Human Herpesvirus-6 Reactivation and Disease Are Infrequent in Chimeric Antigen Receptor T-cell Therapy Recipients.

Human herpesvirus-6B (HHV-6B) reactivation and disease are increasingly reported after CAR-T-cell therapy (CARTx). HHV-6 reactivation in the CAR-T-cell product was recently reported, raising questions about product and patient management. Due to overlapping manifestations with immune effector cell-associated neurotoxicity syndrome, diagnosing HHV-6B encephalitis is challenging. We provide two lines of evidence assessing the incidence and outcomes of HHV-6B after CARTx. First, in a prospective study with weekly HHV-6B testing for up to 12 weeks post-infusion, HHV-6B reactivation occurred in eight of 89 participants; three had chromosomally integrated HHV-6 and were excluded, resulting in a cumulative incidence of HHV-6B reactivation of 6% (95% confidence interval (CI), 2.2-12.5%). HHV-6B detection was low level (median peak, 435 copies/mL; IQR, 164-979) and did not require therapy. Second, we retrospectively analyzed HHV-6B detection in blood and/or cerebrospinal fluid (CSF) within 12 weeks post-infusion in CARTx recipients. Of 626 patients, 24 had symptom-driven plasma testing with detection in one. Among 34 patients with CSF HHV-6 testing, one patient had possible HHV-6 encephalitis for a cumulative incidence of 0.17% (95% CI, 0.02-0.94%), although symptoms improved without treatment. Our data demonstrate that HHV-6B reactivation and disease are infrequent after CARTx. Routine HHV-6 monitoring is not warranted.

Cytomegalovirus (CMV) Reactivation and CMV-Specific Cell-Mediated Immunity After Chimeric Antigen Receptor T-Cell Therapy.

BACKGROUND: The epidemiology of cytomegalovirus (CMV) after chimeric antigen receptor-modified T-cell immunotherapy (CARTx) is poorly understood owing to a lack of routine surveillance. METHODS: We prospectively enrolled 72 adult CMV-seropositive CD19-, CD20-, or BCMA-targeted CARTx recipients and tested plasma samples for CMV before and weekly up to 12 weeks after CARTx. We assessed CMV-specific cell-mediated immunity (CMV-CMI) before and 2 and 4 weeks after CARTx, using an interferon γ release assay to quantify T-cell responses to IE-1 and pp65. We tested pre-CARTx samples to calculate a risk score for cytopenias and infection (CAR-HEMATOTOX). We used Cox regression to evaluate CMV risk factors and evaluated the predictive performance of CMV-CMI for CMV reactivation in receiver operator characteristic curves. RESULTS: CMV was detected in 1 patient (1.4%) before and in 18 (25%) after CARTx, for a cumulative incidence of 27% (95% confidence interval, 16.8-38.2). The median CMV viral load (interquartile range) was 127 (interquartile range, 61-276) IU/mL, with no end-organ disease observed; 5 patients received preemptive therapy based on clinical results. CMV-CMI values reached a nadir 2 weeks after infusion and recovered to baseline levels by week 4. In adjusted models, BCMA-CARTx (vs CD19/CD20) and corticosteroid use for >3 days were significantly associated with CMV reactivation, and possible associations were detected for lower week 2 CMV-CMI and more prior antitumor regimens. The cumulative incidence of CMV reactivation almost doubled when stratified by BCMA-CARTx target and use of corticosteroids for >3 days (46% and 49%, respectively). CONCLUSIONS: CMV testing could be considered between 2 and 6 weeks in high-risk CARTx recipients.

The acceptability of exercise prehabilitation before cancer surgery among patients, family members and health professionals: a mixed methods evaluation.

PURPOSE: Exercise prehabilitation aims to increase preoperative fitness, reduce post-operative complications, and improve health-related quality of life. For prehabilitation to work, access to an effective programme which is acceptable to stakeholders is vital. The aim was to explore acceptability of exercise prehabilitation before cancer surgery among key stakeholders specifically patients, family members and healthcare providers. METHODS: A mixed-methods approach (questionnaire and semi-structured interview) underpinned by the Theoretical Framework of Acceptability was utilised. Composite acceptability score, (summation of acceptability constructs and a single-item overall acceptability construct), and median of each construct was calculated. Correlation analysis between the single-item overall acceptability and each construct was completed. Qualitative data was analysed using deductive and inductive thematic analysis. RESULTS: 244 participants completed the questionnaire and n=31 completed interviews. Composite acceptability was comparable between groups (p=0.466). Four constructs positively correlated with overall acceptability: affective attitude (r=0.453), self-efficacy (r=0.399), ethicality (r=0.298) and intervention coherence (r=0.281). Qualitative data confirmed positive feelings, citing psychological benefits including a sense of control. Participants felt flexible prehabilitation program would be suitable for everyone, identifying barriers and facilitators to reduce burden. CONCLUSION: Exercise prehabilitation is highly acceptable to key stakeholders. Despite some burden, it is a worthwhile and effective intervention. Stakeholders understand its purpose, are confident in patients' ability to participate, and regard it is an important intervention contributing to patients' psychological and physical wellbeing. IMPLICATIONS: •Introduction should be comprehensively designed and clearly presented, providing appropriate information and opportunity for questions. •Programmes should be patient-centred, designed to overcome barriers and address patients' specific needs and goals. •Service must be appropriately resourced with a clear referral-pathway.

Acceptability Assessment in HIV Prevention and Treatment Intervention and Service Delivery Research: A Systematic Review and Qualitative Analysis.

We reviewed the literature on the assessment of acceptability of HIV prevention and treatment interventions and service delivery strategies. Following PRISMA guidelines, we screened 601 studies published from 2015 to 2020 and included 217 in our review. Of 384 excluded studies, 21% were excluded because they relied on retention as the sole acceptability indicator. Of 217 included studies, only 16% were rated at our highest tier of methodological rigor. Operational definitions of acceptability varied widely and failed to comprehensively represent the suggested constructs in current acceptability frameworks. Overall, 25 studies used formal quantitative assessments (including four adapted measures used in prior studies) and six incorporated frameworks of acceptability. Findings suggest acceptability assessment in recent HIV intervention and service delivery research lacks harmonization and rigor. We offer guidelines for best practices and future research, which are timely and critical in this era of informed choice and novel options for HIV prevention and treatment.

Predictors of health-related quality of life after cardiac surgery: a systematic review.

BACKGROUND: Health-related quality of life (HRQoL) is important in determining surgical success, particularly from the patients' perspective. AIMS: To identify predictors for HRQoL outcome after cardiac surgery in order to identify potentially modifiable factors where interventions to improve patient outcomes could be targeted. METHODS: Electronic databases (including MEDLINE, CINAHL, Embase) were searched between January 2001 and December 2020 for studies determining predictors of HRQoL (using a recognised and validated tool) in adult patients undergoing cardiac surgery. Data extraction and quality assessments were undertaken and data was summarised using descriptive statistics and narrative synthesis, as appropriate. RESULTS: Overall, 3924 papers were screened with 41 papers included in the review. Considerable methodological heterogeneity between studies was observed. Most were single-centre (75.6%) prospective observational studies (73.2%) conducted in patients undergoing coronary artery bypass graft (CABG) (n = 51.2%) using a version of the SF-36 (n = 63.4%). Overall, 103 independent predictors (62 pre-operative, five intra-operative and 36 post-operative) were identified, where 34 (33.0%) were reported in more than one study. Potential pre-operative modifiable predictors include alcohol use, BMI/weight, depression, pre-operative quality of life and smoking while in the post-operative period pain and strategies to reduce post-operative complications and intensive care and hospital length of stay are potential therapeutic targets. CONCLUSION: Despite a lack of consistency across studies, several potentially modifiable predictors were identified that could be targeted in interventions to improve patient or treatment outcomes. This may contribute to delivering more person-centred care involving shared decision-making to improve patient HRQoL after cardiac surgery.

Development of a theory-informed questionnaire to assess the acceptability of healthcare interventions.

BACKGROUND: The theoretical framework of acceptability (TFA) was developed in response to recommendations that acceptability should be assessed in the design, evaluation and implementation phases of healthcare interventions. The TFA consists of seven component constructs (affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy) that can help to identify characteristics of interventions that may be improved. The aim of this study was to develop a generic TFA questionnaire that can be adapted to assess acceptability of any healthcare intervention. METHODS: Two intervention-specific acceptability questionnaires based on the TFA were developed using a 5-step pre-validation method for developing patient-reported outcome instruments: 1) item generation; 2) item de-duplication; 3) item reduction and creation; 4) assessment of discriminant content validity against a pre-specified framework (TFA); 5) feedback from key stakeholders. Next, a generic TFA-based questionnaire was developed and applied to assess prospective and retrospective acceptability of the COVID-19 vaccine. A think-aloud method was employed with two samples: 10 participants who self-reported intention to have the COVID-19 vaccine, and 10 participants who self-reported receiving a first dose of the vaccine. RESULTS: 1) The item pool contained 138 items, identified from primary papers included in an overview of reviews. 2) There were no duplicate items. 3) 107 items were discarded; 35 new items were created to maximise coverage of the seven TFA constructs. 4) 33 items met criteria for discriminant content validity and were reduced to two intervention-specific acceptability questionnaires, each with eight items. 5) Feedback from key stakeholders resulted in refinement of item wording, which was then adapted to develop a generic TFA-based questionnaire. For prospective and retrospective versions of the questionnaire, no participants identified problems with understanding and answering items reflecting four TFA constructs: affective attitude, burden, perceived effectiveness, opportunity costs. Some participants encountered problems with items reflecting three constructs: ethicality, intervention coherence, self-efficacy. CONCLUSIONS: A generic questionnaire for assessing intervention acceptability from the perspectives of intervention recipients was developed using methods for creating participant-reported outcome measures, informed by theory, previous research, and stakeholder input. The questionnaire provides researchers with an adaptable tool to measure acceptability across a range of healthcare interventions.

Effect of a Home-Based, Walking Exercise Behavior Change Intervention vs Usual Care on Walking in Adults With Peripheral Artery Disease: The MOSAIC Randomized Clinical Trial.

Importance: Home-based walking exercise interventions are recommended for people with peripheral artery disease (PAD), but evidence of their efficacy has been mixed. Objective: To investigate the effect of a home-based, walking exercise behavior change intervention delivered by physical therapists in adults with PAD and intermittent claudication compared with usual care. Design, Setting, and Participants: Multicenter randomized clinical trial including 190 adults with PAD and intermittent claudication in 6 hospitals in the United Kingdom between January 2018 and March 2020; final follow-up was September 8, 2020. Interventions: Participants were randomized to receive a walking exercise behavior change intervention delivered by physical therapists trained to use a motivational approach (n = 95) or usual care (n = 95). Main Outcomes and Measures: The primary outcome was 6-minute walking distance at 3-month follow-up (minimal clinically important difference, 8-20 m). There were 8 secondary outcomes, 3 of which were the Walking Estimated Limitation Calculated by History (WELCH) questionnaire (score range, 0 [best performance] to 100), the Brief Illness Perceptions Questionnaire (score range, 0 to 80 [80 indicates negative perception of illness]), and the Theory of Planned Behavior Questionnaire (score range, 3 to 21 [21 indicates best attitude, subjective norms, perceived behavioral control, or intentions]); a minimal clinically important difference was not defined for these instruments. Results: Among 190 randomized participants (mean age 68 years, 30% women, 79% White race, mean baseline 6-minute walking distance, 361.0 m), 148 (78%) completed 3-month follow-up. The 6-minute walking distance changed from 352.9 m at baseline to 380.6 m at 3 months in the intervention group and from 369.8 m to 372.1 m in the usual care group (adjusted mean between-group difference, 16.7 m [95% CI, 4.2 m to 29.2 m]; P = .009). Of the 8 secondary outcomes, 5 were not statistically significant. At 6-month follow-up, baseline WELCH scores changed from 18.0 to 27.8 in the intervention group and from 20.7 to 20.7 in the usual care group (adjusted mean between-group difference, 7.4 [95% CI, 2.5 to 12.3]; P = .003), scores on the Brief Illness Perceptions Questionnaire changed from 45.7 to 38.9 in the intervention group and from 44.0 to 45.8 in the usual care group (adjusted mean between-group difference, -6.6 [95% CI, -9.9 to -3.4]; P < .001), and scores on the attitude component of the Theory of Planned Behavior Questionnaire changed from 14.7 to 15.4 in the intervention group and from 14.6 to 13.9 in the usual care group (adjusted mean between-group difference, 1.4 [95% CI, 0.3 to 2.5]; P = .02). Thirteen serious adverse events occurred in the intervention group, compared with 3 in the usual care group. All were determined to be unrelated or unlikely to be related to the study. Conclusions and Relevance: Among adults with PAD and intermittent claudication, a home-based, walking exercise behavior change intervention, compared with usual care, resulted in improved walking distance at 3 months. Further research is needed to determine the durability of these findings. Trial Registrations: ISRCTN Identifier: 14501418; ClinicalTrials.gov Identifier: NCT03238222.

Inconsistent relationship between depth of sedation and intensive care outcome: systematic review and meta-analysis.

PURPOSE: To determine the effect of depth of sedation on intensive care mortality, duration of mechanical ventilation, and other clinically important outcomes. METHODS: We searched MEDLINE, Embase, Cochrane Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, PsycINFO from 2000 to 2020. Randomised controlled trials (RCTs) and cohort studies that examined the effect of sedation depth were included. Two reviewers independently screened, selected articles, extracted data and appraised quality. Data on study design, population, setting, patient characteristics, study interventions, depth of sedation and relevant outcomes were extracted. Quality was assessed using Critical Appraisal Skills Programme tools. RESULTS: We included data from 26 studies (n=7865 patients): 8 RCTs and 18 cohort studies. Heterogeneity of studies was substantial. There was no significant effect of lighter sedation on intensive care mortality. Lighter sedation did not affect duration of mechanical ventilation in RCTs (mean difference (MD): -1.44 days (95% CI -3.79 to 0.91)) but did in cohort studies (MD: -1.52 days (95% CI -2.71 to -0.34)). No statistically significant benefit of lighter sedation was identified in RCTs. In cohort studies, lighter sedation improved time to extubation, intensive care and hospital length of stay and ventilator-associated pneumonia. We found no significant effects for hospital mortality, delirium or adverse events. CONCLUSION: Evidence of benefit from lighter sedation is limited, with inconsistency between observational and randomised studies. Positive effects were mainly limited to low quality evidence from observational studies, which could be attributable to bias and confounding factors.

How actionable are staff behaviours specified in policy documents? A document analysis of protocols for managing deteriorating patients.

BACKGROUND: To optimise care of deteriorating patients, healthcare organisations have implemented rapid response systems including an "afferent" and "efferent" limb. Afferent limb behaviours include monitoring vital signs and escalating care. To strengthen afferent limb behaviour and reduce adverse patient outcomes, the National Early Warning Score was implemented in the UK. There are no published reports of how National Early Warning Score guidance has translated into trust-level deteriorating patient policy and whether these documents provide clear, actionable statements guiding staff. AIM: To identify how deteriorating patient policy documents provide "actionable" behavioural instruction for staff, responsible for actioning the afferent limb of the rapid response system. DESIGN: A structured content analysis of a national guideline and local policies using a behaviour specification framework. METHODS: Local deteriorating patient policies were obtained. Statements of behaviour were extracted from policies; coded using a behaviour specification framework: Target, Action, Context, Timing and Actor and scored for specificity (1 = present, nonspecific; 2 = present, specific). Frequencies and proportions of statements containing elements of the Target, Action, Context, Timing and Actor framework were summarised descriptively. Reporting was guided by the COREQ checklist. RESULTS: There were more statements related to monitoring than escalation behaviour (65% vs 35%). Despite high levels of clear specification of the action (94%) and the target of the behaviour (74%), context, timing and actor were poorly specified (37%, 37% and 33%). CONCLUSION: Delay in escalating deteriorating patients is associated with adverse outcomes. Some delay could be addressed by writing local protocols with greater behavioural specificity, to facilitate actionability. RELEVANCE TO CLINICAL PRACTICE: Numerous clinical staff are required for an effective response to patient deterioration. To mitigate role confusion, local policy writers should provide clear specification of the actor. As the behaviours are time-sensitive, clear specification of the time frame may increase actionability of policy statements for clinical staff.

Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework.

BACKGROUND: It is increasingly acknowledged that 'acceptability' should be considered when designing, evaluating and implementing healthcare interventions. However, the published literature offers little guidance on how to define or assess acceptability. The purpose of this study was to develop a multi-construct theoretical framework of acceptability of healthcare interventions that can be applied to assess prospective (i.e. anticipated) and retrospective (i.e. experienced) acceptability from the perspective of intervention delivers and recipients. METHODS: Two methods were used to select the component constructs of acceptability. 1) An overview of reviews was conducted to identify systematic reviews that claim to define, theorise or measure acceptability of healthcare interventions. 2) Principles of inductive and deductive reasoning were applied to theorise the concept of acceptability and develop a theoretical framework. Steps included (1) defining acceptability; (2) describing its properties and scope and (3) identifying component constructs and empirical indicators. RESULTS: From the 43 reviews included in the overview, none explicitly theorised or defined acceptability. Measures used to assess acceptability focused on behaviour (e.g. dropout rates) (23 reviews), affect (i.e. feelings) (5 reviews), cognition (i.e. perceptions) (7 reviews) or a combination of these (8 reviews). From the methods described above we propose a definition: Acceptability is a multi-faceted construct that reflects the extent to which people delivering or receiving a healthcare intervention consider it to be appropriate, based on anticipated or experienced cognitive and emotional responses to the intervention. The theoretical framework of acceptability (TFA) consists of seven component constructs: affective attitude, burden, perceived effectiveness, ethicality, intervention coherence, opportunity costs, and self-efficacy. CONCLUSION: Despite frequent claims that healthcare interventions have assessed acceptability, it is evident that acceptability research could be more robust. The proposed definition of acceptability and the TFA can inform assessment tools and evaluations of the acceptability of new or existing interventions.

Patient acceptability of intravitreal complement inhibitors in geographic atrophy (GA): protocol for a UK-based cross-sectional study.

INTRODUCTION: Geographic atrophy (GA) is the advanced form of the non-neovascular ('dry') type of age-related macular degeneration (AMD). Previously untreatable, complement inhibitors delivered by regular intravitreal injections have recently been demonstrated to slow down the progression of GA lesions in phase 3 trials. One such treatment, Syfovre (pegcetacoplan), was approved by the US Food and Drug Administration in February 2023. These therapies slow down, but do not stop or reverse, the progression of GA; they may also increase the risk of developing the neovascular ('wet') type of AMD. In light of these developments, this study aims to quantify the acceptability of these new intravitreal injection treatments to patients with GA in the UK and explore factors that may influence the acceptability of these treatments. METHODS AND ANALYSIS: In this cross-sectional, non-interventional study, the primary objective is to determine the proportion of patients with GA that find regular intravitreal therapy acceptable for slowing the progression of GA. We will use a validated acceptability questionnaire in order to quantify the acceptability of new treatments among patients with GA. The correlation between acceptability and functional and structural biomarkers of GA will be established. We will also explore demographic, general health and ocular factors that may influence acceptability. 180 individuals with a diagnosis of GA will be recruited from 7 to 8 participating National Health Service trusts across the UK. Multiple regression analysis will be conducted to determine the simultaneous effects of multiple factors on patient acceptability. ETHICS AND DISSEMINATION: The study received ethical approval from the Health Research Authority on 14 March 2023 (IRAS Project ID: 324854). Findings will be disseminated through peer-reviewed publications and conference presentations to the medical retina community, as well as through dialogue with patients and macular disease charities.

Participants' experiences and acceptability of a home-based walking exercise behaviour-change intervention (MOtivating Structure walking Activity in people with Intermittent Claudication (MOSAIC)).

OBJECTIVES: This study explored the experiences and acceptability of a novel, home-based, walking exercise behaviour-change intervention (MOtivating Structured walking Activity in people with Intermittent Claudication (MOSAIC)) in adults with Peripheral Arterial Disease (PAD). DESIGN AND SETTING: Individual semi-structured audio-recorded interviews were conducted with adults with Peripheral Arterial Disease who had completed the MOSAIC intervention as part of a randomised clinical trial. Data were analysed using inductive reflexive thematic analysis and interpreted using the seven-construct theoretical framework of acceptability of healthcare interventions (TFA). PARTICIPANTS: Twenty participants (mean age (range) 67(54-80) years, 70% male, 55% White British) were interviewed. RESULTS: One central theme was identified: Acceptability of walking exercise as a treatment. This theme was explained by four linked themes: Exploring walking exercise with a knowledgeable professional, Building confidence with each step, Towards self-management-learning strategies to continue walking and The impact of walking exercise. These themes were interpreted using six of the seven TFA constructs: affective attitude, burden, perceived effectiveness, intervention coherence, opportunity costs, and self-efficacy. CONCLUSIONS: Participants perceived MOSAIC as an effective, acceptable, and low burden intervention. Physiotherapists were regarded as knowledgeable and supportive professionals who helped participants understand PAD and walking exercise as a treatment. Participants developed confidence to self-manage their condition and their symptoms. As participants confidence and walking capacity improved, they expanded their activities and gained a more positive outlook on their future. MOSAIC is an acceptable intervention that may facilitate adoption of and access to exercise for people with PAD.

Synthesis of guidance available for assessing methodological quality and grading of evidence from qualitative research to inform clinical recommendations: a systematic literature review.

OBJECTIVE: To understand (1) what guidance exists to assess the methodological quality of qualitative research; (2) what methods exist to grade levels of evidence from qualitative research to inform recommendations within European Alliance of Associations for Rheumatology (EULAR). METHODS: A systematic literature review was performed in multiple databases including PubMed/Medline, EMBASE, Web of Science, COCHRANE and PsycINFO, from inception to 23 October 2020. Eligible studies included primary articles and guideline documents available in English, describing the: (1) development; (2) application of validated tools (eg, checklists); (3) guidance on assessing methodological quality of qualitative research and (4) guidance on grading levels of qualitative evidence. A narrative synthesis was conducted to identify key similarities between included studies. RESULTS: Of 9073 records retrieved, 51 went through to full-manuscript review, with 15 selected for inclusion. Six articles described methodological tools to assess the quality of qualitative research. The tools evaluated research design, recruitment, ethical rigour, data collection and analysis. Seven articles described one approach, focusing on four key components to determine how much confidence to place in findings from systematic reviews of qualitative research. Two articles focused on grading levels of clinical recommendations based on qualitative evidence; one described a qualitative evidence hierarchy, and another a research pyramid. CONCLUSION: There is a lack of consensus on the use of tools, checklists and approaches suitable for appraising the methodological quality of qualitative research and the grading of qualitative evidence to inform clinical practice. This work is expected to facilitate the inclusion of qualitative evidence in the process of developing recommendations at EULAR level.

The challenge of exercise (non-)adherence: a scoping review of methods and techniques applied to improve adherence to physical activity and exercise in people with inflammatory arthritis.

Objectives: The aims were to explore the nature of methods/techniques applied to improve adherence to physical activity (PA) and exercise in people with inflammatory arthritis and to identify whether studies were theory based and/or used behaviour change techniques (BCTs). Methods: Searches were undertaken of English language articles within four databases: Embase, Medline, PsycINFO and Cochrane. Articles were included if they assessed adherence to a PA and/or exercise intervention. A narrative synthesis of the findings is reported. Results: Of 1909 studies screened, 18 studies met inclusion criteria. Adherence was most frequently included as a secondary outcome. Reporting of adherence measures was poor, in that 13 studies did not use a validated measure of adherence, with only three validated measures being identified. The majority of studies were not theory driven (n = 13), although the health belief model was the most used theoretical framework (n = 5). Only two studies mentioned both theory and BCTs. Four studies reported components that were mapped onto BCTs, with goal setting being the most prevalent. Conclusion: This scoping review found that adherence to PA and/or exercise interventions was rarely the focus of research, despite its importance in maintaining health in people with inflammatory arthritis. Where research has been conducted in this area, serious shortcomings were revealed, in that psychological theory, evidence-based BCTs derived from theory and valid adherence measures were not used to inform intervention design and target adherence, meaning that interventions were suboptimal. These results suggest that there is considerable room for improvement and that more high-quality research is required to investigate determinants of adherence and develop impactful interventions.

Towards a Therapy for Geographic Atrophy: A Patient's Experience.

Purpose: Geographic atrophy (GA) is the advanced form of the non-neovascular (dry) type of age-related macular degeneration. Presently, GA cannot be treated. However, new therapies administered by intravitreal injection are in late-stage development. These can slow down, but do not stop or reverse, GA progression. The acceptability of these emerging therapies to people with GA is currently unknown. The present case study explores the perspectives of a person living with GA who took part in the terminated Phase 3 clinical trial of Lampalizumab, a candidate intravitreal treatment for GA. We explored this patient's perspective on the retrospective acceptability of regular Lampalizumab injections, and the prospective acceptability of future intravitreal therapies for GA. Patients and Methods: A 78-year-old woman living in the UK was recruited as part of a mixed-methods pilot study and interviewed by telephone, regarding: her experience of the Lampalizumab trial injections; and her thoughts regarding emerging intravitreal therapies for GA. The Framework Method was used for initial inductive analysis of the interview transcript. Subsequently, deductive analysis was undertaken, informed by the Theoretical Framework of Acceptability (TFA). Results: For this participant, intravitreal injections in the Lampalizumab trial were acceptable, although streamlining processes within the clinic would have improved the patient experience. Regarding prospective acceptability of new intravitreal therapies, the participant considered a delay in progression of GA a valuable goal. Potential discomfort, anxiety and inconvenience associated with regular intravitreal injections would be acceptable in the context of preserving her vision for as long as possible. Conclusion: Analysis of one participant's experience demonstrates the value of exploring GA patients' unique views on the acceptability of new intravitreal treatments. Larger prospective studies will provide more insight that help to optimise treatment design and delivery, thereby maximising likelihood of adherence and persistence when these therapies eventually arrive in clinic.

Exploring patient acceptability of emerging intravitreal therapies for geographic atrophy: A mixed-methods study.

BACKGROUND/OBJECTIVES: The acceptability of emerging intravitreal therapies for patients with Geographic Atrophy (GA) is currently unknown. This study therefore aimed to investigate the extent to which regular intravitreal injections may be acceptable to GA patients. SUBJECTS/METHODS: Thirty UK-based individuals with GA secondary to age-related macular degeneration (AMD), recruited from two London-based hospitals, were interviewed in April-October 2021 regarding acceptability of new GA treatments. Participants responded to a structured questionnaire, as well as open-ended questions in a semi-structured interview. The Theoretical Framework of Acceptability (TFA) informed framework analysis of the qualitative data. RESULTS: Twenty participants (67%) were female, and median (interquartile range (IQR)) age was 83 (78, 87) years. 37% of participants had foveal centre-involving GA, and better eye median (IQR) logMAR visual acuity was 0.30 (0.17, 0.58). Data suggested that 18 participants (60% (95% CI: 41-79%)) would accept the treatment, despite awareness of potential drawbacks. Eight participants (27% (95% CI: 10-43%) were ambivalent or undecided about treatment, and four (13%) (95% CI: 0-26%) would be unlikely to accept treatment. Reducing the frequency of injections from monthly to every other month increased the proportion of participants who considered the treatments acceptable. Conversely, factors limiting acceptability clustered around: the limited magnitude of treatment efficacy; concerns about side effects or the increased risk of neovascular AMD; and the logistical burden of regular clinic visits for intravitreal injections. Misunderstandings of potential benefits indicate the need for appropriately-designed patient education tools to support decision-making. CONCLUSIONS: Our study suggests a majority of participants would be positive about intravitreal treatment for GA, in spite of potential burdens.

Piloting a forced-choice task to elicit treatment preferences in geographic atrophy.

OBJECTIVE: Geographic Atrophy (GA) is the advanced form of the non-neovascular ('dry') type of age-related macular degeneration (AMD) and responsible for one-quarter of legal blindness in the UK. New therapies delivered by intravitreal injection are in late-stage development, and two such therapies (pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay)) have now been approved for clinical use by the US Food and Drug Administration. These therapies slow down, but do not stop or reverse, progression of GA and they may also increase the risk of developing the neovascular ('wet') type of AMD. Within a larger study exploring the acceptability of these new treatments to people living with GA, we developed a forced-choice exercise to evaluate how participants weigh up benefits and drawbacks of different treatment regimens. This research note reports quantitative and qualitative findings from this exercise. RESULTS: Twenty-eight participants took part in this exercise. The exercise demonstrated that participants were generally, although not unanimously, in favour of less frequent treatment for GA that was slightly less efficacious in terms of preserving visual function but presented a lower risk of developing wet AMD. Even among a small sample, the exercise demonstrated the highly personal and idiosyncratic decision-making processes influencing participants' choices of preferred hypothetical GA treatment.

Acceptability of restrictions in the COVID-19 pandemic: a population-based survey in Denmark and Sweden.

Introduction: Denmark and Sweden initially adopted different responses to the COVID-19 pandemic although the two countries share many characteristics. Denmark responded swiftly with many mandatory restrictions. In contrast, Sweden relied on voluntary restrictions and a more "relaxed" response during the first wave of the pandemic. However, increased rates of COVID-19 cases led to a new approach that involved many more mandatory restrictions, thus making Sweden's response similar to Denmark's in the second wave of the pandemic. Aim: The aim was to investigate and compare the extent to which the populations in Denmark and Sweden considered the COVID-19 restrictions to be acceptable during the first two waves of the pandemic. The study also aimed to identify the characteristics of those who were least accepting of the restrictions in the two countries. Materials and methods: Cross-sectional surveys were conducted in Denmark and Sweden in 2021. The study population was sampled from nationally representative web panels in the two countries, consisting of 2,619 individuals from Denmark and 2,633 from Sweden. The questionnaire captured key socio-demographic characteristics. Acceptability was operationalized based on a theoretical framework consisting of seven constructs and one overarching construct. Results: The respondents' age and gender patterns were similar in the two countries. The proportion of respondents in Denmark who agreed with the statements ("agree" alternative) that captured various acceptability constructs was generally higher for the first wave than the second wave of the pandemic. The opposite pattern was seen for Sweden. In Denmark, 66% in the first wave and 50% in the second wave were accepting of the restrictions. The corresponding figures for Sweden was 42% (first wave) and 47% (second wave). Low acceptance of the restrictions, defined as the 25% with the lowest total score on the seven acceptability statements, was associated with younger age, male gender and lower education levels. Conclusion: Respondents in Sweden were more accepting of the restrictions in the second wave, when the country used many mandatory restrictions. In contrast, respondents in Denmark were more accepting of the restrictions in the first wave than in the second wave, implying an increased weariness to comply with the restrictions over time. There were considerable socio-demographic differences between those who expressed low acceptance of the restrictions and the others in both countries, suggesting the importance of tailoring communication about the pandemic to different segments of the population.

Unmet need for patient involvement in rheumatology registries and observational studies: a mixed methods study.

OBJECTIVE: The contribution of patient research partners (PRPs) is well established in EULAR recommendation development. However, in observational and registry studies, PRP involvement is not well-defined and remains limited. METHODS: Based on a round table discussion during the EULAR Registries and Observational Drug Studies (RODS) meeting in 2019, a mixed methods study was undertaken, including a survey to RODS participants and EULAR PRPs and focus groups with volunteers from the survey. An inductive thematic analysis approach was applied to qualitative data and descriptive statistics to survey data. RESULTS: We retrieved 45 survey responses and ran 3 focus groups with a total of 17 participants. The notion of PRP involvement in research was positively perceived by PRPs and the wider academic rheumatology community. There is universal agreement that PRP involvement in registry research is low and inclusion in different parts of the research cycle is limited. Potential benefits of PRP involvement include: input on the research objectives based on patients' needs, advice and support regarding recruitment and retention strategies, obtaining patient views on analysis and interpretation, and assistance in disseminating results. Researchers and PRPs highlighted that education, inclusion of PRPs with diverse backgrounds and a welcoming environment as important facilitators for PRP involvement. On the other hand, preconceptions of researchers and insufficient budget allocation have been identified as barriers. CONCLUSION: There is an unmet need to involve PRPs in registries and observational studies and to better define their required input during all research stages. This study provides suggestions for successful PRP integration.

Gait rehabilitation for foot and ankle impairments in early rheumatoid arthritis: a feasibility study of a new gait rehabilitation programme (GREAT Strides).

BACKGROUND: Foot impairments in early rheumatoid arthritis are common and lead to progressive deterioration of lower limb function. A gait rehabilitation programme underpinned by psychological techniques to improve adherence, may preserve gait and lower limb function. This study evaluated the feasibility of a novel gait rehabilitation intervention (GREAT Strides) and a future trial. METHODS: This was a mixed methods feasibility study with embedded qualitative components. People with early (< 2 years) rheumatoid arthritis (RA) and foot pain were eligible. Intervention acceptability was evaluated using a questionnaire. Adherence was evaluated using the Exercise Adherence Rating Scale (EARS). Safety was monitored using case report forms. Participants and therapists were interviewed to explore intervention acceptability. Deductive thematic analysis was applied using the Theoretical Framework of Acceptability. For fidelity, audio recordings of interventions sessions were assessed using the Motivational Interviewing Treatment Integrity (MITI) scale. Measurement properties of four candidate primary outcomes, rates of recruitment, attrition, and data completeness were evaluated. RESULTS: Thirty-five participants (68.6% female) with median age (inter-quartile range [IQR]) 60.1 [49.4-68.4] years and disease duration 9.1 [4.0-16.2] months), were recruited and 23 (65.7%) completed 12-week follow-up. Intervention acceptability was excellent; 21/23 were confident that it could help and would recommend it; 22/23 indicated it made sense to them. Adherence was good, with a median [IQR] EARS score of 17/24 [12.5-22.5]. One serious adverse event that was unrelated to the study was reported. Twelve participants' and 9 therapists' interviews confirmed intervention acceptability, identified perceptions of benefit, but also highlighted some barriers to completion. Mean MITI scores for relational (4.38) and technical (4.19) aspects of motivational interviewing demonstrated good fidelity. The Foot Function Index disability subscale performed best in terms of theoretical consistency and was deemed most practical. CONCLUSION: GREAT Strides was viewed as acceptable by patients and therapists, and we observed high intervention fidelity, good patient adherence, and no safety concerns. A future trial to test the additional benefit of GREAT Strides to usual care will benefit from amended eligibility criteria, refinement of the intervention and strategies to ensure higher follow-up rates. The Foot Function Index disability subscale was identified as the primary outcome for the future trial. TRIAL REGISTRATION: ISRCTN14277030.