Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT.

BACKGROUND: Oral mucositis is a debilitating and painful complication of head and neck cancer irradiation that is characterised by inflammation of the mucous membranes, erythema and ulceration. Oral mucositis affects 6000 head and neck cancer patients per year in England and Wales. Current treatments have not proven to be effective. International studies suggest that low-level laser therapy may be an effective treatment. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of low-level laser therapy in the management of oral mucositis in head and neck cancer irradiation. To identify barriers to and facilitators of implementing low-level laser therapy in routine care. DESIGN: Placebo-controlled, individually randomised, multicentre Phase III superiority trial, with an internal pilot and health economic and qualitative process evaluations. The participants, outcome assessors and therapists were blinded. SETTING: Nine NHS head and neck cancer sites in England and Wales. PARTICIPANTS: A total of 87 out of 380 participants were recruited who were aged ≥ 18 years and were undergoing head and neck cancer irradiation with ≥ 60 Gy. INTERVENTION: Random allocation (1 : 1 ratio) to either low-level laser therapy or sham low-level laser therapy three times per week for the duration of irradiation. The diode laser had the following specifications: wavelength 660 nm, power output 75 mW, beam area 1.5 cm2, irradiance 50 mW/cm2, exposure time 60 seconds and fluence 3 J/cm2. There were 20-30 spots per session. Sham low-level laser therapy was delivered in an identical manner. MAIN OUTCOME MEASURE: The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks following the start of irradiation. Higher scores indicate a worse outcome. RESULTS: A total of 231 patients were screened and, of these, 87 were randomised (low-level laser therapy arm, n = 44; sham arm, n = 43). The mean age was 59.4 years (standard deviation 8.8 years) and 69 participants (79%) were male. The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4 (standard deviation 13.8) in the sham arm. LIMITATIONS: The trial lacked statistical power because it did not meet the recruitment target. Staff and patients willingly participated in the trial and worked hard to make the LiTEFORM trial succeed. However, the task of introducing, embedding and sustaining new low-level laser therapy services into a complex care pathway proved challenging. Sites could deliver low-level laser therapy to only a small number of patients at a time. The administration of low-level laser therapy was viewed as straightforward, but also time-consuming and sometimes uncomfortable for both patients and staff, particularly those staff who were not used to working in a patient's mouth. CONCLUSIONS: This trial had a robust design but lacked power to be definitive. Low-level laser therapy is relatively inexpensive. In contrast with previous trials, some patients found low-level laser therapy sessions to be difficult. The duration of low-level laser therapy sessions is, therefore, an important consideration. Clinicians experienced in oral cavity work most readily adapt to delivering low-level laser therapy, although other allied health professionals can be trained. Blinding the clinicians delivering low-level laser therapy is feasible. There are important human resource, real estate and logistical considerations for those setting up low-level laser therapy services. FUTURE WORK: Further well-designed randomised controlled trials investigating low-level laser therapy in head and neck cancer irradiation are needed, with similar powered recruitment targets but addressing the recruitment challenges and logistical findings from this research. TRIAL REGISTRATION: This trial is registered as ISRCTN14224600. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 46. See the NIHR Journals Library website for further project information.

Around 9 out of 10 head and neck cancer patients undergoing treatment experience pain, swelling and sores in their mouth (oral mucositis). This can lead to weight loss, painful ulcers, difficulty talking, eating and drinking, and even hospitalisation. Current care includes helping patients to keep their mouth and teeth clean, encouraging them to have a healthy diet and prescribing mouthwashes, painkillers and mouth-coating gels. However, these treatments give limited help in preventing or treating this condition. The LiTEFORM trial looked at whether or not low-level laser therapy could be used to prevent and treat oral mucositis. Patients were allocated to one of two arms at random: active laser or fake (sham) laser. Neither the patients nor the hospital staff knew which laser was being used. Eighty-seven people joined the study during the time allowed (44 received low-level laser therapy and 43 received sham treatment); however, this was a smaller number than the planned target of 380 people. As a result, no meaningful conclusion can be drawn from the results about whether the therapy is beneficial or cost-effective. People receiving the low-level laser therapy reported slightly more soreness in their mouth than those receiving the sham laser, but this could be down to chance. The number of participants is too small to draw conclusions about whether or not the low-level laser is helpful. Some patients found the laser treatment sessions to be difficult. Setting up a new service delivering laser therapy at the same time as cancer treatments was more complicated than originally anticipated. Problems included the scheduling of appointments, finding suitable rooms and having enough trained staff with time to deliver laser therapy. However, this study has provided us with knowledge on how best to set up a laser therapy service in the NHS as part of the cancer treatment pathway and the costs involved. These findings could help future studies looking into low-level laser therapy for those with head and neck cancer.

Acipimox in Mitochondrial Myopathy (AIMM): study protocol for a randomised, double-blinded, placebo-controlled, adaptive design trial of the efficacy of acipimox in adult patients with mitochondrial myopathy.

