and physical health, as well as ageing and longevity. Study registration: The present study protocol has been registered at(registration nr, date 03.05.2019).Peer reviewe

Third follow-up of the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) cohort investigating determinants of cognitive, physical, and psychosocial wellbeing among the oldest old : the CAIDE85+study protocol

Background: The oldest old is the fastest growing age group worldwide and the most prone to severe disability, especially in relation to loss of cognitive function. Improving our understanding of the predictors of cognitive, physical and psychosocial wellbeing among the oldest old can result in substantial benefits for the individuals and for the society as a whole. The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study investigated risk factors and determinants of cognitive impairment in a population-based longitudinal cohort, which was first examined between 1972 and 1992, when individuals were in their midlife, and re-assessed in 1998 and 2005-2009. Most of the study participants are currently aged 85 years or older. We aim to re-examine the cohort's survivors and gain further insights on the mechanisms underlying both cognitive and overall healthy ageing at old age. Methods: CAIDE85+ is the third follow-up of the CAIDE study participants. All individuals still alive and living in the Kuopio and Joensuu areas of Eastern Finland, from the original CAIDE cohort (two random samples,N = 2000 + similar to 900), will be invited to a re-examination. The assessment includes self-reported data related to basic demographics and lifestyle, as well as psychosocial and physical health status. Cognitive and physical evaluations are also conducted. Blood biomarkers relevant for dementia and ageing are assessed. Primary outcomes are the measurements related to cognition and daily life functioning (CERAD, Trail Making Test-A, Letter-Digit Substitution Test, Clinical Dementia Rating and Activities of Daily Living). Secondary endpoints of the study are outcomes related to physical health status, psychosocial wellbeing, as well as age-related health indicators. Discussion: Through a follow-up of more than 40 years, CAIDE85+ will provide invaluable information on the risk and protective factors that contribute to cognitive and physical health, as well as ageing and longevity. Study registration: The present study protocol has been registered at(registration nr, date 03.05.2019).Peer reviewe

A comprehensive pharmacogenomic study indicates roles for SLCO1B1, ABCG2 and SLCO2B1 in rosuvastatin pharmacokinetics

AimsThe aim was to comprehensively investigate the effects of genetic variability on the pharmacokinetics of rosuvastatin.MethodsWe conducted a genome-wide association study and candidate gene analyses of single dose rosuvastatin pharmacokinetics in a prospective study (n = 159) and a cohort of previously published studies (n = 88).ResultsIn a genome-wide association meta-analysis of the prospective study and the cohort of previously published studies, the SLCO1B1 c.521 T > C (rs4149056) single nucleotide variation (SNV) associated with increased area under the plasma concentration–time curve (AUC) and peak plasma concentration of rosuvastatin (P = 1.8 × 10−12 and P = 3.2 × 10−15). The candidate gene analysis suggested that the ABCG2 c.421C > A (rs2231142) SNV associates with increased rosuvastatin AUC (P = .0079), while the SLCO1B1 c.388A > G (rs2306283) and SLCO2B1 c.1457C > T (rs2306168) SNVs associate with decreased rosuvastatin AUC (P = .0041 and P = .0076). Based on SLCO1B1 genotypes, we stratified the participants into poor, decreased, normal, increased and highly increased organic anion transporting polypeptide (OATP) 1B1 function groups. The OATP1B1 poor function phenotype associated with 2.1-fold (90% confidence interval 1.6–2.8, P = 4.69 × 10−5) increased AUC of rosuvastatin, whereas the OATP1B1 highly increased function phenotype associated with a 44% (16–62%; P = .019) decreased rosuvastatin AUC. The ABCG2 c.421A/A genotype associated with 2.2-fold (1.5–3.0; P = 2.6 × 10−4) increased AUC of rosuvastatin. The SLCO2B1 c.1457C/T genotype associated with 28% decreased rosuvastatin AUC (11–42%; P = .01).ConclusionThese data suggest roles for SLCO1B1, ABCG2 and SLCO2B1 in rosuvastatin pharmacokinetics. Poor SLCO1B1 or ABCG2 function genotypes may increase the risk of rosuvastatin-induced myotoxicity. Reduced doses of rosuvastatin are advisable for patients with these genotypes.</p

Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics : The FINGER trial

Introduction: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition. Methods: The FINGER recruited 1260 people from the general Finnish population (60-77 years, at risk for dementia). Participants were randomized 1: 1 to multidomain intervention (diet, exercise, cognition, and vascular risk management) and regular health advice. Primary outcome was change in cognition (Neuropsychological Test Battery z-score). Prespecified analyses to investigate whether participants' characteristics modified response to intervention were carried out using mixed-model repeated-measures analyses. Results: Sociodemographics (sex, age, and education), socioeconomic status (income), cognition (Mini-Mental State Examination), cardiovascular factors (body mass index, blood pressure, cholesterol, fasting glucose, and overall cardiovascular risk), and cardiovascular comorbidity did not modify response to intervention (P-values for interaction > .05). Conclusions: The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia. (C) 2017 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.Peer reviewe

