The test-retest reliability of non-navigated transcranial magnetic stimulation (TMS) measures of corticospinal pathway excitability early after stroke.

PURPOSE: Motor evoked potential (MEP) characteristics are potential biomarkers of whether rehabilitation interventions drive motor recovery after stroke. The test-retest reliability of Transcranial Magnetic Stimulation (TMS) measurements in sub-acute stroke remains unclear. This study aims to determine the test-retest reliability of upper limb MEP measures elicited by non-neuronavigated transcranial magnetic stimulation in sub-acute-stroke. METHODS: In two identical data collection sessions, 1-3 days apart, TMS measures assessed: motor threshold (MT), amplitude, latency (MEP-L), silent period (SP), recruitment curve slope in the biceps brachii (BB), extensor carpi radialis (ECR), and abductor pollicis brevis (APB) muscles of paretic and non-paretic upper limbs. Test-retest reliability was calculated using the intra-class correlation coefficient (ICC) and 95% confidence intervals (CI). Acceptable reliability was set at a lower 95% CI of 0.70 or above. The limits of agreement (LOA) and smallest detectable change (SDC) were calculated. RESULTS: 30 participants with sub-acute stroke were included (av 36 days post stroke) reliability was variable between poor to good for the different MEP characteristics. The SDC values differed across muscles and MEP characteristics in both paretic and less paretic limbs. CONCLUSIONS: The present findings indicate there is limited evidence for acceptable test-retest reliability of non-navigated TMS outcomes when using the appropriate 95% CI for ICC, SDC and LOA values. CLINICAL TRIAL REGISTRATION: Current Controlled Trials: ISCRT 19090862, http://www.controlled-trials.com.

This study identified that Non-navigated Transcranial Magnetic Stimulation (TMS) demonstrates low reliability of TMS measures in upper limb with variation between muscles and measures in sub-acute strokeWhen using non-navigated TMS to explore corticospinal pathway excitability the individual target muscle and TMS measure should be taken into considerationNon-navigated TMS may be more useful in exploring group differences rather than individual differences in corticospinal pathway excitabilityNon-navigated TMS could provide a means of measuring recovery in clinical practice and could inform the development of more effective interventions but this needs further development before it can be used as a clinical recovery biomarker.

Assessment of the impact of social deprivation, distance to hospital and time to diagnosis on survival in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive condition associated with a variable prognosis. The relationship between socioeconomic status or distance travelled to respiratory clinics and prognosis is unclear. RESEARCH QUESTION: To determine whether socioeconomic status, distance to hospital and time to referral affects survival in patients with IPF. STUDY DESIGN AND METHODS: In this retrospective cohort study, we used data collected from the British Thoracic Society Interstitial Lung Diseases Registry, between 2013 and 2021 (n = 2359) and calculated the quintile of Index of Multiple Deprivation 2019 score, time from initial symptoms to hospital attendance and distance as the linear distance between hospital and home post codes. Survival was assessed using Cox proportional hazards models. RESULTS: There was a significant association between increasing quintile of deprivation and duration of symptoms prior to hospital presentation, Gender Age Physiology (GAP) index and receipt of supplemental oxygen and antifibrotic therapies at presentation. The most deprived patients had worse overall survival compared to least deprived after adjusting for smoking status, GAP index, distance to hospital and time to referral (HR = 1.39 [1.11, 1.73]; p = 0.003). Patients living furthest from a respiratory clinic also had worse survival compared to those living closest (HR = 1.29 [1.01, 1.64]; p = 0.041). INTERPRETATION: The most deprived patients with IPF have more severe disease at presentation and worse outcomes. Living far from hospital was also associated with poor outcomes. This suggests inequalities in access to healthcare and requires consideration in delivering effective and equitable care to patients with IPF.

Developing a core outcome set for evaluating medication adherence interventions for adults prescribed long-term medication in primary care.

