Factors that influence women's enrolment and ongoing participation in a partially decentralised randomised controlled dermatology trial: a qualitative interview study with participants in the SAFA (Spironolactone for Adult Female Acne) trial.

BACKGROUND: The use of decentralised clinical trials (which bring trials to patients through remote processes and technology versus central on-site visits) has been thought to be a potential solution to common recruitment and retention barriers. However, there is a lack of evidence to understand the experiences, needs and preferences of the public to inform trial methodologies that appeal to different populations. We report participant experiences of SAFA, a partially decentralised randomised clinical trial, to inform the methodology used in future dermatology trials that aim to appeal to women aged 18 and over. METHODS: Participants of the SAFA (Spironolactone for Adult Female Acne) trial were invited to take part in a qualitative semi-structured interview to explore their experience and perspectives of taking part in the trial. Questions focused on their experience of using decentralised methods to access and enrol in the trial (e.g. social media advertising), in addition to the decentralised trial visit and data collection methods used throughout. Interviews were conducted remotely, recorded, and transcribed. Data were analysed using reflexive thematic analysis. RESULTS: Twelve SAFA participants (all women, age range 22-36 years) were interviewed. Initially, participants were influenced to enrol by trusted online information, the feeling of validation the trial provided, and the convenience and flexibility offered by the decentralised methods and research staff made participants feel valued and enabled them to engage in the trial with minimal interference to existing commitments. SAFA participants were generally accepting of trial demands, such as the text-heavy paperwork and on-site visits for blood collection and highlighted several areas relevant for trial conduct going forwards including where decentralised methods may (and may not) be accepted and how trial accessibility and understanding could be improved. CONCLUSIONS: The study has shown that decentralised methods used by responsive and approachable staff were widely accepted in the SAFA trial. Interviewees found the methods adopted in the SAFA trial helped the trial to fit with their needs and promoted a sense of feeling valued that encouraged ongoing trial engagement. Decentralised methods should be considered favourably when designing a dermatology trial as they can potentially enhance both recruitment and retention. TRIAL REGISTRATION NUMBER: ISRCTN 12892056. Registered on October 15, 2018.

Feasibility of home administration of nebulised interferon ß-1a (SNG001) for COVID-19: a remote study.

BACKGROUND: Effective therapeutics given early to high-risk ambulatory patients with coronavirus disease 2019 (COVID-19) could improve outcomes and reduce overall healthcare burden. However, conducting site visits in non-hospitalised patients, who should remain isolated, is problematic. AIM: To evaluate the feasibility of a purely remote (virtual) study in non-hospitalised patients with COVID-19; and the efficacy and safety of nebulised recombinant interferon-ß1a (SNG001) in this setting. DESIGN & SETTING: Randomised, double-blind, parallel-group study, which was conducted remotely. METHOD: Eligible patients aged ≥65 years (or ≥50 years with risk factors) with COVID-19 and not requiring hospital admission were recruited remotely. They were randomised to SNG001 or placebo once-daily via nebuliser for 14 days. The main outcomes were assessments of feasibility and safety, which were all conducted remotely. RESULTS: Of 114 patients treated, 111 (97.4%) completed 28 days of follow-up. Overall compliance to study medication was high, with ≥13 doses taken by 89.7% and 92.9% of treated patients in the placebo and SNG001 groups, respectively. Over the course of the study, only two patients were hospitalised, both in the placebo group; otherwise there were no notable differences between treatments for the efficacy parameters. No patients withdrew owing to an adverse event, and a similar proportion of patients experienced on-treatment adverse events in the two treatment groups (64.3% and 67.2% with SNG001 and placebo, respectively); most were mild or moderate and not treatment-related. CONCLUSION: This study demonstrated that it is feasible to conduct a purely virtual study in community-based patients with COVID-19, when the study included detailed daily assessments and with medication administered via nebuliser.

A multicentre randomised controlled trial of a guided self-help cognitive behavioural therapy to MANage the impact of hot flushes and night sweats in patients with prostate CANcer undergoing androgen deprivation therapy (MANCAN2).

BACKGROUND: Androgen deprivation therapy (ADT) is prescribed to almost half of all men diagnosed with prostate cancer. Although ADT is effective treatment, with virtually all men with advanced disease showing initial clinical response, it is associated with troublesome side effects including hot flushes and night sweats (HFNS). HFNS can be both frequent and severe and can have a significant impact on quality of life (QoL). They can occasionally be so debilitating that patients stop ADT altogether, despite the increased risk of disease relapse or death. Previous research has found that guided self-help cognitive behavioural therapy (CBT) can be effective in reducing HFNS due to ADT when delivered by a clinical psychologist. MANCAN2 aims test whether we can train the existing NHS Prostate Cancer Nurse Specialist (CNS) team to deliver guided self-help CBT and whether it is effective in reducing the impact of HFNS in men undergoing ADT. METHODS: MANCAN2 is a phase III multicentre randomised controlled trial and process evaluation. Between 144 and 196 men with prostate cancer who are currently receiving ADT and are experiencing problematic HFNS will be individually randomised in a 1:1 ratio in groups of 6-8 participants to either treatment as usual (TAU) or participation in the guided self-help CBT intervention plus TAU. A process evaluation using the normalisation process theory (NPT) framework will be conducted, to understand the CNS team's experiences of delivering the intervention and to establish the key influencers to its implementation as a routine practice service. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost-effectiveness of the intervention and participant adherence to the trial intervention will also be assessed. DISCUSSION: MANCAN2 will advance the program of work already conducted in development of management strategies for HFNS. This research will determine whether the severity of ADT-induced HFNS in men with prostate cancer can be reduced by a guided self-help CBT intervention, delivered by the existing NHS prostate cancer CNS team, within a multicentre study. The emphasis on this existing team, if successful, should facilitate translation through to implementation in routine practice. TRIAL REGISTRATION: ISRCTN reference 58720120 . Registered 13 December 2022.

Effectiveness of nurse-led group CBT for hot flushes and night sweats in women with breast cancer: Results of the MENOS4 randomised controlled trial.

OBJECTIVE: Troublesome hot flushes and night sweats (HFNS) are experienced by many women after treatment for breast cancer, impacting significantly on sleep and quality of life. Cognitive behavioural therapy (CBT) is known to be effective for the alleviation of HFNS. However, it is not known if it can effectively be delivered by specialist nurses. We investigated whether group CBT, delivered by breast care nurses (BCNs), can reduce the impact of HFNS. METHODS: We recruited women with primary breast cancer following primary treatment with seven or more HFNS/week (including 4/10 or above on the HFNS problem rating scale), from six UK hospitals to an open, randomised, phase 3 effectiveness trial. Participants were randomised to Group CBT or usual care (UC). The primary endpoint was HFNS problem rating at 26 weeks after randomisation. Secondary outcomes included sleep, depression, anxiety and quality of life. RESULTS: Between 2017 and 2018, 130 participants were recruited (CBT:63, control:67). We found a 46% (6.9-3.7) reduction in the mean HFNS problem rating score from randomisation to 26 weeks in the CBT arm and a 15% (6.5-5.5) reduction in the UC arm (adjusted mean difference -1.96, CI -3.68 to -0.23, P = .039). Secondary outcomes, including frequency of HFNS, sleep, anxiety and depression all improved significantly. CONCLUSION: Our results suggest that specialist nurses can be trained to deliver CBT effectively to alleviate troublesome menopausal hot flushes in women following breast cancer in the NHS setting.

Using digital tools in the recruitment and retention in randomised controlled trials: survey of UK Clinical Trial Units and a qualitative study.

BACKGROUND: Recruitment and retention of participants in randomised controlled trials (RCTs) is a key determinant of success but is challenging. Trialists and UK Clinical Research Collaboration (UKCRC) Clinical Trials Units (CTUs) are increasingly exploring the use of digital tools to identify, recruit and retain participants. The aim of this UK National Institute for Health Research (NIHR) study was to identify what digital tools are currently used by CTUs and understand the performance characteristics required to be judged useful. METHODS: A scoping of searches (and a survey with NIHR funding staff), a survey with all 52 UKCRC CTUs and 16 qualitative interviews were conducted with five stakeholder groups including trialists within CTUs, funders and research participants. A purposive sampling approach was used to conduct the qualitative interviews during March-June 2018. Qualitative data were analysed using a content analysis and inductive approach. RESULTS: Responses from 24 (46%) CTUs identified that database-screening tools were the most widely used digital tool for recruitment, with the majority being considered effective. The reason (and to whom) these tools were considered effective was in identifying potential participants (for both Site staff and CTU staff) and reaching recruitment target (for CTU staff/CI). Fewer retention tools were used, with short message service (SMS) or email reminders to participants being the most reported. The qualitative interviews revealed five themes across all groups: 'security and transparency'; 'inclusivity and engagement'; 'human interaction'; 'obstacles and risks'; and 'potential benefits'. There was a high level of stakeholder acceptance of the use of digital tools to support trials, despite the lack of evidence to support them over more traditional techniques. Certain differences and similarities between stakeholder groups demonstrated the complexity and challenges of using digital tools for recruiting and retaining research participants. CONCLUSIONS: Our studies identified a range of digital tools in use in recruitment and retention of RCTs, despite the lack of high-quality evidence to support their use. Understanding the type of digital tools in use to support recruitment and retention will help to inform funders and the wider research community about their value and relevance for future RCTs. Consideration of further focused digital tool reviews and primary research will help to reduce gaps in the evidence base.

MENOS4 trial: a multicentre randomised controlled trial (RCT) of a breast care nurse delivered cognitive behavioural therapy (CBT) intervention to reduce the impact of hot flushes in women with breast cancer: Study Protocol.

BACKGROUND: Women who have been treated for breast cancer may identify vasomotor symptoms, such as hot flushes and night sweats (HFNS), as a serious problem. HFNS are unpleasant to experience and can have a significant impact on daily life, potentially leading to reduced adherence to life saving adjuvant hormonal therapy. It is known that Cognitive Behavioural Therapy (CBT) is effective for the alleviation of hot flushes in both well women and women who have had breast cancer. Most women with breast cancer will see a breast care nurse and there is evidence that nurses can be trained to deliver psychological treatments to a satisfactory level, whilst also maintaining treatment fidelity. The research team will assess whether breast care nurses can effectively deliver a CBT intervention to alleviate hot flushes in women with breast cancer. METHODS: This study is a multi-centre phase III individually randomised controlled trial of group CBT versus usual care to reduce the impact of hot flushes in women with breast cancer. 120-160 women with primary breast cancer experiencing seven or more problematic HFNS a week will be randomised to receive either treatment as usual (TAU) or participation in the group CBT intervention plus TAU (CBT Group). A process evaluation using May's Normalisation Process Theory will be conducted, as well as practical and organisational issues relating to the implementation of the intervention. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost effectiveness of the intervention will also be assessed. DISCUSSION: There is a need for studies that enable effective interventions to be implemented in practice. There is good evidence that CBT is helpful for women with breast cancer who experience HFNS, yet it is not widely available. It is not yet known whether the intervention can be effectively delivered by breast care nurses or implemented in practice. This study will provide information on both whether the intervention can effectively help women with hot flushes and whether and how it can be translated into routine clinical practice. TRIAL REGISTRATION: ISRCTN 12824632 . Registered 25-01-2017.

Seal or Varnish? A randomised controlled trial to determine the relative cost and effectiveness of pit and fissure sealant and fluoride varnish in preventing dental decay.

BACKGROUND: Fissure sealant (FS) and fluoride varnish (FV) have been shown to be effective in preventing dental caries when tested against a no-treatment control. However, the relative clinical effectiveness and cost-effectiveness of these interventions is unknown. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of FS and FV in preventing dental caries in first permanent molars (FPMs) in 6- and 7-year-olds and to determine their acceptability. DESIGN: A randomised controlled allocation-blinded clinical trial with two parallel arms. SETTING: A targeted population programme using mobile dental clinics (MDCs) in schools located in areas of high social and economic deprivation in South Wales. PARTICIPANTS: In total, 1016 children were randomised, but one parent subsequently withdrew permission and so the analysis was based on 1015 children. The randomisation of participants was stratified by school and balanced for sex and primary dentition baseline caries levels using minimisation in a 1 : 1 ratio for treatments. A random component was added to the minimisation algorithm, such that it was not completely deterministic. Of the participants, 514 were randomised to receive FS and 502 were randomised to receive FV. INTERVENTIONS: Resin-based FS was applied to caries-free FPMs and maintained at 6-monthly intervals. FV was applied at baseline and at 6-month intervals over the course of 3 years. MAIN OUTCOME MEASURES: The proportion of children developing caries into dentine (decayed, missing, filled teeth in permanent dentition, i.e. D4-6MFT) on any one of up to four treated FPMs after 36 months. The assessors were blinded to treatment allocation; however, the presence or absence of FS at assessment would obviously indicate the probable treatment received. Economic measures established the costs and budget impact of FS and FV and the relative cost-effectiveness of these technologies. Qualitative interviews determined the acceptability of the interventions. RESULTS: At 36 months, 835 (82%) children remained in the trial: 417 in the FS arm and 418 in the FV arm. The proportion of children who developed caries into dentine on a least one FPM was lower in the FV arm (73; 17.5%) than in the FS arm (82, 19.6%) [odds ratio (OR) 0.84, 95% confidence interval (CI) 0.59 to 1.21; p = 0.35] but the difference was not statistically significant. The results were similar when the numbers of newly decayed teeth (OR 0.86, 95% CI 0.60 to 1.22) and tooth surfaces (OR 0.85, 95% CI 0.59 to 1.21) were examined. Trial fidelity was high: 95% of participants received five or six of the six scheduled treatments. Between 74% and 93% of sealants (upper and lower teeth) were intact at 36 months. The costs of the two technologies showed a small but statistically significant difference; the mean cost to the NHS (including intervention costs) per child was £500 for FS, compared with £432 for FV, a difference of £68.13 (95% CI £5.63 to £130.63; p = 0.033) in favour of FV. The budget impact analysis suggests that there is a cost saving of £68.13 (95% CI £5.63 to £130.63; p = 0.033) per child treated if using FV compared with the application of FS over this time period. An acceptability score completed by the children immediately after treatment and subsequent interviews demonstrated that both interventions were acceptable to the children. No adverse effects were reported. LIMITATIONS: There are no important limitations to this study. CONCLUSIONS: In a community oral health programme utilising MDCs and targeted at children with high caries risk, the twice-yearly application of FV resulted in caries prevention that is not significantly different from that obtained by applying and maintaining FSs after 36 months. FV proved less expensive. FUTURE WORK: The clinical effectiveness and cost-effectiveness of FS and FV following the cessation of active intervention merits investigation. TRIAL REGISTRATION: EudraCT number 2010-023476-23, Current Controlled Trials ISRCTN17029222 and UKCRN reference 9273. FUNDING: This 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. 21, No. 21. See the NIHR Journals Library website for further project information.

Antibiotic prescribing and associated diarrhoea: a prospective cohort study of care home residents.

BACKGROUND: the risk factors for and frequency of antibiotic prescription and antibiotic-associated diarrhoea (AAD) among care home residents are unknown. AIM: to prospectively study frequency and risks for antibiotic prescribing and AAD for care home residents. DESIGN AND SETTING: a 12-month prospective cohort study in care homes across South Wales. METHOD: antibiotic prescriptions and the development of AAD were recorded on case report forms. We defined AAD as three or more loose stools in a 24-h period occurring within 8 weeks of exposure to an antibiotic. RESULTS: we recruited 279 residents from 10 care homes. The incidence of antibiotic prescriptions was 2.16 prescriptions per resident year (95% CI: 1.90-2.46). Antibiotics were less likely to be prescribed to residents from dual-registered homes (OR compared with nursing homes: 0.38, 95% CI: 0.18-0.79). For those who were prescribed antibiotics, the incidence of AAD was 0.57 episodes per resident year (95% CI: 0.41-0.81 episodes). AAD was more likely in residents who were prescribed co-amoxiclav (hazards ratio, HR = 2.08, 95% confidence interval, CI: 1.18-3.66) or routinely used incontinence pads (HR = 2.54, 95% CI: 1.26-5.13) and less likely in residents from residential homes (HR compared with nursing homes: 0.14, 95% CI: 0.06-0.32). CONCLUSION: residents of care homes, particularly of nursing homes, are frequently prescribed antibiotics and often experience diarrhoea following such prescriptions. Co-amoxiclav is associated with greater risk of AAD.

Fibrinogen concentrate versus placebo for treatment of postpartum haemorrhage: study protocol for a randomised controlled trial.

BACKGROUND: Postpartum haemorrhage (PPH) is a major cause of maternal morbidity. Bleeding is caused by a combination of physical causes, such as failure of the uterus to contract or operations, and is made worse by impairment of the blood clotting system. A number of studies have shown that low levels of the blood clotting factor fibrinogen are associated with progression of bleeding, the need for invasive interventions and transfusions of red blood cells and fresh frozen plasma (FFP). This trial will investigate whether early infusion of fibrinogen concentrate during a major PPH, with the aim of correcting a low fibrinogen to a level that is normal for delivery, based on the Fibtem test, reduces the total number of allogeneic blood products (red blood cells, FFP, cryoprecipitate and platelets) transfused after study medication until discharge, compared to placebo. METHODS/DESIGN: This is a prospective, randomised, double-blind placebo controlled trial. Women will enter an observational phase and if their Fibtem levels fall they will be randomised in the interventional phase. A total of 60 women will be randomised and women are eligible for the trial if they meet all of the following inclusion criteria: age 18 years or over, gestation ≥24 + 0 weeks, haemorrhage of about 1500 ml and on-going bleeding without another complication or haemorrhage of about 1000 ml and caesarean section/uterine atony/placental abruption/placenta praevia/cardiovascular instability or microvascular oozing. Participants with a Fibtem A5 < 16 mm will be randomly allocated to receive either a bolus infusion of fibrinogen concentrate or placebo (isotonic saline). The dose of fibrinogen concentrate or placebo will be calculated based on the woman's ideal body weight for height and the measured Fibtem A5 with the aim of increasing the Fibtem A5 to 23 mm. DISCUSSION: The trial aims to provide evidence on the efficacy and safety of fibrinogen concentrate during acute bleeding in an obstetric setting. TRIAL REGISTRATION: ISRCTN ref: ISRCTN46295339 (01.07.2013); EudraCT: 2012-005511-11 (28.11.2012), UKCRN ref: 13940.

