Generation and Characterization of iPS Cells Derived from APECED Patients for Gene Correction

APECED (Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal-Dystrophy) is a severe and incurable multiorgan autoimmune disease caused by mutations in the AIRE (autoimmune regulator) gene. Without functional AIRE, the development of central and peripheral immune tolerance is severely impaired allowing the accumulation of autoreactive immune cells in the periphery. This leads to multiple endocrine and non-endocrine autoimmune disorders and mucocutaneous candidiasis in APECED patients. Recent studies have suggested that AIRE also has novel functions in stem cells and contributes to the regulatory network of pluripotency. In preparation of therapeutic gene correction, we generated and assessed patient blood cell-derived iPSCs, potentially suitable for cell therapy in APECED. Here, we describe APECED-patient derived iPSCs's properties, expression of AIRE as well as classical stem cell markers by qPCR and immunocytochemistry. We further generated self-aggregated EBs of the iPSCs. We show that APECED patient-derived iPSCs and EBs do not have any major proliferative or apoptotic defects and that they express all the classical pluripotency markers similarly to healthy person iPSCs. The results suggest that the common AIRE R257X truncation mutation does not affect stem cell properties and that APECED iPSCs can be propagated in vitro and used for subsequent gene-correction. This first study on APECED patient-derived iPSCs validates their pluripotency and confirms their ability for differentiation and potential therapeutic use.Peer reviewe

Asiakkaan kokemuksia fysioterapeutin suoravastaanotosta selkäkipujen varhaisvaiheessa: Retrospektiivinen kuvaileva kyselytutkimus

Tutkimuksen tarkoituksena oli selvittää alaselkäkipuisten asiakkaiden kokemuksia käynnistään terveyskeskuksessa fysioterapeutin suoravastaanotolla. Tutkimus on retrospektiivinen, kuvaileva kyselytutkimus, joka toteutettiin strukturoidulla kyselylomakkeella kolme kuukautta fysioterapeutin vastaanotolla käynnin jälkeen. Lomakkeella selvitettiin selkäkivun lievittymisestä, ohjattujen harjoitteiden toteutumisesta, kivun uusiutumisesta, asiakkaan käsityksistä uusiutumisen syistä, kipuun liittyvästä pelosta, uudelleen hakeutumisesta lääkärin tai fysioterapeutin vastaanotolle ja työssäkäyvien sairauspoissaoloista. Lähetettyyn 150 kyselyyn vastasi 80 henkilöä (53 %), jotka jakaantuivat kolmeen ryhmään: 1. eläkeläiset (n = 26), 2. työttömät (n = 15) ja 3. työssä olevat/opiskelijat (n = 39). Aineisto analysoitiin SPSS-tilasto-ohjelmalla ja avointen kysymysten vastaukset litteroitiin ja luokiteltiin yhtäläisyyksien mukaan. Tulokset osoittivat, että 80–82 prosenttia asiakkaista kaikissa ryhmissä koki hyötyvänsä fysioterapeutilla käynnistään paljon tai kohtalaisesti. Kolmen kuukauden aikana selkäkivun uusiutuminen oli vähäisintä työssä olevat/opiskelijat -ryhmässä (5 %) ja suurinta eläkeläisten ryhmässä (30 %). Saman selkäongelman vuoksi vain 10 prosenttia vastanneista hakeutui uudelleen fysioterapeutille tai lääkärille. Työssä olevien ja opiskelijoiden ryhmässä ainoastaan yksi henkilö ilmoitti olevansa kyselyhetkellä sairauslomalla. Tutkimuksen tulokset viittaavat siihen, että fysioterapeutin suoravastaanotolla käyneet asiakkaat ovat tyytyväisiä toimintaan ja ovat kokeneet saaneensa apua selkäkipuunsa. Yhteiskunnallisen kustannus-hyöty ajattelun mukaan vähäiset uusintakäynnit fysioterapeutin tai lääkärin vastaanotolla, sekä alhaiset sairauspoissaolot vaikuttavat merkittäviltä. Jatkossa tarvitaan korkeatasoisia, pidemmällä seuranta-ajalla toteutettuja satunnaistettuja tutkimuksia kustannusanalyyseineen fysioterapian varhaisesta toteuttamisesta. Abstract Patients’ experiences of their visit to direct access physiotherapists in the early phase of low back pain: A retrospective descriptive survey The purpose of the study was to investigate the experiences of low back pain patients regarding their visit to direct access physiotherapists at a health center. The study is a retrospective descriptive survey conducted in a structured questionnaire three months after a visit to a physiotherapist. The questionnaire included questions, in particular, information on the relief of back pain, the management of the instructed exercises, the recurrence of back pain, patients’ perceptions of the causes of pain, the fear of pain, reasons for a repeat visit to a doctor or physiotherapist, and eventual absences due to sickness. The questionnaire was sent to 150 people who were picked up from the health care centers. Eighty (53%) low back pain patients responded. They were divided into three groups: retired people (n=26); unemployed people (n=15); and students and employed people (n=39). The data were analyzed using SPSS statistical software. The open answers were transcribed and the similarities of the answers were combined. The results showed that 80-82% of patients in all groups experienced the benefits from their visit to a physiotherapist as being great or moderate. During the three months after their visit, the recurrence of back pain was at its lowest among students and employed people (5%) and the highest among retired people (30%). Only 10% of the respondents made a repeat visit to a physiotherapist or doctor for the same back problem. Only one person in the students and employed people group was on sick leave. The results show that the patients viewed the early visit to a physiotherapist as useful in the treatment of back pain and in the prevention of new episodes. From a social cost–benefit point of view the results; the low need for repeat visits to the physiotherapist or to the doctor, and the low rates of absence due to sickness let us assume those to be notable. Additional high-quality research involving longer prospective randomized designs and economic impact analyses is required to further investigate the outcomes associated with early initiation of physiotherapy. Keywords: physiotherapy, direct access, low back pain, patients` experience