BACKGROUND: Mitochondrial disease is a heterogenous group of rare, complex neurometabolic disorders. Despite their individual rarity, collectively mitochondrial diseases represent the most common cause of inherited metabolic disorders in the UK; they affect 1 in every 4300 individuals, up to 15,000 adults (and a similar number of children) in the UK. Mitochondrial disease manifests multisystem and isolated organ involvement, commonly affecting those tissues with high energy demands, such as skeletal muscle. Myopathy manifesting as fatigue, muscle weakness and exercise intolerance is common and debilitating in patients with mitochondrial disease. Currently, there are no effective licensed treatments and consequently, there is an urgent clinical need to find an effective drug therapy. AIM: To investigate the efficacy of 12-week treatment with acipimox on the adenosine triphosphate (ATP) content of skeletal muscle in patients with mitochondrial disease and myopathy. METHODS: AIMM is a single-centre, double blind, placebo-controlled, adaptive designed trial, evaluating the efficacy of 12 weeks' administration of acipimox on skeletal muscle ATP content in patients with mitochondrial myopathy. Eligible patients will receive the trial investigational medicinal product (IMP), either acipimox or matched placebo. Participants will also be prescribed low dose aspirin as a non-investigational medical product (nIMP) in order to protect the blinding of the treatment assignment. Eighty to 120 participants will be recruited as required, with an interim analysis for sample size re-estimation and futility assessment being undertaken once the primary outcome for 50 participants has been obtained. Randomisation will be on a 1:1 basis, stratified by Fatigue Impact Scale (FIS) (dichotomised as < 40, ≥ 40). Participants will take part in the trial for up to 20 weeks, from screening visits through to follow-up at 16 weeks post randomisation. The primary outcome of change in ATP content in skeletal muscle and secondary outcomes relating to quality of life, perceived fatigue, disease burden, limb function, balance and walking, skeletal muscle analysis and symptom-limited cardiopulmonary fitness (optional) will be assessed between baseline and 12 weeks. DISCUSSION: The AIMM trial will investigate the effect of acipimox on modulating muscle ATP content and whether it can be repurposed as a new treatment for mitochondrial disease with myopathy. TRIAL REGISTRATION: EudraCT2018-002721-29 . Registered on 24 December 2018, ISRCTN 12895613. Registered on 03 January 2019, https://www.isrctn.com/search?q=aimm.

The FiCTION trial: Child oral health-related quality of life and dental anxiety across three treatment strategies for managing caries in young children.

OBJECTIVES: The FiCTION trial compared co-primary outcomes (dental pain and/or infection) and secondary outcomes (child oral health-related quality of life [COHRQOL], child dental anxiety, cost-effectiveness, caries development/progression and acceptability) across three treatment strategies (Conventional with Prevention [C + P]; Biological with Prevention [B + P]; Prevention Alone [PA]) for managing caries in children in primary care. COHRQOL and child dental anxiety experiences are reported upon here. METHODS: A multi-centre, 3-arm, parallel-group, unblinded patient-randomized controlled trial of 3- to 7-year-olds treated under NHS contracts was conducted in 72 general dental practices in England, Wales and Scotland. Child participants (with at least one primary molar with dentinal caries) were randomized (1:1:1) to one of three treatment arms with the intention of being managed according to allocated arm for 3 years (minimum 23 months). Randomization was via a centrally administered system using random permuted blocks of variable length. At baseline and final visit, accompanying parents/caregivers completed a parental questionnaire including COHRQOL (16 item P-CPQ-16), and at every visit, child- and parental-questionnaire-based data were collected for child-based dental trait and state anxiety. Statistical analyses were conducted on complete cases from the modified intention-to-treat (mITT) analysis set. RESULTS: A total of 1144 children were randomized (C + P: 386; B + P: 381; PA: 377). The mITT analysis set included the 1058 children who attended at least one study visit (C + P: 352; B + P: 352; PA: 354). Median follow-up was 33.8 months (IQR: 23.8, 36.7). The P-CPQ-16 overall score could be calculated after simple imputation at both baseline and final visit for 560 children (C + P: 189; B + P: 189; PA: 182). There was no evidence of a difference in the estimated adjusted mean P-CPQ-16 at the final visit which was, on average, 0.3 points higher (97.5% CI: -1.1 to 1.6) in B + P than C + P and 0.2 points higher, on average, (97.5% CI: -1.2 to 1.5) in PA than for C + P. Child dental trait anxiety and child dental state anxiety, measured at every treatment visit, showed no evidence of any statistically or clinically significant difference between arms in adjusted mean scores averaged over all follow-up visits. CONCLUSIONS: The differences noted in COHRQOL and child-based dental trait and dental state anxiety measures across three treatment strategies for managing dental caries in primary teeth were small, and not considered to be clinically meaningful. The findings highlight the importance of including all three strategies in a clinician's armamentarium, to manage childhood caries throughout the young child's life and achieve positive experiences of dental care.

