The measurement of applied forces during anterior single rod correction of adolescent idiopathic scoliosis

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity in paediatrics, prevalent in approximately 2-4% of the general population. While it is a complex three-dimensional deformity, it is clinically characterised by an abnormal lateral curvature of the spine. The treatment for severe deformity is surgical correction with the use of structural implants. Anterior single rod correction employs a solid rod connected to the anterior spine via vertebral body screws. Correction is achieved by applying compression between adjacent vertebral body screws, before locking each screw onto the rod. Biomechanical complication rates have been reported as high as 20.8%, and include rod breakage, screw pull-out and loss of correction. Currently, the corrective forces applied to the spine are unknown. These forces are important variables to consider in understanding the biomechanics of scoliosis correction. The purpose of this study was to measure these forces intra-operatively during anterior single rod AIS correction

Undertaking a randomised controlled trial in the police setting : methodological and practical challenges

BACKGROUND: There has been an increased drive towards Evidence Based Policing in recent years. Unlike in other public sector services, such as health and education, randomised controlled trials in the police setting are relatively rare. This paper discusses some of the methodological and practical challenges of conducting a randomised controlled trial in the police setting in the UK, based on our experience of the Connect trial. This pragmatic, cluster-randomised controlled trial investigated the effectiveness of a face-to-face training intervention for frontline officers in comparison to routine training. The primary outcome was the number of incidents which resulted in a police response reported to North Yorkshire Police control room in a 1-month period up to 6 months after delivery of training. MAIN TEXT: The methodological and practical challenges that we experienced whilst conducting the Connect trial are discussed under six headings: establishing the unit of randomisation; population of interest and sample size; co-production of evidence; time frame; outcomes; and organisational issues. CONCLUSION: Recommendations on the conduct of future randomised controlled trials in the police setting are made. To understand the context in which research is undertaken, collaboration between police and academia is needed and police officers should be embedded within trial management groups. Engagement with police data analysts to understand what data is available and facilitate obtaining trial data is also recommended. Police forces may wish to review their IT systems and recording practices. Pragmatic trials are encouraged and time frames need to allow for trial set-up and obtaining relevant ethical approvals. TRIAL REGISTRATION: ISRCTN Registry, ID: ISRCTN11685602 . Retrospectively registered on 13 May 2016

Partnerships between deaf people and hearing dogs (PEDRO) : Effectiveness and Cost-Effectiveness of Receiving a Hearing Dog on Mental Well-Being and Health in People With Hearing Loss: Protocol for a Randomized Controlled Trial

Background People with hearing loss, particularly those who lose their hearing in adulthood, are at increased risk of social isolation, mental health difficulties, unemployment, loss of independence, risk of accidents, and impaired quality of life. In the United Kingdom (UK), a single third sector organisation provides hearing dogs, a specific type of assistance dog trained to provide sound support to people with hearing loss. These dogs may also deliver numerous psychosocial benefits to recipients. This has not previously been fully investigated. Objective To evaluate the impact of a hearing dog partnership on the lives of individuals with severe or profound hearing loss. Methods and Analysis A two-arm, randomised controlled trial conducted within the UK, with 162 hearing dog applicants, aged 18 years and over. Participants will be randomised 1:1 using a matched-pairs design to receive a hearing dog sooner than usual (intervention arm – Arm B) or to receive a hearing dog within the usual timeframe (comparator arm – Arm A). In the effectiveness analysis, the primary outcome is a comparison of mental wellbeing six-months after Arm B have received a hearing dog (Arm A: not yet received hearing dog), measured using the Short Warwick Edinburgh Mental Wellbeing Scale. Secondary outcome measures include the PHQ-9, GAD-7 and WSAS. An economic evaluation will assess cost-effectiveness including health-related quality-adjusted life years using the EQ-5D-5L and social-care-related-quality-adjusted life-years. Participants will be followed up for up to two years. A nested qualitative study will investigate the impacts of having a hearing dog and how these impacts come about. Results The study was funded by the National Institute for Health Research’s School for Social Care Research. Recruitment commenced in March 2017 and is now complete. 165 participants were randomised. Data collection will continue until January 2020. Results will be published in peer-reviewed journals and at conferences. A summary of the findings will be made available to participants. Ethical approval was received from the University of York’s Department of Social Policy and Social Work Research Ethics Committee (reference SPSW/S/17/1). Conclusions The findings from this study will provide, for the first time, strong and reliable evidence on the impact of having a hearing dog on people’s lives in terms of their quality of life, well-being and mental health. Trial registration The trial has been retrospectively registered International Standard Randomised Controlled Trial Number (ISRCTN) 36452009; https://doi.org/10.1186/ISRCTN36452009. Trial status: Ongoing