Febuxostat, but not allopurinol, markedly raises the plasma concentrations of rosuvastatin

Kihtilääke febuksostaatin on havaittu solukokeissa estävän rintasyöpäresistenssiproteiinin toimintaa. Rintasyöpäresistenssiproteiini on elimistön rajakudoksissa kuten ohutsuolessa ja sappitiehyissä esiintyvä uloskuljetusproteiini. Se voi pienentää kuljettamiensa lääkeaineiden kuten kolesterolilääke rosuvastatiinin pitoisuuksia verenkierrossa. Tämän tutkimuksen tavoitteena oli selvittää febuksostaatin ja toisen kihtilääkkeen, allopurinolin vaikutuksia rosuvastatiinin farmakokinetiikkaan. Kolmivaiheisessa, satunnaistetussa vaihtovuoroisessa tutkimuksessa 10 vapaaehtoista tutkittavaa otti esilääkityksenä suun kautta joko seitsemän päivän ajan lumevalmistetta, seitsemän päivän ajan 300 mg allopurinolia tai kolmen päivän ajan lumevalmistetta ja neljän päivän ajan 120 mg febuksostaattia. Esilääkityksen kuudentena päivänä tutkittavat saivat lisäksi suun kautta kerta-annoksena 10 mg kolesterolilääke rosuvastatiinia. Rosuvastatiinin ottamisen jälkeen tutkittavilta otettiin plasma- ja virtsanäytteitä, joista määritettiin tutkittavien lääkkeiden pitoisuudet. Tutkimuksessa havaittiin, että febuksostaatti nosti rosuvastatiinin huippupitoisuuden plasmassa yli kaksinkertaiseksi ja rosuvastatiinin pitoisuus-aikakäyrän alle jäävän pinta-alan lähes kaksinkertaiseksi. Allopurinolilla ei sen sijaan ollut tilastollisesti merkitsevää vaikutusta rosuvastatiinin pitoisuuksiin. Febuksostaatin ja rosuvastatiinin yhteisvaikutus on todennäköisesti seurausta febuksostaatin kyvystä estää rintasyöpäresistenssiproteiinin toimintaa ohutsuolessa. Yhteisvaikutuksen seurauksena rosuvastatiinin hyötyosuus kasvaa. Febuksostaatin käyttö yhdessä rosuvastatiinin kanssa saattaa lisätä rosuvastatiiniin liittyvien lihashaittojen riskiä. Rosuvastatiiniannoksen pienentämistä tulisikin harkita, jos potilaalla on samanaikaisesti käytössä febuksostaattivalmiste. Tutkielman tekijä on osallistunut tämän tutkimuksen tutkimussuunnitelman laatimiseen sekä vastannut tutkimuksen käytännön toteutuksesta (tutkittavien rekrytoiminen tutkimukseen, koepäivien järjestelyt) ja tulosten analysoinnista ja raportoinnista.The xanthine oxidase inhibitor febuxostat was recently found to inhibit the breast cancer resistance protein (BCRP) in vitro. Rosuvastatin is a substrate of BCRP and genetic variability in BCRP markedly affects rosuvastatin pharmacokinetics. The aim of this study was to investigate possible effects of febuxostat and allopurinol, another xanthine oxidase inhibitor, on rosuvastatin pharmacokinetics. In a randomized, crossover study with three phases, 10 healthy volunteers ingested once daily placebo for 7 days, 300 mg allopurinol for 7 days, or placebo for 3 days followed by 120 mg febuxostat for 4 days, and a single 10 mg dose of rosuvastatin on day 6. Febuxostat increased the peak plasma rosuvastatin concentration 2.1-fold (90% confidence interval 1.8-2.6; P=5·10-5) and the area under the plasma rosuvastatin concentration-time curve 1.9-fold (1.5-2.5; P=0.001). Allopurinol, however, had no effect on rosuvastatin pharmacokinetics. These findings suggest that febuxostat inhibits BCRP-mediated rosuvastatin efflux in the small intestine. Concomitant use of febuxostat may increase the risk of rosuvastatin-induced muscle toxicity

Elämän Loppuvaihe: Opas Pohjois-Satakunnan Peruspalvelukuntayhtymän kotisairaalalle

