Substrate promiscuity of Dicer toward precursors of the let-7 family and their 3'-end modifications.

The human let-7 miRNA family consists of thirteen members that play critical roles in many biological processes, including development timing and tumor suppression, and their levels are disrupted in several diseases. Dicer is the endoribonuclease responsible for processing the precursor miRNA (pre-miRNA) to yield the mature miRNA, and thereby plays a crucial role in controlling the cellular levels of let-7 miRNAs. It is well established that the sequence and structural features of pre-miRNA hairpins such as the 5'-phosphate, the apical loop, and the 2-nt 3'-overhang are important for the processing activity of Dicer. Exceptionally, nine precursors of the let-7 family (pre-let-7) contain a 1-nt 3'-overhang and get mono-uridylated in vivo, presumably to allow efficient processing by Dicer. Pre-let-7 are also oligo-uridylated in vivo to promote their degradation and likely prevent their efficient processing by Dicer. In this study, we systematically investigated the impact of sequence and structural features of all human let-7 pre-miRNAs, including their 3'-end modifications, on Dicer binding and processing. Through the combination of SHAPE structural probing, in vitro binding and kinetic studies using purified human Dicer, we show that despite structural discrepancies among pre-let-7 RNAs, Dicer exhibits remarkable promiscuity in binding and cleaving these substrates. Moreover, the 1- or 2-nt 3'-overhang, 3'-mono-uridylation, and 3'-oligo-uridylation of pre-let-7 substrates appear to have little effect on Dicer binding and cleavage rates. Thus, this study extends current knowledge regarding the broad substrate specificity of Dicer and provides novel insight regarding the effect of 3'-modifications on binding and cleavage by Dicer.

Production and use of rapid responses during the COVID-19 pandemic in Quebec (Canada): perspectives from evidence synthesis producers and decision makers.

BACKGROUND: The COVID-19 pandemic has required evidence to be made available more rapidly than usual, in order to meet the needs of decision makers in a timely manner. These exceptional circumstances have caused significant challenges for organizations and teams responsible for evidence synthesis. They had to adapt to provide rapid responses to support decision-making. This study aimed to document (1) the challenges and adaptations made to produce rapid responses during the pandemic, (2) their perceived usefulness, reported use and factors influencing their use and (3) the methodological adaptations made to produce rapid responses. METHODS: A qualitative study was conducted in 2021 with eight organizations in the health and social services system in Quebec (Canada), including three institutes with a provincial mandate. Data collection included focus groups (n = 9 groups in 8 organizations with 64 participants), interviews with decision makers (n = 12), and a document analysis of COVID-19 rapid responses (n = 128). A thematic analysis of qualitative data (objectives 1 and 2) and a descriptive analysis of documents (objective 3) were conducted. RESULTS: The results highlight the teams and organizations' agility to deal with the many challenges encountered during the pandemic (e.g., increased their workloads, adoption of new technological tools or work processes, improved collaboration, development of scientific monitoring, adaptation of evidence synthesis methodologies and products). The challenge of balancing rigor and speed was reported by teams and organizations. When available at the right time, rapid responses have been reported as a useful tool for informing or justifying decisions in a context of uncertainty. Several factors that may influence their use were identified (e.g., clearly identify needs, interactions with producers, perceived rigor and credibility, precise and feasible recommendations). Certain trends in the methodological approaches used to speed up the evidence synthesis process were identified. CONCLUSIONS: This study documented rapid responses producers' experiences during the COVID-19 pandemic in Quebec, and decision makers who requested, consulted, or used these products. Potential areas of improvements are identified such as reinforce coordination, improve communication loops, clarify guidelines or methodological benchmarks, and enhance utility of rapid response products for decision makers.

Preferences of patients with chronic low back pain about nonsurgical treatments: Results of a discrete choice experiment.

INTRODUCTION: This study aimed to assess patients' preferences of nonsurgical treatments for chronic low back pain (CLBP). METHOD: We conducted a discrete choice experiment (DCE) in Quebec, Canada, in 2018. Seven attributes were included: treatment modality, pain reduction, the onset of treatment efficacy, duration effectiveness, difficulties with daily activities, sleep problems, and knowledge of the patient's body and pain location. Treatment modalities were corticosteroid injections, supervised body-mind physical activities, supervised sports physical activities, physical manipulations, self-management courses, and psychotherapy. Utility levels were estimated using a logit model, a latent class model and a Bayesian hierarchical model. RESULTS: Analyses were conducted on 424 $424$ individuals. According to the Bayesian hierarchical model, the conditional relative importance weights of attributes were as follows: (1) treatment modality (34.79%), (2) pain reduction (18.73%), (3) difficulties with daily activities (11.71%), (4) duration effectiveness (10.06%), (5) sleep problems (10.05%), (6) onset of treatment efficacy (8.60%) and (7) knowledge of the patient's body and pain location (6.06%). According to the latent class model that found six classes of respondents with different behaviours (using Akaike and Bayesian criteria), the treatment modality was the most important attribute for all classes, except for class 4 for which pain reduction was the most important. In addition, classes 2 and 5 refused corticosteroid injections, while psychotherapy was preferred only in class 3. CONCLUSION: Given the preference heterogeneity found in the analysis, it is important that patient preferences are discussed and considered by the physicians. This will help to improve the patient care pathway in a context of a patient-centred model for a disease with growing prevalence. PATIENT OR PUBLIC CONTRIBUTION: A small group of patients was involved in the conception, design and interpretation of data. Participants in the DCE were all CLBP patients.

An integrative NMR-SAXS approach for structural determination of large RNAs defines the substrate-free state of a trans-cleaving Neurospora Varkud Satellite ribozyme.

The divide-and-conquer strategy is commonly used for protein structure determination, but its applications to high-resolution structure determination of RNAs have been limited. Here, we introduce an integrative approach based on the divide-and-conquer strategy that was undertaken to determine the solution structure of an RNA model system, the Neurospora VS ribozyme. NMR and SAXS studies were conducted on a minimal trans VS ribozyme as well as several isolated subdomains. A multi-step procedure was used for structure determination that first involved pairing refined NMR structures with SAXS data to obtain structural subensembles of the various subdomains. These subdomain structures were then assembled to build a large set of structural models of the ribozyme, which was subsequently filtered using SAXS data. The resulting NMR-SAXS structural ensemble shares several similarities with the reported crystal structures of the VS ribozyme. However, a local structural difference is observed that affects the global fold by shifting the relative orientation of the two three-way junctions. Thus, this finding highlights a global conformational change associated with substrate binding in the VS ribozyme that is likely critical for its enzymatic activity. Structural studies of other large RNAs should benefit from similar integrative approaches that allow conformational sampling of assembled fragments.

A multi-axial RNA joint with a large range of motion promotes sampling of an active ribozyme conformation.

Investigating the dynamics of structural elements in functional RNAs is important to better understand their mechanism and for engineering RNAs with novel functions. Previously, we performed rational engineering studies with the Varkud satellite (VS) ribozyme and switched its specificity toward non-natural hairpin substrates through modification of a critical kissing-loop interaction (KLI). We identified functional VS ribozyme variants with surrogate KLIs (ribosomal RNA L88/L22 and human immunodeficiency virus-1 TAR/TAR*), but they displayed ∼100-fold lower cleavage activity. Here, we characterized the dynamics of KLIs to correlate dynamic properties with function and improve the activity of designer ribozymes. Using temperature replica exchange molecular dynamics, we determined that the natural KLI in the VS ribozyme supports conformational sampling of its closed and active state, whereas the surrogate KLIs display more restricted motions. Based on in vitro selection, the cleavage activity of a VS ribozyme variant with the TAR/TAR* KLI could be markedly improved by partly destabilizing the KLI but increasing conformation sampling. We formulated a mechanistic model for substrate binding in which the KLI dynamics contribute to formation of the active site. Our model supports the modular nature of RNA in which subdomain structure and dynamics contribute to define the thermodynamics and kinetics relevant to RNA function.

