Impact of the Preservation of Residual Kidney Function on Hemodialysis Survival: Results from the BISTRO Trial.

BACKGROUND: Preservation of residual kidney function (RKF) in dialysis patients has been associated with improved survival. RKF in the BISTRO trial was relatively well preserved and here we describe its association with survival during the trial and extended follow-up. METHODS: RKF, measured as the average urea and creatinine clearance (GFR) or 24-hour urine volume was assessed at baseline, one, two and three months and three-monthly up to 2 years in incident haemodialysis patients. Time to event survival data or competing events (transplantation, modality change) were obtained for 50 months post enrolment via data linkage with the UK Renal Registry. Cox proportional hazards regression survival models, including those incorporating change in GFR from baseline as a time-varying variable and joint regression models for longitudinal and survival data (longitudinal models for GFR or urine volume) were used to explore the relationship of RKF preservation with survival. Analyses were adjusted for age, sex, comorbidity and ethnicity. RESULTS: 2919 measures of RKF were made in 387 patients from 32 UK dialysis units. Higher age and comorbidity score associated with increased mortality in all models. Baseline GFR reduced the risk of death (Hazard Ratio: 0.918 95%CI: 0.844, 0.999) per ml/min/1.73m2. A greater fall in GFR and urine volume from baseline was associated with a non-significant increased risk of death as visualised on spline plots. In the joint survival models higher GFR (adjusted HR: 0.88 95%CI 0.80, 0.97) or urine volume (adjusted HR: 0.75 95%CI 0.57, 0.95 per L) at any time point associated with better survival. CONCLUSIONS: Lower RKF during the first two years of haemodialysis is associated with an increased death risk for up to 50 months following dialysis initiation. This adds to a growing body of evidence that interventions to preserve RKF should be developed and tested in clinical trials.

Cost-effectiveness of bioimpedance-guided fluid management in patients undergoing haemodialysis: the BISTRO RCT.

Background: The BioImpedance Spectroscopy to maintain Renal Output randomised controlled trial investigated the effect of bioimpedance spectroscopy added to a standardised fluid management protocol on the risk of anuria and preservation of residual kidney function (primary trial outcomes) in incident haemodialysis patients. Despite the economic burden of kidney disease, the cost-effectiveness of using bioimpedance measurements to guide fluid management in haemodialysis is not known. Objectives: To assess the cost-effectiveness of bioimpedance-guided fluid management against current fluid management without bioimpedance. Design: Within-trial economic evaluation (cost-utility analysis) carried out alongside the open-label, multicentre BioImpedance Spectroscopy to maintain Renal Output randomised controlled trial. Setting: Thirty-four United Kingdom outpatient haemodialysis centres, both main and satellite units, and their associated inpatient hospitals. Participants: Four hundred and thirty-nine adult haemodialysis patients with > 500 ml urine/day or residual glomerular filtration rate > 3 ml/minute/1.73 m2. Intervention: The study intervention was the incorporation of bioimpedance technology-derived information about body composition into the clinical assessment of fluid status in patients with residual kidney function undergoing haemodialysis. Bioimpedance measurements were used in conjunction with usual clinical judgement to set a target weight that would avoid excessive fluid depletion at the end of a dialysis session. Main outcome measures: The primary outcome measure of the BioImpedance Spectroscopy to maintain Renal Output economic evaluation was incremental cost per additional quality-adjusted life-year gained over 24 months following randomisation. In the main (base-case) analysis, this was calculated from the perspective of the National Health Service and Personal Social Services. Sensitivity analyses explored the impact of different scenarios, sources of resource use data and value sets. Results: The bioimpedance-guided fluid management group was associated with £382 lower average cost per patient (95% CI -£3319 to £2556) and 0.043 more quality-adjusted life-years (95% CI -0.019 to 0.105) compared with the current fluid management group, with neither values being statistically significant. The probability of bioimpedance-guided fluid management being cost-effective was 76% and 83% at commonly cited willingness-to-pay threshold of £20,000 and £30,000 per quality-adjusted life-year gained, respectively. The results remained robust to a series of sensitivity analyses. Limitations: The missing data level was high for some resource use categories collected through case report forms, due to COVID-19 disruptions and a significant dropout rate in the informing BioImpedance Spectroscopy to maintain Renal Output trial. Conclusions: Compared with current fluid management, bioimpedance-guided fluid management produced a marginal reduction in costs and a small improvement in quality-adjusted life-years. Results from both the base-case and sensitivity analyses suggested that use of bioimpedance is likely to be cost-effective. Future work: Future work exploring the association between primary outcomes and longer-term survival would be useful. Should an important link be established, and relevant evidence becomes available, it would be informative to determine whether and how this might affect longer-term costs and benefits associated with bioimpedance-guided fluid management. Funding details: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number HTA 14/216/01 (NIHR136142).

'Bioimpedance' is a measure of how difficult it is for an electric current to pass through a biological object. Bioimpedance is used in devices that assess fluid status (over- or under-hydration) because it is very sensitive to the amount of water in tissue. Bioimpedance can be used in addition to clinical judgement when deciding how much water should be removed from someone with kidney failure during a dialysis treatment session. This is the first study to examine whether using this treatment represents a cost-effective use of National Health Service resources. We carried out an economic evaluation within a large randomised controlled trial in patients with kidney disease undergoing haemodialysis. We calculated the additional costs and quality-adjusted life-years (a measure that combines quality and quantity of life) using established methods. Over 2 years, our study showed that taking into account bioimpedance measurements about target weight resulted in slightly lower costs and marginally more quality-adjusted life-years, although there is uncertainty around these findings.

Are return-to-play times longer in lower-limb muscle injuries involving the intramuscular tendon? A systematic review.

OBJECTIVES: To determine the influence of severity and direction (craniocaudal length vs cross-sectional area) of intramuscular tendon tears in the lower limb on return-to-play times, compared to muscle injuries without intramuscular tendon involvement. DESIGN: Systematic review with meta-analysis. METHODS: AMED, CINAHL, SPORTDiscus, ScienceDirect, PubMed (MEDLINE) and Web-of-Science were searched from inception to 31st July 2023, retrieving 666 records, of which nine were deemed eligible. A random-effects meta-analysis was performed on time to return-to-play for British Athletics Muscle Injury Classification 'b' vs 'c'. RESULTS: On the Quality in Prognosis Studies tool, one study had low risk of bias and eight had high risk. Using a best-evidence synthesis, no strong evidence emerged for a difference in time to return-to-play between injuries with or without intramuscular tendon involvement. Moderate evidence was found for an association between increased return-to-play time and the presence of "waviness" on magnetic resonance imaging and loss of tendon tension, but no association with longitudinal extent of tendon involvement. Pooled analysis revealed a medium effect-size difference between British Athletics Muscle Injury Classification 'b' and 'c' injuries, favouring classification 'b' (Hedges g = 0.67; 95% confidence interval 0.20 to 1.15; P = 0.002). CONCLUSIONS: It remains difficult to provide an accurate prognosis for muscle injuries involving the intramuscular tendon due to high risk of bias and moderate heterogeneity across studies. Moderate evidence favoured the prognosis for injuries at the musculotendinous junction (British Athletics Muscle Injury Classification 'b') over intratendinous injuries (British Athletics Muscle Injury Classification 'c').

Measuring Vulnerability in Grief: The Psychometric Properties of the Italian Adult Attitude to Grief Scale.

Although experiences of loss and the consequent grief are natural in human life, some individuals may have difficulty managing these events, to the point of developing significant impairment in their functioning in important life areas. Given this, the present research aimed to explore the psychometric properties of the Italian version of the Adult Attitude to Grief scale (AAG) to facilitate research on adult vulnerability to grief among Italian-speaking populations. A sample of 367 participants (Mage = 30.44, SD = 11.21; 78% females) participated in this research. A back-translation procedure was implemented to develop the Italian AAG. Then, participants completed the Italian AAG alongside a battery of other self-report psychometric scales in order to assess aspects of the construct validity of the AAG: the Forty-Item Defense Style Questionnaire, the Impact of Event Scale-Revised, and the Beck Depression Inventory-II. A bifactor structure was found to have the best fit to the data, supporting the possibility of using both the general factor (i.e., vulnerability) and three dimensions (i.e., overwhelmed, controlled, and resilient). Unlike the original version, the control dimension emerged as a "protective" factor in the Italian population, together with the resilient factor. Furthermore, results provided satisfactory indications of internal consistency and construct validity. In conclusion, the Italian AAG was shown to be a valid, reliable, quick, and easy-to-use scale that can be used both for research and clinical practice in the Italian context.

Bio-impedance spectroscopy added to a fluid management protocol does not improve preservation of residual kidney function in incident hemodialysis patients in a randomized controlled trial.

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: -0.178 (-0.196, -0.159)), year 2: -0.061 (-0.086, -0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: -0.04 kg; Control: -0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this.

The Effect of the COVID-19 Pandemic on HbA1c Testing: Prioritization of High-Risk Cases and Impact of Social Deprivation.

INTRODUCTION: Studies show that the COVID-19 pandemic disproportionately affected people with diabetes and those from disadvantaged backgrounds. During the first 6 months of the UK lockdown, > 6.6 M glycated haemoglobin (HbA1c) tests were missed. We now report variability in the recovery of HbA1c testing, and its association with diabetes control and demographic characteristics. METHODS: In a service evaluation, we examined HbA1c testing across ten UK sites (representing 9.9% of England's population) from January 2019 to December 2021. We compared monthly requests from April 2020 to those in the equivalent 2019 months. We examined effects of (i) HbA1c level, (ii) between-practice variability, and (iii) practice demographics. RESULTS: In April 2020, monthly requests dropped to 7.9-18.1% of 2019 volumes. By July 2020, testing had recovered to 61.7-86.9% of 2019 levels. During April-June 2020, we observed a 5.1-fold variation in the reduction of HbA1c testing between general practices (12.4-63.8% of 2019 levels). There was evidence of limited prioritization of testing for patients with HbA1c > 86 mmol/mol during April-June 2020 (4.6% of total tests vs. 2.6% during 2019). Testing in areas with the highest social disadvantage was lower during the first lockdown (April-June 2020; trend test p < 0.001) and two subsequent periods (July-September and October-December 2020; both p < 0.001). By February 2021, testing in the highest deprivation group had a cumulative fall in testing of 34.9% of 2019 levels versus 24.6% in those in the lowest group. CONCLUSION: Our findings highlight that the pandemic response had a major impact on diabetes monitoring and screening. Despite limited test prioritization in the > 86 mmol/mol group, this failed to acknowledge that those in the 59-86 mmol/mol group require consistent monitoring to achieve the best outcomes. Our findings provide additional evidence that those from poorer backgrounds were disproportionately disadvantaged. Healthcare services should redress this health inequality.

Parental acceptance of and preferences for administration of routine varicella vaccination in the UK: A study to inform policy.

OBJECTIVES: To explore acceptability of and preferences for the introduction of varicella vaccination to the UK childhood immunisation schedule. DESIGN: We conducted an online cross-sectional survey exploring parental attitudes towards vaccines in general, and varicella vaccine specifically, and their preferences for how the vaccine should be administered. PARTICIPANTS: 596 parents (76.3% female, 23.3% male, 0.4% other; mean age 33.4 years) whose youngest child was aged 0-5 years. MAIN OUTCOME MEASURES: Willingness to accept the vaccine for their child and preferences for how the vaccine should be administered (in combination with the MMR vaccine [MMRV], on the same day as the MMR vaccine but as a separate injection [MMR + V], on a separate additional visit). RESULTS: 74.0% of parents (95% CI 70.2% to 77.5%) were extremely/somewhat likely to accept a varicella vaccine for their child if one became available, 18.3% (95% CI 15.3% to 21.8%) were extremely/somewhat unlikely to accept it and 7.7% (95% CI 5.7% to 10.2%) were neither likely nor unlikely. Reasons provided by parents likely to accept the vaccine included protection from complications of chickenpox, trust in the vaccine/healthcare professionals, and wanting their child to avoid their personal experience of chickenpox. Reasons provided by parents who were unlikely included chickenpox not being a serious illness, concern about side effects, and believing it is preferable to catch chickenpox as a child rather than as an adult. A combined MMRV vaccination or additional visit to the surgery were preferred over an additional injection at the same visit. CONCLUSIONS: Most parents would accept a varicella vaccination. These findings highlight parents' preferences for varicella vaccine administration, information needed to inform vaccine policy and practice and development of a communication strategy.

Psychosocial factors affecting COVID-19 vaccine uptake in the UK: A prospective cohort study (CoVAccS - Wave 3).

Background: We investigated factors associated with COVID-19 vaccine uptake, future vaccination intentions, and changes in beliefs and attitudes over time. Methods: Prospective cohort study. 1500 participants completed an online survey in January 2021 (T1, start of vaccine rollout in the UK), of whom 1148 (response rate 76.5 %) completed another survey in October 2021 (T2, all UK adults offered two vaccine doses). Binary logistic regression analysis was used to investigate factors associated with subsequent vaccine uptake. Content analysis was used to investigate the main reasons behind future vaccine intentions (T2). Changes in beliefs and attitudes were investigated using analysis of variance. Findings: At T2, 90.0 % (95 % CI 88.2-91.7 %) of participants had received two doses of a COVID-19 vaccine, 2.2 % (95 % CI 1.3-3.0 %) had received one dose, and 7.4 % (95 % CI 5.9-8.9 %) had not been vaccinated. Uptake was associated with higher intention to be vaccinated at T1, greater perceived vaccination social norms, necessity of vaccination, and perceived safety of the vaccine. People who had initiated vaccination reported being likely to complete it, while those who had not yet received a vaccine reported being unlikely to be vaccinated in the future. At T2, participants perceived greater susceptibility to, but lower severity of, COVID-19 (p < 0.001) than at T1. Perceived safety and adequacy of vaccine information were higher (p < 0.001). Interpretation: Targeting modifiable beliefs about the safety and effectiveness of vaccination may increase uptake.

Psychological factors associated with reporting side effects following COVID-19 vaccination: A prospective cohort study (CoVAccS - Wave 3).

OBJECTIVE: To investigate symptom reporting following the first and second COVID-19 vaccine doses, attribution of symptoms to the vaccine, and factors associated with symptom reporting. METHODS: Prospective cohort study (T1: 13-15 January 2021, T2: 4-15 October 2021). Participants were aged 18 years or older, living in the UK. Personal, clinical, and psychological factors were investigated at T1. Symptoms were reported at T2. We used logistic regression analyses to investigate associations. RESULTS: After the first COVID-19 vaccine dose, 74.1% (95% CI 71.4% to 76.7%, n = 762/1028) of participants reported at least one injection-site symptom, while 65.0% (95% CI 62.0% to 67.9%, n = 669/1029) reported at least one other (non-injection-site) symptom. Symptom reporting was associated with being a woman and younger. After the second dose, 52.9% (95% CI 49.8% to 56.0%, n = 532/1005) of participants reported at least one injection-site symptom and 43.7% (95% CI 40.7% to 46.8%, n = 440/1006) reported at least one other (non-injection-site) symptom. Symptom reporting was associated with having reported symptoms after the first dose, having an illness that put one at higher risk of COVID-19 (non-injection-site symptoms only), and not believing that one had enough information about COVID-19 to make an informed decision about vaccination (injection-site symptoms only). CONCLUSIONS: Women and younger people were more likely to report symptoms from vaccination. People who had reported symptoms from previous doses were also more likely to report symptoms subsequently, although symptom reporting following the second vaccine was lower than following the first vaccine. Few psychological factors were associated with symptom reporting.

Stroke survivors' views on their priorities for upper-limb recovery and the availability of therapy services after stroke: a longitudinal, phenomenological study.

PURPOSE: Forty percent of stroke survivors have a persistent lack of function in the upper limb, causing significant disability. Most personal-care tasks and meaningful activities require bi-manual function of both upper limbs. However, lower-limb mobility is often viewed as the priority in stroke services. Perspectives of stroke survivors on priorities for upper-limb recovery and therapy have not been investigated in detail. Therefore, this study aimed to explore their views. MATERIALS AND METHODS: Thirteen stroke survivors each engaged in up to four semi-structured interviews over 18 months. A phenomenological approach guided the research. RESULTS: Three themes were identified. Priorities change on coming home: recovery of walking is a priority early after stroke but upper-limb recovery becomes equally important over time, particularly once living at home. Limited therapy services: therapy has a short duration, prioritizes lower-limb mobility, and is short-lived in the community; people feel abandoned by services. Active partners in recovery: stroke survivors want intermittent access to review and advice so they can be active partners with therapists to manage their upper-limb recovery. CONCLUSION: Therapy services should recognize stroke survivors' changing priorities and work with them as active partners in upper-limb recovery. Intermittent access to review and advice should be included in service design.Implications for rehabilitationStroke survivors' priorities may change over time from recovery of walking toward upper-limb recovery.Post-stroke services can be perceived as insufficient to meet the needs of stroke survivors who want to participate actively in rehabilitation of their upper limb.Stroke survivors may prefer services that are more flexible to provide regular review of their progress, access to guidance and support to self-manage their recovery.

Parents' intention to vaccinate their child for COVID-19: A mixed-methods study (CoVAccS-wave 3).

AIM: To investigate UK parents' vaccination intention at a time when COVID-19 vaccination was available to some children. METHODS: Data reported are from the second wave of a prospective cohort study. We conducted a mixed-methods study using an online survey of 270 UK parents (conducted 4-15 October 2021). At this time, vaccination was available to 16- and 17-year-olds and had become available to 12- to 15-year-olds two weeks prior. We asked participants whose child had not yet been vaccinated how likely they were to vaccinate their child for COVID-19. Linear regression analyses were used to investigate factors associated with intention (quantitative component). Parents were also asked for their main reasons behind vaccination intention. Open-ended responses were analysed using content analysis (qualitative component). RESULTS: Parental vaccination intention was mixed (likely: 39.3%, 95% CI 32.8%, 45.7%; uncertain: 33.9%, 95% CI 27.7%, 40.2%; unlikely: 26.8%, 95% CI 20.9%, 32.6%). Intention was associated with: parental COVID-19 vaccination status; greater perceived necessity and social norms regarding COVID-19 vaccination; greater COVID-19 threat appraisal; and lower vaccine safety and novelty concerns. In those who intended to vaccinate their child, the main reasons for doing so were to protect the child and others. In those who did not intend to vaccinate their child, the main reason was safety concerns. CONCLUSIONS: Parent COVID-19 vaccination status and psychological factors explained a large percentage of the variance in vaccination intention for one's child. Further study is needed to see whether parents' intention to vaccinate their child is affected by fluctuating infection rates, more children being vaccinated, and the UK's reliance on vaccination as a strategy to live with COVID-19.

Effectiveness of Somatosensory Stimulation for the Lower Limb and Foot to Improve Balance and Gait after Stroke: A Systematic Review.

This systematic review's purpose was to evaluate the effectiveness of lower-limb and foot somatosensory stimulation to improve balance and gait post-stroke. PRISMA reporting guidelines were followed. Included studies: randomized controlled trials (RCTs), published in English with ethical approval statement. Studies of conditions other than stroke, functional electrical stimulation, and interventions eliciting muscle contraction, were excluded. AgeLine, AMED, CINAHL PLUS, EMBASE, EMCARE MEDLINE, PEDro, PsycARTICLES, PsycINFO, SPORTDiscus, Web of Science and Cochrane central register of controlled trials were searched from 1 January 2002 to 31 March 2022. Two authors independently screened results, extracted data and assessed study quality using Cochrane Risk of Bias 2 tool; 16 RCTs (n = 638) were included. Four studies showed a medium or large standardized between-group effect size (Cohen's d) in favor of somatosensory stimulation, in relation to: customized insoles (d = 0.527), taping (d = 0.687), and electrical stimulation (two studies: d = 0.690 and d = 1.984). Although limited by study quality and heterogeneity of interventions and outcomes, with only one study's results statistically significant, several interventions showed potential for benefit, exceeding the minimally important difference for gait speed. Further research with larger trials is required. This unfunded systematic review was registered with PROSPERO (number CRD42022321199).

Barriers and facilitators related to self-management of shoulder pain: a systematic review and qualitative synthesis.

OBJECTIVE: The objective of this review was to identify barriers and facilitators related to self-management from the perspectives of people with shoulder pain and clinicians involved in their care. DATA SOURCES: CINAHL, MEDLINE, PsycINFO, SPORTDiscus, Embase, ProQuest Health, Web of Science, and Scopus were searched from inception to March 2022. REVIEW METHODS: A meta-aggregative approach to the synthesis of qualitative evidence was used. Two independent reviewers identified eligible articles, extracted the data, and conducted a critical appraisal. Two reviewers independently identified and developed categories, with validation by two further researchers. Categories were discussed among the wider research team and a comprehensive set of synthesized findings was derived. RESULTS: Twenty studies were included. From the perspective of patients, three synthesized findings were identified that influenced self-management: (1) support for self-management, including subthemes related to patient-centred support, knowledge, time, access to equipment, and patient digital literacy; (2) personal factors, including patient beliefs, patient expectations, patient motivation, pain, and therapeutic response; and (3) external factors, including influence of the clinician and therapeutic approach. From the perspective of clinicians, two synthesized findings were identified that influenced self-management: (1) support for self-management, including education, patient-centred support, patient empowerment, time, and clinician digital literacy; and (2) preferred management approach, including clinician beliefs, expectations, motivation, therapeutic approach, and therapeutic response. CONCLUSION: The key barriers and facilitators were patient-centred support, patient beliefs, clinician beliefs, pain, and therapeutic response. Most of the included studies focused on exercise-based rehabilitation, and therefore might not fully represent barriers and facilitators to broader self-management.

Are Corticosteroid Injections Associated With Secondary Adrenal Insufficiency in Adults With Musculoskeletal Pain? A Systematic Review and Meta-analysis of Prospective Studies.

BACKGROUND: Corticosteroid injection is a common treatment for individuals experiencing musculoskeletal pain, and it is part of the management of numerous orthopaedic conditions. However, there is concern about offering corticosteroid injections for musculoskeletal pain because of the possibility of secondary adrenal insufficiency. QUESTIONS/PURPOSES: In this systematic review and meta-analysis of prospective studies, we asked: (1) Are corticosteroid injections associated with secondary adrenal insufficiency as measured by 7-day morning serum cortisol? (2) Does this association differ depending on whether the shot was administered in the spine or the appendicular skeleton? METHODS: We searched the Allied and Complementary Medicine (AMED), Embase, EmCare, MEDLINE, CINAHL, and Web of Science from inception to January 22, 2021. We retrieved 4303 unique records, of which 17 were eventually included. Study appraisal was via the Downs and Black tool, with an average quality rating of fair. A Grading of Recommendations, Assessment, Development, and Evaluations assessment was conducted with the overall certainty of evidence being low to moderate. Reflecting heterogeneity in the study estimates, a pooled random-effects estimate of cortisol levels 7 days after corticosteroid injection was calculated. Fifteen studies or subgroups (254 participants) provided appropriate estimates for statistical pooling. A total of 106 participants received a spine injection, and 148 participants received an appendicular skeleton injection, including the glenohumeral joint, subacromial bursa, trochanteric bursa, and knee. RESULTS: Seven days after corticosteroid injection, the mean morning serum cortisol was 212 nmol/L (95% confidence interval 133 to 290), suggesting that secondary adrenal insufficiency was a possible outcome. There is a difference in the secondary adrenal insufficiency risk depending on whether the injection was in the spine or the appendicular skeleton. For spinal injection, the mean cortisol was 98 nmol/L (95% CI 48 to 149), suggesting secondary adrenal insufficiency was likely. For appendicular skeleton injection the mean cortisol was 311 nmol/L (95% CI 213 to 409) suggesting hypothalamic-pituitary-adrenal axis integrity was likely. CONCLUSION: Clinicians offering spinal injections should discuss the possibility of short-term secondary adrenal insufficiency with patients, and together, they can decide whether the treatment remains appropriate and whether mitigation strategies are needed. Clinicians offering appendicular skeleton injections should not limit care because of concerns about secondary adrenal insufficiency based on the best available evidence, and clinical guidelines could be reviewed accordingly. Further research is needed to understand whether age and/or sex determine risk of secondary adrenal insufficiency and what clinical impact secondary adrenal insufficiency has on patients undergoing spinal injection. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Adrenal Incidentaloma: Prevalence and Referral Patterns From Routine Practice in a Large UK University Teaching Hospital.

CONTEXT: Adrenal incidentalomas (AIs) are increasingly being identified during unrelated imaging. Unlike AI clinical management, data on referral patterns in routine practice are lacking. OBJECTIVE: This work aimed to identify factors associated with AI referral. METHODS: We linked data from imaging reports and outpatient bookings from a large UK teaching hospital. We examined (i) AI prevalence and (ii) pattern of referral to endocrinology, stratified by age, imaging modality, scan anatomical site, requesting clinical specialty, and temporal trends. Using key radiology phrases to identify scans reporting potential AI, we identified 4097 individuals from 479 945 scan reports (2015-2019). Main outcome measures included prevalence of AI and referral rates. RESULTS: Overall, AI lesions were identified in 1.2% of scans. They were more prevalent in abdomen computed tomography and magnetic resonance imaging scans (3.0% and 0.6%, respectively). Scans performed increased 7.7% year-on-year from 2015 to 2019, with a more pronounced increase in the number with AI lesions (14.7% per year).Only 394 of 4097 patients (9.6%) had a documented endocrinology referral code within 90 days, with medical (11.8%) more likely to refer than surgical (7.2%) specialties (P < .001). Despite prevalence increasing with age, older patients were less likely to be referred (P < .001). CONCLUSION: While overall AI prevalence appeared low, scan numbers are large and rising; the number with identified AI are increasing still further. The poor AI referral rates, even in centers such as ours where dedicated AI multidisciplinary team meetings and digital management systems are used, highlights the need for new streamlined, clinically effective systems and processes to appropriately manage the AI workload.

Side-effect expectations from COVID-19 vaccination: Findings from a nationally representative cross-sectional survey (CoVAccS - wave 2).

OBJECTIVES: Concern about side effects is one of the most common reasons for refusing vaccination. Side-effect expectations are known to predict perception of side effects. We aimed to investigate the percentage of people who thought side effects from COVID-19 vaccination were likely and investigate factors associated with side-effect expectation. METHODS: Online cross-sectional survey of 1470 UK adults who had not been vaccinated for COVID-19 (conducted 13 to 15 January 2021). We asked participants how likely they thought side effects from COVID-19 vaccination were. Linear regression analyses were used to investigate associations with side-effect expectations. RESULTS: Most participants were uncertain whether they would experience side effects from a COVID-19 vaccine; only a minority reported that side effects were very likely (9.4%, 95% CI 7.9% to 10.9%, n = 138/1470). Personal and clinical characteristics, general, and COVID-19 vaccination beliefs and attitudes explained 29.7% of the variance in side-effect expectation, with COVID-19 vaccination beliefs alone accounting for 17.2%. Side-effect expectations were associated with: older age, being clinically extremely vulnerable to COVID-19, being afraid of needles, lower perceived social norms for COVID-19 vaccination, lower perceived necessity and safety of COVID-19 vaccination, and perceived lack of information about COVID-19 and vaccination. CONCLUSIONS: Side-effect expectation was associated with believing that COVID-19 vaccination was unsafe, ineffective and that others would be less likely to approve of you having a COVID-19 vaccination. Communications should emphasise the safety, effectiveness, and widespread uptake of vaccination, while promoting accurate perceptions of the incidence of vaccination side effects.

Sensory Stimulation of the Foot and Ankle Early Post-stroke: A Pilot and Feasibility Study.

Background: Somatosensory stimulation of the lower extremity could improve motor recovery and walking post-stroke. This pilot study investigated the feasibility of a subsequent randomized controlled trial (RCT) to determine whether task-specific gait training is more effective following either (a) intensive hands-on somatosensory stimulation or (b) wearing textured insoles. Objectives: Determine recruitment and attrition rates, adherence to intervention, acceptability and viability of interventions and outcome measures, and estimate variance of outcome data to inform sample size for a subsequent RCT. Methods: Design: randomized, single-blinded, mixed-methods pilot study. Setting: In-patient rehabilitation ward and community. Participants: n = 34, 18+years, 42-112 days following anterior or posterior circulation stroke, able to follow simple commands, able to walk independently pre-stroke, and providing informed consent. Intervention: Twenty 30-min sessions of task-specific gait training (TSGT) (delivered over 6 weeks) in addition to either: (a) 30-60 min mobilization and tactile stimulation (MTS); or (b) unlimited textured insole (TI) wearing. Outcomes: Ankle range of movement (electrogoniometer), touch-pressure sensory thresholds (Semmes Weinstein Monofilaments), motor impairment (Lower Extremity Motricity Index), walking ability and speed (Functional Ambulation Category, 5-m walk test, pressure insoles) and function (modified Rivermead Mobility Index), measured before randomization, post-intervention, and 1-month thereafter (follow-up). Adherence to allocated intervention and actual dose delivered (fidelity) were documented in case report forms and daily diaries. Focus groups further explored acceptability of interventions and study experience. Analysis: Recruitment, attrition, and dose adherence rates were calculated as percentages of possible totals. Thematic analysis of daily diaries and focus group data was undertaken. Standard deviations of outcome measures were calculated and used to inform a sample size calculation. Results: Recruitment, attrition, and adherence rates were 48.57, 5.88, and 96.88%, respectively. Focus groups, daily-diaries and case report forms indicated acceptability of interventions and outcome measures to participants. The 5-m walk was selected as primary outcome measure for a future trial [mean (SD) at end of intervention: 16.86 (11.24) MTS group and 21.56 (13.57) TI group]; sample size calculation indicated 60 participants are required per group. Conclusion: Recruitment, attrition and adherence rates and acceptability of interventions and outcomes justify a subsequent powered RCT of MTS+TSGT compared with TI+TSGT.

Intention to have the seasonal influenza vaccination during the COVID-19 pandemic among eligible adults in the UK: a cross-sectional survey.