Bronchiectasis Information and Education: a randomised, controlled feasibility trial.

BACKGROUND: There has been comparatively little patient information about bronchiectasis, a chronic lung disease with rising prevalence. Patients want more information, which could improve their understanding and self-management. A novel information resource meeting identified needs has been co-developed in prior work. We sought to establish the feasibility of conducting a multi-centre randomised controlled trial to determine effect of the information resource on understanding, self-management and health outcomes. METHODS/DESIGN: We conducted an unblinded, single-centre, randomised controlled feasibility trial with two parallel groups (1:1 ratio), comparing a novel patient information resource with usual care in adults with bronchiectasis. Integrated qualitative methods allowed further evaluation of the intervention and trial process. The setting was two teaching hospitals in North East England. Participants randomised to the intervention group received the information resource (website and booklet) and instructions on its use. Feasibility outcome measures included willingness to enter the trial, in addition to recruitment and retention rates. Secondary outcome measures (resource use and satisfaction, quality of life, unscheduled healthcare presentations, exacerbation frequency, bronchiectasis knowledge and lung function) were recorded at baseline, 2 weeks and 12 weeks. RESULTS: Sixty-two participants were randomised (control group = 30; intervention group = 32). Thirty-eight (61%) were female, and the participants' median age was 65 years (range 15-81). Median forced expiratory volume in 1 s percent predicted was 68% (range 10-120). Sixty-two of 124 (50%; 95% CI, 41-59%) of potentially eligible participants approached were recruited. Sixty (97%) of 62 participants completed the study (control group, 29 of 30 [97%]; 95% CI, 83-99%; 1 unrelated death; intervention group, 31 [97%] of 32; 95% CI, 84-99%; 1 withdrawal). In the intervention group, 27 (84%) of 32 reported using the information provided, and 25 (93%) of 27 of users found it useful, particularly the video content. Qualitative data analysis revealed acceptability of the trial and intervention. Web analytics recorded over 20,000 page views during the 16-month study period. CONCLUSION: The successful recruitment process, high retention rate and study form completion rates indicate that it appears feasible to conduct a full trial based on this study design. Worldwide demand for online access to the information resource was high. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN84229105. Registered on 25 July 2014.

Age-Related Serum Thyroid-Stimulating Hormone Reference Range in Older Patients Treated with Levothyroxine: A Randomized Controlled Feasibility Trial (SORTED 1).

INTRODUCTION: Serum thyroid-stimulating hormone (TSH) increases with age but target TSH is similar in younger and older hypothyroid patients on treatment. It is unknown if quality of life (QoL), hypothyroid symptoms and cardiovascular risk factors change in older hypothyroid patients treated to an age-appropriate reference range. OBJECTIVE: To assess if a higher target serum TSH of 4.01-8.0 mU/L is feasible in, and acceptable to, older treated hypothyroid patients. METHODS: A single-blind (participant) randomised controlled feasibility trial involving 48 hypothyroid patients aged ≥80 years on established and stable levothyroxine (LT4) therapy with serum TSH levels within the standard reference range (0.4-4.0 mU/L) was conducted. Standard (0.4-4.0 mU/L) or higher (4.1-8.0 mU/L) TSH target (standard TSH [ST] or higher TSH [HT] groups) LT4 for 24 weeks was administered. The outcome measures evaluated were thyroid function tests, QoL, hypothyroid symptoms, cardiovascular risk factors and serum marker of bone resorption in participants that completed the trial (n = 21/24 ST group, n = 19/24 HT group). RESULTS: At 24 weeks, in the ST and HT groups, respectively, median (interquartile range) serum TSH was 1.25 (0.76-1.72) and 5.50 (4.05-9.12) mU/L, mean (± SD) free thyroxine (FT4) was 19.4 ± 3.5 and 15.9 ± 2.4 pmol/L, and daily LT4 dose was 82.1 ± 26.4 and 59.2 ± 23.9 µg. There was no suggestion of adverse impact of a higher serum TSH in the HT group with regard to any of the outcomes assessed. CONCLUSIONS: In hypothyroid patients aged ≥80 years on LT4 therapy for 24 weeks, there was no evidence that a higher target serum TSH was associated with an adverse impact on patient reported outcomes, cardiovascular risk factors or bone resorption marker over 24 weeks. Longer-term trials assessing morbidity and mortality outcomes and health-utility in this age group are feasible and should be performed.

Cost-effectiveness of child caries management: a randomised controlled trial (FiCTION trial).

