Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.Peer reviewe

Laatujärjestelmän viitekehyksen suunnittelu terveysteknologian teollisuudessa

Terveysteknologian teollisuudessa tuotteiden ja tuotannon suunnittelu, toteutus ja laadunhallinta ovat kansainvälisesti säännösteltyä, ohjeistettua ja valvottua toimintaa. Pienelle ja aloittelevalle yritykselle lakisääteiset vaatimukset ja asiakasvaatimukset täyttävän laatujärjestelmän rakentaminen on raskas ja vaativa kehitysvaihe, missä organisaation tulee olla kyvykäs tunnistamaan asiakkaiden tarpeet sekä lainsäädännön ja viranomaisohjeistuksen asettamat rajoitukset ja suositukset järjestelmällisellä ja suunnitelmallisella tavalla. Viranomaisvaatimukset huomioivan ja toteuttavan laatujärjestelmän avulla yritys varmistaa, että tuotteet täyttävät asiakasvaatimukset, projektit täyttävät asiakkaiden tarpeet ja koko organisaatio on sitoutunut toimittamaan regulatiiviset vaatimukset täyttäviä, turvallisia ja tehokkaita terveysteknologian tuotteita ja palveluja. Tutkimuksen tavoitteena oli selvittää mitä laatuvaatimuksia terveysteknologian tuotantoon automaatiojärjestelmiä myyvän toimittajan tulee ottaa huomioon uuden laatujärjestelmän suunnittelussa ja rakentamisessa. Laatujärjestelmän viitekehys suunniteltiin teorian pohjalta laaditun konstruktion avulla. Teorettisessa ja empiirisessä tutkimuksessa selvitettiin tuotteisiin kohdistuvia laatuvaatimuksia ja laatujärjestelmävaatimuksia viranomaisvaatimuksien, organisaation omien tarpeiden ja asiakasvaatimuksien näkökulmista. Tutkimus kokonaisuutena muodosti viitekehyksen, jonka avulla organisaatio kykenee sopeuttamaan, laajentamaan, uudistamaan ja parantamaan laatujärjestelmää myös tulevaisuudessa muuttuvien asiakastarpeiden ja liiketoiminnan kehitystarpeiden mukaan. GxP-periaatteiden mukaiset viranomaisvaatimukset eivät suoraan sido automaatiojärjestelmän toimittajaa, mutta ne sitovat asiakkaiden tuotantoprosesseja ja järjestelmiä. Asiakkaat kuitenkin odottavat, että automaatiojärjestelmän toimittaja noudattaa tai vähintään soveltaa viranomaisvaatimuksia laatujärjestelmässä, tuotteissa ja palveluissa. Tutkimuksen merkittävimpänä tuloksena laadittiin ehdotus laatujärjestelmästä Global Innovation Network Oy:n valmistamille automaatiojärjestelmille. Laatujärjestelmä suunniteltiin täyttämään ISO 9001-standardin vaatimukset sekä soveltamaan ISO 13485 -standardin vaatimuksia, FDA:n lääkinnällisille laitteille asettamia laatujärjestelmävaatimuksia ja teollisuuden luomaa ohjeistoa. Moderneja regulatiivisia laatusuunnittelun periaatteita noudattaen tuotteiden ja palvelujen toteutus sidottiin riskitasoon perustuvaan elinkaarimalliin, joten laatujärjestelmä sisältää tuotekohtaisten riskien arvioinnin ja hallinnan menetelmät.In health tech and life science industries, product and production design, implementation and quality control are covered by international laws, regulations, guidelines and monitored inspections. For a start-up business to fulfill statutory and client requirements is a strenuous and demanding phase, during which the organization should be capable to recognize the customer needs as well as the legislative limitations and recommendations systematically. By building-up a quality control and quality management system implementing laws, directives and regulatory requirements, an organization assures commitment in delivering projects which meet customer needs as well as products and services which are safe and effective to use, and fulfill customer requirements. The aim of the research was to clarify what quality requirements automated systems supplier for health tech and life science industries has to take into account while designing and implementing a new quality management system. The framework of the quality system was designed using constructive research process and a novel construct developed according to theoretical findings. Theoretic and empiric studies clarified product specific quality requirements and quality system requirements from the perspectives of regulatory and customer requirements as well as organization and business needs. The study itself formed a framework which supports the organization’s capability to utilize, adapt, expand and enhance the quality management system according to changing customer and business needs in the future. Regulatory requirements following global GxP principles do not confine the supplier, but they have that effect on the system owner’s production processes and automated systems. Customers however expect that the automated systems supplier implements or applies regulatory requirements in the supplier’s quality system as well as in the products and services. The most significant result of this study was a proposal of a new quality management system for automated systems manufactured by Global Innovation Network Oy. The quality system was designed to fulfill the requirements of ISO 9001 standard and to apply to requirements of ISO 13485 standard. Accordingly, proposed quality system applies to quality requirements of 21 CFR Part 820 for medical devices set by the FDA as well as regulatory guidelines and practical guidance created by authorities and industry representatives. The design, development and manufacturing phases of the products and services were bound to modern life cycle and validation models based on the Quality by Design principles and identification of risk levels. Hence, the quality system contains procedures and methods for a product specific risk assessment and control