Characterization of iPS cells derived from APECED patients for gene correction

APECED (Autoimmuunipolyendokrinopatia-kandidiaasi-ektodermidystrofia) on vakava monielimellinen autoimmuunisairaus, joka johtuu mutaatioista AIRE (autoimmune regulator) -geenissä. APECED on yleisesti harvinainen oireyhtymä. Suomessa esiintyvyys on kuitenkin korkea (1:25 000) ja APECED kuuluu suomalaiseen tautiperintöön. Niin kutsuttu Finn-major -mutaatio R257X on myös maailmanlaajuisesti yleisin. Mutaation seurauksena AIRE-proteiini on typistynyt ja sen keskeiset toiminnot estyneet. Normaalisti immuunireaktiot kehon omia komponentteja vastaan ehkäistään moninaisilla sentraalisilla ja perifeerisillä immuunitoleranssimekanismeilla, joiden kehittymisessä AIRE on välttämätön. Toimivan AIRE:n puutos johtaa immuunitoleranssin menetykseen ja monenlaisiin autoimmuunioireisiin. Viimeaikaisten tutkimusten perusteella AIRE:n on esitetty toimivan myös kantasoluissa ja aktiivisesti osallistuvan pluripotenssiverkoston säätelyyn. Indusoituja pluripotentteja (eli monikykyisiä) kantasoluja (iPSC) hyödyntävän teknologian kehittyminen on avannut mahdollisuuksia täsmälääketieteessä ja geneettisten sairauksien, kuten APECED, hoidon kehittämisessä. Tutkimusryhmämme perimmäinen tavoite on selvittää, voisiko APECED:n parantaa autologisilla eli potilaalta itseltä kerätyillä, geenikorjatuilla solusiirteillä käyttäen iPSC-tekniikkaa. Tämä myöhempi terapeuttinen käyttö ja iPS -solujen erilaistaminen edellyttävät APECED-potilaista tuotettujen iPS-solujen yksityiskohtaista karakterisointia. Tutkielman tarkoituksena oli selvittää, aiheuttaako APECED-potilaista tuotettujen iPS-solujen R257X-mutaatio puutteita näiden solujen kantasoluominaisuuksiin. AIRE:n ja klassisten kantasolumerkkiaineiden ilmenemistä tutkittiin qPCR:lla sekä immunosytokemiallisin värjäyksin ja verrattiin terveen verrokin iPS-soluihin. AIRE R257X-mutaation mahdollista vaikutusta iPS-solujen spontaaniin erilaistumiseen selvitettiin käsittelemällä iPS-soluja spontaania erilaistumista aiheuttavalla dimetyylisulfoksidilla (DMSO). APECED-potilaista tuotettujen iPS-solujen kantasolu- ja varhaisen kehityksen ominaisuuksia kartoitettiin edelleen tuottamalla iPS-soluista alkiokantasolujen keräymiä (embryoid bodies, EB) ja viljelemällä näitä. Immunosytokemiallisilla värjäyksillä kartoitettiin, eroavatko APECED EB:t terveestä verrokista tuotetuista EB:istä kantasolu-, proliferaatio-, ja apoptoosiominaisuuksiensa suhteen. Vertaileva Ct-analyysi (ΔΔCt) osoitti, että APECED-iPS-solut ilmensivät kaikkia klassisia kantasolumerkkiaineita samalla tavoin kuin terveen verrokin iPS-solut. DMSO-käsittely vähensi kantasolumerkkiaineiden ilmentymistä sekä terveen verrokin että APECED-potilaiden iPS-soluissa. Immunovärjäystulokset olivat yhtenevät qPCR-tulosten kanssa. APECED-potilaista ja terveestä verrokista tuotettujen EB:iden välillä ei havaittu eroa yleisissä kasvuominaisuuksissa eikä kantasolu-, proliferaatio-, ja apoptoosimerkkiaineiden ilmentymisessä. Nämä tulokset osoittavat, että APECED-potilaiden R257X-mutaatio ei vaikuta iPS-solujen kantasoluominaisuuksiin, kuten kantasolumerkkiaineiden ilmentymiseen ja pesäkkeiden tai EB:iden muodostamiseen. Tulokset ovat vastakkaiset aiempiin hiirikokeisiin verrattuna havainnollistaen lajienvälistä eroa hiiren ja ihmisen välillä ja osoittavat humaaninäytteiden tarpeellisuuden eläinmalleilla saatujen tulosten täydentämiseksi. Tulosten perusteella APECED-potilaista tuotettujen iPS-solujen myöhemmälle erilaistamiselle ja terapeuttiselle käytölle ei vaikuttaisi olevan estettä. Lisätutkimuksia kuitenkin tarvitaan. Otoskoko oli tässä ensimmäisen vaiheen tutkimuksessa vielä pieni, mikä saattoi aiheuttaa tutkimusharhaa ja rajoitti tilastollista merkitsevyyttä. Tästä riippumatta, projektissa ensimmäistä kertaa toteutettu APECED-potilaista tuotettuja iPS-soluja karakterisointi antoi uutta