BACKGROUND: A three-arm parallel group, randomised controlled trial set in general dental practices in England, Scotland, and Wales was undertaken to evaluate three strategies to manage dental caries in primary teeth. Children, with at least one primary molar with caries into dentine, were randomised to receive Conventional with best practice prevention (C + P), Biological with best practice prevention (B + P), or best practice Prevention Alone (PA). METHODS: Data on costs were collected via case report forms completed by clinical staff at every visit. The co-primary outcomes were incidence of, and number of episodes of, dental pain and/or infection avoided. The three strategies were ranked in order of mean cost and a more costly strategy was compared with a less costly strategy in terms of incremental cost-effectiveness. Costs and outcomes were discounted at 3.5%. RESULTS: A total of 1144 children were randomised with data on 1058 children (C + P n = 352, B + P n = 352, PA n = 354) used in the analysis. On average, it costs £230 to manage dental caries in primary teeth over a period of up to 36 months. Managing children in PA was, on average, £19 (97.5% CI: -£18 to £55) less costly than managing those in B + P. In terms of effectiveness, on average, there were fewer incidences of, (- 0.06; 97.5% CI: - 0.14 to 0.02) and fewer episodes of dental pain and/or infection (- 0.14; 97.5% CI: - 0.29 to 0.71) in B + P compared to PA. C + P was unlikely to be considered cost-effective, as it was more costly and less effective than B + P. CONCLUSIONS: The mean cost of a child avoiding any dental pain and/or infection (incidence) was £330 and the mean cost per episode of dental pain and/or infection avoided was £130. At these thresholds B + P has the highest probability of being considered cost-effective. Over the willingness to pay thresholds considered, the probability of B + P being considered cost-effective never exceeded 75%. TRIAL REGISTRATION: The trial was prospectively registered with the ISRCTN (reference number ISRCTN77044005) on the 26th January 2009 and East of Scotland Research Ethics Committee provided ethical approved (REC reference: 12/ES/0047).

Best-practice prevention alone or with conventional or biological caries management for 3- to 7-year-olds: the FiCTION three-arm RCT.

BACKGROUND: Historically, lack of evidence for effective management of decay in primary teeth has caused uncertainty, but there is emerging evidence to support alternative strategies to conventional fillings, which are minimally invasive and prevention orientated. OBJECTIVES: The objectives were (1) to assess the clinical effectiveness and cost-effectiveness of three strategies for managing caries in primary teeth and (2) to assess quality of life, dental anxiety, the acceptability and experiences of children, parents and dental professionals, and caries development and/or progression. DESIGN: This was a multicentre, three-arm parallel-group, participant-randomised controlled trial. Allocation concealment was achieved by use of a centralised web-based randomisation facility hosted by Newcastle Clinical Trials Unit. SETTING: This trial was set in primary dental care in Scotland, England and Wales. PARTICIPANTS: Participants were NHS patients aged 3-7 years who were at a high risk of tooth decay and had at least one primary molar tooth with decay into dentine, but no pain/sepsis. INTERVENTIONS: Three interventions were employed: (1) conventional with best-practice prevention (local anaesthetic, carious tissue removal, filling placement), (2) biological with best-practice prevention (sealing-in decay, selective carious tissue removal and fissure sealants) and (3) best-practice prevention alone (dietary and toothbrushing advice, topical fluoride and fissure sealing of permanent teeth). MAIN OUTCOME MEASURES: The clinical effectiveness outcomes were the proportion of children with at least one episode (incidence) and the number of episodes, for each child, of dental pain or dental sepsis or both over the follow-up period. The cost-effectiveness outcomes were the cost per incidence of, and cost per episode of, dental pain and/or dental sepsis avoided over the follow-up period. RESULTS: A total of 72 dental practices were recruited and 1144 participants were randomised (conventional arm, n = 386; biological arm, n = 381; prevention alone arm, n = 377). Of these, 1058 were included in an intention-to-treat analysis (conventional arm, n = 352; biological arm, n = 352; prevention alone arm, n = 354). The median follow-up time was 33.8 months (interquartile range 23.8-36.7 months). The proportion of children with at least one episode of pain or sepsis or both was 42% (conventional arm), 40% (biological arm) and 45% (prevention alone arm). There was no evidence of a difference in incidence or episodes of pain/sepsis between arms. When comparing the biological arm with the conventional arm, the risk difference was -0.02 (97.5% confidence interval -0.10 to 0.06), which indicates, on average, a 2% reduced risk of dental pain and/or dental sepsis in the biological arm compared with the conventional arm. Comparing the prevention alone arm with the conventional arm, the risk difference was 0.04 (97.5% confidence interval -0.04 to 0.12), which indicates, on average, a 4% increased risk of dental pain and/or dental sepsis in the prevention alone arm compared with the conventional arm. Compared with the conventional arm, there was no evidence of a difference in episodes of pain/sepsis among children in the biological arm (incident rate ratio 0.95, 97.5% confidence interval 0.75 to 1.21, which indicates that there were slightly fewer episodes, on average, in the biological arm than the conventional arm) or in the prevention alone arm (incident rate ratio 1.18, 97.5% confidence interval 0.94 to 1.48, which indicates that there were slightly more episodes in the prevention alone arm than the conventional arm). Over the willingness-to-pay values considered, the probability of the biological treatment approach being considered cost-effective was approximately no higher than 60% to avoid an incidence of dental pain and/or dental sepsis and no higher than 70% to avoid an episode of pain/sepsis. CONCLUSIONS: There was no evidence of an overall difference between the three treatment approaches for experience of, or number of episodes of, dental pain or dental sepsis or both over the follow-up period. FUTURE WORK: Recommendations for future work include exploring barriers to the use of conventional techniques for carious lesion detection and diagnosis (e.g. radiographs) and developing and evaluating suitable techniques and strategies for use in young children in primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77044005. 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. 24, No. 1. See the NIHR Journals Library website for further project information.

