Feasibility of a pain informed movement program for people with symptomatic knee osteoarthritis

Purpose: Disability in knee osteoarthritis (KOA) is known to be largely due to pain, the mechanism of which is complex and multidimensional with alterations in nociceptive processing in the peripheral and central nervous system (CNS) leading to persistent pain. Current clinical practice guidelines for KOA provide strong recommendations for education and exercise including land-based or mind-body approaches. However, individually these strategies are only moderately effective. One potential reason for this is a lack of understanding of their underlying mechanisms and how their combination might impact nervous system modulation. Neuromuscular exercise is known to improve lower extremity strength. Mind-body approaches as well as pain neuroscience education (PNE) are uniquely positioned to potentially reverse CNS adaptations by inducing positive neuroplastic changes and improving descending modulation of pain resulting in decreased pain. To our knowledge, neuromuscular exercise, mind-body techniques, and PNE have not been studied in combination. We therefore aimed to establish the feasibility of an intervention consisting of these three elements referred to as Pain Informed Movement (PIM). The results of this study will inform necessary modifications for a two-arm pilot randomized controlled trial (RCT). Method(s): This study was a single-arm feasibility trial with a nested qualitative component and the primary feasibility outcome of complete follow up. Inclusion criteria: age >= 40 years, KOA clinical diagnosis or people fulfilling the NICE diagnostic criteria, and average pain intensity >=3/10 on the numeric pain rating scale. PIM consisted of twice weekly in-person exercise sessions and a third home exercise session for 8 weeks. In addition, PNE, provided as online videos, covered the following topics: purpose of pain, neurophysiological changes associated with pain, movement guidelines when pain persists, mind-body techniques to impact neurophysiology and support moving with ease that included breath awareness and regulation, muscle tension regulation, awareness of pain related thoughts and emotions, and relaxation. The mind-body techniques and the PNE topics were implemented during the group exercise sessions that included evidence-based neuromuscular exercises aimed at improving sensorimotor control and functionality of the knee joint. Participants completed questionnaires and in-person assessments at baseline and at program completion. Assessments included weight and height, chair stands as a measure of functional leg strength, and conditioned pain modulation to assess efficiency of the descending modulatory pathways. Participants also had their blood drawn to monitor changes in brain derived neurotrophic factor (BDNF), a marker of neuroplasticity. Questionnaires included the Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale, the Knee Injury and Osteoarthritis Outcome Score - function and pain subscales, Chronic Pain Self Efficacy scale, pain intensity rated in the past 24 hours, the past week, and worst pain in the past 24 hours. Secondary feasibility outcomes included acceptability of the intervention, burden of assessments, recruitment rate, compliance rate, adherence rate, and self-reported adverse events. Feasibility findings were evaluated against a-priori success criteria. In the qualitative component, participants were invited to an online focus group and were asked about their experience and perceptions of the program. Interview recordings were analyzed using thematic content analysis to identify suggestions for program modification. Result(s): In total, 19 participants (mean age 63.3 years (SD 10.5), 73% female) were enrolled, with a complete follow up rate of 74% (n=14) for our primary objective, indicating that modifications would be needed to proceed. Of the 5 dropouts, only one was study related. We will be adding additional inclusion criteria of: ability to get up and down from the floor independently, and no use of mobility aids. Adherence to in-person treatment sessions was 91%, hich indicates proceeding with the protocol for the next phase (i.e., pilot RCT). Some absences were due to unmodifiable factors (e.g., COVID-19). We will make protocol amendments for the purpose of improving the adherence rate to include 'no planned absences'. All other success criteria were met: recruitment rate, compliance to exercise sessions, program acceptability, duration, frequency, and delivery, likelihood of recommending the program to others and taking the program again, burden, and adverse events (Table 1). Analysis of the focus groups revealed that the video content pertaining to the mind-body techniques would benefit from on screen demonstrations by the instructor to assist with participants' execution of breath and muscle tension regulation. The majority of participants improved in most of the physical assessment outcomes and questionnaires (Table 2). Conclusion(s): The PIM program is feasible, acceptable, not burdensome, does not cause adverse events, and had an excellent compliance rate. Minor modifications are needed to optimize enrolment and adherence rates. Although improvements in pain, function, and psychological measures were observed, the feasibility nature of this study precludes any conclusions regarding efficacy. A pilot two-arm RCT will be conducted to establish the feasibility and explore potential effects of PIM when compared to conventional neuromuscular exercise and standard OA education. [Formula presented] [Formula presented]Copyright © 2023

Is Treating Post-Menopausal Women With Symptomatic Hand Osteoarthritis With Hormone Replacement Therapy Feasible?: Results From The Hope-E Randomised, Placebo-Controlled Feasibility Study

Purpose: Hand osteoarthritis (OA) is more common in women. Hand OA incidence increases further in females around the age of 50, the typical age of menopause. Estrogen-deficient states are associated with increased musculoskeletal pain and inflammation and with increased rates of symptomatic OA. Estrogen replacement and selective estrogen receptor modulators (SERMs) can improve pain and structure in some pre-clinical models of OA associated with estrogen loss, and in exploratory analysis from hormone replacement therapy (HRT) trials. However, no randomised clinical trials (RCTs) of HRT had been performed in symptomatic OA populations, specifically hand OA. By carrying out a RCT feasibility study of a form of HRT (conjugated estrogens (CE)-bazedoxifene) in post-menopausal women with painful hand OA, we set out to determine the feasibility and acceptability of this. We also aimed to generate proof-of concept data on likely outcomes, calculate a sample size and refine methods for a full trial. Method(s): We recruited females aged 40-65 years and 1-10 years after final menstrual period with definite hand OA and >=2 painful hand joints across three primary/secondary care sites and from the community. Medical exclusions included those typical for clinical HRT use. Design was parallel group, double-blind 1:1 randomisation of CE-bazedoxifene or placebo, taken orally once daily for 24 weeks, then tapering for 4 weeks before study end at Week 28. Primary feasibility outcomes were rates of eligible participant identification, recruitment, randomisation, retention, compliance, and likelihood of unblinding. Adverse events (AEs) were collected. Secondary clinical outcomes included the anticipated primary outcome in a full trial of mean hand pain over 14 days prior to each visit, scored on a 0-10 numerical rating scale (NRS) where 10 is worst pain possible, as well as hand function, appearance and menopause symptoms. Progression criteria to a full RCT were: (i) recruitment >=30 participants across all sites in 18 months (or proportionate to time open);(ii) a drop-out rate of <=30% of randomised individuals;and (iii) acceptability to the majority of participants, including acceptable AE rates. All clinical outcomes were analysed on an intention-to-treat basis. Though not powered to detect a treatment difference, change and treatment effects (the difference in the outcome between the two groups) were indicated with 95% CIs, with all models adjusted for clinical subtype of painful hand joint, study site, and baseline values. The sample size for a full trial was estimated using the standard deviation (SD) of week 24 mean hand pain. Result(s): Due to the COVID-19 pandemic, the recruitment window was reduced to 12-15 months. From May 2019 to December 2020, 434 enquiries/referrals were received. Of 96 telephone pre-screens, 35 individuals were potentially eligible and of these, 33 gave consent to participate. Of the remaining, 250/401 (62%) were ineligible, whilst 55/401 (14%) chose not to proceed, with the most common reason being not wanting to take HRT. 28/35 (80% (95%CI 63%,92%)) eligible participants were randomised to study medication. All 28 participants completed all follow-ups with high compliance (100% active, 13/14[93%] placebo) and outcome measure completeness (100%, mean hand pain). All three AE-related treatment withdrawals were on placebo when unblinded. No serious AEs occurred. Participants/investigators were well blinded (participant blinding index 0.50[95%CI 0.25 to 0.75]). All three prespecified progression criteria were therefore met for a full trial. The treatment effect difference over 24 weeks in mean hand pain between active and placebo was -0.71 (95% CI -2.20 to 0.78) (Fig 1A). During tapering/stopping medication, mean hand pain increased by 1.31 points in the active arm compared with 0.17 in the placebo arm, indicating a possible effect of cessation of medication (Fig 1A). Furthermore, 6/13 (46%) participants in the active group reported worsening pain at week 28 compared with week 24, but only 2/12 (17%) were worse on withdrawing placebo (Fig 1B). The sample size for a full trial was estimated as 296 (based on MCID 0.8 on NRS, SD 2.0, 90% power, 10% drop-out, alpha 5%). Conclusion(s): This first study of a RCT of HRT for painful hand OA met its progression criteria, indicating that a full trial of an HRT in this population is feasible and acceptable. Although not powered to detect an effect, there was a trend towards improvement in hand pain on treatment and worsening of hand pain on tapering in the active arm only. This adds to proof-of-concept data in this area, justifying more work.ISRCTN12196200. Funded by Research for Patient Benefit programme, National Institute for Health Research (UK) PB-PG-0416-20023 [Formula presented]Copyright © 2023

Centering Group Treatment for Women With Interstitial Cystitis/Bladder Pain Syndrome: A Prospective, Parallel-Group Cohort Study

Importance: Women with interstitial cystitis/bladder pain syndrome (ICBPS) face isolation and treatment challenges. Group medical visits using Centering models have successfully treated other conditions but have not been explored in ICBPS. Objective(s): This study aimed to describe ICBPS pain and symptom control comparing standard treatment alone versus standard treatment augmented with Centering visits. Study Design: This prospective cohort study recruited women with ICBPS receiving standard care (control) or standard care augmented with group Centering. We administered validated questionnaires at baseline and monthly for 12 months. The primary outcome was change in the pain numerical rating scale, with Patient-Reported Outcomes Measurement Information System Pain Interference Scale and Bladder Pain/Interstitial Cystitis Symptom Score change as secondary measures. Result(s): We enrolled 45 women (20 Centering, 25 controls). Centering had significantly better numerical rating scale pain scores at 1 month (mean difference [diff], -3.45) and 2 months (mean diff, -3.58), better Patient-Reported Outcomes Measurement Information System Pain Interference Scale scores at 1 month (mean diff, -10.62) and 2 months (mean diff, -9.63), and better Bladder Pain/Interstitial Cystitis Symptom Score scores at 2 months (mean diff, -13.19), and 3 months (mean diff, -12.3) compared with controls. In modeling, treatment group (Centering or control) and educational levels were both associated with all the outcomes of interest. Beyond 6 months, there were too few participants for meaningful analyses. Conclusion(s): Women with ICBPS participating in a Centering group have, in the short term, less pain, pain interference, and ICBPS-specific symptoms than patients with usual care alone. Larger studies with more follow-up are needed to determine if this treatment effect extends over time.Copyright © 2022 American Urogynecologic Society. All rights reserved.

Age, COVID-19-related fear, insomnia symptoms and cyberchondria: a mediation model

Introduction: The subject of our study was the role of age, fear of COVID-19 infection and insomnia as predictors of cyberchondria in a Polish sample. We were also interested in whether insomnia mediated the relationship between fear of COVID-19 infection and cyberchondria in the entire sample. Material(s) and Method(s): The study sample consisted of 504 people, including 420 women and 84 men, aged 18 to 76 years (M +/-SD 30.49 +/-10.28), who were recruited through an online platform. Cyberchondria was assessed using the Polish version of the Cyberchondria Severity Scale. An 11-point numerical rating scale was used to measure the intensity of fear of COVID-19 infection for oneself. Insomnia symptoms were measured using the Polish version of the Athenian Insomnia Scale. Result(s): The correlation coefficients indicated positive relationships between the fear of COVID-19 infection and insomnia and cyberchondria, while age correlated negatively with cyberchondria. The hierarchical multivariate linear regression analysis revealed that COVID-19-related fear was the best predictor of cyberchondria. Insomnia and age were also cyberchondria predictors, but to a lesser extent. The mediation analysis revealed a significant indirect relationship between COVID-19-related fear and cyberchondria through insomnia symptoms. Conclusion(s): We observed that COVID-19-related fear and, to a lesser extent, age and insomnia were cyberchondria predictors. We also found both direct and indirect relationships between COVID-19-related fear and cyberchondria through insomnia.Copyright © 2022 Termedia Publishing House Ltd.. All rights reserved.