Hearing dogs for people with severe and profound hearing loss: a wait-list design randomised controlled trial investigating their effectiveness and cost-effectiveness

Abstract Background Hearing loss increases the risk of poor outcomes across a range of life domains. Where hearing loss is severe or profound, audiological interventions and rehabilitation have limited impact. Hearing dogs offer an alternative, or additional, intervention. They live permanently with recipients, providing sound support and companionship. Methods A single-centre, randomised controlled trial (RCT) evaluated the impacts of a hearing dog on mental well-being, anxiety, depression, problems associated with hearing loss (responding to sounds, fearfulness/social isolation), and perceived dependency on others. Participants were applicants to the UK charity ‘Hearing Dogs for Deaf People’. Eligibility criteria were as follows: first-time applicant; applying for a hearing dog (as opposed to other support provided by the charity). Participants were randomised 1:1 to the following: receive a hearing dog sooner than usual [HD], or within the usual application timeframe (wait-list [WL] comparator). The primary outcome was mental well-being (Short Warwick-Edinburgh Mental Well-Being Scale) 6 months (T1) after HD received a hearing dog. The cost-effectiveness analysis took a health and social care perspective. Results In total, 165 participants were randomised (HD n = 83, WL n = 82). A total of 112 (67.9%) were included in the primary analysis (HD n = 55, WL n = 57). At T1, mental well-being was significantly higher in the HD arm (adjusted mean difference 2.53, 95% CI 1.27 to 3.79, p < 0.001). Significant improvements in anxiety, depression, functioning, fearfulness/social isolation, and perceived dependency, favouring the HD arm, were also observed. On average, HD participants had used fewer statutory health and social care resources. In a scenario whereby costs of provision were borne by the public sector, hearing dogs do not appear to be value for money. If the public sector made a partial contribution, it is possible that hearing dogs would be cost-effective from a public sector perspective. Conclusions Hearing dogs appear to benefit recipients across a number of life domains, at least in the short term. Within the current funding model (costs entirely borne by the charity), hearing dogs are cost-effective from the public sector perspective. Whilst it would not be cost-effective to fully fund the provision of hearing dogs by the public sector, a partial contribution could be explored. Trial registration The trial was retrospectively registered with the International Standard Randomised Controlled Trial Number (ISRCTN) registry on 28.1.2019: ISRCTN36452009

The CALM trial protocol: a randomised controlled trial of a guided self-help cognitive behavioural therapy intervention to reduce dental anxiety in children

Background: Globally, around 13% of children experience dental anxiety (DA). This group of patients frequently miss dental appointments, have greater reliance on treatment under general anaesthesia (GA) and have poorer oral health-related quality of life (OHRQoL) than their non-dentally anxious peers. Recently, a low-intensity cognitive behavioural therapy (CBT)-based, self-help approach has been recommended for management of childhood anxiety disorders. A feasibility study conducted in secondary care found this guided self-help CBT resource reduced DA and a randomised controlled trial was recommended. The present study aims to establish the clinical and cost-effectiveness of a guided self-help CBT intervention to reduce DA in children attending primary dental care sites compared to usual care. Methods: This 4-year randomised controlled trial will involve 600 children (aged 9–16 years) and their parent/carers in 30 UK primary dental care sites. At least two dental professionals will participate in each site. They will be assigned, using random allocation, to receive the CBT training and deliver the intervention or to deliver usual care. Children with DA attending these sites, in need of treatment, will be randomly allocated to be treated either by the intervention (CBT) or control (usual care) dental professional. Children will complete questionnaires relating to DA, OHRQoL and HRQoL before treatment, immediately after treatment completion and 12 months post-randomisation. Attendance, need for sedation/GA and costs of the two different approaches will be compared. The primary outcome, DA, will be measured using the Modified Child Dental Anxiety Scale. Scores will be compared between groups using a linear mixed model. Discussion: Treating dentally anxious patients can be challenging and costly. Consequently, these children are frequently referred to specialist services for pharmacological interventions. Longer waiting times and greater travel distances may then compound existing healthcare inequalities. This research will investigate whether the intervention has the potential to reduce DA and improve oral health outcomes in children over their life-course, as well as upskilling primary dental healthcare professionals to better manage this patient group. Trial registration: This clinical trial has been registered with an international registry and has been allocated an International Standard Randomised Controlled Trial Number (ISRCTN27579420)

