Combining biological therapies in patients with inflammatory bowel disease : a Finnish multi-centre study

Background and aims Therapy with two concomitant biologicals targeting different inflammatory pathways has emerged as a new therapy option for treatment refractory inflammatory bowel disease (IBD). Data on the efficacy and safety of dual biological therapy (DBT) are scarce and are investigated in this study. Materials and methods Data on all patients treated with a combination of two biologicals in four Finnish tertiary centres were collected and analysed. Remission was assessed by a physician on the basis of biomarkers, endoscopic evaluation and alleviation of symptoms. Results A total of 16 patients with 22 trials of DBT were included. Fifteen patients had Crohn's disease. The most common combination of DBT was adalimumab (ADA) and ustekinumab (USTE; 36%) with median follow-up of nine months (range 2-31). Altogether seven (32%) patients were in remission at the end of follow-up and in two trials response to DBT was assessed to be partial with the relief of patient symptoms. In a total of four trials DBT reduced the need for corticosteroids. The majority of patients achieving a response to DBT were treated with the combination of ADA and USTE (56%). At the end of follow-up all nine (41%) patients responding to DBT continued treatment. Infection complications occurred in three patients (19%). Conclusion DBT is a promising alternative treatment for refractory IBD, and half of our patients benefitted from it. More data on the efficacy and safety of DBT are needed especially in long-term follow up.Peer reviewe

Mortality and causes of death in different celiac disease phenotypes during long-term follow-up

Background: Celiac disease has been associated with increased mortality, but data on long-term mortality are scarce. Aims: To determine long-term mortality in celiac disease. Methods: The study cohort consisted of all celiac disease patients (n=1,392) diagnosed in Tampere University Hospital catchment area 1960 – 2000. Patients were categorized into subgroups based on demographic (age, gender, decade of diagnosis) and celiac disease characteristics (e.g., phenotype, severity of villous atrophy) collected from medical records. Overall and cause-specific mortality was compared to those of age-, sex-, and place of residence matched reference individuals (n=4,177) over time. Results: During the 41 years of follow-up (median 26.5 years), 376 celiac disease patients and 1,155 reference individuals died. All-cause mortality was not increased (hazard ratio (HR) 0.96, 95% confidence intervals (CI) 0.85–1.08). Mortality from lymphoproliferative diseases and diseases of the central nervous system was increased (HR 2.42, 95% CI 1.38–4.24 and HR 2.14, 95% CI 1.05–4.36 respectively) while the risk from alcohol related diseases was decreased (HR 0.31, 95% CI 0.09–1.00). Examination of various celiac disease phenotypes revealed no significant differences in mortality Conclusions: Overall mortality was not increased in any celiac disease phenotype during a very long-term follow-up.publishedVersionPeer reviewe

Combining biological therapies in patients with inflammatory bowel disease: a Finnish multi-centre study

Background and aims: Therapy with two concomitant biologicals targeting different inflammatory pathways has emerged as a new therapy option for treatment refractory inflammatory bowel disease (IBD). Data on the efficacy and safety of dual biological therapy (DBT) are scarce and are investigated in this study.Materials and methods: Data on all patients treated with a combination of two biologicals in four Finnish tertiary centres were collected and analysed. Remission was assessed by a physician on the basis of biomarkers, endoscopic evaluation and alleviation of symptoms.Results: A total of 16 patients with 22 trials of DBT were included. Fifteen patients had Crohn's disease. The most common combination of DBT was adalimumab (ADA) and ustekinumab (USTE; 36%) with median follow-up of nine months (range 2-31). Altogether seven (32%) patients were in remission at the end of follow-up and in two trials response to DBT was assessed to be partial with the relief of patient symptoms. In a total of four trials DBT reduced the need for corticosteroids. The majority of patients achieving a response to DBT were treated with the combination of ADA and USTE (56%). At the end of follow-up all nine (41%) patients responding to DBT continued treatment. Infection complications occurred in three patients (19%).Conclusion: DBT is a promising alternative treatment for refractory IBD, and half of our patients benefitted from it. More data on the efficacy and safety of DBT are needed especially in long-term follow up.</p

Authors' reply : The risk of renal comorbidities in celiac disease patients depends on the phenotype of celiac disease

acceptedVersionNon peer reviewe

Diagnostic yield of genetic testing in a multinational heterogeneous cohort of 2088 DCM patients