Characteristics and risk factors for persistent breathlessness after hospitalisation for COVID-19

Background: Persisting breathlessness after COVID-19 infection is common and debilitating. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation. Method(s): PHOSP-COVID is a multi-centre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a research visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID breathlessness as an increase in score of 1 or more compared to the preCOVID-19 level. Multivariable logistic regression was used to identify risk factors. Result(s): We included 1,226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median five months after discharge, 50% reported post-COVID breathlessness. Risk factors for post-COVID breathlessness were socio-economic deprivation (adjusted odds ratio, 1.67;95% confidence interval, 1.14-2.44), pre-existing depression/anxiety (1.58;1.06-2.35), female sex (1.56;1.21-2.00) and admission duration (1.01;1.00- 1.02). Black ethnicity (0.56;0.35-0.89) and older age groups (0.31;0.14-0.66) were less likely to report post-COVID breathlessness. Post-COVID breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. Conclusion(s): Half of this national cohort of patients hospitalised for COVID-19 experienced persistent breathlessness at follow up. The risk factors identified for post-COVID breathlessness should inform mechanistic work to understand causal processes and develop future interventions to improve outcomes in this growing population.

A Placebo-Controlled, Single-Blind Extension Study Evaluating The Safety And Efficacy Of Lorecivivint In Subjects With Structurally Advanced Osteoarthritis Of The Knee (Oa-07): Radiographic And Pain Outcomes At 24 And 30 Month

Purpose: Knee osteoarthritis (OA) is a common joint disorder associated with pain, disability, and joint damage. An unmet need remains for safe, efficacious treatments for symptoms and disease modification. Lorecivivint (LOR), a novel intra-articular (IA) CLK/DYRK inhibitor thought to modulate Wnt and inflammatory pathways, has previously appeared safe, demonstrated patient-reported outcome (PRO) improvements compared with placebo (PBO), and maintenance of radiographic medial joint space width (mJSW). A LOR trial, OA-11, enrolled participants with structurally advanced (mJSW 1.5-4 mm) knee OA. OA-11 did not meet its primary endpoint;however, greater treatment effects were observed in subjects with less advanced/earlier (Kellgren Lawrence [KL] grade 2) OA. Additionally, the COVID pandemic potentially confounded pain reporting and expected mJSW progression. An ongoing 4-year extension study, OA-07 (NCT04520607), continues to evaluate LOR safety and efficacy with primary and secondary efficacy outcomes of mJSW (mm) and Pain Numerical Rating Scale (NRS [0-10]) respectively. Data up to 30 months from this study are reported. Method(s): Subjects who completed OA-11, a 13-month Phase 3 LOR trial, were enrolled into OA-07, an extension study designed to evaluate safety and efficacy of long-term LOR treatment. During the single-blinded Year 1 of OA-07, subjects received repeat injection according to their randomized treatment received in OA-11 (LOR or PBO). In Year 2 and annually thereafter, all subjects (LOR and PBO) received an open-label 0.07 mg IA LOR injection. OA-07 commenced in July 2020 and is planned to continue over a 4-year period with clinic visits every six months. Result(s): 277 subjects (mean age 61.0 +/- 8.2 years, BMI 31.8 +/- 4.9 kg/m2, female 62.8%, KL3 45.5%, 67.1% bilaterally symptomatic, mean baseline mJSW 2.63 +/- 0.69 mm, 68.6% mJSW < 3 mm) were enrolled. LOR appears safe and well-tolerated, consistent with its previously observed safety profile. At 24 months, the LOR treatment arm shows reduced mJSW loss compared to placebo, LOR -0.13 (+/- 0.06) mm (n=103) vs. PBO -0.22 (+/- 0.05) mm (n=112) (DELTA=0.10 mm, 95% CI [-0.05, 0.25], P=0.199, Figure 1A) for Full Analysis Set (FAS) and LOR +0.02 (+/- 0.07) mm (n=61) vs. PBO -0.15 (+/- 0.07) mm (n=63) (DELTA=0.17 mm, 95% CI [-0.02, 0.37], P=0.077, Figure 1B) for KL2. Average change from OA-07 baseline to 24 months in Pain NRS is -0.25 (+/- 0.19) for LOR (n=121) compared to 0.11 (+/- 0.19) for placebo (n=130) (DELTA=-0.36, 95% CI [-0.89, 0.17], P=0.179, Figure 2A). For WOMAC Function, LOR (n=96) change from baseline was -5.33 (+/- 1.84) vs PBO (n=104) -0.43 (+/-1.76), (DELTA=-4.90, 95% CI [-9.92, 0.13], P=0.056, Figure 2B);for WOMAC Pain, LOR (n=96) change from baseline of -4.80 (+/-1.87) vs PBO (n=106) 0.38 (+/-1.78), (DELTA=-5.18, 95% CI [-10.28, -0.08], P=0.047, Figure 2C). At 30 months (Figure 2A), unblinded IA injection of LOR (n=60) shows additional Pain NRS improvements with change from OA-07 baseline of -0.57 (+/-0.39) and cross-over to LOR from PBO (n=76) shows an improvement of -0.37 (+/-0.26). Larger improvements in PROs were observed in the KL2 subgroup, with month 24 improvements for LOR over PBO (DELTA= -0.48 (95% CI -1.20, 0.23), P=0.183 in Pain NRS, (DELTA -6.05 (95% CI -12.87, 0.78), P=0.082 in WOMAC Function, and (DELTA -6.58 (95% CI -13.18, 0.02), P=0.051, in WOMAC Pain. Conclusion(s): LOR continues to appear safe and well tolerated. A potential benefit of LOR 0.07 mg compared with PBO in mJSW is observed 12 months after OA-07 baseline injection. Potential LOR benefit compared to PBO is also seen across PROs. Within this structurally advanced knee OA cohort, both mJSW and PROs treatment effects appear enhanced in earlier/ less advanced KL2 knee OA subjects relative to those with more advanced KL3 graded knees. This study is ongoing. [Formula presented] [Formula presented]Copyright © 2023

Effect of Proximal Oxygen Adding to a Bag Valve Mask with a Mechanical Filter in Healthy Volunteers: A Randomized Crossover Trial

Background: Preoxygenation using a bag valve mask (BVM) with a filter is recommended to reduce the risk of viral transmission. Preoxygenation in hypoxaemic patients may require a positive end-expiratory pressure (PEEP) valve. Applying a filter to a BVM with or without a PEEP valve can increase resistance and work of breathing. Objective(s): To evaluate the efficacy of proximal oxygen added to BVM with mechanical filter in healthy volunteers. Material(s) and Method(s): The present study was a crossover trial that randomized 48 volunteers to receive four preoxygenation techniques: BVM with a filter as group F, BVM with a filter and proximal oxygen as group FO, BVM with a filter and PEEP valve as group FP, and BVM with a filter, PEEP valve, and proximal oxygen as group FPO. Fraction of expired oxygen (FEO2) and continuous positive airway pressure (CPAP) were measured. Comfort was assessed using a numerical rating scale (NRS). The primary outcome was FEO2 at five minutes. Result(s): Data from 46 volunteers were analyzed. Adding oxygen proximal to the filter in the FO group increased FEO2 at five minutes by 7.07% (95% CI 4.87 to 9.26) and decreased the time to reach FEO2 90% by 301.74 seconds (95% CI 282.82 to 320.66) compared with the times in group F. Similarly, supplemental proximal oxygen including a PEEP valve increased FEO2 at five minutes by 6.07% (95% CI 3.87 to 8.26) and decreased the time to reach FEO2 90% by 242.13 seconds (95% CI 223.21 to 261.05). CPAP was 2.27, 3.61, 11.65, and 13.14 mmHg in group F, FO, FP, and FPO, respectively. The NRS score was 6.51 and 6.07 in groups F and FO, and 3.15 and 3.70 in groups FP and FPO, respectively. Conclusion(s): Adding proximal oxygen to a BVM with a filter improved the efficacy of preoxygenation. Copyright © 2023 JOURNAL OF THE MEDICAL ASSOCIATION OF THAILAND.

Xylofuns: Xylocaine to Freeze during Unpleasant Nasopharyngeal Swabs in Children - a Randomized Controlled Trial

BACKGROUND: Nasopharyngeal (NP) swabs have been recommended to detect SARS-CoV-2 since the beginning of the COVID-19 pandemic, but are reported to be at least moderately painful. OBJECTIVE(S): To evaluate the efficacy of intranasal vaporized lidocaine compared to a sham treatment in reducing pain in children undergoing a NP swab in the Emergency Department (ED). DESIGN/METHODS: A randomized double-blinded clinical trial was conducted in a pediatric ED. Both participants and the researcher evaluating the primary outcome were blinded. Children 6 to 17 years old requiring a NP swab were eligible. Participants were randomly allocated to receive intranasal lidocaine or a sham treatment prior to their NP swab. The primary outcome measure was pain during the swab as assessed by the visual analog scale. Secondary outcome measures were pain using the verbal numeric rating scale, fear using the children fear scale, and side effects of the intervention. RESULT(S): Eighty-eight participants were enrolled: 45 to the lidocaine group and 43 to the control group. The mean visual analog scale scores for pain were 46 mm in the lidocaine group and 53 mm in the control group (mean difference 7 mm;95%CI -5 to 19 mm). The numeric rating scale and children fear scale were not statistically different between groups. No serious adverse events were observed. Fear prior to the test and younger age were associated with higher pain scores. CONCLUSION(S): Intranasal lidocaine administered prior to NP swabs in the ED did not lower pain scores for school-aged children and youth.

SkinTracker: A novel smartphone app enabling remote clinical research in dermatology

A highly visual practice, dermatology as a field has significant potential to use emerging technology such as mobile applications for research and patient-centered mapping of the disease process. The UCSF team is working to create SkinTracker, a mobile application for patients with skin disease to remotely participate in clinical trials and research studies. The initial iteration of the application focuses on atopic dermatitis. The application includes an enrollment and consent module, validated surveys including the Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numerical Rating Scale (NRS) for itch, link to a wearable device that collects biometric data, a voice diary, and a patient-directed photography module to facilitate physician evaluation of disease. Also included is the ability to report medication use, adverse events, and the ability to chat with the study team. The patient information is available to the research team on a secure online website, where researchers can assess patient photographs to perform Eczema Area and Severity Index (EASI) scoring, note important patient observations from the voice diary, and view quantitative data from both patient surveys and health measures like physical activity, sleep, and environmental factors. We believe this application and website will facilitate patient interest and participation in research, continue research despite in-person restrictions placed during the COVID-19 pandemic, and allow enrollment of more diverse patients for clinical studies who would otherwise be less likely to participate in research due to time or financial constraints.

CLINICIAN-RELATED FACTORS MAY INFLUENCE REMOTE CONSULTATIONS in RHEUMATOLOGY-ANALYSIS of SENIOR VS TRAINEE CLINICIANS' OUTCOMES from A COVID-19 INITIATIVE

Background: Since COVID-19 pandemic started, there have been changes in clinical practice to limit transmission, such as switching from face-to-face to remote consultations. Our department switched to delivering remote consultations without suspending service. Patients were offered the preference of either video or telephone consultation. It is unclear what factors including clinician-related factors significantly influence remote consultations in Rheumatology. Objectives: We aimed to study the influence of senior (substantively employed) vs trainee status of clinicians on remote consultations in our experience during the pandemic. Methods: Between 15/10/2020 and 09/11/2020, 12 clinicians in our department completed data collection forms after each remote consultation, recording the technology used (video vs phone);technical problems encountered;discharge and subsequent appointment status;and technical aspects of the consultation itself using 11-point numerical rating scales (NRS) (Time Adequate;Relevant History;Physical Exam;Management Plan;and Communication Quality). Data were collated on an MS Access 2016 database, and transferred to SPSS version 25 for statistics. Results: Nine senior clinicians (3 consultant rheumatologists, 3 Specialist Nurses, 1 Advanced Rheumatology Practitioner and 2 Senior Rheumatology Pharmacists) and 3 trainee clinicians (2 Specialty Trainee Registrars and 1 Foundation Year 2 doctor) completed forms. 285 forms were validated for analysis. The majority of consultations were completed by senior clinicians (266, 93.3% vs 19, 6.7%). Senior and trainee clinicians had a similar proportion of new patients compared to follow-up patients (18%, n=48 vs 15.8%, n=3;p=0.80);of female patients (68%, n=181 vs 63.2%, n=12;p=0.66);and video consultations (17.3%, n=43 vs 10.5%, n=2;p=0.45);and similar mean age of their patients (59.5 vs 56.7years;p=0.72) respectively. Senior clinicians accounted for all the technical issues reported (20%, n=48 vs 0%, n=0;p=0.03). Senior clinicians had lower mean scores compared to the trainee clinicians on NRS for Relevant History (8.68 vs 9.68;p<0.001), Physical Exam (1.49 vs 2.95;p=0.045), and Communication Quality (8.02 vs 9.37, p=0.002);and had no signifcant differences in scores for Time Adequate (8.46 vs 9.00;p=0.10) and Management Plan (7.17 vs 7.84;p=0.16). Senior and trainee clinicians and a similar proportion requests for subsequent face-to-face appointments (21.9%, n=51 vs 25%, n=4;p=0.77). Conclusion: There were no signifcant differences between senior and trainee clinicians in distributions of patients and proportion of video consultations. While no technical issues were reported by the trainee clinicians, this may in part be a refection of their smaller proportion of overall consultations. Although senior clinicians rated their consultations somewhat lower in some of the NRS, there was no signifcant difference in management plan scores and subsequent face-to-face appointment status compared to trainee clinicians. While the lower scores may partly refect the technical issues reported by the senior clinicians, longer clinical experience and greater knowledge may also be an underlying factor for this. Further studies with larger numbers may clarify these issues.