Development of a scale to measure fidelity to manualized group-based cognitive behavioural interventions for people with intellectual disabilities.

The context for the present study was a cluster-randomized controlled trial of a group-based anger-management intervention, delivered by day-service staff. We aimed to develop a scale to measure the fidelity of manualized cognitive-behavioural therapy (CBT) delivered to adults with intellectual disabilities in group-based settings. A 30-item monitoring instrument (the MAnualized Group Intervention Check: MAGIC) was adapted from an existing fidelity-monitor instrument for individual CBT. Two sessions for 27 groups were observed by pairs of monitors who had no other contact with the intervention. 16 observers participated, in 15 unique pairings. Observers recorded high levels of inter-rater reliability and the scale had good internal consistency. Fidelity ratings predicted two key outcomes of the intervention, and were themselves predicted by the therapists' clinical supervisors.

Different factors influence self-reports and third-party reports of anger by adults with intellectual disabilities.

BACKGROUND: Many people with intellectual disabilities display high levels of anger, and cognitive-behavioural anger management interventions are used routinely. However, for these methods to be used optimally, a better understanding is needed of different forms of anger assessment. The aim of this study was to investigate the relationship of a range of measures to self- and carer reports of anger expression, including instruments used to assess mental health and challenging behaviour. METHOD: Adults with intellectual disabilities, who had been identified as having problems with anger control, their key-workers and home carers all rated the service users' trait anger, using parallel versions of the same instrument (the Provocation Inventory). In addition, service users completed a battery of mental health assessments (the Glasgow Depression Scale, Glasgow Anxiety Scale and Rosenberg Self-Esteem Scale), and both groups of carers completed a battery of challenging behaviour measures (the Hyperactivity and Irritability domains of the Aberrant Behavior Checklist and the Modified Overt Anger Scale). RESULTS: Participants had high levels of mental health problems (depression: 34%; anxiety: 73%) and severe challenging behaviour (26%). Hierarchical linear regression analysis was used to explore the extent to which anger ratings by the three groups of respondents were predicted by demographic factors, mental health measures and challenging behaviour measures. Older service users rated themselves as less angry and were also rated as less angry by home carers, but not by key-workers. More intellectually able service users were rated as more angry by both sets of carers, but not by the service users themselves. Significantly, mental health status (but not challenging behaviour) predicted service users' self-ratings of anger, whereas challenging behaviour (but not mental health status) predicted carers' ratings of service users' anger. CONCLUSIONS: Service users and their carers appear to use different information when rating the service users' anger. Service users' self-ratings reflect their internal emotional state and mental health, as reflected by their ratings of anxiety and depression, whereas staff rate service users' anger on the basis of overt behaviours, as measured by challenging behaviour scales.

Consent, including advanced consent, of older adults to research in care homes: a qualitative study of stakeholders' views in South Wales.

BACKGROUND: Care home residents, especially those lacking capacity to provide consent for themselves, are frequently excluded from research, thus limiting generalisability of study findings. We set out to explore stakeholders' views about the ethical and practical challenges associated with recruiting care home residents into research studies. METHODS: Qualitative individual interviews with care home residents (n = 14), their relatives (n = 14), and general practitioners (GPs) (n = 10), and focus groups (n = 2) with care home staff. Interviews focused on the issues of older adults consenting to research in care homes, including advanced consent, in general and through reference to a particular study on the use of probiotics to prevent Antibiotic Associated Diarrhoea. Data were analysed using a thematic approach incorporating themes that had been identified in advance, and themes derived from the data. Researchers discussed evidence for themes, and reached consensus on the final themes. RESULTS: Respondents were generally accepting of low risk observational studies and slightly less accepting of low risk randomised trials of medicinal products. Although respondents identified some practical barriers to informed consent, consenting arrangements were considered workable. Residents and relatives varied in the amount of detail they wanted included in information sheets and consent discussions, but were generally satisfied that an advanced consent model was acceptable and appropriate. Opinions differed about what should happen should residents lose capacity during a research study. CONCLUSIONS: Research staff should be mindful of research guidance and ensure that they have obtained an appropriate level of informed consent without overwhelming the participant with unnecessary detail. For research involving medicinal products, research staff should also be more explicit when recruiting that consent is still valid should an older person lose capacity during a trial provided the individual did not previously state a wish to be withdrawn if they lose capacity, and provided they do not indicate objection or resistance after loss of capacity.

Group-based cognitive-behavioural anger management for people with mild to moderate intellectual disabilities: cluster randomised controlled trial.

BACKGROUND: Many people with intellectual disabilities find it hard to control their anger and this often leads to aggression which can have serious consequences, such as exclusion from mainstream services and the need for potentially more expensive emergency placements. AIMS: To evaluate the effectiveness of a cognitive-behavioural therapy (CBT) intervention for anger management in people with intellectual disabilities. METHOD: A cluster-randomised trial of group-based 12-week CBT, which took place in day services for people with intellectual disabilities and was delivered by care staff using a treatment manual. Participants were 179 service users identified as having problems with anger control randomly assigned to either anger management or treatment as usual. Assessments were conducted before the intervention, and at 16 weeks and 10 months after randomisation (trial registration: ISRCTN37509773). RESULTS: The intervention had only a small, and non-significant, effect on participants' reports of anger on the Provocation Index, the primary outcome measure (mean difference 2.8, 95% CI -1.7 to 7.4 at 10 months). However, keyworker Provocation Index ratings were significantly lower in both follow-up assessments, as were service-user ratings on another self-report anger measure based on personally salient triggers. Both service users and their keyworkers reported greater usage of anger coping skills at both follow-up assessments and keyworkers and home carers reported lower levels of challenging behaviour. CONCLUSIONS: The intervention was effective in improving anger control by people with intellectual disabilities. It provides evidence of the effectiveness of a CBT intervention for this client group and demonstrates that the staff who work with them can be trained and supervised to deliver such an intervention with reasonable fidelity.

The impact of using different tariffs to value EQ-5D health state descriptions: an example from a study of acute cough/lower respiratory tract infections in seven countries.

When using the EQ-5D in European cross-national studies, there is no consensus over whether the European value set (EVS), country specific value sets (CVS) or UK value set (UKVS) should be used. Data on health outcomes were collected in 7 countries. EQ-5D index scores were generated for each country using all three value sets. QALYs gained over 4 weeks based on EQ-5D scores were also generated in order to investigate the implications for cost-utility analysis. EQ-5D scores obtained using the EVS were similar to values obtained using the CVS and UKVS in all countries. CVS-based EQ-5D scores were on average associated with a smaller baseline-to-week 4 change/improvement in all countries (except in Wales and Belgium) while UKVS-based EQ-5D scores showed the largest improvement over the same period for every country. With regards to cost-utility analysis, the results suggest that in most countries (with the exception of Belgium and Finland), using different tariffs to value EQ-5D would not have made a difference to the decisions based on the results of cost-utility analysis.

Protocol for "Seal or Varnish?" (SoV) trial: a randomised controlled trial to measure the relative cost and effectiveness of pit and fissure sealants and fluoride varnish in preventing dental decay.

BACKGROUND: Dental caries remains a significant public health problem, prevalence being linked to social and economic deprivation. Occlusal surfaces of first permanent molars are the most susceptible site in the developing permanent dentition. Cochrane reviews have shown pit and fissure sealants (PFS) and fluoride varnish (FV) to be effective over no intervention in preventing caries. However, the comparative cost and effectiveness of these treatments is uncertain. The primary aim of the trial described in this protocol is to compare the clinical effectiveness of PFS and FV in preventing dental caries in first permanent molars in 6-7 year-olds. Secondary aims include: establishing the costs and the relative cost-effectiveness of PFS and FV delivered in a community/school setting; examining the impact of PFS and FV on children and their parents/carers in terms of quality of life/treatment acceptability measures; and examining the implementation of treatment in a community setting. METHODS/DESIGN: The trial design comprises a randomised, assessor-blinded, two-arm, parallel group trial in 6-7 year old schoolchildren. Clinical procedures and assessments will be performed at 66 primary schools, in deprived areas in South Wales. Treatments will be delivered via a mobile dental clinic. In total, 920 children will be recruited (460 per trial arm). At baseline and annually for 36 months dental caries will be recorded using the International Caries Detection and Assessment System (ICDAS) by trained and calibrated dentists. PFS and FV will be applied by trained dental hygienists. The FV will be applied at baseline, 6, 12, 18, 24 and 30 months. The PFS will be applied at baseline and re-examined at 6, 12, 18, 24, and 30 months, and will be re-applied if the existing sealant has become detached/is insufficient. The economic analysis will estimate the costs of providing the PFS versus FV. The process evaluation will assess implementation and acceptability through acceptability scales, a schools questionnaire and interviews with children, parents, dentists, dental nurses and school staff. The primary outcome measure will be the proportion of children developing new caries on any one of up to four treated first permanent molars. DISCUSSION: The objectives of this study have been identified by the National Institute for Health Research as one of importance to the National Health Service in the UK. The results of this trial will provide guidance on which of these technologies should be adopted for the prevention of dental decay in the most susceptible tooth-surface in the most at risk children. TRIAL REGISTRATIONS: ISRCTN ref: ISRCTN17029222 EudraCT: 2010-023476-23 UKCRN ref: 9273.

Delayed antibiotic prescribing and associated antibiotic consumption in adults with acute cough.

BACKGROUND: Delayed antibiotic prescribing is promoted as a strategy to reduce antibiotic consumption, but its use and its effect on antibiotic consumption in routine care is poorly described. AIM: To quantify delayed antibiotic prescribing in adults presenting in primary care with acute cough/lower respiratory tract infection (LRTI), duration of advised delay, consumption of delayed antibiotics, and factors associated with consumption. DESIGN AND SETTING: Prospective observational cohort in general practices in 14 primary care networks in 13 European countries. METHOD: GPs recorded clinical features and antibiotic prescribing for adults presenting with an acute infective illness with cough as the dominant symptom. Patients recorded their consumption of antibiotics from any source during the 28-day follow up. RESULTS: Two hundred and ten (6.3%) of 3368 patients with usable consultation data were prescribed delayed antibiotics. The median recommended delay period was 3 days. Seventy-five (44.4%) of the 169 with consumption data consumed the antibiotic course and a further 18 (10.7%) took another antibiotic during the study period. 50 (29.6%) started their delayed course on the day of prescription. Clinician diagnosis of upper respiratory tract/viral infection and clinician's perception of patient's wanting antibiotics were associated with less consumption of the delayed prescription. Patient's wanting antibiotics was associated with greater consumption. CONCLUSION: Delayed antibiotic prescribing was used infrequently for adults presenting in general practice with acute cough/LRTI. When used, the effect on antibiotic consumption was less than found in most trials. There are opportunities for standardising the intervention and promoting wider uptake.

Antibiotics for acute cough: an international observational study of patient adherence in primary care.

BACKGROUND: Non-adherence to acute antibiotic prescriptions is poorly described and may impact on clinical outcomes, healthcare costs, and interpretation of research. It also results in leftover antibiotics that could be used inappropriately. AIM: To describe adherence to antibiotics prescribed for adults presenting with acute cough in primary care, factors associated with non-adherence, and associated recovery. DESIGN AND SETTING: Prospective observational cohort study in general practices in 14 European primary care networks. METHOD: GPs recorded patient characteristics and prescribing decisions for adults with acute cough or clinical presentation suggestive of lower respiratory tract infection. Patients recorded antibiotic consumption and daily symptoms over 28 days. Rates of adherence to prescribed antibiotics were assessed, and factors associated with non-adherence were identified using logistic regression. Recovery was compared using a Cox proportional hazards model. RESULTS: Of 2520 patients prescribed immediate or no antibiotics at the index consultation, 282 (11.2%) took an antibiotic during the follow-up period that was not prescribed for them at the index consultation. Of these, 38.1% had no reconsultations during this period. Prior duration of symptoms, antibiotic treatment duration, antibiotic choice, and primary care network were all associated with adherence. There was no difference in time to recovery between those who were prescribed antibiotics at the index consultation and were fully adherent, partially adherent, and non-adherent. CONCLUSION: Non-adherence to antibiotics for acute cough or lower respiratory tract infection is common. Duration of treatment, choice of antibiotic, and setting were associated with adherence but adherence to treatment was not associated with differences in recovery.

Building an international network for a primary care research program: reflections on challenges and solutions in the set-up and delivery of a prospective observational study of acute cough in 13 European countries.

BACKGROUND: Implementing a primary care clinical research study in several countries can make it possible to recruit sufficient patients in a short period of time that allows important clinical questions to be answered. Large multi-country studies in primary care are unusual and are typically associated with challenges requiring innovative solutions. We conducted a multi-country study and through this paper, we share reflections on the challenges we faced and some of the solutions we developed with a special focus on the study set up, structure and development of Primary Care Networks (PCNs). METHOD: GRACE-01 was a multi-European country, investigator-driven prospective observational study implemented by 14 Primary Care Networks (PCNs) within 13 European Countries. General Practitioners (GPs) recruited consecutive patients with an acute cough. GPs completed a case report form (CRF) and the patient completed a daily symptom diary. After study completion, the coordinating team discussed the phases of the study and identified challenges and solutions that they considered might be interesting and helpful to researchers setting up a comparable study. RESULTS: The main challenges fell within three domains as follows:i) selecting, setting up and maintaining PCNs;ii) designing local context-appropriate data collection tools and efficient data management systems; andiii) gaining commitment and trust from all involved and maintaining enthusiasm.The main solutions for each domain were:i) appointing key individuals (National Network Facilitator and Coordinator) with clearly defined tasks, involving PCNs early in the development of study materials and procedures.ii) rigorous back translations of all study materials and the use of information systems to closely monitor each PCNs progress;iii) providing strong central leadership with high level commitment to the value of the study, frequent multi-method communication, establishing a coherent ethos, celebrating achievements, incorporating social events and prizes within meetings, and providing a framework for exploitation of local data. CONCLUSIONS: Many challenges associated with multi-country primary care research can be overcome by engendering strong, effective communication, commitment and involvement of all local researchers. The practical solutions identified and the lessons learned in implementing the GRACE-01 study may assist in establishing other international primary care clinical research platforms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00353951.

