Nanosuspensions of a poorly soluble investigational molecule ODM-106 : Impact of milling bead diameter and stabilizer concentration

Aqueous solubility of a drug substance is an important attribute affecting oral bioavailability. Nanonization, particle size reduction to submicron level, is an elegant approach to improve drug solubility and dissolution by increasing the surface energy, which in turn necessitates the use of stabilizers. The purpose of this study was to develop a nanosuspension of a practically water-insoluble investigational molecule by nanomilling approach using wet media milling. A variety of polymeric and surface active excipients were tested for their wettability. A combination of hydroxypropyl methylcellulose and sodium lauryl sulfate (SLS) were selected as stabilizers on the bases of compatibility studies and efficient wettability behaviour in contact angle measurements (≈80˚). A factorial design set-up was used to study the effect of milling bead diameter and stabilizer concentration on the efficiency of particle size reduction. Nanonization outcome was different when milling beads of 0.5 mm and 1 mm diameter were used at different concentrations of the stabilizers, which demonstrated the complex nature of the whole system. Storage of the nanosuspensions under different temperature conditions resulted only in minor changes of the particle size fractions.Peer reviewe

Opioidiriippuvaisen persoonallisuushäiriö – katsaus diagnostiikan ja hoidon haasteisiin

Persoonallisuushäiriöt ovat yleisempiä opioidiriippuvaisten keskuudessa kuin yleisväestössä. Etenkin antisosiaalisen persoonallisuuden on todettu olevan opioidiriippuvaisissa yliedustettuna. Toisaalta on tärkeää ymmärtää päihdehäiriön aiheuttamaa riippuvuuskäyttäytymistä ja erottaa päihteiden suorat vaikutukset itsenäisistä psyykkisistä oireista. Järjestelmällinen ja asianmukainen psykiatristen oheissairauksien seulonta ja diagnostiikka on tähdellistä opioidiriippuvaisilla, jotta yksilön oikeus parhaaseen mahdolliseen hoitoon mahdollistuisi. Persoonallisuushäiriöihin liittyvä stigmatisaatio on hoitojärjestelmässämme edelleen ongelma, minkä vuoksi diagnoosin asettamisen on oltava harkittu ja hyvin perusteltu. Tässä artikkelissa käsitellään katsauksenomaisesti opioidiriippuvaisten persoonallisuushäiriöitä. Kirjallisuus antaa olennaista tietoa persoonallisuushäiriöiden ja päihderiippuvuusoireyhtymän yhteisistä kliinisistä piirteistä ja taustoista, sekä erotusdiagnostiikan ongelmakohdista ja hoidollisista haasteista

Hydroxychloroquine in the treatment of adult patients with Covid-19 infection in a primary care setting (LIBERTY): A structured summary of a study protocol for a randomised controlled trial