tietoa AIRE-mutaation vaikutuksesta APECED-potilaista tuotettuihin iPS-soluihin.APECED (Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal-Dystrophy) is a severe, multiorgan autoimmune disease caused by mutations in the AIRE (autoimmune regulator) gene. APECED is a rare disease, however in Finland the frequency is significantly high (1:25 000) and APECED belongs to the ‘Finnish Disease Heritage’. The most common mutation worldwide is the so-called Finn-major mutation R257X that results in a truncation of the AIRE protein, which disrupts the indispensable functions of AIRE. Immune reactions towards body’s own components are typically prevented with various central and peripheral immune tolerance mechanisms. AIRE is essential for the proper development of central and peripheral tolerance and the absence of functional AIRE leads to a loss of immune tolerance and various autoimmune manifestations. Recent studies have suggested that AIRE also has functions in stem cells and actively contributes to the regulation network of pluripotency. Currently, the development of induced pluripotent stem cell (iPSC) technology has opened opportunities for precision medicine and for defining the cure for genetic diseases, such as APECED. The ultimate objective of our research group is to examine whether APECED could be cured via autologous, gene-corrected cell transplants with the use of induced pluripotent stem cells (iPSCs). As a requirement for such later therapeutic use and iPSC differentiation, the APECED patient-derived iPS cells needed to be characterized in detail. To assess, whether AIRE R257X mutation, present in APECED patients’ iPSCs, would cause defects in their stemness properties, the expression of AIRE and classical stem cell markers were examined with qPCR and immunocytochemistry and compared to healthy control iPSCs. The iPSC cells were also treated with spontaneous differentiation -inducing dimethyl sulfoxide (DMSO) to study, whether AIRE R257X mutation would affect the spontaneous differentiation of iPS cells. To further investigate the stemness and early developmental phase properties of APECED patient derived iPSCs, self-aggregated embryoid bodies (EBs) were generated and cultured. Immunocytochemistry was used to examine whether APECED EBs differ in stemness, proliferation or apoptosis from healthy individual’s EBs. The comparative Ct method (ΔΔCt) i.e. fold change revealed that APECED iPSC clones expressed all the classical stem cell markers similarly to healthy control iPSCs. DMSO treatment reduced the expression of stem cell markers in both healthy and APECED-derived iPSCs. The immunostaining results of iPSCs were consistent with the qPCR analysis. The overall growth properties as well as the immunocytochemical assays of stemness, proliferation and apoptosis markers did not show any significant difference between the APECED patient and healthy control derived EBs. Together the results indicate that the R257X mutation of the APECED patients does not affect stem cell properties such as stem cell marker expression and colony or the EB formation of the iPSCs. The results are contrary to previous studies in mice demonstrating the interspecific difference between mouse and human and denoting the importance of human samples completing the studies with animal models. As the APECED patient derived iPSCs did not exhibit any defects in their stemness properties, the later iPS differentiation and therapeutic use could be accomplished without hindrance. However, future work is still needed, as the small sample size in this preliminary test might introduce some biases to the results and hindered a relevant statistical analysis. Nevertheless, this thesis project was the first time APECED patient-derived iPSCs were characterized and has provided new information about the effect of AIRE mutation in APECED patient derived iPSCs