OBJECTIVE: To investigate the likelihood of having the seasonal influenza vaccination during the COVID-19 pandemic in individuals who were eligible to receive it. DESIGN: We conducted a cross-sectional online survey in July 2020. We included predictors informed by previous research, in the following categories: sociodemographic variables; uptake of influenza vaccine last winter and beliefs about vaccination. PARTICIPANTS: 570 participants (mean age: 53.07; 56.3% female, 87.0% white) who were eligible for the free seasonal influenza vaccination in the UK. RESULTS: 59.7% of our sample indicated they were likely to have the seasonal influenza vaccination, 22.1% reported being unlikely to have the vaccination and 18.2% were unsure. We used logistic regression to investigate variables associated with intention to receive a seasonal influenza vaccine in the 2020-2021 season. A positive attitude to vaccination in general predicted intention to have the influenza vaccine in 2020-2021 (OR 1.45, 95% CI 1.19 to 1.77, p<0.001) but the strongest predictor of intention was previous influenza vaccination behaviour (OR 278.58, 95% CI 78.04 to 994.46, p<0.001). CONCLUSIONS: Previous research suggests that increasing uptake of the influenza vaccination may help contain a COVID-19 outbreak, so steps need to be taken to convert intention into behaviour and to reach those individuals who reported being unlikely or unsure about having the vaccine.

Distinctive aspects of consent in pilot and feasibility studies.

Prior to a main randomized clinical trial, investigators often carry out a pilot or feasibility study in order to test certain trial processes or estimate key statistical parameters, so as to optimize the design of the main trial and/or determine whether it can feasibly be run. Pilot studies reflect the design of the intended main trial, whereas feasibility studies may not do so, and may not involve allocation to different treatments. Testing relative clinical effectiveness is not considered an appropriate aim of pilot or feasibility studies. However, consent is no less important than in a main trial as a means of morally legitimizing the investigator's actions. Two misperceptions are central to consent in clinical studies-therapeutic misconception (a tendency to conflate research and therapy) and therapeutic misestimation (a tendency to overestimate possible benefits and/or underestimate possible harms associated with participation). These phenomena may take a distinctive form in pilot and feasibility studies, owing to potential participants' likely prior unfamiliarity with the nature and purposes of such studies. Thus, participants may confuse the aims of a pilot or feasibility study (developing or optimizing trial design and processes) with those of a main trial (testing treatment effectiveness) and base consent on this misconstrual. Similarly, a misunderstanding of the ability of pilot and feasibility studies to provide information that will inform clinical care, or the underdeveloped nature of interventions included in such studies, may lead to inaccurate assessments of the objective possibility of benefit, and weaken the epistemic basis of consent accordingly. Equipoise may also be particularly challenging to grasp in the context of a pilot study. The consent process in pilot and feasibility studies requires a particular focus, and careful communication, if it is to carry the appropriate moral weight. There are corresponding implications for the process of ethical approval.

The experience of upper-limb dysfunction after stroke: a phenomenological study.

BACKGROUND: Stroke can bring about a profound disruption to people's lives, but what is less understood is the effect that specific dysfunctions can have. The aim of this study was to explore stroke survivors' experiences of upper-limb dysfunction over time. METHODS: 13 adult stroke survivors engaged in a series of up to four semi-structured interviews over an 18-month period after stroke. Data were interpreted through a method based on framework analysis. An interpretive phenomenological approach guided the research. RESULTS: Upper-limb dysfunction brought substantial challenges for people, identified in a main theme of an altered way of life. Subordinate themes that contributed to this alteration were challenges in personal care, participating in meaningful and valued activities, and managing life roles and relationships. The second main theme was the disrupted self, with subordinate themes of feeling devalued, disrupted self-image and changes in identity. CONCLUSION: The impact of upper-limb dysfunction on people's lives after stroke should be understood and acknowledged by rehabilitation professionals. Restoring some functional upper-limb activity could play an important role in enabling a person to regain a meaningful life and a coherent sense of self after stroke.IMPLICATIONS FOR REHABILITATIONUpper-limb dysfunction after stroke, and the loss of bimanual hand function, can profoundly alter a person's life, rendering them unable to manage simple tasks of personal care, participate in valued activities and fulfil important life roles.These functional and social limitations can then disrupt their sense of self, with feelings of low self-worth, and changes in self-image and identity.It is important that these changes in stroke survivors' lives are acknowledged and understood by rehabilitation professionals. More prolonged periods of therapy for recovery of upper-limb function, or for developing compensatory strategies, should be considered so that people can regain some meaning in life and maintain a coherent sense of self.