Objectives: The primary objective of this study is to evaluate the therapeutic potential of hydroxychloroquine (HCQ) in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo. The study hypothesis is that treatment with HCQ will reduce the risk of hospitalization because of Covid-19 infection, and the sample size estimate of the study is based on the need to test this hypothesis.The secondary objectives of the study are:to evaluate the safety and tolerability of HCQ in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo;to collect experience of the use of HCQ in the treatment of Covid-19 infection in outpatients, in order to be able to identify patient characteristics that predict specific treatment responses (favourable or unfavourable); this objective will also be addressed by post-hoc subgroup analysis of the study results and by meta-analysis of pooled patient data from other clinical trials of HCQ in outpatients; andto evaluate the impact of Covid-19 infection and its treatment on the mental health and well-being of the study participants.In addition, if the data allow, the study has the following exploratory objectives:to evaluate the extent and duration of SARS-CoV-2 viral shedding by PCR testing of nasopharyngeal swab samples in study subjects treated with HCQ, as compared to placebo;to evaluate the extent and time course of SARS-CoV-2 virus-specific antibody responses in serum of study subjects treated with HCQ, as compared to placebo;to evaluate other possible biomarker changes in blood in study subjects treated with HCQ, as compared to placebo;to explore the possible effects of genetic variation in drug metabolizing enzymes on HCQ-related outcomes in the study population;to explore the associations of HCQ-related outcome variables with other patient characteristics, e.g. HLA haplotypes, HCQ concentrations, demographic variables, disease history and concomitant medications.Trial design: This is a phase 2, placebo-controlled, double-blind, randomized, parallel-group treatment trial comparing HCQ with placebo in outpatients with Covid-19 infection. Participants will be randomized in a 1:1 ratio to the two treatment arms.Participants:Main inclusion criteria: 1. Males and females >40 years of age, or 18-40 years of age with one or both of the following: i. diabetes mellitus (type 1 or type 2); ii. BMI > 35 kg/m(2);2. Valid independent informed consent obtained;3. Symptoms typical of Covid-19 infection, according to criteria specified in the study protocol. The onset of symptoms must be within 5 days of enrolment;4. Positive SARS-CoV-2 PCR test result of a nasopharyngeal swab sample.Main exclusion criteria:1. Suspected severe or moderately severe pneumonia, presenting with any of the following: respiratory rate > 26 breaths/min; significant respiratory distress; or SpO(2) <= 94% on room air;2. Requiring treatment in the hospital, according to the treating physician's judgement;3. Any contraindication to treatment with HCQ;4. Pregnancy or lactation.The trial will be conducted at seven study sites in a primary public health care setting in the region of Satakunta, Finland.Intervention and comparator: Participants will be randomized to receive either HCQ capsules at 300 mg twice a day for one day and then 200 mg twice a day for 6 days, or placebo capsules for 7 days.Main outcomes: The primary endpoint of the study is the number of hospitalizations due to Covid-19 infection within four weeks of entry into the study.The secondary endpoints of the study include the following:duration and severity of Covid-19-related symptoms, as reported by daily self-assessments;number of Intensive Care Unit treatment episodes due to Covid-19 infection within four weeks of entry into the study;number of deaths due to Covid-19 infection within four weeks of entry into the study;number of treatment-related adverse events (AEs) and serious AEs (SAEs);all-cause hospitalizations and mortality within six months of entry into the study; andself-assessed symptoms of anxiety, as assessed with repeated administration of the Generalized Anxiety Disorder 7-item scale (GAD-7).The exploratory endpoints of the study include the following:extent and duration of SARS-CoV-2 viral shedding and virus-specific antibody responses in serum; andpossible other blood biomarker changes.Randomisation: Eligible study participants are randomly allocated into two treatment arms (1:1 ratio). The randomization list has been generated using Viedoc (TM) (Viedoc Technologies AB, Uppsala, Sweden) that is used as an electronic data capture system for this study.Blinding (masking): The participants and all study personnel remain blinded to the treatment allocation by having both IMPs packed in identical containers. Masking of the treatments was performed by re-formulation of the IMPs so that the HCQ capsules and the placebo capsules have identical appearance.Numbers to be randomised (sample size): 600 participants are to be randomised with 300 in each arm.Trial Status: Protocol version 2, dated 14 July 2020; recruitment is expected to start in December, 2020, and to be completed in June, 2021.Trial registration: EudraCT 2020-002038-33, registered 26 June 2020Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). The protocol has been redacted to conform with privacy regulations by deleting the names and contact information of individuals mentioned in the protocol but not listed as authors in this communication. In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol

Baltic herring as nutrition – Risk-benefit analysis

Tämän tutkimuksen tarkoitus oli selvittää, onko silakansyönnistä enemmän terveyshyötyä kuin -haittaa Suomessa ja millainen tilanne on eri ikäryhmissä. Aiemmat hyöty-riskiarviot ovat osoittaneet, että kalansyönti on yleensä terveellisempää kuin sen syömättä jättäminen. Tämä johtuu erityisesti kalan terveellisistä omega-3-rasvahapoista. Kuitenkin iso osa hyödyistä tulee aikuisille, joilla on suurentunut sydäntautiriski, ja osa mahdollisista haitoista tulee lapsille hammasvaurioiden ja muiden kehityshäiriöiden riskinä. Eviran toimeksiantona, yhteistyössä THL:n kanssa on vuoden 2014 aikana tehty hyöty-haitta-analyysi, jossa on tarkasteltu nimenomaan eri ikäryhmiä erikseen nykyisen kalankäytön mukaan. Tulokset perustuvat Taloustutkimuksen tekemän kyselyn aineistoon vuodelta 2013, jonka pohjalta on tehty varsinainen terveysvaikutusten tarkastelu. Tulokset ilmaistiin käyttäen haittapainotettuja elinvuosia (Disability Adjusted Life Year DALY) eli yksi DALY vastaa yhtä menetettyä tervettä elinvuotta. Hyödyllisistä ravintoaineista raportissa tarkasteltiin omega-3-rasvahappoja, eikosapentaeenihappoa (EPA) ja dokosaheksaeenihappoa (DHA) sekä D-vitamiinia. Silakassa esiintyvistä terveydelle haitallisista ympäristömyrkyistä tarkasteltiin dioksiineihin luettavia yhdisteitä, joihin kuuluvat polyklooratut dibentso-p-dioksiinit ja polyklooratut furaanit sekä dioksiininkaltaiset polyklooratut bifenyylit (PCB:t). Tulosten mukaan silakansyönti aiheuttaa Suomessa noin 11 (95 % luottamusväli LV 0 – 54) DALY kehityshäiriöistä (hammasvaurio) johtuvaa haittapainotettua elinvuotta (DALY), jotka kaikki kohdistuvat lapsiin äidin välityksellä raskausajan ja imetyksen kautta. Lisäksi silakansyönti aiheuttaa noin 12 (95 % LV 1.7 – 56) DALY dioksiinien aiheuttaman syöpäriskin kautta koko väestössä. Yli 50-vuotiailla naisilla ja varsinkin miehillä silakansyönnin terveyshyödyt ovat selkeästi suuremmat kuin terveyshaitat. Suurimmat terveyshyödyt saadaan sydäntautia ja sydänkuolleisuutta vähentävästä vaikutuksesta, noin -688 (95 % LV -2126 – -41) DALY/vuosi. Tulosten mukaan silakan syönti on vähentynyt väestössä niin paljon, että nykyiset suomalaiset kalan yleiset syöntisuositukset ovat riittävät suojaamaan väestöä dioksiinien ja dioksiinien kaltaisten yhdisteiden aiheuttamilta terveyshaitoilta. Hyöty-haitta-analyysissä tulisi kuitenkin tulevaisuudessa arvioida myös muiden rasvaisten kalojen keräämien ympäristömyrkkyjen kumulatiivisia terveysvaikutuksia ja yleisten syöntisuositusten riittävyyttä.Syftet med denna undersökning var att utreda om konsumtion av strömming från Östersjön ger mer hälsofördelar än hälsoskador i Finland och hurdant läget i olika ålderskategorier är. Tidigare nytta/riskvärderingar har visat att det i allmänhet är hälsosammare att äta fisk än att låta bli att göra det. Det beror särskilt på de hälsosamma omega-3-fettsyrorna i fisken. En stor del av fördelarna tillkommer ändå vuxna personer med förhöjd risk för hjärtsjukdomar och en stor del av skadorna tillkommer barn i form av risk för skador på tänderna och andra utvecklingsstörningar. På uppdrag från Evira och i samarbete med THL har under året 2014 gjorts en nytta/riskanalys, där man uttryckligen granskat olika ålderskategorier skilt för sig i ljuset av den nuvarande konsumtionen av strömming. Resultaten bygger på ett enkätmaterial som Taloustutkimus inhämtat år 2013. Utgående från detta material har sedan den egentliga granskningen av hälsoeffekterna gjorts. Resultaten angavs i form av funktionsjusterade levnadsår (Disability Adjusted Life Year DALY). För de nyttiga näringsämnenas del granskades i rapporten omega-3-fettsyrorna eikosapentaensyra (EPA) och dokosahexaensyra (DHA) och vitamin D. Av de hälsovådliga miljögifterna som förekommer i strömming granskades dioxiner, polyklorerade dibenzo-p-dioxinerna och plyklorerade dibenzofuranerna jämte dioxinliknande polyklorerade bifenylerna (PCB). Resultaten visar att konsumtion av strömming i Finland orsakar cirka 11 (95 % förtroende intervall , FI 0-54) funktionsjusterade levnadsår (DALY) som beror på utvecklingsstörningar (tandskada) och som alla via modern drabbar barn under graviditeten och amningen. Konsumtion av strömming medför också cirka 12 (95 %, FI 1,7-56) DALY via den cancerrisk som dioxinerna orsakar i hela befolkningen. Hos över 50 åriga kvinnor och framförallt män är fördelarna av att äta strömming klart större än hälsoskadorna. De största hälsofördelarna kommer av att risken för hjärtsjukdomar och dödligheten i hjärtsjukdomar minskar, cirka -688 (95 %, FI -2126 -41) DALY/år. Enligt resultaten konsumtion av strömming I Finland har sjunkit till en så låg nivå , att de nuvarande allmänna rekommenderade intagen av fisk konsumtion är tillräckliga för att skydda befolkningen mot hälsoskador av dioxiner eller dioxinlika föreningar. I risk-nytta-analys i framtiden bör ändå utvärderas totala hälsoeffekter av olika miljögifter i andra feta fiskarter ock kolla lämpligheten av rekommendationer av fisk konsumtion.The objective of this study was to determine whether the benefits of eating Baltic Sea herring exceed the risks in Finland, and what the situation is in different age groups. Previous risk-benefit analyses have shown that eating fish is in general healthier than not eating fish. This is particularly due to the healthy omega 3 fatty acids of fish. However, the benefits are largely enjoyed by adults with an elevated risk of heart disease, while children suffer the majority of the risks in the form of dental problems and other developmental disorders. In the riskbenefit analysis carried out to the order of Evira in collaboration with THL during 2014, different age groups were specifically considered separately in the light of current fish consumption. The results are based on the survey of the consumption of Baltic herring conducted by Taloustutkimus in 2013, which was used as the basis for the actual analysis of health effects. The results were expressed as Disability Adjusted Life Years (DALY). Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as well as vitamin D were analysed in the report as beneficial nutrients. As far as environmental toxins harmful to health are concerned, Baltic herring were analysed for compounds classified as dioxins, which include polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans, as well dioxin-like biphenyls (PCB). According to the results, in Finland eating herring causes ca. 11 (95% confidence interval, CI 0-54) Disability Adjusted Life Years (DALYs) resulting from developmental disorders (dental damage); these affect children via the mother during pregnancy and breastfeeding. In addition, eating herring causes a ca. 12 (95%, CI 1,7-56) DALY cancer risk due to dioxins in the entire population. The health benefits of eating herring clearly exceed risks to health for women and particularly men after the age of 50 years. The greatest health benefits result from the reduction in heart disease and heart-related fatality, ca. –688 (95%, CI -2126 -41) DALY/year. The results show that the consumption of Baltic herring has decreased in Finland to a low level and that the current common dietary advices on fish consumption are adequate to protect the population against the adverse health effects of dioxins and dioxin-like compounds. However, in risk benefit analysis in future it is important to estimate the total health effects of different environmental pollutants and of other fatty fish, and the sufficiency of dietary advices on fish consumption