BACKGROUND: Approximately half of people prescribed medications do not take them as prescribed. There is a significant unmet need regarding the barriers to medication adherence not being addressed in primary care. There is no agreement on which outcomes should be measured and reported in trials of medication adherence interventions. OBJECTIVE: To develop a core outcome set (COS) for trials of medication adherence interventions in primary care for adults prescribed medications for long-term health conditions. METHODS: A list of potentially relevant outcomes from the literature was developed. Using a two-round Delphi survey of stakeholder groups representing patients and their carers; primary care staff; and academic researchers with an interest in medication adherence; each outcome was scored in terms of importance for determining the effectiveness of medication adherence interventions in primary care. This was followed by two consensus workshops, where importance, as well as feasibility and acceptability of measurement, were considered in order to finalise the COS. RESULTS: One hundred and fifty people took part in Delphi Round 1 and 101 took part in Round 2. Eight people attended the workshops (four attendees per workshop). Seven outcomes were identified as most important, feasible and acceptable to collect in medication adherence trials: Health-related quality of life, number of doses taken, persistence with medicines, starting (initiating) a medicine, relevance of the medication adherence intervention for an individual, mortality, and adverse medicine events. CONCLUSIONS: This COS represents the minimum outcomes that should be collected and reported in all medication adherence trials undertaken in primary care. When developing and finalizing the COS, feasibility and acceptability of collection of outcomes has been considered. In addition to the COS, medication adherence trials can choose to include outcomes to suit their specific context such as the health condition associated with their medication adherence intervention.

Cessation of Smoking Trial in the Emergency Department (COSTED): a multicentre randomised controlled trial.

BACKGROUND: Supporting people to quit smoking is one of the most powerful interventions to improve health. The Emergency Department (ED) represents a potentially valuable opportunity to deliver a smoking cessation intervention if it is sufficiently resourced. The objective of this trial was to determine whether an opportunistic ED-based smoking cessation intervention can help people to quit smoking. METHODS: In this multicentre, parallel-group, randomised controlled superiority trial conducted between January and August 2022, adults who smoked daily and attended one of six UK EDs were randomised to intervention (brief advice, e-cigarette starter kit and referral to stop smoking services) or control (written information on stop smoking services). The primary outcome was biochemically validated abstinence at 6 months. RESULTS: An intention-to-treat analysis included 972 of 1443 people screened for inclusion (484 in the intervention group, 488 in the control group). Of 975 participants randomised, 3 were subsequently excluded, 17 withdrew and 287 were lost to follow-up. The 6-month biochemically-verified abstinence rate was 7.2% in the intervention group and 4.1% in the control group (relative risk 1.76; 95% CI 1.03 to 3.01; p=0.038). Self-reported 7-day abstinence at 6 months was 23.3% in the intervention group and 12.9% in the control group (relative risk 1.80; 95% CI 1.36 to 2.38; p<0.001). No serious adverse events related to taking part in the trial were reported. CONCLUSIONS: An opportunistic smoking cessation intervention comprising brief advice, an e-cigarette starter kit and referral to stop smoking services is effective for sustained smoking abstinence with few reported adverse events. TRIAL REGISTRATION NUMBER: NCT04854616.

Is there a lower visual field advantage for object affordances? A registered report.

It's been repeatedly shown that pictures of graspable objects can facilitate visual processing, even in the absence of reach-to-grasp actions, an effect often attributed to the concept of affordances. A classic demonstration of this is the handle compatibility effect, characterised by faster reaction times when the orientation of a graspable object's handle is compatible with the hand used to respond, even when the handle orientation is task-irrelevant. Nevertheless, it is debated whether the speeded reaction times are a result of affordances or spatial compatibility. First, we investigated whether we could replicate the handle compatibility effect while controlling for spatial compatibility. Participants (N = 68) responded with left or right-handed keypresses to whether the object was upright or inverted and, in separate blocks, whether the object was red or green. We failed to replicate the handle compatibility effect, with no significant difference between compatible and incompatible conditions, in both tasks. Second, we investigated whether there is a lower visual field (VF) advantage for the handle compatibility effect in line with what has been found for hand actions. A further 68 participants responded to object orientation presented either in the upper or lower VF. A significant handle compatibility effect was observed in the lower VF, but not the upper VF. This suggests that there is a lower VF advantage for affordances, possibly as the lower VF is where our actions most frequently occur. However, future studies should explore the impact of eye movements on the handle compatibility effect and tool affordances.

Hospital-based caregiver intervention for people following hip fracture surgery (HIP HELPER): multicentre randomised controlled feasibility trial with embedded qualitative study in England.