SOURCES of INFORMATION about SARS-COV-2 USED by PATIENTS with CHRONIC INFLAMMATORY RHEUMATIC DISEASES (CIRD)

Background: Patients with chronic infammatory rheumatic diseases (CIRD) may be at increased risk of Corona Virus Disease 2019 (COVID-19).1 The quality of information obtained plays a crucial role for patients' decision to be vaccinated. Knowing patients' needs for information and which sources are used is important for the management of CIRD patients by rheumatologists and other physicians. Objectives: To identify main sources of information on SARS-CoV-2 used by patients with CIRD and to analyze their influence on opinions and willingness to be vaccinated. Methods: CIRD patients presenting to our tertiary rheumatology hospital were, after informed consent, consecutively included in the study once the vaccination campaign in Germany had started, to fll out a questionnaire. Next to sociode-mographic and disease-specifc data, vaccination willingness and knowledge regarding SARS-CoV-2 were assessed. Furthermore, patients' sources of information and their concerns about accuracy of information were evaluated. A numerical rating scale (NRS) ranging from 0 (completely disagree) to 10 (completely agree) was used. Values between ≥7 were taken as positive answer. Nonparametric tests and multivariate linear regression analyses were performed. Results: In early 2021, a total of 514 patients were interviewed (Table 1). The majority (63.9 %) reported to be well-informed (NRS ≥7), whereas 18% had doubts regarding information on SARS-CoV-2. The most often used source of information was television, and only 8.6% reported to have been informed by a rheumatologist (Figure 1). About 20% of patients were no longer interested in receiving any information on SARS-CoV-2 through media. Information from rheumatologists, general practitioners, public health authorities or health related web sites did not reach 30.5% of patients. Of interest, 16% of subjectively well-informed patients were hesitant towards vaccination. As many as 43.6% of patients with doubts regarding information about SARS-CoV-2 indicated that they were not willing to be vaccinated. No source of information showed a strong correlation with SARS-CoV-2 vaccination willingness or with knowledge on SARS-CoV-2. Weak positive correlations were found between age and education level on the one hand and information sources about SARS-CoV-2 on the other hand. A weak negative correlation was found between doubts about information and health authorities, whereas positive correlations were found with social networks, friends and family. Conclusion: Most CIRD patients think that they are well-informed about SARS-CoV-2. However, their information rarely comes from expert-based sources and rarely from rheumatologists. Thus, there is an unmet need for CIRD patients to receive appropriate and comprehensive information about SARS-CoV-2, its infu-ence on rheumatic diseases, and about vaccination of patients with CIRD.

SARS-COV-2 VACCINATION WILLINGNESS and PREDICTORS in PATIENTS with CHRONIC INFLAMMATORY RHEUMATIC DISEASES (CIRD) and WITHOUT CIRD

Background: Recent surveys in chronic infammatory rheumatic diseases (CIRD) showed a high degree of vaccine hesitancy. Current knowledge about patients' attitudes towards vaccination against SARS-CoV-2 is limited. Objectives: To assess the willingness of CIRD patients to be vaccinated against SARS-CoV-2 and to identify influencing factors compared to non-CIRD patients. Methods: In this cross-sectional study, two cohorts of consecutively in parallel recruited patients with and without CIRD presenting to our tertiary hospital answered questions of a structured interview to assess vaccination willingness to SARS-CoV-2, experience with SARS-CoV2 in their environment and their personal history of infections and vaccinations. Vaccination willingness was assessed by a numerical rating scale (0: fully disagree;10: fully agree). Arbitrarily defned cut-offs were used to defne defnite (score ≥7) and probable willingness (scores of 5 or 6) to be vaccinated. Statistical analyses were performed with appropriate tests such as Kendall-tau b. Results: A total of 514 CIRD and 100 non-CIRD patients, mean age 54.7±12.8 and 55.6±9.8 years, were included. Defnite and probable willingness to be vaccinated against SARS-CoV-2 was declared by 79.6% and 90.7% vs. 76.0% and 85.0% of CIRD and non-CIRD patients, respectively. Only 60% of CIRD patients believed that the vaccines against SARS-CoV-2 were safe, and 42% indicated to be afraid of side effects. Vaccination willingness correlated signifcantly with the degree of education, age, identifcation with a risk group for COVID-19 disease, hypertension, and the degree of information about preventable diseases. There was no correlation with the history of infections or with immunosuppressive therapy. Conclusion: Although our results show a high willingness for vaccination against SARS-CoV-2 in both groups, there was quite some uncertainty regarding the safety and efficacy of the vaccines. Since major influencing factors were education and information about SARS-CoV-2 and COVID-19, patient education should be immediately improved.