TIIVISTELMÄ Katja Lahtinen, Minna-Mari Lehtisalo, Teemu Lehtisalo ja Henna Syrjälä Elämän loppuvaihe, Opas Pohjois-Satakunnan peruspalvelukuntayhtymän koti- sairaalalle 28 sivua ja 1 liite 2021, kevätlukukausi Diakonia-ammattikorkeakoulu Sosiaali- ja terveysalan ammattikorkeakoulututkinto Sairaanhoitaja (AMK) Sairaanhoitaja (AMK) Diakoninen hoitotyö Tämä opinnäytetyö toteutettiin toiminnallisena opinnäytetyönä, johon sisältyivät oppaan kehitystyö ja opinnäytetyön raportti. Tämän opinnäytetyön tarkoituksena oli laatia opas hoitajille kuolevan potilaan ja hänen läheistensä ohjaamisen ja kohtaamisen tueksi. Hoitajat voivat luovuttaa oppaan omaiselle ja potilaalle hoi- toprosessin tueksi. Oppaan tavoitteena on myös yhtenäistää ja tukea kuolevan potilaan sekä hänen omaistensa ohjausta. Opinnäytetyömme yhteistyötahona toimi Pohjois-Satakunnan peruspalvelukuntayhtymä, joka tunnetaan lyhenteellä PoSa. He esittivät toiveen oppaasta ja opas tehtiin heidän käyttöönsä. Opas koostuu erilaisista hoitotyön käsitteistä sekä auttamismenetelmistä kuolevan po- tilaan hoidossa. Oppaan tavoitteena on tuoda esiin ammatillisia ja hengellisiä toi- mintatapoja haastavan työn tueksi. Opas on PoSan työelämässä oleville hoitajille, erityisesti niille, jotka työskentele- vät kuolevien potilaiden kanssa. Etsimme tietoa kuolevan potilaan omaisten eri- laisista auttamismenetelmistä. Opinnäytetyössä ja oppaassa huomioitiin koko- naisvaltaisuus sekä hengellisyys potilaan sekä läheisten kohtaamisessa. Opinnäytetyön raportissa käsitellään kuolevan potilaan hoidossa esiintyviä käsit- teitä ja auttamismenetelmiä, jotka sisältyvät oppaaseen. Opinnäytetyö raportti si- sältää myös tietoa oppaan tuotteistamisprosessista, kuten oppaan ideoinnista, luonnostelusta, ammattilaisten palautteesta ja valmiista oppaasta. Valmis opas luovutettiin yhteistyötahon eli PoSan kotisairaalan käyttöön. Asiasanat: Opas, Omaisten tukeminen, Elämän loppuvaiheen hoito, Hoitolinjauk- set, Hoitosuunnitelma, Kuolevan potilaan hoito ABSTRACT Katja Lahtinen, Minna-Mari Lehtisalo, Teemu Lehtisalo and, Henna Syrjälä The final stages of life. A guide for the Hospital at Home of the Joint Municipal Authority for Basic Services in Northern Satakunta 28 pages and 1 appendices Spring 2021 Diaconia University of Applied Sciences Bachelor’s Degree Programme in Health Care Option in Diaconal Nursing Registered Nurse This thesis was implemented conducted as a functional thesis, including the development work of the guide and the report of the thesis report. The purpose of this functional thesis was to compile a guide for medical staff to support the challenging work with dying patients and their families. It was done in cooperation with the joint municipal authority for basic services in Northern Satakunta, Finland also known as PoSa, and the guide was given for their use, upon their request. The guide is meant to be given to clients to support them in the nursing process, when facing an illness or the death of a loved one. The guide also aims to unify and support the guidance of the dying patient and of his or her relatives. The guide consists of nursing concepts and ways of helping in hospice care. The goal was to highlight professional and spiritual courses of action to support nurses in their challenging work and help clients to understand the process of hospice end-of-life care and grief. The guide is for PoSa's in-work carers employed by PoSa, especially for those who work with dying patients. The information was searched on different methods of assisting the relatives of the Information on different methods of assisting the relatives of a dying patient were searched. The thesis and guide took into account the holistic approach and spirituality in meeting the patient and loved ones. The thesis report itself includes nursing concepts and helping methods of assisting which are used when treating a dying patient, but also information of the process of creating, such as ideation, outlining and received feedback. Finished guide was handed for the use of the cooperative entity, the home hospital of POSA. Keywords: Guide, End-of-life care, Hospice car

Psyykenlääkkeet ja farmakogeneettiset laboratoriotutkimukset - miten hyödynnät?

Vertaisarvioitu.• Monet masennus- ja psykoosilääkkeet metaboloituvat CYP2C19- ja CYP2D6-entsyymien välityksellä. • Näiden entsyymien aktiivisuudessa tunnetaan yleistä perinnöllistä vaihtelua, joka voi vaikuttaa psyykenlääkkeiden pitoisuuksiin ja tätä kautta tehoon ja haittavaikutusten riskiin. • Tässä katsauksessa kuvataan yleisesti käytettyjen psyykenlääkkeiden tieteelliseen näyttöön perustuvat farmakogeneettiset annossuositukset. • Farmakogeneettinen laboratoriotutkimus voi olla kustannusvaikuttava erityisesti masennuslääkityksen valinnassa.Peer reviewe