WHAT WAS THE QUESTION?: Tooth decay is common; it can lead to pain, days off school for children and days off work for parents and is a financial burden to the NHS. There is uncertainty about the best way of managing decay in young children. This trial aimed to find out whether or not there was a difference in the amount of pain and/or infection suffered by children having their decay treated with one of the following: fillings, having decay sealed in or using preventative treatment alone. Which method represented the best value was also explored. WHAT DID WE DO?: For young children with decay, the Filling Children's Teeth: Indicated Or Not? (FiCTION) trial compared the difference between fillings, sealing in the decay and using preventative treatment alone over 3 years in NHS dental practices in Scotland, England and Wales. We recruited 1144 children aged 3­7 years with one or more holes in their baby back teeth (molars), but without pain/infection, and placed them at random into one of three groups: (1) tooth numbing, removing decay and filling(s) with preventative treatment; (2) sealing in decay with fillings or caps and preventative treatment but no numbing; or (3) preventative treatment alone. WHAT DID WE FIND?: Recruitment was challenging but was achieved. There was no evidence of a difference in children's experience of pain or infection, quality of life or dental anxiety between groups. All three ways of treating decay were acceptable to children, parents and dental professionals. Sealing in with preventative treatment was most likely to be considered the best way of managing children's decay if we are willing to pay a minimum of £130 to avoid an episode of pain or infection. WHAT DOES THIS MEAN?: As there was no evidence of a difference between the three treatment groups in pain/infection experienced, treatment choice should continue to be based on shared decision-making between the child, parent and clinician to agree the best option for the individual child.

A feasibility study with embedded pilot randomised controlled trial and process evaluation of electronic cigarettes for smoking cessation in patients with periodontitis.

BACKGROUND: Tobacco smoking is a major risk factor for several oral diseases, including periodontitis, and electronic cigarettes (e-cigarettes) are increasingly being used for smoking cessation. This study aimed to assess the viability of delivering and evaluating an e-cigarette intervention for smoking cessation within the dental setting, prior to a definitive study. METHODS: A feasibility study, comprising a pilot randomised controlled trial and qualitative process evaluation, was conducted over 22 months in the Newcastle upon Tyne Hospitals NHS Dental Clinical Research Facility, UK. The pilot trial comprised a two-armed, parallel group, individually randomised, controlled trial, with 1:1 allocation. Participant eligibility criteria included being a tobacco smoker, having periodontitis and not currently using an e-cigarette. All participants received standard non-surgical periodontal therapies and brief smoking cessation advice. The intervention group additionally received an e-cigarette starter kit with brief training. Proposed outcomes for a future definitive trial, in terms of smoking behaviour and periodontal/oral health, were collected over 6 months to assess data yield and quality and estimates of parameters. Analyses were descriptive, with 95% confidence intervals presented, where appropriate. RESULTS: Eighty participants were successfully recruited from a range of dental settings. Participant retention was 73% (n = 58; 95% CI 62-81%) at 6 months. The e-cigarette intervention was well received, with usage rates of 90% (n = 36; 95% CI 77-96%) at quit date. Twenty percent (n = 8; 95% CI 11-35%) of participants in the control group used an e-cigarette at some point during the study (against advice). The majority of the outcome measures were successfully collected, apart from a weekly smoking questionnaire (only 30% of participants achieved ≥ 80% completion). Reductions in expired air carbon monoxide over 6 months of 6 ppm (95% CI 1-10 ppm) and 12 ppm (95% CI 8-16 ppm) were observed in the control and intervention groups, respectively. Rates of abstinence (carbon monoxide-verified continuous abstinence for 6 months) for the two groups were 5% (n = 2; 95% CI 1-17%; control group) and 15% (n = 6; 95% CI 7-29%; intervention group). CONCLUSIONS: Data suggest that a definitive trial is feasible and that the intervention may improve smoking quit rates. Insights were gained into how best to conduct the definitive trial and estimates of parameters to inform design were obtained. TRIAL REGISTRATION: ISRCTN, ISRCTN17731903; registered 19 September 2016 http://www.isrctn.com/ISRCTN17731903.

Randomised, double-blind, placebo-controlled pilot trial of omeprazole in idiopathic pulmonary fibrosis.