BackgroundFamilial dilated cardiomyopathy (DCM) causes heart failure and may lead to heart transplantation. DCM is typically a monogenic disorder with autosomal dominant inheritance. Currently disease-causing variants have been reported in over 60 genes that encode proteins in sarcomeres, nuclear lamina, desmosomes, cytoskeleton, and mitochondria. Over half of the patients undergoing comprehensive genetic testing are left without a molecular diagnosis even when patient selection follows strict DCM criteria.Methods and resultsThis study was a retrospective review of patients referred for genetic testing at Blueprint Genetics due to suspected inherited DCM. Next generation sequencing panels included 23–316 genes associated with cardiomyopathies and other monogenic cardiac diseases. Variants were considered diagnostic if classified as pathogenic (P) or likely pathogenic (LP). Of the 2,088 patients 514 (24.6%) obtained a molecular diagnosis; 534 LP/P variants were observed across 45 genes, 2.7% (14/514) had two diagnostic variants in dominant genes. Nine copy number variants were identified: two multigene and seven intragenic. Diagnostic variants were observed most often in TTN (45.3%), DSP (6.7%), LMNA (6.7%), and MYH7 (5.2%). Clinical characteristics independently associated with molecular diagnosis were: a lower age at diagnosis, family history of DCM, paroxysmal atrial fibrillation, absence of left bundle branch block, and the presence of an implantable cardioverter-defibrillator.ConclusionsPanel testing provides good diagnostic yield in patients with clinically suspected DCM. Causative variants were identified in 45 genes. In minority, two diagnostic variants were observed in dominant genes. Our results support the use of genetic panels in clinical settings in DCM patients with suspected genetic etiology

Ustekinumab for Crohn's disease: a nationwide real-life cohort study from Finland (FINUSTE)

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn's Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD. Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48 CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey-Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn's disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up. Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p = .0001) and SES-CD from 12 to 3 (p = .009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up. Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed

Ustekinumab for Crohn’s disease: a nationwide real-life cohort study from Finland (FINUSTE)

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn?s Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD.Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48?CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey?Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn?s disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up.Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p?=?.0001) and SES-CD from 12 to 3 (p?=?.009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up.Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed.Peer reviewe

Alaraajatrauman kuvantaminen : suunnitelma CareMe-simulaatiopelin sisällöstä

Tämä opinnäytetyö on osa Metropolia Ammattikorkeakoulun radiografian ja sädehoidon koulutusohjelman digitalisaatiohanketta. Työn tarkoituksena on luoda lonkan traumakuvantamista käsittelevä osuus CareMe- simulaatiopeliin. Opetuspelin tarkoitus on olla työväline, joka auttaa vapauttamaan opettajien resursseja ja oppilaitoksen tiloja opiskelijan voidessa kerrata aihetta itsenäisesti. Opiskelijalle oppimispeli on työväline, jonka kanssa opittavia asioita voi käydä läpi uudenlaisella tavalla. CareMe on monivalintapeli, joka lähtee liikkeelle potilastapauksen esittelyllä. Pelissä käydään läpi natiivikuvantamisen eri vaiheet ennen ja jälkeen varsinaisen kuvanoton. Pelaajan tulee poimia olennaiset tiedot lähetteestä, huomioida, mitä pyydetyssä kuvassa tulee näkyä ja huomioida fiktiivisen potilaan erityistarpeet. Teoriapohjaksi työssä käsitellään laajasti traumakuvantamista sekä erilaisia alaraajavammoja. Kuvantamisen lisäksi työ sisältää pienen katsauksen videopelien kautta oppimiseen ja oppimispelien taustaan. CareMe-pelin on kehittänyt start-up yritys Practigame Oy. Peliin on luoto erilaisia potilastapauksia, jotka on suunnattu lähinnä sairaan- ja ensihoitajaopiskelijoille. Röntgenhoitajaopiskelijoita varten on suunniteltu peliosuus keuhkokuvantamisesta, mutta varsinaiseen peliin sitä ei ole vielä tämän opinnäytetyön tekohetkenä viety. Seuraava askel olisi luoda suunnitelman pohjalta osuus varsinaiseen peliin ja luoda sinne ympäristö röntgenkuvausta varten. Tämän jälkeen peliin voitaisiin suunnitella lisää erilaisia röntgenkuvausta käsitteleviä osioita.Purpose of this thesis was to develop a patient scenario to the CareMe-simulation game.The scenario addresses x-ray imaging of a hip in a trauma situation. The learning game is intended to be a tool that frees up the teacher's resources and school facilities when students can practice independently what they have learned. It is also good for the students to recap with the new method. CareMe is multiple-choice based game. It starts with an introduction of the patient case. The game goes through different phases of x-ray imaging, before and after taking the actual image. The player needs to recognize the important information from the referral, notice what needs to be seen in the image that was asked and pay attention to patient’s special needs. As a theoretical basis a lot of information about traumatic imaging and different kind of lower body injuries were gathered. Theoretical basis also contains a small overview of the game based learning and the background of learning games. CareMe -game was developed by start-up company Practigame. The game contains different kinds of scenarios that are targeted mainly for nurse and paramedic students. There is no finished scenario for the radiographer students but one plan addressing the lung x-ray has been made. Next step would be to develop an actual scenario to the game based on this plan. Also environment of the x-ray imaging room needs to be created. After this countless more scenarios for the radiographer students can be developed