Selkäkipuasiakkaan fysioterapia suoravastaanottotoiminnassa : osaamista ja toteutusta

nonPeerReviewe

Physiotherapy for Low Back Pain Clients in Direct Access Practice: Competences and Implementations

Although previous research conducted in Finland and other countries has shown direct access in physiotherapy to be an important method in preventing the recurrence of low back pain (LBP), data are still lacking on the level of required competences of physiotherapists, suitable classifications of LBP and the implementation of direct access practice after a continuing education program for physiotherapists. The purpose of this study was to examine two areas: physiotherapists’ core competences in direct access practice for LBP clients in the early phase of pain using tissue-structural classification, and the implementation of this practice after a continuing education program with clients’ and physiotherapists’ experiences. Participants consisted of 34 physiotherapists and 80 low back pain clients from public health care organizations in southern Finland. Data were collected from questionnaires, interviews and by physiotherapists’ reports of their clients. Both quantitative and qualitative methods were used when analyzing the data. The results showed that the physiotherapists’ core competences of clinical reasoning and critical reflection were on a good level when used with tissue-structural classification and the hypothetico-deductive method in the assessment of low back pain clients. Physiotherapists made constantly accurate diagnostic subgroups for their LBP clients. The agreement percentage between the physiotherapists and two reviewers was 74% (kappa 0.63; 95% CI, 0.47 to 0.77). Physiotherapists also analyzed their clinical reasoning systematically from their clients’ history to their choice of clinical tests and conclusions. They were able to justify their manual skills and the adequacy of the LBP classification in use and suggest other alternatives for their performance. Most of the clients (80%) were satisfied with the implementation of direct access physiotherapy in the early visit to a physiotherapist and with the information and advice they received. Three months after the physiotherapy visit, repeat visits were on a low level and only one of the employed people was on sick leave. The physiotherapists reported having felt their work to be meaningful which, according to a qualitative analysis, was connected with client satisfaction, reasonable division of labor, cooperation with their co-workers and an increase in professional appreciation. This research demonstrates the benefits, as outlined by clients and physiotherapists, of direct access to physiotherapy in the early phase of LBP as well as the use of tissue-structural classification (nociceptive pain mechanism) as one of the classifications in this stage. Clinical reasoning and critical reflection competences in the assessment of clients were shown to be important during the subclassification of LBP clients and during the evaluation of physiotherapists’ own performance. Continuing learning of these competences should also be included in education programs. The results of this research can be utilized in physiotherapists’ direct access practice as well as when planning the content of the education program for the practice.Suomessa ja muualla tehdyt tutkimukset ovat osoittaneet fysioterapeuttien suoravastaanoton olevan yhtenä tärkeänä keinona selkäkivun pitkittymisen ehkäisyssä asiakastyytyväisyyden ja tehokkaan työnjaon näkökulmasta tarkasteltuna. Useista tutkimuksista ja hoitosuosituksista huolimatta edelleen puuttuu tietoa fysioterapeuteilta vaadittavasta osaamisesta suoravastaanotossa, sopivan selkäkipuluokituksen käytöstä ja suoravastaanoton implementoinnista käytäntöön asiakkaiden ja fysioterapeuttien kokemuksina. Tämän neljästä osajulkaisusta koostuvan tutkimuksen tarkoitus oli selvittää toteutetun lisäkoulutuksen jälkeen fysioterapeutin