BACKGROUND: Cough is a common, disabling symptom of idiopathic pulmonary fibrosis (IPF), which may be exacerbated by acid reflux. Inhibiting gastric acid secretion could potentially reduce cough. This study aimed to determine the feasibility of a larger, multicentre trial of omeprazole for cough in IPF, to assess safety and to quantify cough. METHODS: Single-centre, double-blind, randomised, placebo-controlled pilot trial of the proton pump inhibitor (PPI) omeprazole (20 mg twice daily for 3 months) in patients with IPF. Primary objectives were to assess feasibility and acceptability of trial procedures. The primary clinical outcome was cough frequency. RESULTS: Forty-five participants were randomised (23 to omeprazole, 22 to placebo), with 40 (20 in each group) having cough monitoring before and after treatment. 280 patients were screened to yield these numbers, with barriers to discontinuing antacids the single biggest reason for non-recruitment. Recruitment averaged 1.5 participants per month. Geometric mean cough frequency at the end of treatment, adjusted for baseline, was 39.1% lower (95% CI 66.0% lower to 9.3% higher) in the omeprazole group compared with placebo. Omeprazole was well tolerated and adverse event profiles were similar in both groups, although there was a small excess of lower respiratory tract infection and a small fall in forced expiratory volume and forced vital capacity associated with omeprazole. CONCLUSIONS: A large randomised controlled trial of PPIs for cough in IPF appears feasible and justified but should address barriers to randomisation and incorporate safety assessments in relation to respiratory infection and changes in lung function.

Study of Optimal Replacement of Thyroxine in the Elderly (SORTED) - results from the feasibility randomised controlled trial.

BACKGROUND: Hypothyroidism is a common condition, particularly in the older population. Thyroid hormone requirements change with age and serum TSH levels also alter, especially in older patients. However, in practice laboratory reference ranges for thyroid function are not age-specific and treatment in older patients aims to achieve a similar target thyroid function level as younger age groups. METHODS: A dual centre, single blind, randomised controlled trial was conducted to determine the feasibility of a future definitive RCT in hypothyroid individuals aged 80 years or older who were treated with levothyroxine. Potential participants were identified from 17 research-active GP practices (n = 377), by opportunistic invitations (n = 9) or in response to publicity (n = 4). Participants were randomly allocated to either usual (0.4-4.0 mU/L) or a higher (4.1-8.0 mU/L) target serum TSH range. Information on participants' willingness to enter the trial, acceptability of study design, length of time to complete recruitment and dose titration strategy was collected. RESULTS: Fifteen percent (57/390) of potentially eligible hypothyroid individuals consented to participate in this trial and 48 were randomised to trial medication for 24 weeks, giving a recruitment rate of 12 %. Recruitment averaged 5.5 participants per month over approximately 9 months. Eight participants withdrew (3/24 and 5/24 in the usual and higher TSH arms, respectively) with the commonest reason cited (5 patients) being tiredness. Interestingly, 3/5 participants withdrew from the site that required a visit to a Research Facility whereas only 5/43 participants withdrew from the site that offered home visits. In the higher TSH arm, of those participants who completed the study, approximately half of participants (10/19) reached target TSH. CONCLUSIONS: It is feasible to perform a randomised controlled trial of thyroid hormones in hypothyroid patients aged 80 or older. A definitive trial would require collaboration with a large number of General Practices and the provision of home visits to achieve recruitment to time and target. Power calculations should take into account that approximately 12 % of those approached will be randomised and 1 in 6 participants are likely to withdraw from the study. Finally, several dose adjustments may be required to achieve target serum TSH levels in this age group. TRIAL REGISTRATION: ISRCTN Number: 16043724 Registered 22 June 2012 Clinicaltrial.gov Number: NCT01647750 EudraCT Number: 2011-004425-27.

Alcohol-related risk and harm amongst young offenders aged 11-17.

PURPOSE: The purpose of this paper is to examine the prevalence of alcohol use disorders (AUDs) amongst young people in the criminal justice system (CJS) in the North East of England and to compare the ability of the Alcohol Use Disorders Identification Test (AUDIT) to the Youth Justice Board ASSET tool in identifying alcohol-related need in Youth Offending Team (YOT) clients. DESIGN/METHODOLOGY/APPROACH: A validated screening tool (AUDIT) was used to identify alcohol-related health risk or harm. Findings from AUDIT were compared with those of the standard criminogenic risk screening tool used in CJS (ASSET). An anonymous cross-sectional questionnaire was administered during a one-month period in 2008. The questionnaires were completed by 11-17-year-old offenders who were in contact with three YOTs, one Youth Offending Institution and one Secure Training Estate. FINDINGS: In total, 429 questionnaires were completed out of a possible 639 (67 per cent). The majority (81 per cent) of the young offenders were identified as experiencing alcohol-related health risk or harm and 77 per cent scored within a possibly alcohol-dependent range. In total, 77 (30 per cent) of young people completing both assessments were identified as having an AUD by AUDIT but not identified as needing alcohol-related treatment using ASSET. RESEARCH LIMITATIONS/IMPLICATIONS: This research was confined to one geographical area of England, however, the results show that even in this area of high drinking by young people the levels of AUDs amongst young people in the CJS are very high. Social implications - There are major social implications to this research. It is imperative for changes to be made to the care pathways in place in the UK for young people coming through the CJS with alcohol-related issues. ORIGINALITY/VALUE: This paper adds to the evidence base by using well-validated tools to measure alcohol use amongst young people in the CJS in the UK.

INVESTIGATING THE MANAGEMENT OF CARIOUS PRIMARY TEETH IN GENERAL DENTAL PRACTICE: AN OVERVIEW OF THE DEVELOPMENT AND CONDUCT OF THE FICTION TRIAL.

The management of carious primary teeth is a challenge for patients, parents and clinicians. Most evidence supporting different management strategies originates from a specialist setting and therefore its relevance to the primary care setting is questionable. The UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) has commissioned the FiCTION (Filling Children's Teeth: Indicated Or Not?) trial; a multi-centre primary dental care randomised controlled trial (RCT) to determine the most clinically and cost- effective approach to managing caries in the primary dentition in the UK. This large trial began in 2012, is due to be completed in late 2017 and involves 72 practices and 1,124 children initially aged three to seven years with dentine caries, following randomisation to one of three caries management strategies. Clinical, radiographic, quality of life, treatment acceptability and health economics data are collected during the three-year follow up period. This article provides an overview of the development and conduct of FiCTION and discusses some approaches adopted to manage challenges and achieve the patient recruitment target.

A feasibility study of a Family Focused Treatment for Adolescents with Bipolar Disorder-the FAB study.

BACKGROUND: The aim of this study is to examine the feasibility of a future definitive randomised controlled trial of Family Focused Treatment for Adolescents UK (FFT-A UK) in the management of early-onset bipolar disorder (EOBD) (under 18 years). The FFT-A has been evaluated in the USA to augment the pharmacological treatment of adolescents with bipolar disorder (BD). The FFT-A UK has been condensed to 16 sessions over approximately 6 months to be utilised within the UK National Health Service. Research from the USA suggests that families experience high levels of distress, stress, burden and family disharmony when living with a young person who has BD. The FFT-A UK is a family-based approach designed to increase understanding of BD (psycho-education), improve communication and increase ability to problem-solve. METHODS/DESIGN: The trial will examine the feasibility of a randomised, parallel group, non-blinded design and the procedures of a subsequent definitive trial. Thirty-three young people with BD and their families will be recruited. Participants will complete measures at baseline, on completion of the 6-month treatment and again after a further 6 months. The self-report measures include the Warwick Edinburgh Mental Well-being Scale, The McMaster Family Assessment Device (FAD), Conflict Behaviour Questionnaire aka 'Interaction Behaviour Questionnaire', EuroQuol EQ-5D-3L and EQ-5D-Y. Primary outcomes will be rates of eligibility, recruitment and retention, estimates of the variability in the self-report measures and assessment of the intervention delivery in the study population. Participants' qualitative views on the measures and intervention will be sought to confirm the acceptability of intervention and study design. The health economics component will establish how cost-effectiveness will be assessed in a future definitive trial. DISCUSSION: The study will produce a full trial protocol and amendments to the FFT-A UK to inform a well-designed multi-centre randomised controlled trial (RCT) as an adjunct to pharmacotherapy in the management of EOBD. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59769322.

Feasibility, acceptability and outcomes at a 12-month follow-up of a novel community-based intervention to prevent type 2 diabetes in adults at high risk: mixed methods pilot study.

OBJECTIVES AND DESIGN: Lifestyle interventions can prevent type 2 diabetes (T2D) in adults with impaired glucose tolerance. In a mixed methods pilot study, we aimed to assess the feasibility, acceptability and outcomes at a 12-month follow-up of a behavioural intervention for adults at risk of T2D. PARTICIPANTS: Adults aged 45-65 years with a Finnish Diabetes Risk Score (FINDRISC) ≥11. SETTING: The intervention was delivered in leisure and community settings in a local authority that ranks in the 10 most socioeconomically deprived in England. INTERVENTION: A 10-week supported programme to promote increased physical activity (PA), healthy eating and weight loss was delivered by fitness trainers as twice-weekly group PA or cookery sessions, each followed by behavioural counselling with support to 12 months. OUTCOME MEASURES: We assessed feasibility and acceptability of the intervention, and change in behavioural and health-related outcomes at 6 and 12 months. RESULTS: From 367 registers of interest, 218 participants were recruited to the programme with baseline mean (SD): age 53.6 (6) years, FINDRISC 13.9 (3.1), body mass index 33.5 (5.9) kg/m(2), waist circumference 108.1 (13.7) cm, PA levels (self-report): daily total 49.1 (5.9) metabolic-equivalent (MET) h/day. Follow-up at 12 months was completed by 134 (61%) participants, with an estimated mean (95% CI) change from baseline in weight -5.7 (-7.8 to -2.8); -2.8 (-3.8 to -1.9) kg, waist circumference -7.2 (-9.2 to -5.2); -6.0 (-7.1 to -5.0) cm, and PA level 7.9 (5.8 to 10.1); 6.7 (5.2 to 8.2) MET h/day equivalent, for men and women, respectively (from covariance pattern mixed models). Participants reported an enjoyable, sociable and supportive intervention experience. CONCLUSIONS: Participants' views indicated a high level of intervention acceptability. High retention and positive outcomes at 12 months provide encouraging indications of the feasibility and potential effectiveness of the intervention. A definitive trial of this intervention is warranted.