Development of a checklist to guide equity considerations in health technology assessment.

OBJECTIVES: Health technology assessment (HTA) can impact health inequities by informing healthcare priority-setting decisions. This paper presents a novel checklist to guide HTA practitioners looking to include equity considerations in their work: the equity checklist for HTA (ECHTA). The list is pragmatically organized according to the generic HTA phases and can be consulted at each step. METHODS: A first set of items was based on the framework for equity in HTA developed by Culyer and Bombard. After rewording and reorganizing according to five HTA phases, they were complemented by elements emerging from a literature search. Consultations with method experts, decision makers, and stakeholders further refined the items. Further feedback was sought during a presentation of the tool at an international HTA conference. Lastly, the checklist was piloted through all five stages of an HTA. RESULTS: ECHTA proposes elements to be considered at each one of the five HTA phases: Scoping, Evaluation, Recommendations and Conclusions, Knowledge Translation and Implementation, and Reassessment. More than a simple checklist, the tool provides details and examples that guide the evaluators through an analysis in each phase. A pilot test is also presented, which demonstrates the ECHTA's usability and added value. CONCLUSIONS: ECHTA provides guidance for HTA evaluators wishing to ensure that their conclusions do not contribute to inequalities in health. Several points to build upon the current checklist will be addressed by a working group of experts, and further feedback is welcome from evaluators who have used the tool.

Integration of ethical considerations into HTA reports: an analysis of integration levels using a systematic review.

OBJECTIVE: To describe the type and level of ethical integration in published health technology assessment (HTA) reports and systematically identify the ethical approaches utilized. METHODS: A literature search was conducted with the Google™ search engine using the keyword "ethic" between 1 January 2015 and 20 August 2019. Only HTA assessment reports with a section on ethics were retained and classified according to their level of ethical integration: no ethical analysis, ethical issues highlighted, assessments according to legal or social norms, and assessments from a moral or axiological perspective-using a qualitative methodology to distinguish such integration. RESULTS: This review yielded 188 reports with a section identified as being on ethics, produced by seventeen HTA agencies in eleven countries. One hundred and thirty-six reports did not develop an ethical analysis, thirty-one highlighted ethical issues, seventeen conducted a norm-based ethical assessment using a descriptive approach grounded in social norms, and four developed an assessment grounded in a moral or axiological perspective. The bioethical "four-principles" framework was used, but mainly for presenting ethical issues and not as a moral framework. CONCLUSIONS: The majority of reports featuring a section on ethics mention ethical considerations without ethical analysis. Ethical issues are grouped with legal, social, and organizational issues and treated as contextual considerations that decision makers should be aware of. When reports present systematic norm-based ethical assessments from a descriptive perspective or ethical assessment based on a moral or axiological perspective, there is a tendency to ground these analyses in frameworks created for the purpose and reliant on a concept of ethics supporting them.

The Accuracy and Precision of Gait Spatio-Temporal Parameters Extracted from an Instrumented Sock during Treadmill and Overground Walking in Healthy Subjects and Patients with a Foot Impairment Secondary to Psoriatic Arthritis.

The objectives of this study were to assess the accuracy and precision of a system combining an IMU-instrumented sock and a validated algorithm for the estimation of the spatio-temporal parameters of gait. A total of 25 healthy participants (HP) and 21 patients with foot impairments secondary to psoriatic arthritis (PsA) performed treadmill walking at three different speeds and overground walking at a comfortable speed. HP performed the assessment over two sessions. The proposed system's estimations of cadence (CAD), gait cycle duration (GCD), gait speed (GS), and stride length (SL) obtained for treadmill walking were validated versus those estimated with a motion capture system. The system was also compared with a well-established multi-IMU-based system for treadmill and overground walking. The results showed a good agreement between the motion capture system and the IMU-instrumented sock in estimating the spatio-temporal parameters during the treadmill walking at normal and fast speeds for both HP and PsA participants. The accuracy of GS and SL obtained from the IMU-instrumented sock was better compared to the established multi-IMU-based system in both groups. The precision (inter-session reliability) of the gait parameter estimations obtained from the IMU-instrumented sock was good to excellent for overground walking and treadmill walking at fast speeds, but moderate-to-good for slow and normal treadmill walking. The proposed IMU-instrumented sock offers a novel form factor addressing the wearability issues of IMUs and could potentially be used to measure spatio-temporal parameters under clinical conditions and free-living conditions.

Implementing a fracture follow-up liaison service: perspective of key stakeholders.

Fracture liaison services (FLS) have been shown to prevent efficiently subsequent fragility fractures (FF). However, very few studies have examined their implementation in depth. The purpose of this research was to identify factors influencing the implementation of a FLS at three sites in Quebec, Canada. From 2013 to 2015, individual and group interviews focused on experiences of FLS stakeholders, including implementation committee members, coordinators, and orthopaedic surgeons and their teams. Emerging key implementation factors were triangulated with the FLS patients' clinico-administrative data. The Consolidated Framework for Implementation Research guided the analysis of perceived factors influencing four intervention outputs: investigation of FF risk (using the FRAX score), communication with the participant primary care provider, initiation of anti-osteoporosis medications (when relevant), and referral to organized fall prevention activities (either governmental or community based). Among the 454 FLS patients recruited to the intervention group, 83% were investigated for FF risk, communication with the primary care provider was established for 98% of the participants, 54% initiated medication, and 35% were referred to organized fall prevention activities. Challenges related to restricted rights to prescribe medication and access to organized fall prevention activities were reported. FLS coordinator characteristics to overcome those challenges included self-efficacy beliefs, knowledge of community resources, and professional background. This study highlighted the importance of enabling access to services for subsequent FF prevention, consolidating the coordinator's role to facilitate a more integrated intervention, and involving local leaders to promote the successful implementation of the FLS.

How does HTA addresses current social expectations? An international survey.

OBJECTIVES: Integration of ethics into technology assessment in healthcare (HTA) reports is directly linked to the need of decision makers to provide rational grounds justifying their social choices. In a decision-making paradigm, facts and values are intertwined and the social role of HTA reports is to provide relevant information to decision makers. Since 2003, numerous surveys and discussions have addressed different aspects of the integration of ethics into HTA. This study aims to clarify how HTA professionals consider the integration of ethics into HTA, so an international survey was conducted in 2018 and the results are reported here. METHODS: A survey comprising twenty-two questions was designed and carried out from April 2018 to July 2018. Three hundred and twenty-eight HTA agencies from seventy-five countries were invited to participate in this survey. RESULTS: Eighty-nine participants completed the survey, representing a participation rate of twenty-seven percent. As to how HTA reports should fulfill their social role, over 84 percent of respondents agreed upon the necessity to address this role for decision makers, patients, and citizens. At a lower level, the same was found regarding the necessity to make value-judgments explicit in different report sections, including ethical analysis. This contrasts with the response-variability obtained on the status of ethical analysis with the exception of the expertise required. Variability in stakeholder-participation usefulness was also observed. CONCLUSIONS: This study reveals the importance of a three-phase approach, including assessment, contextual data, and recommendations, and highlights the necessity to make explicit value-judgments and have a systematic ethical analysis in order to fulfill HTA's social role in guiding decision makers.

Better care through an optimized mental health services continuum (Eastern Townships, Québec, Canada): A systematic and multisource literature review.

INTRODUCTION: In 2014, the health authorities of the Eastern Townships (Québec, Canada) commissioned an evaluation of the mental health admission system for adults (GASMA) to identify the best GASMA organizational or structural elements and optimize the mental health services continuum. METHODS: To develop better services, seven indicators (ie, accessibility to services, integration of levels of services, user satisfaction, guidance and management time, evaluation tools, professional composition, and interprofessional collaboration) were examined through four evaluation questions. A three-step systematic and multisource evaluation was realized. A systematic review of the scientific and gray literature was performed. This evaluation also included key informant opinions to contextualize results from this review. RESULTS: Results from 91 scientific articles, 40 gray literature documents, and 10 interviews highlighted determinants and barriers associated with the examined indicators. From these results, 24 preliminary recommendations were formulated and discussed in a steering committee. These recommendations were then weighted and validated. This served to formulate three final recommendations. CONCLUSION: To optimize the regional mental health services continuum, stakeholders should (1) implement a single-window access for adults with mental health needs, (2) develop alternative services based on users' needs, and (3) test the effectiveness of new methods, initiatives, and tools.

Rational engineering of the Neurospora VS ribozyme to allow substrate recognition via different kissing-loop interactions.

The Neurospora VS ribozyme is a catalytic RNA that has the unique ability to specifically recognize and cleave a stem-loop substrate through formation of a highly stable kissing-loop interaction (KLI). In order to explore the engineering potential of the VS ribozyme to cleave alternate substrates, we substituted the wild-type KLI by other known KLIs using an innovative engineering method that combines rational and combinatorial approaches. A bioinformatic search of the protein data bank was initially performed to identify KLIs that are structurally similar to the one found in the VS ribozyme. Next, substrate/ribozyme (S/R) pairs that incorporate these alternative KLIs were kinetically and structurally characterized. Interestingly, several of the resulting S/R pairs allowed substrate cleavage with substantial catalytic efficiency, although with reduced activity compared to the reference S/R pair. Overall, this study describes an innovative approach for RNA engineering and establishes that the KLI of the trans VS ribozyme can be adapted to cleave other folded RNA substrates.

IMPACT OF HEALTH TECHNOLOGY ASSESSMENT REPORTS ON HOSPITAL DECISION MAKERS - 10-YEAR INSIGHT FROM A HOSPITAL UNIT IN SHERBROOKE, CANADA: IMPACT OF HEALTH TECHNOLOGY ASSESSMENT ON HOSPITAL DECISIONS.

OBJECTIVES: The overarching goal of this research was to (i) evaluate the impact of reports with recommendations provided by a hospital-based health technology assessment (HB-HTA) unit on the local hospital decision-making processes and implementation activities and (ii) identify the underlying factors of the nonimplementation of recommendations. METHODS: All reports produced by the HB-HTA unit between December 2003 and March 2013 were retrieved, and hospital decision makers who requested these reports were solicited for enrolment. Participants were interviewed using a mixed design survey. RESULTS: Twenty reports, associated with fifteen decision makers, fulfilled the study criteria. Nine decision makers accepted to participate, corresponding to thirteen reports and twenty-three recommendations. Of the twenty-three recommendations issued, 65 percent were implemented, 9 percent were accepted for implementation but not implemented, and 26 percent were declined. In terms of the utility of each report to guide decision makers, 92 percent of the reports were considered in the decision-making process; 85 percent had one or more recommendations adopted; and 77 percent had recommendations implemented. The most frequently mentioned reasons for nonimplementation were related to contextual factors (64 percent), production/diffusion process factors (14 percent), content/format factors (14 percent), or other factors (9 percent). Among the contextual factors, the complexity of the changes (i.e., administrative reasons), budget and resources constraints, failure to identify administrative responsibility to carry out the recommendation, and nonpriority status of the HTA recommendation, were provided. CONCLUSIONS: This study highlights that although HB-HTA reports are useful to hospital managers in their decision-making processes, certain barriers such as contextual factors need to be better addressed to improve HB-HTA efficiency and usefulness.

ETHICS IN HEALTH TECHNOLOGY ASSESSMENT: A SYSTEMATIC REVIEW.

OBJECTIVES: Integration of ethics into health technology assessment (HTA) remains challenging for HTA practitioners. We conducted a systematic review on social and methodological issues related to ethical analysis in HTA. We examined: (1) reasons for integrating ethics (social needs); (2) obstacles to ethical integration; (3) concepts and processes deployed in ethical evaluation (more specifically value judgments) and critical analyses of formal experimentations of ethical evaluation in HTA. METHODS: Search criteria included "ethic," "technology assessment," and "HTA". The literature search was done in Medline/Ovid, SCOPUS, CINAHL, PsycINFO, and the international HTA Database. Screening of citations, full-text screening, and data extraction were performed by two subgroups of two independent reviewers. Data extracted from articles were grouped into categories using a general inductive method. RESULTS: A list of 1,646 citations remained after the removal of duplicates. Of these, 132 were fully reviewed, yielding 67 eligible articles for analysis. The social need most often reported was to inform policy decision making. The absence of shared standard models for ethical analysis was the obstacle to integration most often mentioned. Fairness and Equity and values embedded in Principlism were the values most often mentioned in relation to ethical evaluation. CONCLUSIONS: Compared with the scientific experimental paradigm, there are no settled proceedings for ethics in HTA nor consensus on the role of ethical theory and ethical expertise hindering its integration. Our findings enable us to hypothesize that there exists interdependence between the three issues studied in this work and that value judgments could be their linking concept.

The ARiBo tag: a reliable tool for affinity purification of RNAs under native conditions.

Although RNA-based biological processes and therapeutics have gained increasing interest, purification of in vitro transcribed RNA generally relies on gel-based methods that are time-consuming, tedious and denature the RNA. Here, we present a reliable procedure for affinity batch purification of RNA, which exploits the high-affinity interaction between the boxB RNA and the N-peptide from bacteriophage λ. The RNA of interest is synthesized with an ARiBo tag, which consists of an activatable ribozyme (the glmS ribozyme) and the λBoxB RNA. This ARiBo-fusion RNA is initially captured on Glutathione-Sepharose resin via a GST/λN-fusion protein, and the RNA of interest is subsequently eluted by ribozyme self-cleavage using glucosamine-6-phosphate. Several GST/λN-fusion proteins and ARiBo tags were tested to optimize RNA yield and purity. The optimized procedure enables one to quickly obtain (3 h) highly pure RNA (>99%) under native conditions and with yields comparable to standard denaturing gel-based protocols. It is widely applicable to a variety of RNAs, including riboswitches, ribozymes and microRNAs. In addition, it can be easily adapted to a wide range of applications that require RNA purification and/or immobilization, including isolation of RNA-associated complexes from living cells and high-throughput applications.

Perceptions and Preoccupations of Patients and Physicians Regarding Use of Medical Cannabis as an Intervention Against Chronic Musculoskeletal Pain: Results from a Qualitative Study.

Objective: Explore perceptions and preoccupations regarding use of medical cannabis against chronic musculoskeletal pain, among patients and physicians. Design: Qualitative study using interviews with patients and physicians, based on the Theory of Planned Behavior (TPB). Setting: The study was conducted in Quebec, Canada, in spring 2020. Subjects: We included 27 adult patients and 11 physicians (GPs, anesthesiologists, psychiatrists, and a rheumatologist); the mean age of patients was 48.2 years; 59.3% of patients and 36.4% of physicians were women; 59.3% of patients used no medical cannabis at the time of study; 45.5% of physicians had never authorized it. Methods: Semi-structured interviews were conducted, transcribed and for the qualitative analysis codes were developed in a hybrid, inductive and deductive approach. Guided by the TPB, facilitators and barriers, perceived benefits and harms, and perceived norms that may influence cannabis use or authorization were documented. Results: Although medical cannabis is an interesting avenue for the relief of chronic musculoskeletal pain, doctors and patients agreed that it remained a last line option, due to the lack of scientific evidence regarding its safety and efficacy. The norms surrounding medical cannabis also play an important role in the social and professional acceptance of this therapeutic option. Conclusion: Medical cannabis is seen as a last line option among interventions in the management of chronic pain, and attitudes and prior experiences play a role in the decision to use it. Study results may contribute to improved shared decision making between patients and physicians regarding this option.

Riboswitch structure: an internal residue mimicking the purine ligand.

The adenine and guanine riboswitches regulate gene expression in response to their purine ligand. X-ray structures of the aptamer moiety of these riboswitches are characterized by a compact fold in which the ligand forms a Watson-Crick base pair with residue 65. Phylogenetic analyses revealed a strict restriction at position 39 of the aptamer that prevents the G39-C65 and A39-U65 combinations, and mutational studies indicate that aptamers with these sequence combinations are impaired for ligand binding. In order to investigate the rationale for sequence conservation at residue 39, structural characterization of the U65C mutant from Bacillus subtilis pbuE adenine riboswitch aptamer was undertaken. NMR spectroscopy and X-ray crystallography studies demonstrate that the U65C mutant adopts a compact ligand-free structure, in which G39 occupies the ligand-binding site of purine riboswitch aptamers. These studies present a remarkable example of a mutant RNA aptamer that adopts a native-like fold by means of ligand mimicking and explain why this mutant is impaired for ligand binding. Furthermore, this work provides a specific insight into how the natural sequence has evolved through selection of nucleotide identities that contribute to formation of the ligand-bound state, but ensures that the ligand-free state remains in an active conformation.

Spatiotemporal parameters and gait variability in people with psoriatic arthritis (PsA): a cross-sectional study.

BACKGROUND: Foot involvement is a major manifestation of psoriatic arthritis (PsA) and can lead to severe levels of foot pain and disability and impaired functional mobility and quality of life. Gait spatiotemporal parameters (STPs) and gait variability, used as a clinical index of gait stability, have been associated with several adverse health outcomes, including risk of falling, functional decline, and mortality in a wide range of populations. Previous studies showed some alterations in STPs in people with PsA. However, gait variability and the relationships between STPs, gait variability and self-reported foot pain and disability have never been studied in these populations. Body-worn inertial measurement units (IMUs) are gaining interest in measuring gait parameters in clinical settings. OBJECTIVES: To assess STPs and gait variability in people with PsA using IMUs, to explore their relationship with self-reported foot pain and function and to investigate the feasibility of using IMUs to discriminate patient groups based on gait speed-critical values. METHODS: Twenty-one participants with PsA (age: 53.9 ± 8.9 yrs.; median disease duration: 6 yrs) and 21 age- and sex-matched healthy participants (age 54.23 ± 9.3 yrs) were recruited. All the participants performed three 10-m walk test trials at their comfortable speed. STPs and gait variability were recorded and calculated using six body-worn IMUs and Mobility Lab software (APDM®). Foot pain and disability were assessed in participants with PsA using the foot function index (FFI). RESULTS: Cadence, gait speed, stride length, and swing phase were significantly lower, while double support was significantly higher, in the PsA group (p < 0.006). Strong correlations between STPs and the FFI total score were demonstrated (|r| > 0.57, p < 0.006). Gait variability was significantly increased in the PsA group, but it was not correlated with foot pain or function (p < 0.006). Using the IMUs, three subgroups of participants with PsA with clinically meaningful differences in self-reported foot pain and disability were discriminated. CONCLUSION: STPs were significantly altered in participants with PsA, which could be associated with self-reported foot pain and disability. Future studies are required to confirm the increased gait variability highlighted in this study and its potential underlying causes. Using IMUs has been useful to objectively assess foot function in people with PsA. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05075343 , Retrospectively registered on 29 September 2021.

The effects of custom-made foot orthoses on foot pain, foot function, gait function, and free-living walking activities in people with psoriatic arthritis (PsA): a pre-experimental trial.

INTRODUCTION: Foot involvement is a significant concern in psoriatic arthritis (PsA) as it can lead to severe levels of foot pain and disability and reduced mobility and quality of life. Previous studies have shown moderate efficacy for custom-made foot orthoses (CFO) in reducing foot pain and disability in people with rheumatoid arthritis. However, evidence on the efficacy of CFO in people with PsA is lacking. OBJECTIVES: To explore the effects of CFO on foot function, foot and lower limb pain, gait function, and free-living walking activities (FWA) in people with PsA. METHODS: A pre-experimental study including twenty participants with PsA (mean age: 54.10 ± 9.06 years and disease duration: 11.53 ± 10.22 years) was carried out. All the participants received and wore CFO for 7 weeks. Foot and lower limb pain and foot function were measured before and after the intervention using the numerical rating scale (NRS) and the foot function index (FFI). Gait function was assessed by recording spatiotemporal parameters (STPs) during a 10-m walk test using an instrumented gait analysis system (Mobility Lab). Free-living walking activities (step count, free-living cadence, time spent in different ambulatory physical activities (APA)) were recorded over 7 days using an accelerometer-instrumented sock. RESULTS: The FFI reported scores demonstrated severe baseline levels of foot pain (54.46 ± 14.58 %) and disability (46.65 ± 16.14%). Statistically and clinically significant improvements in foot pain and foot function and large effect sizes (Cohen's effect size > 1, p < 0.005) were observed after the intervention period. A strong correlation (r = -0.64, p < 0.01) between the CFO wearing time and foot function was demonstrated. However, no significant changes were found for gait STP or free-living walking activities after 7 weeks of CFO use. CONCLUSION: Results support the clinical and biomechanical plausibility of using CFO in people with PsA to reduce pain and improve foot function. Large-scale and controlled studies are needed to confirm these findings. Moreover, a multidisciplinary approach including the prescription of exercise therapy and physiotherapy combined with CFO could be required to improve STP and promote APA in people with PsA. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05075343 . Retrospectively registered on September 29, 2021.

Experiences of Using Cochrane Systematic Reviews by Local HTA Units.

This study evaluated the use of Cochrane systematic reviews (CSRs) by Quebec's local health technology assessment (HTA) units to promote efficiency in hospital decision-making. An online survey was conducted to examine: Characteristics of the HTA units; Knowledge about works and services from the Cochrane Collaboration; Level of satisfaction about the use of CSRs; Facilitating factors and barriers to the implementation of CSRs evidence in a local context; Suggestions to improve the use of CSRs. Data accuracy was checked by 2 independent evaluators. Ten HTA units participated. From their implementation a total of 321 HTA reports were published (49.8% included a SR). Works and services provided by the Cochrane collaboration were very well-known and HTA units were highly satisfied with CSRs (80%-100%). As regards to applicability in HTA and use of CSRs, major strengths were as follow: Useful as resource for search terms and background material; May reduce the workload (eg, brief review instead of full SR); Use to update a current review. Major weaknesses were: Limited use since no CSRs were available for many HTA projects; Difficulty to apply findings to local context; Focused only on efficacy and innocuity; Cannot be used as a substitute to a full HTA report. This study provided a unique context of assessment with a familiar group of producers, users and disseminators of CSRs in hospital setting. Since they generally used other articles from the literature or produce an original SR in complement with CSRs, this led to suggestions to improve their use of CSRs. However, the main limit for the use of CRS in local HTA will remain its lack of contextualisation. As such, this study reinforces the need to consider the notion of complementarity of experimental data informing us about causality and contextual data, allowing decision-making adapted to local issues.