ydinosaamisen: kliinisen päättelyn ja kriittisen reflektoinnin siirtymistä käytäntöön sekä selkäkipuasiakkaiden ja fysioterapeuttien kokemuksia suoravastaanotosta. Tutkimukseen osallistui yhteensä 34 fysioterapeuttia ja 80 selkäkipuasiakasta julkisen terveydenhuollon organisaatioista Etelä-Suomesta. Kliinisen päättelyn tarkasteluun valittiin opetuksessa käytetty kudos- ja rakennetason alaselkäkipuluokitus ja hypoteettis-deduktiivinen päättelymalli. Tietoa kerättiin fysioterapeuttien asiakaskirjauksilla, haastatteluilla ja kirjallisilla kyselyillä. Tiedon käsittelyssä käytettiin sekä määrällisiä että laadullisia menetelmiä. Tulokset osoittivat, että fysioterapeutin kliininen päättely ja kriittinen reflektointi tapahtui hyvällä tasolla käyttäen selkäkivun kudos- ja rakennetason luokitusta ja hypoteettis-deduktiivista päättelymallia. Yksimielisyysprosentti selkävaivan alaluokista oli fysioterapeuttien ja kahden arvioijan välillä 74% ja Kappa=0,6 (95%CI; 0,47-77). Fysioterapeutit myös analysoivat kriittisesti ja reflektoivat valintojaan ja johtopäätöksiään. He arvioivat manuaalisia taitojaan kliinisten testien suorittamisessa ja käytetyn selkäkivun luokituksen sopivuutta asiakkaidensa tutkimisessa. Fysioterapeutit esittivät myös muita vaihtoehtoja toteutukseensa. Asiakkaat olivat tyytyväisiä fysioterapeuttien suoravastaanottoon. He kokivat saaneensa selityksen selkäkipunsa mahdollista syistä ja mitä he itse voisivat tehdä kivulleen ja sen uusiutumisen ehkäisemiseksi. Kolme kuukautta fysioterapeutilla käynnin jälkeen uusintakäynnit olivat vähäisiä ja vain yksi työssäkäyvistä oli sairauslomalla. Fysioterapeutit kertoivat työn mielekkyyden kokemuksesta, joka liittyi asiakkaiden tyytyväisyyteen, toimivaan työnjakoon ja yhteistyöhön toimipaikoissa sekä ammatillisen arvostuksen lisääntymiseen. Yhteenvetona voidaan todeta, että fysioterapeuttien suoravastaanotto on hyvä toimintatapa sekä selkäkipuasiakkaiden, että fysioterapeuttien näkökulmasta arvioituna. Selkäkivun varhaisvaiheessa kudos- ja rakennetason kipuluokitus on luotettavasti sovellettavissa käytäntöön fysioterapeuttien jatkokoulutuksen jälkeen. Fysioterapeuttien ydinosaamisessa kliininen päättely ja kriittinen reflektio ovat tärkeitä taitoja fysioterapeutin suoravastaanottotoiminnassa. Näiden taitojen jatkuva kehittäminen tulisi sisällyttää fysioterapeuttien jatko- ja lisäkoulutuksiin. Tutkimuksen tuloksia voidaan hyödyntää fysioterapeuttien suoravastaan-ottotoimintaan sekä tähän liittyvien lisäkoulutusten suunnitteluun

Clinical reasoning and critical reflection in physiotherapists' examinations of patients with low back pain in its early phase : a qualitative study from physiotherapists' point of view

Aim: The aim of this study was to deepen the current understanding of physiotherapists’ decision-making process and more specifically, to investigate their reflections on their clinical reasoning when examining low back pain patients. Method: Data were collected in interviews with six physiotherapists, were the stimulated recall method was used. Interviews were audio-recorded and transcribed and then analysed by content analysis. Results: Physiotherapists critically analysed and reflected their choices and decisions in clinical reasoning with patient’s symptoms, onset of pain, clinical test choices and results. They stopped to consider the adequacy of tests for drawing conclusions and their own manual skills as physiotherapists and also the classification of LBP being used. At critical reflection levels, based on King and Kitchener, physiotherapists’ judgements were at levels four to seven. Conclusions: The results showed that physiotherapists critically justified their clinical reasoning by systemically using a hypothetico-deductive reasoning model and reflected on their decisions in all phases of low back pain patient’s examination, from the history to the physiotherapy diagnosis and also on the classification of non-specific low back pain

Clinical reasoning and critical reflection in physiotherapists’ examinations of patients with low back pain in its early phase : a qualitative study from physiotherapists’ point of view

Aim: The aim of this study was to deepen the current understanding of physiotherapists’ decision-making process and more specifically, to investigate their reflections on their clinical reasoning when examining low back pain patients. Method: Data were collected in interviews with six physiotherapists, were the stimulated recall method was used. Interviews were audio-recorded and transcribed and then analysed by content analysis. Results: Physiotherapists critically analysed and reflected their choices and decisions in clinical reasoning with patient’s symptoms, onset of pain, clinical test choices and results. They stopped to consider the adequacy of tests for drawing conclusions and their own manual skills as physiotherapists and also the classification of LBP being used. At critical reflection levels, based on King and Kitchener, physiotherapists’ judgements were at levels four to seven. Conclusions: The results showed that physiotherapists critically justified their clinical reasoning by systemically using a hypothetico-deductive reasoning model and reflected on their decisions in all phases of low back pain patient’s examination, from the history to the physiotherapy diagnosis and also on the classification of non-specific low back pain.peerReviewe

Physiotherapists’ clinical reasoning in examination of clients with low back pain in direct access practice : a theory-driven qualitative content analysis

Aim The aim of this study was to gain deeper understanding of physiotherapists’ clinical reasoning in examination of clients with low back pain (LBP) in direct access (DA) practice. Method Data were collected through individual semi-structured thematic interviews of ten physiotherapists who described their clinical reasoning in one of their LBP clients in direct access practice. The interviews were recorded and transcribed verbatim and then examined using a theory-driven qualitative content analysis. Four clinical reasoning models, hypothetico-deductive, pattern recognition, narrative and systematic, were used as theoretical frameworks to analyse the descriptions of physiotherapists’ clinical reasoning in examination. Results In this study clinical reasoning in examination manifested as a process where physiotherapist proceeds from interview to clinical assessment and decision-making, simultaneously taking into consideration the DA setting and the specific role of the physiotherapist. As described by the physiotherapists working in DA practice clinical reasoning in examination presented by extracting facts from the interview in relation to symptoms or certain diagnosis, identifying and excluding red flags and identifying the factors that were important to consider in acute musculoskeletal pain in relation to individual client’s problem. Physiotherapists described having improved differential diagnostic skills, wider range of physical assessment techniques and more precise assessment. Based on the data, the physiotherapists presented to use either the hypothetico–deductive or the systematic clinical reasoning model when examining an LBP client in DA practice. Conclusions Clinical reasoning in examination with LBP clients in direct access practice started with anamnesis and proceeded by using either the hypothetico–deductive or the systematic clinical reasoning model.peerReviewe

Physiotherapists’ experiences of direct access for clients with musculoskeletal pain and dysfunction : a qualitative study

Aims: The aim of this study was to qualitatively analyse physiotherapists’ experiences and perspectives for delivering services directly, without prescription or referral, for clients with musculoskeletal pain or dysfunction. Methods: This was a qualitative study where data were collected from questionnaires given to 34 physiotherapists, 18 of them being in direct access for 6 years and 16 for 6 months. There were 15 structured questions and 3 open-ended ones. The answers were analysed with quantitative and qualitative methods. Results: The data analysis of the open-ended questions showed that physiotherapists had positive experiences of direct access. This practice brought meaningfulness, including increased self-respect, to physiotherapists’ work. Meaningfulness was interpreted as being constructed from a client perspective, a work perspective and a working community perspective. The self-respect was connected to experiencing the improvement of skills with their clients. Conclusions: In providing direct access practice, physiotherapists expressed a heightened sense of meaningfulness in their work, which was related to clients’ satisfaction with being in the right place at the right time. They experienced improved competence, which was connected with their self-respect and cooperation with other health care professionals. For future research, we propose to explore of larger samples of physiotherapists, clients and other key stakeholders