Muurit välillämme - Kuvaileva kirjallisuuskatsaus vanhemman vankeusrangaistuksen heijastumisesta lapsen hyvinvointiin

Vanhemman vankeusrangaistus koskettaa tänä päivänä Suomessa tuhansia alaikäisiä lapsia ja nuoria. Siitäkin huolimatta vankien lapset ovat edelleen melko näkymätön ja haavoittuva ryhmä. Vanhemman vankeusrangaistus merkitsee vääjäämättä lapselle jonkinlaista eroa vanhemmastaan. Vaikka lapsi ei ole tehnyt rikosta, hän voi silti kokea tulleensa rangaistuksi. Aiheen herkkyydestä ja ajankohtaisuudesta huolimatta kotimaista tieteellistä tutkimusta aiheeseen liittyen on tehty varsin vähän. Opinnäytetyön tarkoituksena oli lisätä omaa sekä alalla työskentelevien tietoutta ja ymmärrystä vanhemman vankeusrangaistuksen heijastumisesta lapsen hyvinvointiin. Lisäksi tutkimuksessa pyrittiin selvittämään, miten separaatio näyttäytyy vankeusrangaistuksen yhteydessä. Tutkimuksen taustoittamiseksi kuvataan vankeuteen liittyviä käytäntöjä sekä raameja, joiden puitteissa vangin yhteydenpito vankilan ulkopuolelle ja näin ollen lapseen on mahdollista. Teoreettinen viitekehys rakentuu lapsen hyvinvoinnin määrittelemisestä, perheen ja sen merkityksen tarkastelusta sekä lapsen ja vanhemman välisen eron heijastumisesta lapseen. Tutkimusmenetelmänä toimi kuvaileva kirjallisuuskatsaus ja tiedonhaku toteutettiin manuaalihaun lisäksi ProQuest Central- ja Cinahl -tietokantoja hyödyntäen. Tutkimusaineistoksi valikoitui 12 artikkelia ja ne analysoitiin sisällönanalyysin menetelmin teemoittelemalla. Tulosten mukaan vanhemman vankeusrangaistus ja sen aiheuttama lapsen ja vanhemman välinen separaatio näyttäytyi konkreettisesti niin arjen muutoksissa kuin lapsen ja vanhemman välisessä vuorovaikutuksessakin. Sen lisäksi vankeus heijastui lapsen elämään mm. sosiaalisina, psyykkisinä ja emotionaalisina vaikeuksina sekä käyttäytymis- ja koulunkäynnin ongelmina. Tulokset osoittivat, että mm. leimautuminen, katkenneet kiintymyssuhteet ja sosiaaliset ongelmat lisäsivät merkittävästi lasten riskiä epäsosiaaliseen käytökseen ja mielenterveysongelmiin

Leikki-ikäisen lapsen akuutin kivun lääkkeettömät kivunhoitomenetelmät

Opinnäytetyön tarkoituksena oli tuottaa tietoa lasten kivunhoidossa käytetyistä keinoista, joista voisi olla hyötyä sosiaali- ja terveysalan opiskelijoille sekä ammattilaisille hoidettaessa kipua. Aiheena oli lasten kivunhoito, joka oli tarkemmin rajattuna leikki-ikäisten lääkkeettömiin kivunhoitomenetelmiin akuutissa kivussa. Opinnäytetyö toteutettiin kuvailevana kirjallisuuskatsauksena, jonka toimeksiantajana toimi Lahden ammattikorkeakoulu. Kirjallisuuskatsauksen aineistona oli neljä tutkimusta lasten kivunhoidosta. Lasten kivunhoito on ollut puutteellista, joten opinnäytetyössä haluttiin selvittää keinoja, joita kivunhoidossa on hyödynnetty. Tuloksista selvisi, että keinoja käytettiin sekä psykologisista, että fysiologisista menetelmistä. Kuitenkin psykologisten menetelmiä oli hyödynnettynä enemmän ja monipuolisemmin. Lääkkeettömiä menetelmiä kivunhoidossa olisi mahdollista käyttää monipuolisemmin