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Abstract: Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate

A bespoke smoking cessation service compared with treatment as usual for people with severe mental ill health: the SCIMITAR+ RCT

BackgroundThere is a high prevalence of smoking among people with severe mental ill health (SMI). Helping people with SMI to quit smoking could improve their health and longevity, and reduce health inequalities. However, those with SMI are less likely to access and engage with routine smoking cessation services than the general population.ObjectivesTo compare the clinical effectiveness and cost-effectiveness of a bespoke smoking cessation (BSC) intervention with usual stop smoking services for people with SMI.DesignA pragmatic, two-arm, individually randomised controlled trial.SettingPrimary care and secondary care mental health services in England.ParticipantsSmokers aged ≥ 18 years with SMI who would like to cut down on or quit smoking.InterventionsA BSC intervention delivered by mental health specialists trained to deliver evidence-supported smoking cessation interventions compared with usual care.Main outcome measuresThe primary outcome was self-reported, CO-verified smoking cessation at 12 months. Smoking-related secondary outcomes were self-reported smoking cessation, the number of cigarettes smoked per day, the Fagerström Test for Nicotine Dependence and the Motivation to Quit questionnaire. Other secondary outcomes were Patient Health Questionnaire-9 items, Generalised Anxiety Disorder Assessment-7 items and 12-Item Short-Form Health Survey, to assess mental health and body mass index measured at 6 and 12 months post randomisation.ResultsThe trial randomised 526 people (265 to the intervention group, 261 to the usual-care group) aged 19 to 72 years (mean 46 years). About 60% of participants were male. Participants smoked between 3 and 100 cigarettes per day (mean 25 cigarettes per day) at baseline. The intervention group had a higher rate of exhaled CO-verified smoking cessation at 6 and 12 months than the usual-care group [adjusted odds ratio (OR) 12 months: 1.6, 95% confidence interval (CI) 0.9 to 2.8; adjusted OR 6 months: 2.4, 95% CI 1.2 to 4.7]. This was not statistically significant at 12 months (p = 0.12) but was statistically significant at 6 months (p = 0.01). In total, 111 serious adverse events were reported (69 in the BSC group and 42 in the usual-care group); the majority were unplanned hospitalisations due to a deterioration in mental health (n = 98). The intervention is likely (57%) to be less costly but more effective than usual care; however, this result was not necessarily associated with participants’ smoking status.LimitationsFollow-up was not blind to treatment allocation. However, the primary outcome included a biochemically verified end point, less susceptible to observer biases. Some participants experienced difficulties in accessing nicotine replacement therapy because of changes in service provision. Efforts were made to help participants access nicotine replacement therapy, but this may have affected participants’ quit attempt.ConclusionsPeople with SMI who received the intervention were more likely to have stopped smoking at 6 months. Although more people who received the intervention had stopped smoking at 12 months, this was not statistically significant.Future workFurther research is needed to establish how quitting can be sustained among people with SMI.Trial registrationCurrent Controlled Trials ISRCTN72955454.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 50. See the NIHR Journals Library website for further project information

Smoking cessation for people with severe mental illness (SCIMITAR+) : a pragmatic randomised controlled trial