EXPLORING KNEE OSTEOARTHRITIS PAIN TRAJECTORIES and MOVEMENT-EVOKED PAIN CHANGES during A 24-WEEK OUTDOOR WALKING PROGRAM (WALK)

Background: Exercise therapy is recommended as frst line treatment for knee osteoarthritis (OA), but it remains to be sub-optimally applied (1). Movement-evoked pain is a potential barrier to exercise adherence, but recent evidence suggests that such pain can be improved by training (2). Walking programs are low-cost, easily adopted and can be performed outdoors which can minimize the risk of SARS-CoV-2 transmission when in a group (3). Objectives: To explore the acute pain trajectories of individuals with knee OA during a 24-week outdoor walking intervention. In addition, to explore the effect of pain trajectories and/or baseline characteristics on retention and adherence. Methods: Individuals with clinical knee OA and bone marrow lesions (BMLs) on magnetic resonance imaging (MRI) were asked to follow a 24-week walking program. Every week consisted of two one hour supervised group sessions at various outdoor locations and one unsupervised session. At the start and end of every supervised group walk, knee pain was self-reported by participants to their trainer using a numerical rating scale (NRS) (0-10). The difference between the NRS pain values was considered as an acute pain change evoked by that walk. At baseline, the most affected knee of each participant was assessed using the Visual Analogue Scale (VAS) pain, the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) pain, stiffness and function, wellbeing (3 questionnaires) and the Osteoarthritis Research Society International (OARSI) recommended strength and performance measures. Results: In total, N = 24 participants started the program of whom N = 7 (29%) withdrew. Pain at the start of each walk decreased from NRS 2.5 (SD 1.6) at the frst walk (N = 24) to NRS 0.9 (SD 0.8) at the fnal walk (N = 17). This pain was estimated to decrease on NRS by-0.04 (95% CI-0.05 to-0.02) per supervised session, p < 0.001 during the frst 12 weeks and-0.01 (95% CI-0.02 to-0.004), p = 0.004 during the second twelve weeks of the program. The number (%) of participants who experienced an acute increase in pain decreased from 11 (45.8%) at the frst walk to 4 (23.5%) at the last walk. At baseline, non-adherent participants (<70% of group sessions) (N = 11) had lower physical performance scores, including the 30s Chair Stand Test (mean 10 (SD 1.7) stands versus mean 12.0 (SD 1.7) stands, p = 0.011), Fast Past Walk Test (1.23 (SD 0.14) meter per seconds (m/s) vs 1.50 (SD 0.20) m/s, p = 0.001), Six Minute Walk Test (418.8 (SD 75.9) m vs 529 (SD 72.6) m, p = 0.002), compared to adherent participants (N = 13). Non-adherent participants also had less severe self-reported symptoms including WOMAC stiffness (90.7 (SD 44.5) mm vs 121.5 (SD 17.0) mm, p = 0.031), compared to adherent participants. During the frst two weeks of walking, acute increases in pain on average (mean ≥0.5 NRS) were reported by a greater number of non-adherent (N = 5 (45.5%)) than adherent participants (n = 4 (30.8%)). Conclusion: This was an exploratory study and results need to be interpreted with caution due to the small sample size. The walking program resulted in clinically important improvements (MCIIs) (≥ 1 on NRS) (4) in start pain and acute pain changes. Improvements in start pain during the frst 12-weeks were comparable to improvements measured in the NEMEX program (2) and may suggest that 12 weeks of exercise is sufficient to achieve MCIIs in pain. Improvements in acute changes in pain were smaller, which may have been related to a foor effect (5). Lower physical performance scores at baseline and more acute increases in pain during the frst two weeks was associated with non-adherence. Participants with these characteristics may beneft from a lighter introduction to exercise.

EFFECT of PRO-INFLAMMATORY CYTOKINE-INTERLEUKIN 6 on the COURSE of ANKYLOSING SPONDYLITIS in PATIENTS after COVID-19

Background: Everyone knows that COVID-19 not only has a severe effect on the pulmonary system, but also triggers a whole cascade of autoimmune reactions. The study of the effect of the pro-infammatory cytokine-interleukin 6 (IL6) on the clinical course of patients with ankylosing spondylitis (AS) undergoing COVID-19 is an important problem in rheumatology. Objectives: To study the signifcance of the pro-infammatory cytokine-IL-6 on the clinical features of the course of AS in patients who have undergone COVID-19. Methods: In the period from 2020-2021, 44 patients with a diagnosis (AS) were hospitalized in the City Clinical Hospital # 3 of Tashkent city. The patients were divided into two groups: Group I-20 patients with AS who underwent COVID-19 and Group II of 24 patients with no history of AS who had COVID-19 infection. The average age of patients in group I was 32 ± 4.1 years and in group II-36.5 ± 5.2 years. All patients underwent clinical and laboratory studies, including studies of serum IL-6 levels. Disease activity was assessed using the BASDAI and ASDAS scales, pain was assessed using a numerical rating scale (NRS), and peripheral joint damage was assessed by the presence of pain and swelling in 44 joints. All patients underwent PCR, as well as ELISA-IHLA tests for the presence of antibodies to COVID-19. Results: Clinical examination of the patients revealed the presence of pain in the spine, which was assessed using the numerical rating scale-(NRS) in group I it was 8.5 ± 1.2 points and 5.9 ± 2.3 points in patients of group II. Examination of peripheral joints showed an average number of painful joints (PJ) of 16.9 ± 3.2 in group I and 8.6 ± 2.7 in group II, the number of swollen joints (NSJ) 8.8 ± 2.1 in group I and 4.2 ± 1.7 in group II. group. The study of AS activity using the BASDAI scale showed an average level of 5.1 ± 1.7 points in group I and 4.4 ± 2.1 points in group II. And the study of activity on the ASDAS scale showed an average level of 4.0 ± 1.7 points in group I and 2.5 ± 0.8 points in group II, which indicates a very high activity of the pathological process in group I and medium-high activity in group II. The IL-6 level in group I was 10.2 ± pg/mL, 4.2 pg/mL in group II and 1.39 pg/mL in the control group. Conclusion: 1. The clinical course of AS in patients who have undergone COVID-19 is characterized by a more pronounced disease activity according to the BASDAI and ASDAS scales, a high intensity of pain syndrome according to a NRS, as well as a high level of IL-6. 2. A high level of IL-6 in group I indicates the impact of COVID-19 on the course, activity and severity of the autoimmune process in patients with AS, which is many times higher than in patients of group II, which allows us to consider it as a biomarker of damage to the articular and connective tissue in this infection.

EFFICACY and SAFETY of UPADACITINIB in PATIENTS with ACTIVE ANKYLOSING SPONDYLITIS REFRACTORY to BIOLOGIC THERAPY: A DOUBLEBLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE 3 TRIAL

Background: Upadacitinib (UPA) was shown to be safe and effective through 2 years in patients (pts) with active ankylosing spondylitis (AS) naïve to biologic disease-modifying antirheumatic drugs (bDMARDs) in the pivotal phase 2/3 SELECT-AXIS 1 trial.1,2 Objectives: To assess the efficacy and safety of UPA in pts with active AS with an inadequate response (IR) to bDMARDs. Methods: SELECT-AXIS 2 (NCT04169373) was conducted under a master protocol and includes two separate studies (one for AS bDMARD-IR and one for non-radiographic axial spondyloarthritis [nr-axSpA]). The AS bDMARD-IR study is a randomized, double-blind, placebo (PBO)-controlled, phase 3 trial that enrolled adults ≥18 years with AS who met modifed New York criteria, had BAS-DAI and pt's assessment of total back pain scores ≥4 (numeric rating scale 0-10) at study entry, and had an IR to one or two bDMARDs (TNF inhibitor or IL-17 inhibitor). Pts were randomized 1:1 to receive oral UPA 15 mg once daily (QD) or PBO during the 14-week (wk) double-blind treatment period. The primary endpoint was ASAS40 response at wk 14. Multiplicity-controlled secondary endpoints evaluated at wk 14 were improvements from baseline in disease activity (ASDAS [CRP], ASDAS ID [<1.3], ASDAS LDA [<2.1], BASDAI50, ASAS20, and ASAS PR), pain (total and nocturnal back pain), function (BASFI), objective measure of infammation (SPARCC MRI score of the spine), spinal mobility (BASMI), enthesitis (MASES), and quality of life (ASQoL and ASAS HI). Non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle intercurrent events and missing data for binary endpoints. Cochran-Mantel-Haenszel (CMH) test and mixed-effect model for repeated measures (MMRM) were used for analyzing binary and continuous endpoints, respectively. Treatment-emergent adverse events (TEAEs) assessed through wk 14 are reported for pts who had ≥1 dose of study drug. Results: All 420 randomized pts with active AS received assigned treatment (UPA 15 mg, n=211;PBO, n=209);409 (97%) received study drug through wk 14. Baseline demographic and disease characteristics were generally similar between treatment groups and refective of an active AS bDMARD-IR population (74% male;mean age 42.4 years;mean disease duration 7. 7 years;83% HLA-B27 positive;mean BASDAI 6.8). Signifcantly more pts achieved the primary endpoint of ASAS40 response at wk 14 with UPA vs PBO (45% vs 18%;P<0.0001;Figure 1);UPA showed onset of effect in ASAS40 as early as wk 4 (nominal P≤0.05). All multiplicity-controlled secondary endpoints met statistical signifcance for UPA vs PBO at wk 14 across multiple clinical domains of AS (P<0.0001;Figure 1). The rate of TEAEs was similar between treatment groups through wk 14 (UPA, 41%;PBO, 37%). TEAEs led to discontinuation in 3 (1.4%) pts treated with PBO and none with UPA. Serious infections occurred with UPA (2.4%) but not with PBO and included 4 events of COVID-19 and 1 event of uveitis. Additional events of uveitis were reported in 3 (1.4%) pts treated with PBO. Infammatory bowel disease (IBD) occurred in 1 (0.5%) pt on UPA and none on PBO. No malignancy, major adverse cardiovascular events, venous thromboembolic events, or death were reported with UPA;1 event of malignancy was observed with PBO. Conclusion: UPA 15 mg QD was signifcantly more effective than PBO over 14 wks of treatment in pts with active AS and IR to bDMARDs. No new safety risks were identifed with UPA compared with its known safety profile.3,4 These fndings are consistent with and complementary to those of SELECT-AXIS 1 (bDMARD-naïve AS population),1,2 and support the use of UPA in pts with active AS, including those who had a previous IR to bDMARD therapy.

A Feasibility Cluster Randomised Controlled Trial of Paramedic- Administered Breathlessness Management Intervention for Acute- On-Chronic Breathlessness (BREATHE): Study Findings

Background/aims: One-fifth of conveyances to the emergency department (ED) are due to acute-on-chronic breathlessness. Paramedic breathlessness management may ease distress quicker and/or reduce ED conveyances. We evaluated the feasibility of a full trial of a paramedic delivered intervention to reduce avoidable conveyances (recruitment, randomisation, consent, training and intervention acceptability, adherence, data quality, best primary outcome, sample size estimation). The intervention comprised evidence-based non-drug techniques and a self-management booklet. Methods: This mixed-methods feasibility cluster randomised controlled trial (ISRCTN80330546) with embedded qualitative study about trial processes, training and intervention delivery, randomised paramedics to usual care or to intervention + usual care. Retrospective patient consent to use call-out data and prospective patient/carer consent for follow-up was sought. Potential primary outcomes were breathlessness intensity (numerical rating scale) and ED conveyance. Follow-up included an interview for patients/carers and questionnaires at 14 days, 1 and 6 months and paramedic focus groups and survey. Results: Recruitment was during the COVID-19 pandemic, leading to high demands on paramedics and fewer call-outs by eligible patients. We enrolled 29 paramedics;9 withdrew. Randomisation and trial procedures were acceptable. Paramedics recruited 13 patients;8 were followed up. Data quality was good. The intervention did not extend call-out time, was delivered with fidelity and no contamination and was acceptable to patients, carers and paramedics. There were no repeat call-outs < 48 hours. Recruitment stop-go criteria were not met. We had insufficient data for sample size estimation. Conclusions: A full trial in the same circumstances is not feasible. However, valuable information was gained on recruitment, attrition, consent, training and intervention acceptability and adherence, and patient-reported data collection.