Early Environment and Neurobehavioral Development Predict Adult Temperament Clusters

Peer reviewe

The Glanville fritillary genome retains ancient karyotype and reveals selective chromosomal fusions in Lepidoptera

201

Executing circular economy strategies in practice in Finland. Results and experiences from Circwaste project

A Europe-wide circular economy policy was launched in 2014 when the European Commission published the first strategic policy programme for circular economy. It was compiled to provide very comprehensive impacts and dimensions of sustainable development: sustainable growth and a climate neutral, resource efficient and competitive economy. The targets of a circular economy are that the value of products, materials and resources is maintained in the economy for as long as possible, economic growth is decoupled from resource use, generation of waste and environmental loads are minimised, and pressure on the Earth’s resources and biodiversity is minimised. The European Union is supporting the sustainability transition with research and development funding. In Finland, Circwaste – Towards Circular Economy is one of the biggest development projects accelerating the transition to a circular economy. During the period 2016–2020, the project has produced monitoring data on the development of circular economy and the sustainability of waste management, highlighted the circular economy concept, promoted stakeholder collaboration, supported strategic national processes, strengthened know-how and mainstreamed and concretised circular economy thinking. This interim report presents all the relevant results so far. It is crucial that data is produced from different angles on implementing the circular economy. More information is needed both to support decision making and on connections between and reflections on different factors. The key figures for Finland show quite clear coupling of the use of natural resources, waste amounts and economic growth. The circular material use rate is ca. 7%, which can be considered quite modest. Quantitative national targets for decreasing the use of natural resources are needed. Instead of country comparisons, the focus should be on trends in order to learn from the past and to identify the policy instruments needed to achieve the level aspired to. One of the key findings is the need for regional indicators and data for decisionmaking. The work done within Circwaste is the first effort towards a systematic monitoring scheme for monitoring circular economy regionally. The study showed that the production of regional waste data is challenging, that the estimated recycling rates have not increased adequately to reach the EU targets and that there could therefore be a need for municipallevel recycling targets. The transition to a circular economy also causes fundamental social changes in society. In the project, new indicators were developed for measuring social impacts: circular economy employment, education and employment for vulnerable groups, publicly shared resources, accessibility of recycling services and sustainable vehicle fuels. The first baseline data show advances towards the circular economy: the accessibility of waste management services has improved, the Finnish educational system has been able to respond quickly to the need for circular economy education, circular economy activities have potential for the employment of vulnerable groups and economic activities related to recycling, repair and reuse have grown. The regions and municipalities emerge as key actors in facilitating a socially just transition towards a circular economy. The study on innovative material processing technologies gathered data on technologies for elemental recycling, especially for plastic waste but also for making new fibres from textiles waste. Financial issues are key to the survival of these technologies and there is a need for governmental financial support. Public procurers can be considered key players in the circular economy, creating demand for more sustainable products and services. Implementing circular economy in municipalities requires commitment, financial planning, interaction with regional actors and inclusion of circular economy in financial rules. The construction sector is a major consumer of natural resources, but the municipalities can make construction more sustainable through public procurements and planning. As buyers, they can require the use of recycled raw materials and soils in construction projects. Obligations for ecological compensation and goals of no net loss of biodiversity would decrease the pressure on natural resources. To support municipalities in their work, a national organisation for providing municipal auditing, development, education and business support services could be established. Employing circular economy experts in each municipality to work as crossadministrative coordinators could enhance the transition. The project has created a lot of political, theoretical and practical content on the concept and field of circular economy. The next steps are to further develop and widen, as well as deepen, the results and to provide national support in searching for answers and solutions for decreasing the use of natural resources, achieving the MSW recycling targets and creating a more sustainable society