OBJECTIVES: To assess the feasibility of conducting a pragmatic, multicentre randomised controlled trial (RCT) to test the clinical and cost-effectiveness of an informal caregiver training programme to support the recovery of people following hip fracture surgery. DESIGN: Two-arm, multicentre, pragmatic, open, feasibility RCT with embedded qualitative study. SETTING: National Health Service (NHS) providers in five English hospitals. PARTICIPANTS: Community-dwelling adults, aged 60 years and over, who undergo hip fracture surgery and their informal caregivers. INTERVENTION: Usual care: usual NHS care. EXPERIMENTAL: usual NHS care plus a caregiver-patient dyad training programme (HIP HELPER). This programme comprised three, 1 hour, one-to-one training sessions for a patient and caregiver, delivered by a nurse, physiotherapist or occupational therapist in the hospital setting predischarge. After discharge, patients and caregivers were supported through three telephone coaching sessions. RANDOMISATION AND BLINDING: Central randomisation was computer generated (1:1), stratified by hospital and level of patient cognitive impairment. There was no blinding. MAIN OUTCOME MEASURES: Data collected at baseline and 4 months post randomisation included: screening logs, intervention logs, fidelity checklists, acceptability data and clinical outcomes. Interviews were conducted with a subset of participants and health professionals. RESULTS: 102 participants were enrolled (51 patients; 51 caregivers). Thirty-nine per cent (515/1311) of patients screened were eligible. Eleven per cent (56/515) of eligible patients consented to be randomised. Forty-eight per cent (12/25) of the intervention group reached compliance to their allocated intervention. There was no evidence of treatment contamination. Qualitative data demonstrated the trial and HIP HELPER programme was acceptable. CONCLUSIONS: The HIP HELPER programme was acceptable to patient-caregiver dyads and health professionals. The COVID-19 pandemic impacting on site's ability to deliver the research. Modifications are necessary to the design for a viable definitive RCT. TRIAL REGISTRATION NUMBER: ISRCTN13270387.

Validation of the Identification of Medication Adherence Barriers Questionnaire (IMAB-Q); a Behavioural Science-Underpinned Tool for Identifying Non-Adherence and Diagnosing an Individual's Barriers to Adherence.

Purpose: To validate the Identification of Medication Adherence Barriers Questionnaire (IMAB-Q) as a tool to guide practitioners to identify patients who require support to take their medicines as prescribed, their key barriers to adherence and select relevant behaviour change techniques. Patients and Methods: Adults prescribed medication for cardiovascular disease prevention were recruited from nine community pharmacies in England. Participants completed the IMAB-Q comprising 30 items representing potential barriers to adherence developed from our previous mixed methods study (scoping review and focus groups) underpinned by the Theoretical Domains Framework. Participants also self-reported their adherence on a visual analogue scale (VAS) ranging from perfect adherence (100) to non-adherence (1). A subgroup of 30 participants completed the IMAB-Q twice to investigate test-retest reliability using weighted Kappa. Mokken scaling was used to investigate IMAB-Q structure. Spearman correlation was used to investigate IMAB-Q criterion validity compared to the VAS score. Results: From 1407 invitations, 608 valid responses were received. Respondents had a mean (SD) age of 70.12 (9.9) years and were prescribed a median (IQ) 4 (3, 6) medicines. Worry about unwanted effects (n = 212, 34.5%) and negative emotions evoked by medicine taking (n = 99, 16.1%) were most frequently reported. Mokken scaling did not organise related IMAB-Q items according to the TDF domains (scalability coefficient H = 0.3 to 0.6). Lower VAS self-reported adherence correlated with greater IMAB-Q reported barriers (rho = -0.14, p = 0.001). Test-retest reliability of IMAB-Q items ranged from kappa co-efficient 0.9 to 0.3 (p < 0.05). Conclusion: The IMAB-Q is valid and reliable for identifying people not adhering and their barriers to adherence. Each IMAB-Q item is linked to a TDF domain which in turn is linked to relevant behaviour change techniques. The IMAB-Q can therefore guide patients and practitioners to select strategies tailored to a patient's identified barriers.

Perspectives of informal caregivers who support people following hip fracture surgery: a qualitative study embedded within the HIP HELPER feasibility trial.

OBJECTIVES: This study aims to illuminate the perspectives of informal caregivers who support people following hip fracture surgery. DESIGN: A qualitative study embedded within a now completed multicentre, feasibility randomised controlled trial (HIP HELPER). SETTING: Five English National Health Service hospitals. PARTICIPANTS: We interviewed 20 participants (10 informal caregivers and 10 people with hip fracture), following hip fracture surgery. This included one male and nine females who experienced a hip fracture; and seven male and three female informal caregivers. The median age was 72.5 years (range: 65-96 years), 71.0 years (range: 43-81 years) for people with hip fracture and informal caregivers, respectively. METHODS: Semistructured, virtual interviews were undertaken between November 2021 and March 2022, with caregiver dyads (person with hip fracture and their informal caregiver). Data were analysed thematically. FINDINGS: We identified two main themes: expectations of the informal caregiver role and reality of being an informal caregiver; and subthemes: expectations of care and services; responsibility and advocacy; profile of people with hip fracture; decision to be a caregiver; transition from hospital to home. CONCLUSION: Findings suggest informal caregivers do not feel empowered to advocate for a person's recovery or navigate the care system, leading to increased and unnecessary stress, anxiety and frustration when supporting the person with hip fracture. We suggest that a tailored information giving on the recovery pathway, which is responsive to the caregiving population (ie, considering the needs of male, younger and more active informal caregivers and people with hip fracture) would smooth the transition from hospital to home. TRIAL REGISTRATION NUMBER: ISRCTN13270387.Cite Now.

Impact of the increase in tuition fees and demographic factors on medical student intercalation rates between 2006 and 2020.

Introduction: No quantitative research has assessed the trends in English medical student intercalation. In addition, the impacts of the increase in tuition fees, introduced in 2012, and demographic factors on intercalation rates are unknown. Methods: Freedom of information requests were sent to all UK universities. Regression analysis compared intercalation rates before (2006-2012) and after (2012-2020) the tuition fee increase. Student's t-tests compared demographics of medical students who intercalated. Questionnaires were sent to all UK universities to explore reasons for intercalating. Results: In total, 101,085 students from seven universities responded. The intercalation rate increased from 4.70% to 10.53% (mean percentage difference (MPD) 5.84; 95% confidence interval (CI) 2.94-8.73). Intercalating students were more likely to be <25 years of age (MPD 33.36%; 95%CI 28.34-38.39), without a previous degree (MPD 8.56%; 95% CI 7.00-10.11) and without a disability (MPD 3.15%; 95% CI 0.88-5.42). In total, 389 completed questionnaires were received from 10 universities. Medical students believed an intercalated degree made them a better doctor. Discussion: The proportion of students who intercalated was greater following the increase in tuition fees. This might be explained by the value medical that students placed on the skills and opportunities that accompany an intercalated degree.

Trial Protocol: Reaccumulation rate of pleural effusions after therapeutic aspiration: An observational cohort study to determine baseline factors associated with rate of pleural fluid reaccumulation following therapeutic aspiration in patients with malignant pleural effusion attending a pleural clinic (REPEAT).

Background: Malignant pleural effusion (MPE) is the build-up of pleural fluid in the space between the lung and chest wall due to advanced cancer. It is treated initially by large volume drainage (therapeutic aspiration). If the fluid reaccumulates, a definitive procedure is performed. There is wide variation in rate of reaccumulation. Patients with rapid reaccumulation often attend hospital as an emergency. Conversely, patients with slow reaccumulation do not need a definitive procedure and may experience cancelled or unnecessary procedures. This study aims to create and validate a multivariable prediction model to predict how quickly pleural fluid will reaccumulate in patients with MPE following therapeutic aspiration. Research question: Can we predict how quickly pleural fluid will reaccumulate in patients with MPEs? Methods: A total of 200 patients with known or suspected MPE attending for therapeutic aspiration will be recruited from 5-10 UK hospitals over 20 months. Patients will be enrolled prior to undergoing aspiration. Following this, they will undergo chest X-ray, which will be repeated one week later (treatment as usual). Rate of reaccumulation will be calculated based on change of size of the effusion seen on X-ray. Data will be collected on common clinical biomarkers e.g., size of effusion on pre-aspiration chest X-ray, volume of fluid drained. This data will be analysed to create a clinical score.A further validation cohort of 40 patients will be enrolled in parallel with creation of the score. Anticipated impact: The ability to predict rate of reaccumulation of MPE will enable patients and clinicians to make better informed treatment decisions. For patients with predicted rapid reaccumulation, a definitive procedure could be offered as first-line treatment, rather than a therapeutic aspiration. This will prevent emergency hospital admissions and decrease number of procedures. By contrast, patients whose effusions will recur slowly may avoid an unnecessary procedure.

People with incurable cancer commonly feel breathless due to buildup of fluid around the lung. We treat this by draining fluid off, but it often comes back. When this happens, we offer the patient a permanent implanted drain, so they can drain the fluid off at home. However, sometimes the fluid builds up very quickly. The patient becomes very breathless and needs an emergency hospital admission. In other people, the fluid builds up slowly and they may never need another drain. The aim of this study is to improve treatment by finding a way to predict how quickly fluid will come back. It will be run in five hospitals across England and involve 240 patients over three years. When patients first come to have fluid drained, we will record information about them and their disease. We will measure how quickly the fluid comes back and record hospital admissions and need for fluid drainage over the following three months. We will use this information to create a clinical score. We will then test this score in a second group of patients to make sure it works. The idea for this study came from one of our patients who had just had fluid drained and asked, 'when will it come back?' We couldn't answer his question and therefore developed this study. Our patients and the public have been involved in the design of this study and will continue to be involved. This score will be used to inform patients so they can choose the best treatment for them. If we know the fluid will build up quickly, we can offer patients a permanent drain straight away. If patients know their fluid will build up slowly, they may choose to have the fluid drained when needed without a permanent drain.

A double-blinded randomised controlled trial of vitamin A drops to treat post-viral olfactory loss: study protocol for a proof-of-concept study for vitamin A nasal drops in post-viral olfactory loss (APOLLO).

BACKGROUND: Smell loss is a common problem with an estimated 5% of the population having no functioning sense of smell. Viral causes of smell loss are the second most common cause and the coronavirus (COVID-19) pandemic is estimated to have caused 20,000 more people this year to have a lasting loss of smell. Isolation, depression, anxiety, and risk of danger from hazards such as toxic gas and spoiled food are all negative impacts. It also affects appetite with weight loss/gain in two-thirds of those affected. Phantosmia or smell distortion can also occur making most foods seem unpalatable. Smell training has been tried with good results in the immediate post-viral phase. Evidence behind treatment with steroids has not shown to have proven effectiveness. With this, a key problem for patients and their clinicians is the lack of proven effective therapeutic treatment options. Based on previous studies, there is some evidence supporting the regenerative potential of retinoic acid, the metabolically active form of vitamin A in the regeneration of olfactory receptor neurons. It is based on this concept that we have chosen vitamin A as our study comparator. AIM: To undertake a two-arm randomised trial of intranasally delivered vitamin A vs no intervention to determine proof of concept. METHODS/DESIGN: The study will compare 10,000 IU once daily Vitamin A self-administered intranasal drops versus peanut oil drops (placebo) delivered over 12 weeks in patients with post-viral olfactory loss. Potentially eligible patients will be recruited from the Smell & Taste Clinic and via the charity Fifth Sense. They will be invited to attend the Brain Imaging Centre at the University of East Anglia on two occasions, 3 months apart. If they meet the eligibility criteria, they will be consented to enter the study and randomised to receive vitamin A drops or no treatment in a 2:1 ratio. MRI scanning will enable volumetric measurement of the OB and ROS; fMRI will then be conducted using an olfactometer to deliver pulsed odours-phenethylalcohol (rose-like) and hydrogen sulphide (rotten eggs). Participants will also perform a standard smell test at both visits as well as complete a quality-of-life questionnaire. Change in OB volume will be the primary outcome measure. DISCUSSION: We expect the outputs of this study to enable a subsequent randomised controlled trial of Vitamin A versus placebo. With PPI input we will make the outputs publicly available using journals, conferences, and social media via Fifth Sense. We have already prepared a draft RCT proposal in partnership with the Norwich Clinical Trials Unit and plan to develop this further in light of the findings. TRIAL REGISTRATION: ISRCTN registry 39523. Date of registration in the primary registry: 23rd February 2021.

Opioid burden in patients with inoperable pancreatic adenocarcinoma and the development of a multivariable risk prediction model for opioid use: A retrospective cohort study.

INTRODUCTION: Risk prediction models to guide patient selection for early pre-emptive endoscopic ultrasound guided coeliac plexus neurolysis are lacking. This study aimed to determine in patients with inoperable pancreatic cancer: (1) opioid burden, (2) the relationship between opioid use and all-cause mortality, (3) risk factors for opioid use, and (4) develop and internally validate a risk prediction model for opioid use at three months. METHODS: This was a single-centre retrospective cohort study of patients with confirmed pancreatic cancer. Cox proportional hazard regression estimated the association between opioid use at baseline and all-cause mortality. Logistic regression estimated the associations between clinical and radiological variables with opioid use by three months. Two risk prediction models were developed for opioid use (clinical and clinical-radiological). Model discrimination and calibration was assessed. RESULTS: In total, 383 patients with inoperable pancreatic cancer were included. Prevalence of pain ranged between 37% and 47% at three monthly intervals in the first year of diagnosis. Opioid use at baseline was associated with poorer survival. Age, pain at presentation, performance status, tumour distance from the right ganglion, the anterior-posterior and the latero-lateral tumour dimensions were independent risk factors for the opioid use at three months. The Area Under Curve (AUC) for the clinical and clinical-radiological models was 0.81 and 0.84, respectively. Models were well calibrated. CONCLUSIONS: Opioid use is prevalent in patients with pancreatic cancer, associated with poor prognosis, and can be predicted based on clinical and radiological variables. External validation of this predictive model is required.

Test-retest repeatability for Fatigue Assessment Scale, Short-Form 6-Dimension and King's Sarcoidosis Questionnaire in people with sarcoidosis associated fatigue.

BACKGROUND AND AIM: Patient related outcomes are important in sarcoidosis but the medium-term repeatability of the key patient reported outcome measure is not known. We aimed to test the repeatability of the Fatigue Assessment Scale (FAS), Short Form 6-Dimension (SF-6D), and King's Sarcoidosis Questionnaire (KSQ) in free living people with sarcoidosis associated fatigue. METHODS: Twelve people with sarcoidosis associated fatigue completed the FAS, short form 36 questionnaire (SF-36) and the KSQ at baseline and 12 weeks. The SF-6D utility was calculated from the SF-36. The difference between baseline and 12 week assessments was measured. RESULTS: The interclass correlation (95% confidence interval) showed good agreement between the baseline and 3 months measurements: FAS 0.91 (0.74, 0.71), SF-36 0.98 (0.94, 1), KSQ 0.98 (0.93, 0.99), SF-6D utility 0.98 (0.93, 0.99). The baseline (standard deviation) FAS was 27.83 (5.86) and at 12 weeks was 27.25 (7.55) representing 0.58 difference (95% CI for difference (-1.89, 3.06)), SF-6D utility was 0.69 (0.16) at baseline and 0.68 (0.17) after 3 months representing at 0.00 (-0.03, 0.03) difference and corresponding values for KSQ were 59.12 (18.68) and 56.91 (27.26) with a difference of -1.87 (5.49,1.76). CONCLUSIONS: There was good repeatability of FAS, SF-36, SF-6D and KSQ in free living people with sarcoidosis associated fatigue. Fatigue, general and disease specific health related quality of life showed no significant change over a 12 week period. Studies identifying changes in these outcomes can confidently report a true change and not measurement error or regression to the mean.

BabyBreathe trial: protocol for a randomised controlled trial of a complex intervention to prevent postpartum return to smoking.

INTRODUCTION: Many people quit smoking during pregnancy, but postpartum smoking relapse is common. Maintaining smoking abstinence achieved during pregnancy is key to improving maternal and child health. There are no evidence-based interventions for preventing postpartum smoking relapse. This trial aims to determine whether an intervention to prevent postpartum relapse is effective and cost-effective. METHODS AND ANALYSIS: A randomised controlled trial of a complex intervention to prevent postpartum smoking relapse (BabyBreathe), with internal pilot, economic and process evaluations. Participants are adults who are pregnant and who report having quit smoking in the 12 months before, or during pregnancy. Participants are eligible if they read and understand English, and provide informed consent. Following consent and biochemical validation of smoking abstinence, participants are randomised to intervention or usual care/control (no specific relapse prevention support). The BabyBreathe intervention consists of manualised advice from a trained member of the health visiting service, health information leaflets for participants and partners, access to the BabyBreathe website and app. At the time of birth, participants are posted the BabyBreathe box and support is provided by text message for up to 12 months postpartum. Target sample size is 880, recruiting across midwifery services at four hubs in England and Scotland and through remote advertising in England, Scotland, Wales and Northern Ireland. Outcomes are collected at 6 and 12 months. The primary outcome is self-reported sustained smoking abstinence at 12 months, carbon monoxide verified. Secondary outcomes include self-reported abstinence, time to relapse, partner smoking status and quality of life. ETHICS AND DISSEMINATION: The trial was approved by the North West Preston Research Ethics committee (21/NW/0017). Dissemination will include publication in peer-reviewed journals, presentation at academic and public conferences including patient and public involvement and to policymakers and practitioners. TRIAL REGISTRATION NUMBER: ISRCTN70307341.

