Potilasjärjestöjen vaikuttamismahdollisuudet Euroopan unionissa: Tarkastelussa intressien edustaminen harvinaisia sairauksia koskevassa politiikassa

Yhteiskunnallisten ongelmien ratkaisemiseen tarvitaan kansalaisia. Kansalaisten kokemusten ja asiantuntijuuden avulla voidaan ymmärtää ongelma. Toisaalta kansalaisten on myös hyväksyttävä muutokset. Näin ollen tarvitaan osallistavaa hallintoa ja työskentelyä ihmisten kautta. Ongelmanratkaisun tulisi tapahtua alhaalta ylös siten, että kansalaisten mielipide kuullaan. Terveydenhuollossa potilas- ja omaisjärjestöjä tarvitaan palvelujen kehittämiseen. Euroopan unioni on kiinnittänyt huomiota niin kansalaisten osallistumismahdollisuuksien parantamiseen yleisesti kuin myös erityisesti potilaiden mahdollisuuksiin vaikuttaa päätöksiin. Kansalaisten osallistumisesta päätöksentekoon on haettu ratkaisua Euroopan unionin demokratiavajeeseen, jonka pääasiallisena syynä pidetään heikkoa parlamenttia. Merkittävä työkalu unionille huomioida kansalaisten mielipiteet on komission järjestämät konsultaatiot, joissa asiasta kiinnostuneilla on mahdollisuus ilmaista näkemyksensä. Euroopan unionissa toimii myös suuri joukko intressien edustajia kuten järjestöjä, jotka toiminnallaan pyrkivät vaikuttamaan päätöksentekoon. Tässä tutkimuksessa tarkastellaan, miten harvinaisia sairauksia edustavat potilasjärjestöt pystyvät vaikuttamaan Euroopan unionin päätöksentekoon. Tutkimuksen teoreettinen viitekehys rakentuu pirullisia ongelmia ja intressien edustamista Euroopan unionissa käsitteleviin teorioihin. Pirulliset ongelmat ovat ongelmia, joita on vaikea tunnistaa, analysoida ja ratkaista, joten tarvitaan sidosryhmien osallistumista. Harvinaisia sairauksia koskeva politiikka on pirullinen ongelma, sillä siihen liittyy useita erilaisia tarpeita ja se esiintyy muuttuvassa toimintaympäristössä. Nämä seikat tekevät niin ongelman kuin ratkaisun määrittämisestä vaikeaa. Euroopan unionissa toimivilla intressien edustajilla on käytössään erilaisia vaikuttamiskeinoja. Unionin toimielimet tarvitsevat intressien edustajilla olevaa tietoa. Tiedon tarjoamisessa toimijat voivat hyödyntää niin julkista toimintakenttää kuin henkilökohtaisia suhteita päätöksentekijöihin. Pienemmillä resursseilla toimivilla on kuitenkin muita heikommat mahdollisuudet hyödyntää kaikkia vaikutuskeinoja. Tutkimuksen empiirinen osuus perustuu potilasjärjestöjen komissiolle toimittamien konsultaatiovastausten, Eurooppa-tasoisten potilasjärjestöjen Internet-sivuillaan julkaiseman materiaalin sekä kuuden kansallisen ja Eurooppa-tasoisen potilasjärjestön edustajan haastattelun ja kahden edellä mainittujen järjestöjen edustajien kanssa käytyjen sähköpostikeskustelujen analysointiin. Tutkimuksen tulokset osoittavat, että järjestöt kaipaavat Euroopan unionilta toimia usealla osa-alueella harvinaisten sairauksien potilaiden tilanteen parantamiseksi. Järjestöillä on monipuolista intressien edustamistoimintaa. Erityisesti Eurooppa-tasoiset järjestöt hyödyntävät sekä julkisen toimintakentän kautta tapahtuvaa vaikuttamista että kontakteja päätöksentekijöihin. Kansallisten potilasjärjestöjen osalta puolestaan vaikuttaminen perustuu monilta osin kattojärjestöjen kautta vaikuttamiseen. Järjestöt kokevat, että niitä on ainakin jossain määrin kuunneltu. Riskejä kuulluksi tulemisessa on kuitenkin useita liittyen erityisesti järjestöjen ja niiden intressien pienuuteen. Järjestöillä ei välttämättä ole riittäviä resursseja intressien edustamiseen. Lisäksi niiden ajama asia ei välttämättä saavuta suurta kiinnostusta, sillä se koskettaa niin pientä joukkoa.fi=Opinnäytetyö kokotekstinä PDF-muodossa.|en=Thesis fulltext in PDF format.|sv=Lärdomsprov tillgängligt som fulltext i PDF-format

Occupational diseases in Finland in 2012 :New cases of recognized and suspected occupational diseases

This publication presents a statistical summary of recognized and suspected occupational diseases in Finland. The first part of the publication is a review, which aims to give an overall picture of the incidence of occupational diseases in 2012, and of he main trends in recent years. The second part conists of statistical tables, which describe in greater detail the occurrence of occupational diseases in Finland in 2012

Työperäisten sairauksien rekisteriin kirjatut uudet tapaukset.