Anger management for people with mild to moderate learning disabilities: study protocol for a multi-centre cluster randomized controlled trial of a manualized intervention delivered by day-service staff.

BACKGROUND: Cognitive behaviour therapy (CBT) is the treatment of choice for common mental health problems, but this approach has only recently been adapted for people with learning disabilities, and there is a limited evidence base for the use of CBT with this client group. Anger treatment is the one area where there exists a reasonable number of small controlled trials. This study will evaluate the effectiveness of a manualized 12-week CBT intervention for anger. The intervention will be delivered by staff working in the day services that the participants attend, following training to act as 'lay therapists' by a Clinical Psychologist, who will also provide supervision. METHODS/DESIGN: This is a multi-centre cluster randomized controlled trial of a group intervention versus a 'support as usual' waiting-list control group, with randomization at the level of the group. Outcomes will be assessed at the end of the intervention and again 6-months later. After completion of the 6-month follow-up assessments, the intervention will also be delivered to the waiting-list groups. The study will include a range of anger/aggression and mental health measures, some of which will be completed by service users and also by their day service key-workers and by home carers. Qualitative data will be collected to assess the impact of the intervention on participants, lay therapists, and services, and the study will also include a service-utilization cost and consequences analysis. DISCUSSION: This will be the first trial to investigate formally how effectively staff working in services providing day activities for people with learning disabilities are able to use a therapy manual to deliver a CBT based anger management intervention, following brief training by a Clinical Psychologist. The demonstration that service staff can successfully deliver anger management to people with learning disabilities, by widening the pool of potential therapists, would have very significant benefits in relation to the current policy of improving access to psychological therapies, in addition to addressing more effectively an important and often unmet need of this vulnerable client group. The economic analysis will identify the direct and indirect costs (and/or savings) of the intervention and consider these in relation to the range of observed effects. The qualitative analyses will enhance the interpretation of the quantitative data, and if the study shows positive results, will inform the roll-out of the intervention to the wider community. TRIAL REGISTRATION: ISRCTN: ISRCTN37509773.

Effect of using an interactive booklet about childhood respiratory tract infections in primary care consultations on reconsulting and antibiotic prescribing: a cluster randomised controlled trial.

OBJECTIVE: To establish whether an interactive booklet on respiratory tract infections in children reduces reconsultation for the same illness episode, reduces antibiotic use, and affects future consulting intentions, while maintaining parental satisfaction with care. DESIGN: Pragmatic cluster randomised controlled trial. SETTING: 61 general practices in Wales and England. PARTICIPANTS: 558 children (6 months to 14 years) presenting to primary care with an acute respiratory tract infection (7 days or less). Children with suspected pneumonia, asthma or a serious concomitant illness, or needing immediate hospital admission were excluded. Three withdrew and 27 were lost to follow-up, leaving 528 (94.6%) with main outcome data. INTERVENTIONS: Clinicians in the intervention group were trained in the use of an interactive booklet on respiratory tract infections and asked to use the booklet during consultations with recruited patients (and provide it as a take home resource). Clinicians in the control group conducted their consultations as usual. MAIN OUTCOME MEASURES: The proportion of children who attended a face-to-face consultation about the same illness during the two week follow-up period. Secondary outcomes included antibiotic prescribing, antibiotic consumption, future consulting intentions, and parental satisfaction, reassurance, and enablement. RESULTS: Reconsultation occurred in 12.9% of children in the intervention group and 16.2% in the control group (absolute risk reduction 3.3%, 95% confidence interval -2.7% to 9.3%, P=0.29). Using multilevel modelling (at the practice and individual level) to account for clustering, no significant difference in reconsulting was noted (odds ratio 0.75; 0.41 to 1.38). Antibiotics were prescribed at the index consultation to 19.5% of children in the intervention group and 40.8% of children in the control group (absolute risk reduction 21.3%, 95% confidence interval 13.7 to 28.9), P<0.001). A significant difference was still present after adjusting for clustering (odds ratio 0.29; 0.14 to 0.60). There was also a significant difference in the proportion of parents who said they would consult in the future if their child developed a similar illness (odds ratio 0.34; 0.20 to 0.57). Satisfaction, reassurance, and parental enablement scores were not significantly different between the two groups. CONCLUSIONS: Use of a booklet on respiratory tract infections in children within primary care consultations led to important reductions in antibiotic prescribing and reduced intention to consult without reducing satisfaction with care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46104365.