CompreHensive geriAtRician-led MEdication Review (CHARMER): protocol for a feasibility study of a hospital deprescribing behaviour change intervention.

INTRODUCTION: Over 50% of older adults are prescribed a medicine where the risk of harm outweighs the chances of benefit. During a hospital admission, older adults and carers expect medicines to be reviewed for appropriateness and any inappropriate medicines proactively deprescribed. While the principle of proactive deprescribing is an expectation of good prescribing practice, it is yet to become routine. The CompreHensive geriAtRician-led MEdication Review (CHARMER) study aims to develop and test a five-component behaviour change intervention to equip geriatricians and pharmacists to proactively deprescribe inappropriate medicines with older adults in hospital. This study aims to test the feasibility and acceptability of study processes and CHARMER implementation. METHODS AND ANALYSIS: A two-arm purposive allocation feasibility study is being undertaken at four acute hospitals in England, UK (three intervention and one control). The target sample is 400 patients across all hospitals. Primary outcome measures are: (1) participant recruitment rate and (2) participant attrition rate. Secondary outcome measures are: (1) hospital readmission rate; (2) mortality rate and (3) quality of life. Quantitative data will be checked for completeness and quality, and practitioner and patient demographics descriptively analysed. We will undertake a rapid qualitative analysis on observations, interviews and study meeting minutes data. A subsequent thematic analysis will be undertaken with codes mapped to the Theoretical Domains Framework and Normalisation Process Theory. Triangulation of qualitative and quantitative data will be undertaken. ETHICS AND DISSEMINATION: Ethics approval was obtained from Wales Research Ethics Committee 1 (IRAS ID 312494) and study approval from the Health Research Authority (22/WA/0087). Informed consent will be sought from all hospital staff involved in data collection activities and for patients involved in enhanced data collection activities. The findings of this study will be disseminated in peer-reviewed journals and conference presentations. TRIAL REGISTRATION: ISRCTN11899506.

Exploring Endotypes in Chronic Rhinosinusitis (ExpRess): Protocol for a cohort study.

BACKGROUND: Chronic Rhinosinusitis (CRS) affects approximately 1 in 10 UK adults and impacts quality of life quality of life significantly. Response to treatment may be driven by individual CRS endotypes and therefore work to delineate biomarker clusters that may separate responders from non-responders is needed. The ongoing MACRO three-arm parallel-group trial randomises adult CRS patients to endoscopic sinus surgery, macrolide therapy or placebo. AIM: This study aims to correlate CRS endotypes with clinical parameters from the ongoing MACRO trial, including olfactory function and outcomes in terms of response to treatment using core biomarkers sets. METHODS: Adult CRS patients enrolled into the MACRO trial will be recruited from participating UK otorhinolaryngology departments. Nasal tissue samples and swabs will be obtained in theatre or clinic from patients randomised to all three trial arms. Nasal tissue will be analysed with multiplex electrochemiluminescence for 32 cytokines including IL-5, IL-13, IgE and periostin. Bacterial swabs will be analysed using illumina miSeq 16S amplicon sequencing. Mean expression for each biomarker will be reported for treatment responder and non-responder groups. Correlation of biomarkers with MACRO trial outcome data such as endoscopic evaluation scores and quality-of-life improvement scores will be reported. DISCUSSION: Defining clear endotypes in CRS will contribute to refining patient pathways for the efficient use of clinical resources. This work may lay the groundwork for future studies to predict which patients might respond to medical or surgical therapy.

Prevalence and Associated Factors of Medication Non-Adherence in CRS Patients following Endoscopic Sinus Surgery.

This study aimed to evaluate factors that may predispose patients to not adhere to prescribed medication after endoscopic sinus surgery (ESS) and to compare SNOT-22 scores at 0-12 months post-operatively between adherent and non-adherent patients. CRS patients who underwent ESS between 2012 and 2016 were recruited to this retrospective cohort study. Adherence was assessed through a questionnaire and review of medical notes. Ninety-four participants were included (61% male, mean age 60). Of those, 66% did not adhere to their prescribed post-operative CRS medication timing or dosage. The most common reason for non-adherence was improvement of symptoms (17%), followed by deterioration of symptoms (11%) and side effects (10%). Post-operative SNOT-22 scores were lowest for non-intentionally non-adherent (NINA) participants with a mean of 10.5 [95% CI: 7.47-13.5], compared to 25.0 for intentionally non-adherent (INA) [95% CI: 17.6-32.4] and 17.7 for adherent patients [95% CI: 13.7-21.7], p = 0.01. This study identifies that almost two-thirds of patients are not compliant with CRS medications after ESS. NINA participants reported lower post-operative SNOT-22 scores compared to INA and adherent participants. Future studies should focus on educating patients to continue with medications post-operatively despite an initial improvement in symptoms.

Systematic Review of Protein Biomarkers in Adult Patients With Chronic Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by differing inflammatory endotypes. The identification of suitable biomarkers could enable personalized approaches to treatment selection. OBJECTIVE: This study aimed to identify and summarize clinical studies of biomarkers in adults with CRS in order to inform future research into CRS endotypes. METHODS: We conducted systematic searches of MEDLINE and Web of Science from inception to January 30, 2022 and included all clinical studies of adult CRS patients and healthy controls measuring biomarkers using enzyme-linked immunosorbent assays or Luminex immunoassays. Outcomes included the name and tissue type of identified biomarkers and expression patterns within CRS phenotypes. Study quality was assessed using the National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies. A narrative synthesis was performed. RESULTS: We identified 78 relevant studies involving up to 9394 patients, predominantly with CRS with nasal polyposis. Studies identified 80 biomarkers from nasal tissue, 25 from nasal secretions, 14 from nasal lavage fluid, 24 from serum, and one from urine. The majority of biomarkers found to distinguish CRS phenotypes were identified in nasal tissue, especially in nasal polyps. Serum biomarkers were more commonly found to differentiate CRS from controls. The most frequently measured biomarker was IL-5, followed by IL-13 and IL-4. Serum IgE, IL-17, pentraxin-3 and nasal phospho-janus kinase 2, IL-5, IL-6, IL-17A, granulocyte-colony stimulating factor, and interferon gamma were identified as correlated with disease severity. CONCLUSION: We have identified numerous potential biomarkers to differentiate a range of CRS phenotypes. Future studies should focus on the prognostic role of nasal tissue biomarkers or expand on the more limited studies of nasal secretions and nasal lavage fluid.We registered this study in PROSPERO (CRD42022302787).

Aging effects on extrapersonal (far-space) attention: cancellation and line bisection performance from 179 healthy adults.

Assessment of cognitive impairments is a vital part of clinical practice. Cancellation (visual search) and line bisection are commonly used tasks to assess visuospatial attention. Despite the fact visuospatial attention is engaged in both near (within reach) and far-space (out of reach), most studies have been conducted in near-space alone. Moreover, despite their use in clinical practice, it is unclear whether cancellation and bisection tasks are related. Here, we investigated the impact of aging on cancellation and line bisection performance in far-space in a large healthy sample. We provide preliminary age-graded norms for assessing visuospatial attention in far-space calculated from a sample of 179 healthy adults, between the ages of 18-94 (mean age = 49.29). Cancellation and line bisection were presented on a large screen in far-space and completed using a wireless remote. Aging was accompanied by longer task duration for both tasks, slower search speed and poorer quality of search. However, there was no significant effect of aging on line bisection error. There was a significant correlation between the two tasks in that longer task duration in line bisection was associated with slower search speed and poorer quality of search. Overall, participants presented a leftward bias during cancellation and line bisection akin to pseudoneglect. Moreover, we found that irrespective of age, search speed was faster in males than females. We offer novel evidence that performance on cancellation and line bisection tasks are related to one another in far-space, but are also sensitive to age-related decline, and even sex differences.