Työterveyslaitoksen Työperäisten sairauksien rekisteriin (TPSR) kirjattiin vuodelta 2013 yhteensä 4 602 ammattitautia tai ammattitautiepäilyä eli 18,7 tapausta 10 000 työllistä työntekijää kohden. Vahvistettuja ammattitauteja oli 1 811 eli 7,4 10 000 työllistä työntekijää kohden. Viime vuosien lukumäärien lasku näyttää nyt pysähtyneen. Naisten tapausten osuus oli 37 % eli sama kuin vuonna 2012 (37 %)

Predisposal conditioning, treatment, and performance assessment of radioactive waste streams

Before the final disposal of radioactive wastes, various processes can be implemented to optimise the waste form. This can include different chemical and physical treatments, such as thermal treatment for waste reduction, waste conditioning for homogenisation and waste immobilisation for stabilisation prior to packaging and interim storage. Ensuring the durability and safety of the waste matrices and packages through performance and condition assessment is important for waste owners, waste management organisations, regulators and wider stakeholder communities. Technical achievements and lessons learned from the THERAMIN and PREDIS projects focused on low- and intermediate-level waste handling is shared here. The recently completed project on Thermal Treatment for Radioactive Waste Minimization and Hazard Reduction (THERAMIN) made advances in demonstrating the feasibility of different thermal treatment techniques to reduce volume and immobilise different streams of radioactive waste (LILW) prior to disposal. The Pre-Disposal Management of Radioactive Waste (PREDIS) project addresses innovations in the treatment of metallic materials, liquid organic waste and solid organic waste, which can result from nuclear power plant operation, decommissioning and other industrial processes. The project also addresses digitalisation solutions for improved safety and efficiency in handling and assessing cemented-waste packages in extended interim surface storage

Single cell characterization of B-lymphoid differentiation and leukemic cell states during chemotherapy in ETV6-RUNX1-positive pediatric leukemia identifies drug-targetable transcription factor activities

Background Tight regulatory loops orchestrate commitment to B cell fate within bone marrow. Genetic lesions in this gene regulatory network underlie the emergence of the most common childhood cancer, acute lymphoblastic leukemia (ALL). The initial genetic hits, including the common translocation that fuses ETV6 and RUNX1 genes, lead to arrested cell differentiation. Here, we aimed to characterize transcription factor activities along the B-lineage differentiation trajectory as a reference to characterize the aberrant cell states present in leukemic bone marrow, and to identify those transcription factors that maintain cancer-specific cell states for more precise therapeutic intervention. Methods We compared normal B-lineage differentiation and in vivo leukemic cell states using single cell RNA-sequencing (scRNA-seq) and several complementary genomics profiles. Based on statistical tools for scRNA-seq, we benchmarked a workflow to resolve transcription factor activities and gene expression distribution changes in healthy bone marrow lymphoid cell states. We compared these to ALL bone marrow at diagnosis and in vivo during chemotherapy, focusing on leukemias carrying the ETV6-RUNX1 fusion. Results We show that lymphoid cell transcription factor activities uncovered from bone marrow scRNA-seq have high correspondence with independent ATAC- and ChIP-seq data. Using this comprehensive reference for regulatory factors coordinating B-lineage differentiation, our analysis of ETV6-RUNX1-positive ALL cases revealed elevated activity of multiple ETS-transcription factors in leukemic cells states, including the leukemia genome-wide association study hit ELK3. The accompanying gene expression changes associated with natural killer cell inactivation and depletion in the leukemic immune microenvironment. Moreover, our results suggest that the abundance of G1 cell cycle state at diagnosis and lack of differentiation-associated regulatory network changes during induction chemotherapy represent features of chemoresistance. To target the leukemic regulatory program and thereby overcome treatment resistance, we show that inhibition of ETS-transcription factors reduced cell viability and resolved pathways contributing to this using scRNA-seq. Conclusions Our data provide a detailed picture of the transcription factor activities characterizing both normal B-lineage differentiation and those acquired in leukemic bone marrow and provide a rational basis for new treatment strategies targeting the immune microenvironment and the active regulatory network in leukemia

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie