Epistemological beliefs of European physiotherapists – a multi-countrycross-cultural adaptation for the DEBQ and the CAEB questionnaires

[Abstract] This article assumes that epistemological beliefs of physiotherapists are an important determinant in improving the concept of evidence-based practice. Little research has been done on epistemological beliefs in physiotherapy. In order to measure the sophistication of epistemological beliefs in future research, two complementary questionnaires (DEBQ and CAEB) were cross-culturally adapted in nine different countries and seven languages in Europe. A standardized seven-step guideline was used to translate and culturally validate the questionnaires. The questionnaires were distributed in the respective countries, resulting in 1386 participants. The psychometric values were analysed in order to verify consistency and validity. Based on the validation process, the instruments are considered to be validly adapted for the countries involved. The uniformity in the adaptation process allows for future comparison of the countries

Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2.

COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles' inherent chemical combinability, we converted early micromolar hits into nanomolar viral inhibitors through simple multimerization. We also show how combining Bicycles against different epitopes into a single biparatopic agent allows Spike from diverse variants of concern (VoC) to be targeted (Alpha, Beta, Delta and Omicron). Finally, we demonstrate in both male hACE2-transgenic mice and Syrian golden hamsters that both multimerized and biparatopic Bicycles reduce viraemia and prevent host inflammation. These results introduce Bicycles as a potential antiviral modality to tackle new and rapidly evolving viruses

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

W kierunku poprawy jakości staży w medycynie i zawodach pokrewnych związanych ze służbą zdrowia

Introduction: One of the important elements influencing the well-being of society is a highly educated, professional staff of the entire therapeutic team. Physiotherapists play a significant role in this team, which is why the higher education system is expected to make efforts to develop optimal education programs, including the development of practical skills. The purpose of this article is to present the Healint4All project, whose mission is to facilitate international internships for students of physiotherapy and other medical professions, which will allow high-class professionals in the healthcare sector to enter the job market. Material and methods: A step-by-step process of creating a protocol for auditing places of clinical practice was prepared. Virtual, interactive teaching resources were developed to prepare auditors. A literature analysis, focus interviews in groups of academic teachers, practitioners, and students. A pilot study of the protocol in live environments was conducted. Results: Both potential auditees (medical institutions) and auditors (universities) positively assessed the newly created tool. The recommendations included paying attention to transparency, simplicity, and linguistic correctness in all language versions of the protocol. It was suggested that the protocol, containing everything useful, should not be too long and would not burden the user with time. Conclusions: In the opinion of students and experts who evaluated the Healint4All protocol, it will contribute to increasing the supply and quality of international placements offered by healthcare organizations throughout Europe, as well as simplifying the processes involved in organizing these for students, educational institutions, and healthcare organizations.Wstęp: Jednym z ważnych elementów wpływających na dobrostan społeczeństwa jest wysoko wykształcona, profesjonalna kadra całego zespołu terapeutycznego. Istotną rolę w tym zespole odgrywają fizjoterapeuci, dlatego też od systemu szkolnictwa wyższego oczekuje się podejmowania wysiłków na rzecz opracowania optymalnych programów kształcenia, w tym rozwoju umiejętności praktycznych. Celem artykułu jest przedstawienie projektu Healint4All, którego misją jest umożliwienie odbywania międzynarodowych staży studentom fizjoterapii i innych zawodów medycznych, co umożliwi wejście na rynek pracy wysokiej klasy profesjonalistom z sektora opieki zdrowotnej. Materiał i metody: Opracowano etapowy proces tworzenia protokołu audytu miejsc praktyki klinicznej. Aby przygotować audytorów, opracowano wirtualne, interaktywne zasoby dydaktyczne. Przeprowadzono analizę literatury, wywiady fokusowe w grupach nauczycieli akademickich, praktyków i studentów a także pilotażowe badanie protokołu w środowiskach potencjalnych beneficjentów. Wyniki: Zarówno potencjalni audytowani (instytucje medyczne), jak i audytorzy (uczelnie wyższe) pozytywnie ocenili nowo utworzone narzędzie. Zalecenia obejmowały zwrócenie uwagi na przejrzystość, prostotę i poprawność językową we wszystkich wersjach językowych protokołu. Zasugerowano, aby protokół, zawierający wszystko, co przydatne, nie był zbyt długi i nie obciążał użytkownika długim czasem potrzebnym na jego wypełnienie. Wnioski: W opinii studentów i ekspertów, którzy oceniali protokół Healint4All, przyczyni się on do zwiększenia podaży i jakości staży międzynarodowych oferowanych przez organizacje opieki zdrowotnej w całej Europie, a także pozwoli na uproszczenie procesów związanych z organizacją staży dla studentów, instytucji edukacyjnych i organizacje opieki zdrowotnej

Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2.

Acknowledgements: This work was supported by the MRC (UK; U105181010), a Wellcome Trust Investigator Award (223054/Z/21/Z), a Wellcome Trust Collaborator Award (214344/A/18/Z) and Innovate-UK (UKRI Ideas to Address COVID-19 – Innovate UK Article 25 funding strand). AO and JPS acknowledge funding from EPSRC, Unitaid, Wellcome Trust and MRC for funding which supported development of preclinical models for SARS-CoV-2 infection. We would like to thank Viroclinics Xplore for in vivo studies, Evotec for contract research services, Rachel Dods and Gustavo Arruda Bezerra for structural analysis, Radu Aricescu for design of lentiviral S protein expression systems, Andrew Carter for cloning of S-pseudotyped vectors, Dean Clift for Incucyte analysis, Tyler Rhinesmith and Jakub Laptuk for cell culture and assay support and the Bicycle team and James lab for general scientific support.COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles' inherent chemical combinability, we converted early micromolar hits into nanomolar viral inhibitors through simple multimerization. We also show how combining Bicycles against different epitopes into a single biparatopic agent allows Spike from diverse variants of concern (VoC) to be targeted (Alpha, Beta, Delta and Omicron). Finally, we demonstrate in both male hACE2-transgenic mice and Syrian golden hamsters that both multimerized and biparatopic Bicycles reduce viraemia and prevent host inflammation. These results introduce Bicycles as a potential antiviral modality to tackle new and rapidly evolving viruses

Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2.

COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles' inherent chemical combinability, we converted early micromolar hits into nanomolar viral inhibitors through simple multimerization. We also show how combining Bicycles against different epitopes into a single biparatopic agent allows Spike from diverse variants of concern (VoC) to be targeted (Alpha, Beta, Delta and Omicron). Finally, we demonstrate in both male hACE2-transgenic mice and Syrian golden hamsters that both multimerized and biparatopic Bicycles reduce viraemia and prevent host inflammation. These results introduce Bicycles as a potential antiviral modality to tackle new and rapidly evolving viruses