Research For Patient Benefit Programme Research Articles

O.2.2-6 ‘Let’s Ask the Service Users and Staff!’ - Barriers and Facilitators to Increasing Physical Activity in Medium Secure Psychiatric Services in the UK?

Abstract Purpose As part of a four-phase project, ‘Increasing Physical Activity in a Medium Service: The Development and Feasibility of a Physical ACTivity Intervention (IMPACT)’, the barriers and facilitators to increasing physical activity (PA) in medium secure psychiatric services, in the UK, were explored. Previous reviews have called for additional exploration into barriers and facilitators, as evidence has suggested a positive association between PA and the improvement in physical and psychological health for people with serious mental illnesses (SMI) and low activity levels. Methods A mixed-method approach was adopted. Questionnaires, co-developed with service users, were completed across two NHS study sites in England, UK (n = 68), collecting qualitative and quantitative data from service users in medium secure services. Two focus groups were also conducted to collect qualitative data (n = 24) from hospital staff and key stakeholders. Framework Analysis and the COM-B Model of Behaviour Change (C for Capability, O for Opportunity, M for Motivation and B for Behaviour) were used to analyse the data. For this paper, the qualitative data from both the questionnaires and the focus groups will be discussed. Results Similar themes were identified by the service users, hospital staff and key stakeholders. One main barrier discussed was environmental factors in secure services such as sedentary ward environments and the lack of autonomy in secure services. Main facilitators discussed were increasing the knowledge of benefits to PA and having structural guidance for personal development. Conclusion The barriers and facilitators identified will inform the remaining phases of the IMPACT project, including a co-produced PA intervention, based on overcoming the barriers and supporting the facilitators identified. A feasibility study will then test the PA Intervention. This feature of co-producing a PA intervention in medium secure services, based on barriers and facilitators, adds to the limited literature in this area. The aim of the IMPACT project is to inform future a pilot study and policies. Support/Source National Institute for Health and Care Research (NIHR) - Research for Patient Benefit Programme (IRAS ID 297420).

Trends in gabapentinoid prescribing in UK primary care using the Clinical Practice Research Datalink: an observational study

The UK government reclassified gabapentin and pregabalin as 'controlled drugs' from April 2019. This study aimed to describe the trends in gabapentinoid prescribing before and immediately after reclassification, in the UK Clinical Practice Research Datalink, an electronic primary care health record broadly representative of the UK. Separately for gabapentin and pregabalin, we calculated annual incident and prevalent prescribing rates from year of UK approval (April 1997 and 2004 respectively) to September 2019, and monthly incident and prevalent prescribing rates (October 2017-September 2019). Significant changes in temporal trends were determined using joinpoint regression. We also described potential prescribing indications, prior pain-related prescribing, and co-prescribing with potentially interacting medicines. Incident gabapentin prescribing increased annually, peaking in 2016-17, at 625/100,000 patient years before falling steadily to 2019. Incident pregabalin prescribing peaked at 329/100,000 patient years in 2017-18 and did not fall significantly until 2019. Prevalent gabapentin and pregabalin prescribing increased annually to 2017-18 and 2018-19 respectively, before plateauing. Gabapentinoids were commonly co-prescribed with opioids (60%), antidepressants (52%), benzodiazepines (19%), and Z-drugs (10%). Following a dramatic rise, incident gabapentinoid prescribing has started to fall but the specific impact of reclassification on prescribing rates remains unclear. Limited change in prevalent gabapentinoid prescribing during the 6 months following their reclassification as controlled drugs suggests little immediate impact on continued gabapentinoid prescribing for existing users. National Institute for Health and Care Research (NIHR) Research for Patient Benefit Programme. NIHR Applied Research Collaboration West Midlands. NIHR School for Primary Care Research.

Inclusion of progression criteria in external randomised pilot trials: a cross-sectional study of funding applications submitted to the NIHR Research for Patient Benefit Programme

BackgroundExternal randomised pilot trials aim to assess whether a future definitive randomised controlled trial (RCT) is feasible. Pre-specified progression criteria help guide the interpretation of pilot trial findings to decide whether, and how, a definitive trial should be conducted. We aimed to examine how researchers report and plan to assess progression criteria in external pilot trial funding applications submitted to the NIHR Research for Patient Benefit Programme.MethodsWe conducted a cross-sectional study of progression criteria inclusion in Stage 1 (outline) and corresponding Stage 2 (full) funding applications for external randomised external pilot trials submitted to NIHR RfPB between July 2017 and July 2019.ResultsOf the 100 Stage 1 outline applications assessed, 95 were eligible for inclusion (of these, 52 were invited to Stage 2 full application; 43 were rejected) and 49/52 were eligible for inclusion at Stage 2 full application (of these, 35 were awarded funding; 14 were rejected). Over half of applications assessed at Stage 1 (48/95, 51%), and 73% of those assessed at Stage 2 (36/49) included progression criteria in their research plans. Progression criteria were most often reported in a stop-go format, often with additional specified factors that should be considered when determining feasibility (Stage 1 33/48, 69%; Stage 2 21/36, 58%). Recruitment and retention were the most frequent indicators of feasibility to inform progression criteria. One-third of applications provided some justification or rationale for their targets (Stage 1 16/48, 33%; Stage 2 12/36, 33%). Funding committee feedback mentioned progression criteria in over 20% of applications (Stage 1 22/95, 23%; Stage 2 11/49, 22%) to either request the addition of progression criteria or provide justification for the criteria stipulated.ConclusionsOur findings indicate that researchers do not always include progression criteria in external randomised pilot trial applications submitted to research funders. This can result in a lack of transparency in the assessment of randomised pilot trial feasibility.Trial registrationOpen Science Framework osf.io/89ap7, registered 29th June 2021.

Effectiveness and cost effectiveness of digital hearing aids in patients with tinnitus and hearing loss: a randomised feasibility trial (THE HUSH Trial)

BackgroundEducation and advice is provided for tinnitus management in all UK audiology clinics. Sound therapy, including provision of hearing aids may be offered, but this is often dependent on a clinician’s decision rather than UK policy. This inconsistent management reflects a lack of evidence around the effectiveness of hearing aids for tinnitus. This open-label, two-arm multicentre randomised controlled feasibility trial gathered data around recruitment, acceptability and outcome assessments to determine the feasibility of conducting a large randomised controlled trial investigating the effectiveness of hearing aids for tinnitus management.MethodsAdults referred to audiology for tinnitus, with an aidable hearing loss were recruited at five UK audiology clinics. They were randomised 1:1 to either education and advice (treatment as usual (TAU), n = 41) or TAU plus hearing aids (n = 42). Outcomes were collected by questionnaires 12 weeks after randomisation. After participation, interviews were conducted with a subset of both participants and clinicians from each trial centre.ResultsEighty three participants from five sites were randomised. Non-aidable hearing loss was the main reason for ineligibility to participate in the trial reported by the sites. Seventy three percent of participants returned the 12-week questionnaires, with return rates by site ranging from 61 to 100%. Fifteen out of 33 participants (45%) reported using hearing aids for the clinician-recommended time, or longer, during the day. The Tinnitus Functional Index (TFI) was the outcome measure most responsive to change. The majority of participants also agreed it was relevant to their tinnitus and hearing loss. Qualitative data demonstrated that the trial was acceptable to participants. Feedback from clinicians revealed a potential lack of equipoise. It also highlighted the differences in referral and treatment pathways between departments and differences in audiometric criteria for fitting hearing aids. Health economic measures were well completed for those returned. No change in health-related quality of life was observed. Costs were higher in the intervention arm, but self-reports of healthcare service use indicated participant confusion in treatment pathways.ConclusionsThis feasibility trial is the first step towards obtaining high quality evidence to determine potential clinical effectiveness and cost effectiveness of hearing aids for tinnitus versus usual care. A definitive trial was deemed to be feasible, with some modifications based on feasibility findings and using the TFI as the primary outcome.This trial was funded by the National Institute for Health Research, Research for Patient Benefit Programme (PB-PG-0816–20,014) and registered with ISRCTN (ISRCTN14218416).

Hormone replacement therapy (conjugated oestrogens plus bazedoxifene) for post-menopausal women with symptomatic hand osteoarthritis: primary report from the HOPE-e randomised, placebo-controlled, feasibility study.

Symptomatic hand osteoarthritis is more common in women than in men, and its incidence increases around the age of menopause, implicating oestrogen deficiency. No randomised controlled trials of hormone replacement therapy (HRT) have been done in people with hand osteoarthritis. We aimed to determine the feasibility and acceptability of a form of HRT (conjugated oestrogens plus bazedoxifene) in post-menopausal women with painful hand osteoarthritis. The HOPE-e feasibility study was a randomised, double-blind, placebo-controlled trial, for which we recruited women aged 40-65 years, for whom 1-10 years had passed after their final menstrual period, with definite hand osteoarthritis and at least two painful hand joints. Participants were recruited across three primary or secondary care sites and from the community and were randomly assigned (1:1) to receive conjugated oestrogens plus bazedoxifene or placebo, orally once every day for 24 weeks, before weaning for 4 weeks until the end of the study. The primary feasibility outcomes were rates of identification, recruitment, randomisation, retention, and compliance of eligible participants, and the likelihood of unmasking. The secondary objective was to generate proof-of-concept quantitative and qualitative data on the acceptability of proposed clinical outcomes for a full trial and adverse events. We used an intention-to-treat analysis, and criteria for progression to a full trial were pre-defined as recruitment of at least 30 participants across all sites in 18 months; a dropout rate of less than or equal to 30% of randomised individuals; and acceptability to the majority of participants, including acceptable rates of adverse events. Due to the COVID-19 pandemic, the recruitment window was reduced to 12-15 months. A proportionately reduced minimum sample size of 22 was judged to be sufficient to test feasibility. This trial was registered at ISRCTN, ISRCTN12196200. From May 9, 2019 to Dec 31, 2020, 434 enquiries or referrals were received. We did 96 telephone pre-screens; of the 35 eligible participants, seven were excluded as ineligible at the telephone or face-to-face screening and 28 (80% [95% CI 63-92]) were randomly assigned. Of the 406 who were not randomly assigned, 250 (62%) were ineligible (with contraindicated medications accounting for 50 [20%] of these), 101 (25%) did not respond to further enquiries, and 55 (14%) chose not to proceed (with the most common reason being not wanting to take a hormone-based drug). All 28 randomised participants completed all follow-up assessments with high compliance and outcome measure completeness. All three adverse event-related treatment withdrawals were in the placebo group. No serious adverse events were reported. Participants and investigators were successfully masked (participant Bang's blinding index placebo group 0·50 [95% CI 0·25-0·75]). The trial met the prespecified criteria for progression to a full trial. This first-ever feasibility study of a randomised controlled trial of HRT for post-menopausal women with painful hand osteoarthritis met its progression criteria, although it was not powered to detect a clinical effect. This outcome indicates that a full trial of an HRT in this population is feasible and acceptable and identifies potential refinements with regard to the design of such a trial. Research for Patient Benefit programme, National Institute for Health Research.

What factors influence differential uptake of NHS Health Checks, diabetes and hypertension reviews among women in ethnically diverse South London? Cross-sectional analysis of 63,000 primary care records

SummaryBackgroundUptake of health checks among women has not been examined in relation to patient and General Practitioner (GP) practice level factors. We investigated patient and practice level factors associated with differential uptake of health checks.MethodsPrimary care records from 44 practices in Lambeth for women aged 40-74 years old (N = 62,967) from 2000-2018 were analysed using multi-level logistic regression models. An odds ratio (OR) >1 indicates increased occurrence of no health check.FindingsThe mean age (IQR) of the included female sample (aged 40-74 years) was 52.9 years (45.0-59.0). Adjusted for patient-level factors (age, ethnicity, English as first language, overweight/obesity, smoking, attendance to GP practices, and co-morbidity), the odds of non-uptake of health checks were higher for Other White (OR 1.24, 95% confidence interval 1.17-1.33), and Other ethnicity (1.20, 1.07-1.35) vs. White British. It was also higher for 50-69 year olds (1.55, 1.47-1.62), 70-74 year olds (1.60, 1.49-1.72) vs. 40-49 year olds. These ORs did not change on adjustments for practice level factors (proportion of patients living in deprived areas, proportion of patients with ≥1 chronic condition, ≥3 emergency diabetes admissions annually, GP density/1000 patients, quality outcome framework score of ≥ 95%, and patient satisfaction scores of ≥80%). Non-uptake was lower for Black Caribbeans, Bangladeshis, overweight/obese patients, frequent practice attenders and comorbid patients.InterpretationDifferential uptake in health checks remained after adjustment for patient and practice level factors. Better measures of social determinants of health and of practice context are needed.FundingNIHR Research for Patient Benefit Programme (NIHR202769).

Social determinants of diabetes, hypertension, stroke, and coronary heart disease in Black Caribbean and Black African women aged 40 years or older in south London: findings from 70 582 primary care records from 2000–18

BackgroundThe contribution of social determinants, such as deprivation and health-related behaviours, to Black African and Black Caribbean–White differences in cardiovascular risks is uncertain. MethodsPrimary care records from 44 practices in Lambeth (Lambeth DataNet) from Jan 1, 2000, to Oct 27, 2018, for women aged 40 years or older were analysed using multilevel logistic regression models adjusted for age, income deprivation, lifestyles, health-care access, comorbidities (Quality and Outcome Framework disease registers) and medications, and for clustering of patients within practices. FindingsWe studied 70 582 women aged 40 years or older from White (n=35 297), Black African (n=11 206), and Black Caribbean (n=9193) ethnic groups. In women aged 40–69 years, smoking levels were similar in White and Black Caribbean groups (approximately 19%), but much lower in Black African groups (6·1%). In both age groups, obesity levels (ie, a body-mass index of ≥30 kg/m2) in Black Caribbean women (44·3%) and Black African women (48·9%) were around double that in White women (20·8%). Levels of missing data were low (2–10%), and were included as a separate category in each variable. Adjusted for age and income deprivation and compared with White women, excess risks observed at age 40–69 years (n=59 132) for Black African women were diabetes (odds ratio [OR] 2·94, 95% CI 2·69–3·20; p<0·0001), hypertension (3·80, 3·56–4·05; p<0·0001), and stroke (1·43, 1·11–1·85; p=0·006), and for Black Caribbean women were diabetes (3·10, 2·84–3·39; p<0·0001), hypertension (3·57, 3·34–3·82; p<0·0001), and stroke (1·53, 1·17–1·99; p=0·002). In women aged 70 years and older (n=11 450), the excess risks for Black African women were diabetes (2·62, 2·27–3·03; p<0·0001), hypertension (2·13, 1·84–2·47; p<0·0001), and stroke (1·48, 1·12–1·95; p=0·006), and for Black Caribbean women, were diabetes (4·36, 3·88–4·91; p<0·0001), hypertension (3·02, 2·65–3·44; p<0·0001), and stroke (2·01, 1·65–2·47; p<0·0001). Significantly lower coronary heart disease risks were observed only for Black African women aged 40–69 years (0·80, 0·62–1·05; p=0·105), and women aged 70 years or older (0·57, 0·44–0·74; p<0·0001). Adjusting for deprivation accounted for approximately 10–15% attenuation of excess risk in these models. Additional adjustments for smoking and overweight led to further attenuation of excess risk for hypertension and stroke by 2–14% in both groups, and an increase in deficit of 4–15% for cardiovascular disease in Black African women. Among Black Caribbean women, ORs for cardiovascular disease remained non-significant compared with White women in the group aged 40–69 years, but became significantly lower among women aged 70 years or older (0·79, 0·65–0·95; p=0·0110), mainly due to smoking. InterpretationDeprivation and health-related behaviours made notable contributions to differences in cardiovascular risks between Black African, Black Caribbean, and White ethnic groups, consistent with earlier studies. FundingNational Institute of Health Research, Research for Patient Benefit Programme (NIHR202769).

The use of hairdressing and beauty salons as health-promotion environments for the prevention and management of non-communicable diseases in ethnically diverse women

BackgroungWomen from some minoritised ethnic groups are disproportionately affected by non-communicable disease (NCDs), due to socioeconomic disadvantage, underlying health problems, health behaviours, and distrust of mainstream health services. Integrating community structures, such as hairdressing and beauty salons into existing primary care pathways can provide a sustainable process to address inequalities in access to health care. The aim of this global scoping review was to map and summarise the evidence about community salon-based interventions targeting ethnically diverse women (eg, Black African, Black Caribbean, and Asian women) for NCD prevention and management, including formative phases, theoretical approaches, and evaluation. MethodsSix databases (PubMed, Web of Science, Embase, PsycInfo, MEDLINE, and Global Health) were searched for relevant articles published from inception until July 17, 2020. Search terms included women, Black-African, Black-Caribbean, mixed ethnicity, Asian, Indian, Pakistani, nail bar, hair salon, hairdressers, intervention, and non-communicable disease. Reference lists of relevant articles (excluding letters, editorials, and protocols) were screened using a participants, concept, context framework. All authors independently screened the titles and abstracts identified and eligible full-text articles. Disagreements were discussed between authors to reach consensus, and reasons for exclusion documented. Process and outcome evaluation was assessed using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. Thematic synthesis followed previously published guidance. Risk of bias was assessed using the Quality In Prognosis Study tool. Findings525 titles and abstracts were screened, and eight met the inclusion criteria. All eight studies were US based. Two used formative phases to inform intervention development, and five referred to conceptual frameworks (Health Belief Model, Social Cognitive Theory, Chronic Care Model). Three studies described codevelopment with key community stakeholders. All studies reported outcome evaluation and the results generally showed positive changes in retention of knowledge, intention to change behaviour, changes in behaviour and in risk awareness. Five studies conducted process evaluation. Indicators included salon or participant attrition, therapists' insights of the intervention, clients' observations from the intervention, confidence of clients in their therapists to deliver the correct health messages, and the confidence and willingness of therapists to deliver health promotion messages. Sociodemographic characteristics were reported in two studies; however, their role in equity of coverage or influence on outcomes were not described. InterpretationScoped studies were largely US based and applicability to other settings is unclear. More consistent integration of formative phases, community participation, including health or social care partnerships, and process evaluation are crucial to understand the public health impact for women of ethnic minority groups. FundingNational Institute of Health Research, Research for Patient Benefit Programme (grant number NIHR202769).

The metformin in tuberous sclerosis (MiTS) study: A randomised double-blind placebo-controlled trial.

BackgroundTuberous Sclerosis Complex (TSC) is a genetic disorder characterised by the development of benign tumours secondary to loss of inhibitory regulation of the mTOR (mechanistic Target of Rapamycin) intracellular growth pathway. Metformin inhibits the mTOR pathway. We investigated whether metformin would reduce growth of hamartomas associated with tuberous sclerosis complex.MethodsIn this multicentre randomized, double-blind, placebo-controlled trial, patients with a clinical diagnosis of tuberous sclerosis, aged over 10 years and with at least one renal angiomyolipoma of greater than 1 cm in diameter were enrolled. Participants were randomly allocated (1:1) by a secure website to receive metformin or placebo for 12 months. The primary outcome was percentage volume change of renal angiomyolipomas (AML) at 12 months compared to baseline. Secondary outcomes were percentage change at 12 months from baseline in volume of cerebral Subependymal Giant Cell Astrocytomas (SEGA); appearance of facial and ungual hamartomas; frequency of epileptic seizures; and adaptive behaviour. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 92545532, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2011-001319-30.FindingsBetween 1 November 2012 and 30 September 2015 72 patients were screened and 55 were randomly assigned to metformin (28) or placebo (27). Four participants withdrew between randomisation and starting treatment. All 51 patients who started therapy completed the trial and were assessed for outcome at 12 months. The median percentage change in angiomyolipoma (AML) volume was +7.6% (IQR -1.8% to +42.6%) for the placebo group and +8.9% (IQR 1.3% to 19.5%) for the metformin group (p = 0.28). Twenty-seven patients had SEGAs: 13 received placebo and 14 metformin. The median percentage change in SEGA volume was +3.0% (IQR -22.8% to +27.7%) for the placebo group and – 20.8% (IQR – 47.1% to - 5.0%) for the metformin group (p = 0.03). Twenty-one patients were assessed for seizure frequency: 9 received placebo and 12 received metformin. In the metformin group, a mean reduction of 43.7% from baseline in seizures was observed and in the placebo group a 3.1% mean reduction was observed, with a difference in response of 40.6% (95% CI -3.1% to +84.2%, p = 0.03). There were no significant differences between metformin and placebo groups for the other secondary outcomes. There were no deaths. Three serious adverse events (SAEs) occurred during the trial (all patients on metformin).InterpretationMetformin did not reduce AML volume. Metformin did reduce SEGA volume and seizure frequency compared with placebo. There may be a role for metformin in slowing or reversing growth of some life-threatening hamartomas in TSC and for reducing seizure frequency. Further study is justified.FundingThis study was funded by the National Institute for Health and Research (NIHR) through the The Research for Patient Benefit Programme (RfPB).

Onabotulinum toxin-A versus extended release tolterodine in the management of idiopathic overactive bladder in children: A pilot randomised controlled trial (OVERT trial)

Idiopathic Overactive Bladder is the most common cause of urinary incontinence in children. Anticholinergic medications are successful in only 20% of those with daily wetting so there is a real need to find a more effective treatment for this condition. Onabotulinum toxin A injections are often used as a treatment but there have been no randomised controlled trials investigating effectiveness in children. To provide information that would inform the design and conduct of a definitive trial comparing onabotulinum toxin A with extended-release tolterodine for the management of therapy resistant idiopathic overactive bladder in children. Specific objectives were to assess rates of eligibility, recruitment, acceptability of randomisation, loss to follow-up, acceptability of urodynamic assessment and obtain primary outcome data for sample size estimation. Single-centre, parallel, two-arm, open-label pilot randomised controlled trial. Eligible patients (aged 7-16 years) were recruited at Royal Manchester Children's Hospital and randomised (1:1) using a web-based system. EudraCT 2014-001068-36; Funding: UK NIHR Research for Patient Benefit Programme. 98 patients were assessed for eligibility, 85 (87%) were eligible for screening, parents of 62 (73%) provided consent, 46 (74%) remained eligible and were randomised (onabotulinum=22, tolterodine=24). All participants commenced allocated treatment. Two patients withdrew from follow-up. All participants underwent urodynamic assessment at baseline and 35 (76%) additionally at week 6. The mean (standard deviation) number of wetting episodes per day at week 6 was 1.4 (1.7) in the onabotulinum group and 1.6 (1.0) in the tolterodine group. There was one serious adverse event (probably related to the drug) and 22 non-serious adverse events reported by 8 participants in the onabotulinum group (36%). There were 23 non-serious adverse events reported by 9 participants in the tolterodine group (38%). Recruitment was challenging but eligibility and consent rates were high as were retention rates. Treatment compliance in the botox group was high but it was difficult to measure in the tolterodine group. Treatment switching was also an issue. Recruitment to a definitive trial was demonstrated to be feasible if a large number of centres are involved, though further consideration is required regarding trial design.

Psychosocial needs of adolescents and young adults with eczema: A secondary analysis of qualitative data to inform a behaviour change intervention

This study aimed to explore adolescents and young adults' experiences of symptoms related to their eczema in order to determine their psychosocial needs. A secondary qualitative analysis of two data sources collected through semi-structured interviews for two different projects, SKINS project and Eczema Care Online project. In total, there were 28 transcripts with adolescents and young adults with eczema having a mean age of 19.5years available to analyse. Interview data were collected from face-to-face interviews that were recorded and transcribed. Inductive thematic analysis explored data about symptoms and organized according to psychosocial needs. Adolescents and young adults with eczema experience both visible symptoms (such as flaky, dry, and inflamed skin) and invisible symptoms (such as itch, pain, exhaustion, and mental distress) that elicit different psychosocial needs. These psychosocial needs are to (i) be understood; (ii) be perceived as normal; and (iii) receive emotional support. Interviewees described a struggle between wanting their peers and family to understand but take their eczema seriously whilst not wanting to stand out and instead to be perceived as 'normal', which they would define as being perceived as other adolescents. This has implications on behaviours, such as seeking support, avoiding going out, hiding their skin, as well as emotional implications, such as social isolation and feeling anxious and low. Having a better understanding of young people's experiences and psychosocial needs will provide a framework on how best to support adolescents and young adults when managing symptoms related to eczema. Statement of contribution What is already known on this subject? Eczema has a high impact on children and is considered a burden by children and adults with eczema. However, it is unclear what impact eczema has on adolescents and young adults. Adolescents and young adults with chronic conditions are known to be vulnerable to negative psychosocial outcomes but psychosocial needs and how to best support this age group with eczema are unknown What does this add? Three psychosocial needs were developed from evaluating the impact of visible and invisible symptoms of eczema: The need to feel understood (mostly reflective of invisible symptoms such as itch and pain and visible symptoms such as scratching). The need to be perceived as 'normal': visible symptoms such as flaky, inflamed skin make them stand out in comparison with their peers and a need emerged to blend in. The need for emotional support: adolescents and young adults searched for this from their health care providers, from shared experiences and from online resources. Adolescents and young adults with eczema appear to feel ambivalent about wishing the impact of the condition to be acknowledged whilst wishing the condition to be invisible to others. This ambivalence had further impact on feeling self-conscious, seeking support, and dealing with unsolicited advice.

Prevalence, symptom burden, and natural history of deep vein thrombosis in people with advanced cancer in specialist palliative care units (HIDDen): a prospective longitudinal observational study

SummaryBackgroundThe prevalence of deep venous thrombosis in patients with advanced cancer is unconfirmed and it is unknown whether current international thromboprophylaxis guidance is applicable to this population. We aimed to determine prevalence and predictors of femoral deep vein thrombosis in patients admitted to specialist palliative care units (SPCUs).MethodsWe did this prospective longitudinal observational study in five SPCUs in England, Wales, and Northern Ireland (four hospices and one palliative care unit). Consecutive adults with cancer underwent bilateral femoral vein ultrasonography on admission and weekly until death or discharge for a maximum of 3 weeks. Data were collected on performance status, attributable symptoms, and variables known to be associated with venous thromboembolism. Patients with a short estimated prognosis (<5 days) were ineligible. The primary endpoint of the study was the prevalence of femoral deep vein thrombosis within 48 h of SPCU admission, analysed by intention to treat. This study is registered with the ISRCTN registry, number ISRCTN97567719.FindingsBetween June 20, 2016, and Oct 16, 2017, 343 participants were enrolled (mean age 68·2 years [SD 12·8; range 25–102]; 179 [52%] male; mean Australian-modified Karnofsky performance status 49 [SD 16·6; range 20–90]). Of 273 patients with evaluable scans, 92 (34%, 95% CI 28–40) had femoral deep vein thrombosis. Four participants with a scan showing no deep vein thrombosis on admission developed a deep vein thrombosis on repeat scanning over 21 days. Previous venous thromboembolism (p=0·014), being bedbound in the past 12 weeks for any reason (p=0·003), and lower limb oedema (p=0·009) independently predicted deep vein thrombosis. Serum albumin concentration (p=0·43), thromboprophylaxis (p=0·17), and survival (p=0·45) were unrelated to deep vein thrombosis.InterpretationAbout a third of patients with advanced cancer admitted to SPCUs had a femoral deep vein thrombosis. Deep vein thrombosis was not associated with thromboprophylaxis, survival, or symptoms other than leg oedema. These findings are consistent with venous thromboembolism being a manifestation of advanced disease rather than a cause of premature death. Thromboprophylaxis for SPCU inpatients with poor performance status seems to be of little benefit.FundingNational Institute for Health Research (Research for Patient Benefit programme).

Cognitive Remediation Therapy for Patients with Bipolar Disorder: A Randomised Proof-of-Concept Trial