Temperament Clusters in a Normal Population : Implications for Health and Disease

Peer reviewe

Vähäliikenteisten teiden kuivatus, ominaispiirteet ja kunnostaminen : S14 Vähäliikenteisten teiden taloudellinen ylläpito -tutkimusohjelma

320097

Raportointi siirrettävästä potilaasta : kokemuksia ensihoitajien saamasta potilasraportoinnista akuuttivaiheen potilassiirtotilanteessa

Tämän opinnäytetyönä tehdyn tutkimuksen tarkoituksena oli selvittää Pohjois- Savon sairaanhoitopiirin alueella työskentelevien ensihoitajien kokemuksia, koskien potilasraportointia, joka tapahtuu potilaan siirtyessä sairauden akuutissa vaiheessa hoitolaitoksesta toiseen. Tutkimuksemme tavoitteena oli saada kattavasti tietoa ensihoitajien kokemuksista potilasraportoinnin eri osa-alueilta. Kyseessä oli kvantitatiivinen tutkimus ja se toteutettiin strukturoidun kyselylomakkeen avulla. Aikaisempien tutkimusten pohjalta selvitettiin, mitä osa-alueita potilasraportoinnissa tulisi huomioida sujuvan hoitoketjun toteutumiseksi ja näiden esille tulleiden tietojen pohjalta muodostuivat kyselylomakkeen kysymykset. Kysely tavoitti 256 ensihoitajaa ja vastauksia palautui 118 kappaletta, jolloin vastausprosentiksi saatiin 44,5 %, joka oli kattava otanta Pohjois-Savon sairaanhoitopiirin alueella työskentelevistä ensihoitajista. Tutkimuksemme tuloksista kävi ilmi, että ensihoitajien kokemusten mukaan ambulanssilla hoitolaitoksesta toiseen sairauden akuutissa vaiheessa siirrettävän potilaan kohdalla tapahtuvassa potilasraportoinnissa olisi kehittämisen varaa lähes kaikilla osa-alueilla. Tutkimustulokset luovutettiin Pohjois-Savon sairaanhoitopiirin ensihoitokeskuksen käyttöön. Tuloksia voidaan tulevaisuudessa hyödyntää terveydenhuollon yksiköiden ja ensihoidon välistä yhteistyötä kehitettäessä.This thesis, the purpose of which was to investigate the nurse-paramedics´ experiences at Northern Savo Health district about patient reporting with regard to when the patient moves in the acute phase of the disease from one care organization to another. The aim of our study was to obtain comprehensive information about the experiences of the emergency workers as to reporting in different areas. This was a quantitative study and it was carried out by means of a structured questionnaire. What came up as rele-vant things in the previous studies, we focused on the very aspects that should be taken into account in the smooth realization of the chain of care and those things that emerged from the data of our questionnaire. The survey reached 256 paramedics and 118 responses were returned so the response rate was 44.5%, which was a comprehensive sampling of Northern Savo hospital district nurses working in emergency cases. Our study results showed that based on the experience of the ambulance staff transferring the patient in the acute phase of the disease from one care establishment to another there is a lot of room for improvement in all areas with regard to patient reporting. The research was handed over to the Northern Savo hospital emergency care to use. The results can be utilized in the future by health care units and emergency care when developing cooperation