The influence of neighbourhood formality status and socio-economic position on self-rated health among adult men and women: a multilevel, cross sectional, population study from Aleppo, Syria.

BACKGROUND: There is substantial evidence from high income countries that neighbourhoods have an influence on health independent of individual characteristics. However, neighbourhood characteristics are rarely taken into account in the analysis of urban health studies from developing countries. Informal urban neighbourhoods are home to about half of the population in Aleppo, the second largest city in Syria (population>2.5 million). This study aimed to examine the influence of neighbourhood socioeconomic status (SES) and formality status on self-rated health (SRH) of adult men and women residing in formal and informal urban neighbourhoods in Aleppo. METHODS: The study used data from 2038 survey respondents to the Aleppo Household Survey, 2004 (age 18-65 years, 54.8% women, response rate 86%). Respondents were nested in 45 neighbourhoods. Five individual-level SES measures, namely education, employment, car ownership, item ownership and household density, were aggregated to the level of neighbourhood. Multilevel regression models were used to investigate associations. RESULTS: We did not find evidence of important SRH variation between neighbourhoods. Neighbourhood average of household item ownership was associated with a greater likelihood of reporting excellent SRH in women; odds ratio (OR) for an increase of one item on average was 2.3 (95% CI 1.3-4.4 (versus poor SRH)) and 1.7 (95% CI 1.1-2.5 (versus normal SRH)), adjusted for individual characteristics and neighbourhood formality. After controlling for individual and neighbourhood SES measures, women living in informal neighbourhoods were less likely to report poor SRH than women living in formal neighbourhoods (OR= 0.4; 95% CI (0.2- 0.8) (versus poor SRH) and OR=0.5; 95%; CI (0.3-0.9) (versus normal SRH). CONCLUSIONS: Findings support evidence from high income countries that certain characteristic of neighbourhoods affect men and women in different ways. Further research from similar urban settings in developing countries is needed to understand the mechanisms by which informal neighbourhoods influence women's health.

Study of Optimal Replacement of Thyroxine in the ElDerly (SORTED): protocol for a mixed methods feasibility study to assess the clinical utility of lower dose thyroxine in elderly hypothyroid patients: study protocol for a randomized controlled trial.

BACKGROUND: The population of the UK is ageing. There is compelling evidence that thyroid stimulating hormone distribution levels increase with age. Currently, in UK clinical practice elderly hypothyroid patients are treated with levothyroxine to lower their thyroid stimulating hormone levels to a standard non-age-related range. Evidence suggests that mortality is negatively associated with thyroid stimulating hormone levels. We report the protocol of a feasibility study working towards a full-scale randomized controlled trial to test whether lower dose levothyroxine has beneficial cardiovascular outcomes in the oldest old. METHODS/DESIGN: SORTED is a mixed methods study with three components: SORTED A: A feasibility study of a dual-center single-blinded randomized controlled trial of elderly hypothyroid patients currently treated with levothyroxine. SETTING: Patients will be recruited from 20 general practices and two hospital trust endocrine units in Northumberland, Tyne and Wear. PARTICIPANTS: Target recruitment of 50 elderly hypothyroid patients currently treated with levothyroxine, identified in both primary and secondary care settings. INTERVENTION: Reduced dose of levothyroxine to achieve an elevated serum thyroid stimulating hormone (target range 4.1 to 8.0 mU/L) versus standard levothyroxine replacement (target range 0.4 to 4.0 mU/L). RANDOMIZATION: Using random permuted blocks, in a ratio of 1:1, randomization will be carried out by Newcastle Clinical Trials Unit. OUTCOMES: Study feasibility (recruitment and retention rates and medication compliance), acceptability of the trial design, assessment of mobility and falls risk, and change in cardiovascular risk factors. SORTED B: Qualitative study using in-depth interviews to understand patients' willingness to take part in a randomized controlled trial and participants' experience of the intervention. SORTED C: Retrospective cohort study of 400 treated hypothyroid patients aged 80 years or over registered in 2008 in primary care practices, studying their 4-year cardiovascular outcomes to inform the power of SORTED II. DISCUSSION: This is a study to evaluate the feasibility of conducting a randomized controlled trial in elderly hypothyroid patients in general practice and hospital settings. The results will inform the design of the definitive SORTED II trial to evaluate the effects of lower dose thyroxine in elderly hypothyroid patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16043724.