Background: Cognitive remediation therapy (CRT) may benefit people with bipolar disorders but randomised trials of evidenced therapy programmes for those with bipolar type I and II are lacking. The Cognitive Remediation in Bipolar (CRiB) study aimed to determine whether an established CRT programme is feasible and acceptable for people with bipolar disorders. Methods: This proof-of-concept, single-blind randomised trial recruited participants from the community, primary and secondary care to one centre in London, UK. Participants were aged 18-65 with bipolar disorder, not currently experiencing an episode. They were 1:1 block randomised to treatment-as-usual (TAU) with or without individual CRT for 12 weeks. The partly-computerised CRT programme (CIRCuiTS) was therapist-led and evidence-based. Data were collected and analysed by investigators blinded to group allocation. The main outcomes (week 13 and 25) examined participant retention, intervention feasibility and putative effects of CRT on cognitive and psychosocial functioning via intention-to-treat analyses. Trial registration: ISRCTN ID32290525. Findings: 60 participants were recruited (02/2016-06/2018) and randomised to CRT (n=29) or TAU (n=31). Trial withdrawals were equivalent (CRT n=2/29; TAU n=5/31). CRT satisfaction indicated high acceptability. Intention-to-treat analyses (N=60) demonstrated greater improvements for CRT- than TAU-randomised participants: at both week 13 and 25, CIRCuiTS participants showed larger improvements in IQ (SES=0·71, 95% CI [0·29,1·13]), working memory (SES=0·70, 95% CI [0·31,1·10]), executive function (SES=0·93, 95% CI [0·33,1·54]), psychosocial functioning (SES=0·49, 95% CI [0·18,0·80]) and goal attainment (SES=2·02, 95% CI [0·89,3·14]). No serious adverse events were reported. Interpretation: CRT is feasible for individuals with bipolar disorders and may enhance cognition and functioning. The reported effect sizes from this proof-of-concept trial encourages further investigation in a definitive trial. Trial Registration Number: ISRCTN ID32290525. Funding: National Institute for Health Research (NIHR) Research for Patient Benefit Programme (PB-PG-0614-34075) and NIHR Maudsley Biomedical Research Centre. Declaration of Interest: TW and CR were involved with the CIRCuiTs programme development; however, neither author had any involvement with undertaking or supervising any assessment procedures or data analysis, or data collection. AHY has received payment for lectures and advisory boards membership from AstraZenaca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, and Janssen and reports no shareholdings in pharmaceutical companies. He is the lead investigator for the Embolden Study (AZ), BCI Neuroplasticity Sudy, and Aripiprazole Mania Study, and has led investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck, Wyeth, and Janssen. RS has received an honorarium for speaking at a Lundbeck-sponsored event. The remaining authors declare no competing interests (DT, JH, TM, NY, PM, JB, KM, MC, JF). Ethical Approval: The trial protocol contains full details of the study methodology as approved by a UK NHS Research Ethics Committee (16/10/2015, reference 15/LO/1557).

Placental Growth Factor Testing to Assess and Diagnose Preeclampsia: A Stepped Wedge Randomised Controlled Trial

Background Previous prospective cohort studies have demonstrated that angiogenic factor measurements have high diagnostic accuracy in women with suspected pre-eclampsia, but the clinical impact of these tests when revealed to clinicians remains uncertain. Methods We conducted a multi-centre, pragmatic, stepped-wedge cluster randomised controlled trial in eleven UK maternity units (3000-9000 deliveries per annum). Women who presented with suspected pre-eclampsia between 20 0 and 36 6 weeks' gestation were invited to participate. Maternity units were randomly assigned to the order of implementation of revealed PlGF measurement, incorporated within a clinical management algorithm; in the usual care arm, PlGF measurement remained concealed. The primary outcome was time from presentation with suspected pre-eclampsia to documented pre-eclampsia. Secondary outcomes included other maternal and perinatal adverse outcomes. Findings Between June 2016 and October 2017, 1,023 women with suspected pre-eclampsia were enrolled. Median time to preeclampsia diagnosis decreased from 4·1 days (usual care) to 1·9 days (intervention) (time ratio 0·39 (95% CI 0·17-0·91) by parametric survival analysis). Maternal severe adverse outcomes reduced from 5·4% (usual care group) to 3·8% ((intervention group) adjusted OR 0·32 (95% CI 0·11-0·96) with no evidence of a difference in perinatal adverse outcomes. Interpretation PlGF testing has been shown to substantially reduce the time to clinical confirmation of preeclampsia. Where PlGF was implemented there was a reduction in maternal adverse outcomes, consistent with targeted, enhanced surveillance as recommended in the trial management guidance for clinicians. Adoption of PlGF testing in women with suspected pre-eclampsia is supported by the results of this study. Trial Registration Number: ISRCTN 16842031 Funding: This trial was supported by grants from the National Institute for Health Research, Research for Patient Benefit Programme (PB-PG-0214-33054) and National Institute for Health Research Professorship (Chappell RP-2014-05-019). Declaration of Interest: KD, LCC, PS, JM and AS have no conflicts of interest. RH has received writing fees from Alere for previous work Ethical Approval: The trial was approved by the London South East Research Ethics Committee (ref. 15/LO/2058).

Mini-Sternotomy Versus Conventional Sternotomy for Aortic Valve Replacement: Results from the MAVRIC Randomised Controlled Trial

Background: While Aortic Valve Replacement (AVR) outcomes have improved, morbidity remains significant. Need for transfusion is a key indicator of quality; transfusions are linked to prolonged hospital stay and increased mortality. Over one third of patients undergoing AVR via conventional median sternotomy require post-operative red-cell transfusion. Methods: MAVRIC was a single centre, single blind, randomised controlled trial, comparing AVR via manubrium-limited mini-sternotomy (intervention) and conventional median sternotomy (usual care) to assess the impact on post-operative red-cell transfusion. Patients were stratified by baseline logistic EuroSCORE and haemoglobin and followed for 12 weeks. The primary outcome was proportion of patients receiving red-cell transfusion within 7 days of index surgery. Findings: 271 patients were randomised using a central computer system with concealed allocation; 270 received surgery and contributed to the intention to treat analysis. No difference between intervention and usual care in red-cell transfusion within 7 days was found; 23/135 patients in each arm received a transfusion, odds ratio 1·0 (95% CI: 0·5, 2·0) and risk difference 0·0 (95% CI: -0·1, 0·1). Intervention reduced chest drain losses (mean 181·6ml (SD 138·7) vs usual care mean 306·9ml (SD 348·6)); this did not reduce red-cell transfusions. Mean valve size and postoperative valve function were comparable between intervention and usual care; 23mm vs 24mm, and 6/134 moderate or severe aortic regurgitation vs 3/130, respectively. Mini-sternotomy resulted in longer bypass times (82·7 minutes (SD 23·5) vs 59·6 minutes (SD 15·1)) and cross clamp times (64·1 minutes (SD 17·1) vs 46·3 minutes (SD 10·7)). Conventional sternotomy was more cost-effective with only a 5·8% probability of ministernotomy being cost-effective at a willingness to pay of £20,000/QALY. Interpretation: AVR via manubrium-limited mini-sternotomy did not reduce red blood cell transfusion within 7 days following index surgery when compared to conventional sternotomy. Clinical Trial Number: International Standard Randomised Controlled Trial Number (ISRCTN) ISRCTN29567910. Registered on 3 February 2014. Funding Statement: The trial was funded by the NIHR Research for Patient Benefit Programme (grant number PB-PG-1112-29035). GJM is supported by the British Heart Foundation (CH/12/1/29419) and the NIHR Leicester Biomedical Research Centre. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This protocol and all trial-related documents were originally approved by the National Research Ethics Service Committee, North East - Newcastle & North Tyneside 1 in March 2014 (IRAS Project 137295; REC Reference 14/NE/0005). Since initial approval, three amendments have been made and approved; thus, this is version 5 of the protocol. Written informed consent will be obtained from all participants. The trial will be run according to the principles of ICH-GCP and in accordance with relevant UK legislation and the protocol.

Do feasibility studies contribute to, or avoid, waste in research?

In the context of avoiding research waste, the conduct of a feasibility study before a clinical trial should reduce the risk that further resources will be committed to a trial that is likely to ‘fail’. However, there is little evidence indicating whether feasibility studies add to or reduce waste in research. Feasibility studies funded by the National Institute for Health Research’s (NIHR) Research for Patient Benefit (RfPB) programme were examined to determine how many had published their findings, how many had applied for further funding for a full trial and the timeframe in which both of these occurred. A total of 120 feasibility studies which had closed by May 2016 were identified and each Principal Investigator (PI) was sent a questionnaire of which 89 responses were received and deemed suitable for analysis. Based on self reported answers from the PIs a total of 57 feasibility studies were judged as feasible, 20 were judged not feasible and for 12 it was judged as uncertain whether a full trial was feasible. The RfPB programme had spent approximately £19.5m on the 89 feasibility studies of which 16 further studies had been subsequently funded to a total of £16.8m. The 20 feasibility studies which were judged as not feasible potentially saved up to approximately £20m of further research funding which would likely to have not completed successfully. The average RfPB feasibility study took 31 months (range 18 to 48) to complete and cost £219,048 (range £72,031 to £326,830) and the average full trial funded from an RfPB feasibility study took 42 months (range 26 to 55) to complete and cost £1,163,996 (range £321,403 to £2,099,813). The average timeframe of feasibility study and full trial was 72 months (range 56 to 91), however in addition to this time an average of 10 months (range -7 to 29) was taken between the end of the feasibility study and the application for the full trial, and a further average of 18 months (range 13 to 28) between the application for the full trial and the start of the full trial. Approximately 58% of the 89 feasibility studies had published their findings with the majority of the remaining studies still planning to publish. Due to the long time frames involved a number of studies were still in the process of publishing the feasibility findings and/or applying for a full trial. Feasibility studies are potentially useful at avoiding waste and de-risking funding investments of more expensive full trials, however there is a clear time delay and therefore some potential waste in the existing research pathway.

Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial

SummaryBackgroundGraded exercise therapy is an effective and safe treatment for chronic fatigue syndrome, but it is therapist intensive and availability is limited. We aimed to test the efficacy and safety of graded exercise delivered as guided self-help.MethodsIn this pragmatic randomised controlled trial, we recruited adult patients (18 years and older) who met the UK National Institute for Health and Care Excellence criteria for chronic fatigue syndrome from two secondary-care clinics in the UK. Patients were randomly assigned to receive specialist medical care (SMC) alone (control group) or SMC with additional guided graded exercise self-help (GES). Block randomisation (randomly varying block sizes) was done at the level of the individual with a computer-generated sequence and was stratified by centre, depression score, and severity of physical disability. Patients and physiotherapists were necessarily unmasked from intervention assignment; the statistician was masked from intervention assignment. SMC was delivered by specialist doctors but was not standardised; GES consisted of a self-help booklet describing a six-step graded exercise programme that would take roughly 12 weeks to complete, and up to four guidance sessions with a physiotherapist over 8 weeks (maximum 90 min in total). Primary outcomes were fatigue (measured by the Chalder Fatigue Questionnaire) and physical function (assessed by the Short Form-36 physical function subscale); both were self-rated by patients at 12 weeks after randomisation and analysed in all randomised patients with outcome data at follow-up (ie, by modified intention to treat). We recorded adverse events, including serious adverse reactions to trial interventions. We used multiple linear regression analysis to compare SMC with GES, adjusting for baseline and stratification factors. This trial is registered at ISRCTN, number ISRCTN22975026.FindingsBetween May 15, 2012, and Dec 24, 2014, we recruited 211 eligible patients, of whom 107 were assigned to the GES group and 104 to the control group. At 12 weeks, compared with the control group, mean fatigue score was 19·1 (SD 7·6) in the GES group and 22·9 (6·9) in the control group (adjusted difference −4·2 points, 95% CI −6·1 to −2·3, p<0·0001; effect size 0·53) and mean physical function score was 55·7 (23·3) in the GES group and 50·8 (25·3) in the control group (adjusted difference 6·3 points, 1·8 to 10·8, p=0·006; 0·20). No serious adverse reactions were recorded and other safety measures did not differ between the groups, after allowing for missing data.InterpretationGES is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome. These findings need confirmation and extension to other health-care settings.FundingUK National Institute for Health Research Research for Patient Benefit Programme and the Sue Estermann Fund.

Ambulatory oxygen in fibrotic lung disease (AmbOx): study protocol for a randomised controlled trial

BackgroundFibrotic interstitial lung diseases (ILDs) are chronic and often progressive conditions resulting in substantial morbidity and mortality. Shortness of breath, a symptom often linked to oxygen desaturation on exertion, is tightly linked to worsening quality of life in these patients. Although ambulatory oxygen is used empirically in their treatment, there are no ILD-specific guidelines on its use. To our knowledge, no studies are available on the effects of ambulatory oxygen on day-to-day life in patients with ILD.Methods/designAmbulatory oxygen in fibrotic lung disease (AmbOx) is a multicentre, randomised controlled crossover trial (RCT) funded by the Research for Patient Benefit Programme of the National Institute for Health Research. The trial will compare ambulatory oxygen used during daily activities with no ambulatory oxygen in patients with fibrotic lung disease whose oxygen saturation (SaO2) is ≥94% at rest, but drops to ≤88% on a 6-min Walk Test. The randomised controlled trial (RCT) will evaluate the effects on health status (measured by the King’s Brief ILD Questionnaire: K-BILD) of ambulatory oxygen used at home, at an optimal flow rate determined by titration at screening visit, and administered for a 2-week period, compared to 2 weeks off oxygen. Key secondary outcomes will include breathlessness on activity scores, as measured by the University of California San Diego Shortness of Breath Questionnaire, global patient assessment of change scores, as well as quality of life scores (St George’s Respiratory Questionnaire), anxiety and depression scores (Hospital Anxiety and Depression Scale), activity markers measured by SenseWear Armbands, pulse oximetry measurements, patient-reported daily activities, patient- and oxygen company-reported oxygen cylinder use. The study also includes a qualitative component and will explore in interviews patients’ experiences of the use of a portable oxygen supply and trial participation in a subgroup of 20 patients and carers.DiscussionThis is the first RCT of the effects of ambulatory oxygen during daily life on health status and breathlessness in fibrotic lung disease. The results generated should provide the basis for setting up ILD-specific guidelines for the use of ambulatory oxygen.Trial registrationNational Clinical Trials Registry, identifier: NCT02286063. Registered on 8 October 2014 (retrospectively registered).

PP.16.30] INTERPRESS-IPD

Objective: Inter-arm differences in blood pressure (IAD) are associated with increased cardiovascular and all-cause mortality in cohort studies of various populations. Study level meta-analyses confirm these associations, however several questions remain, which such methods cannot answer, including: What is the independent contribution of IAD to prognostic risk estimation for cardiovascular and all-cause mortality? What minimum cut-off value for IAD defines elevated risk? What is the incremental association between increasing IAD and mortality risk? Do different IAD measurement techniques affect prognostic value of IAD measurements? We aim to address these questions by forming an international collaboration, the ‘INTERPRESS-IPD’, to combine individual patient data (IPD) from IAD cohort studies into a single large dataset for IPD meta-analysis. Design and method: The Collaboration will combine IPD from prospective cohorts that measured blood pressure in both arms during recruitment. Lead investigators contributing datasets will be ackowledged in all relevant publications. We will first develop a standardised multivariable Cox regression model using a one-stage meta-analysis of time to event data for risk of cardiovascular and all-cause mortality, taking account of IAD. The project then seeks to develop a new prognostic model for cardiovascular risk estimation that includes IAD. We will explore variations in risk contribution of IAD across pre-defined subgroups, establish the lower limit of IAD that is assocatied with additional cardiovascular risk, and plan subgroup analysis by method of IAD measurement (sequential vs. simultaneous, and single vs. repeated measures). We will perform cross-sectional analyses to describe the epidemiology of IAD in the dataset. The study is registered with PROSPERO: registration number CRD42015031227. Results: The study has secured funding from the NIHR Research for Patient Benefit programme (PB-PG-0215-36009). Searches for IAD datasets are underway and unpublished datasets are sought. Currently 12 eligible studies have been identified and of these, 9 groups have agreed to share data. On this basis the dataset will include at least 1150 all-cause deaths and 681 cardiovascular deaths in 17153 participants. Conclusions: This international collaboration will provide robust evidence on IAD to inform clinical care and future guidelines. Updates will be presented to conference.

Randomized Trial of Labor Induction in Women 35 Years of Age or Older

BackgroundThe risk of antepartum stillbirth at term is higher among women 35 years of age or older than among younger women. Labor induction may reduce the risk of stillbirth, but it also may increase the risk of cesarean delivery, which already is common in this older age group.MethodsWe conducted a randomized, controlled trial involving primigravid women who were 35 years of age or older. Women were randomly assigned to labor induction between 39 weeks 0 days and 39 weeks 6 days of gestation or to expectant management (i.e., waiting until the spontaneous onset of labor or until the development of a medical problem that mandated induction). The primary outcome was cesarean delivery. The trial was not designed or powered to assess the effects of labor induction on stillbirth.ResultsA total of 619 women underwent randomization. In an intention-to-treat analysis, there were no significant between-group differences in the percentage of women who underwent a cesarean section (98 of 304 women in the induction group [32%] and 103 of 314 women in the expectant-management group [33%]; relative risk, 0.99; 95% confidence interval [CI], 0.87 to 1.14) or in the percentage of women who had a vaginal delivery with the use of forceps or vacuum (115 of 304 women [38%] and 104 of 314 women [33%], respectively; relative risk, 1.30; 95% CI, 0.96 to 1.77). There were no maternal or infant deaths and no significant between-group differences in the women’s experience of childbirth or in the frequency of adverse maternal or neonatal outcomes.ConclusionsAmong women of advanced maternal age, induction of labor at 39 weeks of gestation, as compared with expectant management, had no significant effect on the rate of cesarean section and no adverse short-term effects on maternal or neonatal outcomes. (Funded by the Research for Patient Benefit Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN11517275.)