Evaluation of a Remote Reiki Program for Frontline Healthcare Workers in the UK

Methods: Reiki Medic-Care is a non-profit organization that provides remote Reiki to National Health Service healthcare professionals in the UK. Healthcare professionals (e.g., physicians, nurses) negatively impacted by the COVID-19 pandemic were eligible to sign up for the Reiki program and were invited to participate in the research study. Each participant was assigned eight Reiki practitioners who gave them remote Reiki for 20 minutes for four consecutive days. Participants' stress, anxiety, pain, sleep quality and overall wellbeing were evaluated with 7-point numerical rating scales based on the Measure Yourself Medical Outcome Profile-based questionnaire. Measures were completed online when signing up to receive Reiki (pre) and following the final Reiki session (post). Pre and post data were analyzed using Wilcoxon signed ranks tests. Results: Seventy-nine healthcare professionals agreed to be in the study and provided baseline survey data (pre), and N = 40 participants completed both pre and post. Participants were 97% female and mean age was 43.9 years old (21-64 years). Healthcare professional participants included nurses (n = 15;37%), physicians (n = 14;35%), and other clinical staff such as therapists or patient care assistants (n = 11;28%). Statistically significant improvements in stress (p < .001, d = .634), anxiety (p < .001, d = .698), pain (p < .001, d = .630), wellbeing (p < .001, d = .578), and sleep (p = .019, d = .371) were observed from pre to post. Background: To conduct a pragmatic effectiveness trial of a Reiki program for healthcare professionals who have been negatively impacted by the COVID-19 pandemic. Conclusion: The Reiki program for healthcare professionals demonstrates preliminary effectiveness for improving stress, anxiety, pain, wellbeing, and sleep in frontline healthcare workers in the UK impacted by the COVID-19 pandemic. Future research will include a larger sample size and longterm follow-up.

Multiprofessional Neurorehabilitation After COVID-19 Infection Should Include Assessment of Visual Function.

Objective: To report vision-related symptoms and neuro-visual clinical signs in patients approximately 4 months after discharge from hospitalization after COVID-19 infection. To report on coexisting functional and activity limitations. Design: The study is part of an ambidirectional population-based cohort study. Setting: An outpatient setting in a hospital environment. Participants: Patients from a population-based cohort study including all patients with laboratory-confirmed COVID-19 admitted to hospital during a 3-month period in a health care region in Sweden. Among patients who, based on a standardized telephone interview, were identified as having persisting rehabilitation needs 4 months after discharge (n=185), several (n=57) reported vision-related symptoms. All 57 patients were invited to a neuro-visual examination. Six patients declined, 6 were unavailable, and 3 did not fulfil the inclusion criteria. Thus, 42 patients were included in the analysis (N=42). Interventions: Not applicable. Main Outcome Measures: Vision-related symptoms, neuro-visual function, and coexisting impairments affecting activities of daily life and participation. Results: A total of 31% of patients with rehabilitation needs after COVID-19 reported vision-related symptoms. Reading-related issues (73.8%), blurry vision (69.0%), and light sensitivity (66.7%) were the most common symptoms. Patients with reading-related issues showed a higher level of eye strain (P<.001). Neuro-visual deficits were found in 83.3% of the patients, mainly concerning eye teaming (23.1%-66.7%) and eye movement (28.6%-30.8%) functions. Patients with vision-related symptoms reported fatigue and 18 other coexisting symptoms to a greater extent (P≤.0001 to .049). Conclusions: Neuro-visual symptoms and signs should be considered when assessing rehabilitation needs after COVID-19. The association between vision-related issues and coexisting symptoms with an effect on body function and activity and/or participation underlines the need for multiprofessional rehabilitation assessment and intervention.

Psychological Impact of Covid-19 on Orthodontic Patients

Background: Unexpected postponement or delay in various treatment protocols during peak time of COVID-19 cause serious psychological trauma and obstacle to orthodontists and orthodontic patients as well. Objective: To evaluate depression and anxiety level of orthodontic patients during this chaos regarding their treatment even when the treatment was resumed. Study Design: Questionnaire-based cross-sectional study. Place and Duration of Study: Department of Orthodontics, Bacha Khan College of Dentistry, Mardan from 1st July 2021 to 31st December 2021. Methods: One hundred and sixty-six orthodontic patients were enrolled after taking informed consent from the patients. Data were taken in hard form and then later verbally translated into native language of this area. Numerical rating scale was used for psychological assessment and for the determination of anxiety level where 0 refers to no anxiety and 10 interprets extreme anxiety. Results: Ninety-three females and seventy-three males were present in this study. Conclusion: Severe anxiety level was reported and patients were greatly concerned about their health.

Ureteric stent insertion under local anaesthesia (LA): An effective, safe, and welltolerated alternative to general anaesthesia

Background: The placement of ureteric stents under local anaesthesia (LA) offers the potential for an effective and safe alternative to general anaesthesia in the context of an increasingly co-morbid population and the ongoing COVID-19 pandemic. Objectives: (1) To assess the outcomes for patients with acute ureteric stones managed with the insertion of an emergency ureteric stent under LA. (2) To report the key procedural and logistical elements required to undertake successful LA stent placement. Methods: Patients presenting with CT confirmed, obstructing ureteric stones between 17/04/2020 and 06/07/2021 were included where insertion of an LA ureteric stent was undertaken as an emergency. The primary outcome was procedure success rate and secondary outcomes were serious post-procedure complication rate (defined as Clavien-Dindo. 3), time from CT diagnosis to stent placement, and patient tolerability (defined as pain from the procedure measured on a numerical rating scale 0-10, and reported concern regarding undergoing the same procedure in the future with the options of: no problem/minor problem/moderate problem/major problem). Results: Twenty-three patients underwent emergency LA ureteric stent placement for obstructing calculi with sepsis (73.9%, n = 17), uncontrolled pain (17.4%, n = 4) or acute kidney injury (8.7%, n = 2). The procedural success rate was 95.7% (n = 22/23), and the total number of serious complications was one (4.3%) (ureteric stent migration in duplex system). The median time from diagnosis to stent was 5.3 hours (interquartile range (IQR) = 16.3). The median pain score was 2 (IQR = 5.8), and most patients (73.9%, n = 17/23) reported they would have no problem or a minor problem undergoing the same procedure again. Conclusion: The placement of ureteric stents under LA represents an effective, safe, and well-tolerated alternative to general anaesthesia. The 24/7 availability of a flexible cystoscopy suite, C-arm, and fluoroscopy and specialist urology nurse within a dedicated urology unit has facilitated the delivery of this service.