Conservation genetics and phylogeography of endangered boreoarctic seashore plant species

Abstract The amount and distribution of genetic diversity are likely to affect the evolutionary potential of a species. When feasible and cost-effective policies for management and monitoring of endangered populations or species are planned, knowledge of the spatial genetic structure and the type of population dynamics is of great concern. In this thesis the genetic diversity and population structures of two endangered arctic plant species was examined on different geographical scales in Northern Europe. The species were Siberian primrose (Primula nutans) and pendant grass (Arctophila fulva), which both grow in a seashore habitat and have similar distribution patterns on the shores of the Arctic Ocean and the Bothnian Bay. The goal of the present study was to provide basic population genetic information for the study species using microsatellite and AFLP markers. Both markers were used for the first time in these species, and species-specific microsatellite markers were developed during the study. A further aim was to interlink the population genetic processes of the species into distribution patterns at the regional and population levels and to compile a synthesis of the impact of hierarchical spatiotemporal processes and autocorrelation in genetic variation at different levels. The studies of this thesis provided new information on the diversity and population structure of the endangered study species and new markers that are useful in future genetic studies of primrose species. The diversity of Siberian primrose was low, and there was no dispersal between the study regions. In pendant grass, a relatively high amount of variation was found considering the evident clonal reproduction and gene flow that was detected between populations connected by waterways. The results suggested that both clonal and sexual reproduction are important in this species. On a local scale, pendant grass populations had characteristics of “stepping stone” and classical metapopulation models. The results indicated that on a long time scale, both species will continue to decline without efficient management efforts. Most critical for the persistence of the species is the conservation of suitable habitats. Translocations could be considered in order to enhance the diversity of existing populations and establish new populations. By examining the present day structure of Siberian primrose, it was possible to make inferences regarding the colonisation history of the species in the North European area. The current distribution of Siberian primrose seemed to result from a vicariant process that took place after the last ice-age, when the species colonised the area. It spread first to the White Sea area, probably from the east, and subsequently colonised the Bothnian Bay and the Barents Sea in the west. The isostatic land uplift after the retreat of the Eurasian ice sheet uncovered large areas of land from the Baltic Sea basin that previously were under water. These geological changes resulted in the current disjunct distribution of Siberian primrose

Trade fairs to advance SME internationalisation: case China

Abstract This study is part of CHISU-project organised by the Department of Industrial Engineering and Management in the University of Oulu. The purpose of the project is to increase knowledge of Chinese business environment and facilitate Finnish SMEs to establish business in China. The relatively small size of Finnish domestic market restricts SME growth and makes internationalisation a considerable tool to discover new business opportunities. A route to internationalisation is determined by factors that are emphasized differently depending on the approach. The purpose of the study is to find out how trade fairs affect the factors in theory and practice, and how scarce resources should be allocated to gain an efficient trade fair outcome. Research is conducted as a case study with four Finnish SMEs. The companies joined a delegation that participated in a trade fair held in Chengdu, China. The practical arrangements concerning the fair were on the project's responsibility. The first research question is based on literature review, and aims to discover how trade fairs advance SME internationalisation in theory. The second research question analyses the results that the case companies gained from the fair activities. The empirical data is collected mainly by in-depth interviews in the case companies, and by direct observation and participant-observation. Finally, the third research question is a comparison between the theoretical and empirical parts and seeks solutions to improve the whole participation process, including preparation, trade fair and followup phases. Several results were achieved from the study. The major factors advancing internationalisation are listed and further examined in Chinese context. Correspondence between the factors and opportunities provided by trade fairs is compared. The most common theme among trade fairs, SME internationalisation and China is associated with networking. The empirical data indicates that the fair yielded plenty of significant information needed in internationalisation. However, the analysis of different participation phases revealed that trade fair outcome could have been remarkably improved with certain target actions such as creating clear guidelines for follow-up and increasing commitment of the participating companies in the preparation phase. The results need further studies to be verified, though, because of the used case study method

CHISU: Kiinan markkinoille suunnatun kansainvälistymisprosessin rakentaminen – loppuraportti

Tiivistelmä Tämä tutkimusraportti kuvaa vuosina 2009–2010 toteutetun CHISU projektin toiminnan tulokset. CHISU -hankkeen päätavoitteena oli kartoittaa kansainvälistymisprosessiin liittyvät kriittiset kehittämiskohdat ja etsiä ne askeleet joiden avulla Oulun alueen yritykset voivat kehittyä kansainvälistymisen polulla ja hyötyä Kiinan markkinoista. Hankkeen keskeisinä tehtävinä selvitettiin yritysten kansainvälistymisprosessin kriittiset kehittämiskohteet, analysoitiin Kiinan liiketoimintaympäristön tarjoamia liiketoimintamahdollisuuksia, kartoitettiin Kiinan markkinoille suuntautuvien pkyritysten tyypilliset kansainvälistymisprosessit ja analysoitiin kansainvälistymisen parhaita käytänteitä. Hankkeen aikana toteutettiin useita erillistä tutkimusosiota mukaan lukien tapaustutkimuksia, kyselytutkimuksia, ja markkinaselvityksiä. CHISU organisoi kolme yhteyksien luomiseen ja liiketoiminnan edistämiseen keskittyvää matkaa Kiinaan ja Taiwaniin, joihin osallistui useita Pohjois-Suomalaisia pk-yrityksiä. Näihin matkoihin liittyen kustannettiin Oulun seudun yrityselämää esittelevän käsikirjan Kiinan kielellä. CHISU organisoi lisäksi valmentavia kulttuuri ja kielikoulutuksia Oulun seudun yrityksille. Hanke kutsui koolle neljä kansallista seminaaria ja osallistui aihetta käsitteleviin seminaareihin. CHISU -hankkeen aikana kartoitettiin kansainvälistymisprosessiin liittyvät kriittiset kehittämiskohdat ja kuvattiin ne askeleet joiden avulla Oulun alueen yritykset voivat kehittyä kansainvälistymisen polulla ja hyötyä Kiinan markkinoista. Hankkeen tuloksena syntyi yli kaksikymmentä julkaisua pitäen sisällään refereoituja tieteellisiä artikkeleita ja konferenssijulkaisuja, tutkimusraportteja, diplomitöitä, kandidaatintöitä ja erikoistöitä. Hanke organisoi useita seminaareja ja koulutuksia. Kiinaan suuntautuvan liiketoiminnan edistämisen kannalta merkittävin tulos on hankkeen aikana luotu pk-yritysten kansainvälistymistä tukeva toimintamalli – keskeinen tulos on myös hankkeen aikana luotu yhteistyöverkosto ja siihen liittyvä EU-PIC yhteistyösopimus. Tuloksena syntynyttä toimintamallia ja yhteistyöverkostoa hyödyntäen on mahdollista saada aikaan kestäviä tuloksia myös jatkossa

Large registry-based analysis of genetic predisposition to tuberculosis identifies genetic risk factors at HLA

Tuberculosis is a significant public health concern resulting in the death of over 1 million individuals each year worldwide. While treatment options and vaccines exist, a substantial number of infections still remain untreated or are caused by treatment resistant strains. Therefore, it is important to identify mechanisms that contribute to risk and prognosis of tuberculosis as this may provide tools to understand disease mechanisms and provide novel treatment options for those with severe infection. Our goal was to identify genetic risk factors that contribute to the risk of tuberculosis and to understand biological mechanisms and causality behind the risk of tuberculosis. A total of 1895 individuals in the FinnGen study had International Classification of Diseases-based tuberculosis diagnosis. Genome-wide association study analysis identified genetic variants with statistically significant association with tuberculosis at the human leukocyte antigen (HLA) region (P < 5e-8). Fine mapping of the HLA association provided evidence for one protective haplotype tagged by HLA DQB1*05:01 (P = 1.82E-06, OR = 0.81 [CI 95% 0.74-0.88]), and predisposing alleles tagged by HLA DRB1*13:02 (P = 0.00011, OR = 1.35 [CI 95% 1.16-1.57]). Furthermore, genetic correlation analysis showed association with earlier reported risk factors including smoking (P < 0.05). Mendelian randomization supported smoking as a risk factor for tuberculosis (inverse-variance weighted P < 0.05, OR = 1.83 [CI 95% 1.15-2.93]) with no significant evidence of pleiotropy. Our findings indicate that specific HLA alleles associate with the risk of tuberculosis. In addition, lifestyle risk factors such as smoking contribute to the risk of developing tuberculosis.Peer reviewe