BACKGROUND: People with severe mental illnesses such as schizophrenia are three times more likely to smoke than the wider population, contributing to widening health inequalities. Smoking remains the largest modifiable risk factor for this health inequality, but people with severe mental illness have not historically engaged with smoking cessation services. We aimed to test the effectiveness of a combined behavioural and pharmacological smoking cessation intervention targeted specifically at people with severe mental illness. METHODS: In the smoking cessation intervention for severe mental illness (SCIMITAR+) trial, a pragmatic, randomised controlled study, we recruited heavy smokers with bipolar disorder or schizophrenia from 16 primary care and 21 community-based mental health sites in the UK. Participants were eligible if they were aged 18 years or older, and smoked at least five cigarettes per day. Exclusion criteria included substantial comorbid drug or alcohol problems and people who lacked capacity to consent at the time of recruitment. Using computer-generated random numbers, participants were randomly assigned (1:1) to a bespoke smoking cessation intervention or to usual care. Participants, mental health specialists, and primary care physicians were unmasked to assignment. The bespoke smoking cessation intervention consisted of behavioural support from a mental health smoking cessation practitioner and pharmacological aids for smoking cessation, with adaptations for people with severe mental illness-such as, extended pre-quit sessions, cut down to quit, and home visits. Access to pharmacotherapy was via primary care after discussion with the smoking cessation specialist. Under usual care participants were offered access to local smoking cessation services not specifically designed for people with severe mental illnesses. The primary endpoint was smoking cessation at 12 months ascertained via carbon monoxide measurements below 10 parts per million and self-reported cessation for the past 7 days. Secondary endpoints were biologically verified smoking cessation at 6 months; number of cigarettes smoked per day, Fagerström Test for Nicotine Dependence (FTND) and Motivation to Quit (MTQ) questionnaire; general and mental health functioning determined via the Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder-7 (GAD-7) questionnaire, and 12-Item Short Form Health Survey (SF-12); and body-mass index (BMI). This trial was registerd with the ISRCTN registry, number ISRCTN72955454, and is complete. FINDINGS: Between Oct 7, 2015, and Dec 16, 2016, 526 eligible patients were randomly assigned to the bespoke smoking cessation intervention (n=265) or usual care (n=261). 309 (59%) participants were male, median age was 47·2 years (IQR 36·3-54·5), with high nicotine dependence (mean 24 cigarettes per day [SD 13·2]), and the most common severe mental disorders were schizophrenia or other psychotic illness (n=343 [65%]), bipolar disorder (n=115 [22%]), and schizoaffective disorder (n=66 [13%]). 234 (88%) of intervention participants engaged with the treatment programme and attended 6·4 (SD 3·5) quit smoking sessions, with an average duration of 39 min (SD 17; median 35 min, range 5-120). Verified quit data at 12 months were available for 219 (84%) of 261 usual care and 223 (84%) of 265 intervention participants. The proportion of participants who had quit at 12 months was higher in the intervention group than in the usual care group, but non-significantly (34 [15%] of 223 [13% of those assigned to group] vs 22 [10%] of 219 [8% of those assigned to group], risk difference 5·2%, 95% CI -1·0 to 11·4; odds ratio [OR] 1·6, 95% CI 0·9 to 2·9; p=0·10). The proportion of participants who quit at 6 months was significantly higher in the intervention group than in the usual care group (32 [14%] of 226 vs 14 [6%] of 217; risk difference 7·7%, 95% CI 2·1 to 13·3; OR 2·4, 95% CI 1·2 to 4·6; p=0·010). The incidence rate ratio for number of cigarettes smoked per day at 6 months was 0·90 (95% CI 0·80 to 1·01; p=0·079), and at 12 months was 1·00 (0·89 to 1·13; p=0·95). At both 6 months and 12 months, the intervention group was non-significantly favoured in the FTND (adjusted mean difference 6 months -0·18, 95% CI -0·53 to 0·17, p=0·32; and 12 months -0·01, -0·39 to 0·38, p=0·97) and MTQ questionnaire (adjusted mean difference 0·58, -0·01 to 1·17, p=0·056; and 12 months 0·64, 0·04 to 1·24, p=0·038). The PHQ-9 showed no difference between the groups (adjusted mean difference at 6 months 0·20, 95% CI -0·85 to 1·24 vs 12 months -0·12, -1·18 to 0·94). For the SF-12 survey, we saw evidence of improvement in physical health in the intervention group at 6 months (adjusted mean difference 1·75, 95% CI 0·21 to 3·28), but this difference was not evident at 12 months (0·59, -1·07 to 2·26); and we saw no difference in mental health between the groups at 6 or 12 months (adjusted mean difference at 6 months -0·73, 95% CI -2·82 to 1·36, and 12 months -0·41, -2·35 to 1·53). The GAD-7 questionnaire showed no difference between the groups (adjusted mean difference at 6 months -0·32 95% CI -1·26 to 0·62 vs 12 months -0·10, -1·05 to 0·86). No difference in BMI was seen between the groups (adjusted mean difference 6 months 0·16, 95% CI -0·54 to 0·85; 12 months 0·25, -0·62 to 1·13). INTERPRETATION: This bespoke intervention is a candidate model of smoking cessation for clinicians and policy makers to address high prevalence of smoking. The incidence of quitting at 6 months shows that smoking cessation can be achieved, but the waning of this effect by 12 months means more effort is needed for sustained quitting. FUNDING: National Institute for Health Research Health Technology Assessment Programme

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown